Medical uses of bicalutamide: Difference between revisions

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Bicalutamide is mainly used in and is only approved for the following indications:^[1]

Metastatic prostate cancer (mPC) in men in combination with a gonadotropin-releasing hormone (GnRH) analogue or orchiectomy at moderate doses^[2]^[3]
Locally advanced prostate cancer (LAPC) in men as a monotherapy in high doses^[2]^[4]^[5]^[6]

It can also be and is used to a lesser extent for the following off-label (non-approved) indications:

Androgen-dependent skin and hair conditions such as acne, seborrhea, hirsutism, and pattern hair loss (androgenic alopecia) in women at low doses, generally in combination with an oral contraceptive^[7]^[8]^[9]^[10]^[11]
Hyperandrogenism such as due to polycystic ovary syndrome (PCOS) or congenital adrenal hyperplasia (CAH) in women
Hormone therapy for transgender women in combination with estrogen or alone^[12]^[13]^[14]^[15]^[16]
Precocious puberty in boys in moderate doses, especially due to familial male-limited precocious puberty (testotoxicosis)^[17]^[18]^[19]^[20]^[21]^[22]
Priapism in men at low to very low doses^[23]^[24]^[25]^[26]^[27]^[28]^[29]

It has been suggested for but has uncertain effectiveness in the following indications:

Hypersexuality and paraphilias, particularly in combination with chemical castration^[30]^[31]^[32]^[33]^[34]^[35]

Prostate cancer

Bicalutamide is used primarily in the treatment of early and advanced prostate cancer.^[1] It is approved at a dosage of 50 mg/day as a combination therapy with a GnRH or orchiectomy (that is, surgical or medical castration) in the treatment of stage D2 mPC,^[2]^[3] and as a monotherapy at a dosage of 150 mg/day for the treatment of stage C or D1 LAPC.^[2]^[4]^[5]^[6] Although effective in mPC and LAPC, bicalutamide is no longer indicated for the treatment of localized prostate cancer (LPC) due to negative findings in the Early Prostate Cancer (EPC) trial.^[5] Prior to the introduction of the newer NSAA enzalutamide in 2012,^[36] bicalutamide was considered to be the standard-of-care antiandrogen in the treatment of prostate cancer, and still remains widely used for this indication.^[37]^[36]^[38] Compared to earlier antiandrogens like the steroidal antiandrogen (SAA) cyproterone acetate (CPA) and the NSAAs flutamide and nilutamide, bicalutamide shows an improved profile of effectiveness, tolerability, and safety,^[39]^[36]^[40]^[41] and for this reason has largely replaced them in the treatment of prostate cancer.^[2]^[42]^[43]^[39]^[44]^[45]^[46]

Role of antiandrogens in prostate cancer

In the early 1940s, it was discovered that growth of prostate cancer in men regressed with surgical castration or high-dose estrogen treatment, which were associated with very low levels of circulating testosterone, and accelerated with the administration of exogenous testosterone.^[47]^[48] It has since been elucidated that androgens like testosterone and DHT function as trophic factors for the prostate gland, stimulating cell division and proliferation and producing tissue growth and glandular enlargement, which, in the context of prostate cancer, results in stimulation of tumors and a considerable acceleration of disease progression.^[49] As a result of these discoveries, androgen deprivation therapy (ADT), via a variety of modalities including surgical castration, high-dose estrogens, SAAs, GnRH analogues, NSAAs, and androgen biosynthesis inhibitors (e.g., abiraterone acetate), has become the mainstay of treatment for prostate cancer.^[47] Although ADT can shrink or stabilize prostate tumors and hence significantly slow the course of prostate cancer and prolong life, it is, unfortunately, not generally curative.^[50] While effective in slowing the progression of the disease initially, most advanced prostate cancer patients eventually become resistant to ADT and prostate cancer growth starts to accelerate again, in part due to progressive mutations in the AR that result in the transformation of drugs like bicalutamide from AR antagonists to agonists.^[51]

A few observations form the basis of the reasoning behind combined androgen blockade (CAB), in which castration and an NSAA are combined.^[52] It has been found that very low levels of androgens, as in castration, are able to significantly stimulate growth of prostate cancer cells and accelerate disease progression.^[53] Although castration ceases production of androgens by the gonads and reduces circulating testosterone levels by about 95%,^[54] low levels of androgens continue to be produced by the adrenal glands, and this accounts for the residual levels of circulating testosterone.^[55] Moreover, it has been found that prostate gland levels of DHT, which is the major androgen in the prostate, remain at 40 to 50% of their initial values following castration.^[55]^[56] This has been determined to be due to uptake of circulating weak adrenal androgens like dehydroepiandrosterone (DHEA) and androstenedione (A4) by the prostate and their de novo transformation into testosterone and DHT.^[55]^[56]^[57] As such, a considerable amount of androgen signaling continues within the prostate gland even with castration.^[55]^[56]^[57]

In the past, surgical adrenalectomy and early androgen biosynthesis inhibitors like ketoconazole and aminoglutethimide were successfully employed in the treatment of castration-resistant prostate cancer.^[54]^[47]^[58]^[59] However, adrenalectomy is an invasive procedure with high morbidity, ketoconazole and aminoglutethimide have relatively high toxicity, and both treatment modalities require supplementation with corticosteroids, making them in many ways unideal.^[47]^[60]^[61]^[62] The development of CAB with NSAAs like bicalutamide and enzalutamide and with newer and more tolerable androgen biosynthesis inhibitors like abiraterone acetate has since allowed for non-invasive, convenient, and well-tolerated therapies that have replaced the earlier modalities.^[59]^[63]

Subsequent clinical research has found that monotherapy with higher dosages of NSAAs than those used in CAB is roughly equivalent to castration in extending life in men with prostate cancer.^[39]^[47]^[64]^[65] Moreover, NSAA monotherapy is overall better tolerated and associated with greater quality of life than is castration,^[66]^[67]^[68]^[69] which is thought to be related to the fact that testosterone levels do not decrease with NSAA monotherapy and hence by extension that levels of biologically active and beneficial metabolites of testosterone such as estrogens and neurosteroids are preserved.^[68]^[69]^[70]^[71]^[72] For these reasons, NSAA monotherapy has become an important alternative to castration and CAB in the treatment of prostate cancer.^[73]^[74]^[75]

Skin and hair conditions

Androgens like testosterone and DHT play a critical role in the pathogenesis of a number of dermatological conditions including acne, seborrhea, hirsutism (excessive facial/body hair growth in women), and pattern hair loss (androgenic alopecia).^[77] In demonstration of this, women with complete androgen insensitivity syndrome (CAIS) do not produce sebum or develop acne and have little to no body, pubic, or axillary hair.^[78]^[79] Moreover, men with congenital 5α-reductase type II deficiency, 5α-reductase being an enzyme that greatly potentiates the androgenic effects of testosterone in the skin, have little to no acne, scanty facial hair, reduced body hair, and reportedly no incidence of male pattern hair loss.^[80]^[81]^[82]^[83]^[76] Conversely, hyperandrogenism in women, for instance due to PCOS or CAH, is commonly associated with acne and hirsutism as well as virilization (masculinization) in general.^[77] In accordance with the preceding, antiandrogens have been found to be highly effective in the treatment of the aforementioned androgen-dependent skin and hair conditions.^[84]^[85]

Low-dose bicalutamide has been found to be effective in the treatment of hirsutism in women in clinical studies.^[7]^[8]^[86] In one of the studies, the drug was well-tolerated, all of the patients experienced a visible decrease in hair density, and a highly significant clinical improvement was observed with the Ferriman–Gallwey score decreasing by 41.2% at 3 months and by 61.6% at 6 months.^[87]^[88] According to a 2013 review, "Low dose bicalutamide (25 mg/day) was shown to be effective in the treatment of hirsutism related to IH and PCOS. It does not have any significant side effects [or lead] to irregular periods."^[8]

In addition to hirsutism, bicalutamide can also be used in the treatment of acne in women.^[9]^[10] Several studies have observed complete clearing of acne with flutamide in women, and similar benefits would be expected with bicalutamide.^[89]^{: 712–717} Bicalutamide may also treat other androgen-dependent skin and hair conditions like seborrhea and pattern hair loss.^[11] Flutamide has been found to produce a decrease of hirsutism score to normal and an 80% or greater decrease in scores of acne, seborrhea, and androgen-dependent hair loss.^[90] Moreover, in combination with an oral contraceptive, flutamide treatment resulted in an increase in cosmetically acceptable scalp hair density in 6 of 7 women suffering from pattern hair loss.^[89]

Antiandrogens like flutamide and bicalutamide are male-specific teratogens which can feminize male fetuses due to their antiandrogen effects (see below),^[84]^[91]^[92] and for this reason, are not recommended by the FDA for use in women.^[93] Because of this risk, it is strongly recommended that antiandrogens only be used to treat women who are of reproductive age in conjunction with adequate contraception.^[84]^[91]^[92] Oral contraceptives, which contain an estrogen and a progestin, are typically used for this purpose.^[84] Moreover, oral contraceptives themselves are functional antiandrogens and are independently effective in the treatment of androgen-dependent skin and hair conditions, and hence can significantly augment the effectiveness of antiandrogens in the treatment of such conditions.^[84]^[94]

Transgender hormone therapy

Bicalutamide is used as a component of hormone replacement therapy (HRT) for transgender women.^[12]^[13]^[14]^[15]^[16] Beneficial or desired effects consist of demasculinization and feminization, and include breast development,^[95]^[96]^[97] reduced male-pattern hair,^[98] decreased muscle mass,^[99] feminine changes in fat distribution, lowered libido,^[99] and loss of spontaneous erections.^[100] It is also noteworthy that, when used as a monotherapy, bicalutamide significantly increases estradiol levels in biological males and hence can have indirect estrogenic effects in transgender women; this is a property that can be considered to be desirable in transgender women, as it can produce or contribute to feminization.^[101]^[102]

Unlike the SAAs CPA and spironolactone, as well as GnRH analogues,^[103] no clinical studies assessing bicalutamide as an antiandrogen in the hormonal therapy of transgender women appear to have been conducted to date.^[104] In any case, bicalutamide is clinically effective as an antiandrogen in women with hirsutism^[7]^[8] and in boys with precocious puberty,^[17]^[18]^[19]^[22] and demasculinization and feminization are well-documented effects of bicalutamide in men treated with it for prostate cancer (see below).^[98]^[105]^[106] In addition, nilutamide, a closely related antiandrogen that possesses essentially the same mechanism of action as bicalutamide, has been evaluated in transgender women in at least five small clinical studies.^[101]^[107]^[108]^[109]^[110]^[111] It was given at a high dosage of 300 mg/day, the same dosage in which it has been used as a monotherapy in the treatment of prostate cancer.^[101]^[107]^[108]^[109]^[110]^[111] The corresponding monotherapy dosage of bicalutamide in the treatment of prostate cancer is 150 mg/day.^[2]^[4]^[5]

In the clinical studies of nilutamide for transgender hormone therapy, the drug, without being combined with estrogen, induced observable signs of clinical feminization in young transgender women (age range 19–33 years) within 8 weeks,^[108] including breast development, decreased male-pattern hair,^[107] decreased spontaneous erections and sex drive,^[109] and positive psychological and emotional changes.^[109]^[112] Signs of breast development occurred in all subjects within 6 weeks and were associated with increased nipple sensitivity;^[111]^[108]^[109] along with decreased hair growth, these changes were the earliest signs of feminization.^[108] The drug more than doubled luteinizing hormone (LH) and testosterone levels and tripled estradiol levels (see below),^[107]^[108]^[110] and the addition of ethinylestradiol, a potent estrogen, to nilutamide therapy after 8 weeks of treatment abolished the increase in LH, testosterone, and estradiol levels and dramatically suppressed testosterone levels, into the castrate range.^[107]^[108] On the basis of these results, both nilutamide alone, and particularly the combination of nilutamide and an estrogen, were regarded as effective in terms of producing antiandrogen effects and feminization in transgender women.^[107]^[108]

Although nilutamide has been found to be clinically effective for transgender hormone therapy, the use of nilutamide in the treatment of prostate cancer and particularly for other indications that are of a less dire nature is now discouraged due to the unique adverse effects of the drug, most importantly a high incidence of interstitial pneumonitis.^[49]^[113]^[114] This is an adverse effect that can progress to pulmonary fibrosis and can potentially be fatal.^[115] For this reason, newer, safer NSAAs like bicalutamide have largely replaced nilutamide and are now used for such indications instead.^[44]^[45]^[46]

Madeline Deutsch of the Center of Excellence for Transgender Health at the University of California, San Francisco, in her Guidelines for the Primary and Gender-Affirming Care of Transgender and Gender Nonbinary People (2016), has said the following on the topic of bicalutamide in transgender women:^[16]

In many countries, cyproterone acetate, a synthetic progestagen with strong anti-androgen activity is commonly used [as an antiandrogen in feminizing hormone therapy for transgender women]. Cyproterone [acetate] has been associated with uncommon episodes of fulminant hepatitis.[12] Bicalutamide, a direct anti-androgen used for the treatment of prostate cancer, also has a small but not fully quantified risk of liver function abnormalities (including several cases of fulminant hepatitis); while such risks are acceptable when considering the benefits of bicalutamide in the management of prostate cancer, such risks are less justified in the context of gender-affirming treatment.[13] No evidence at present exists to inform such an analysis.^[16]

In spite of its risk of hepatotoxicity, CPA is the most widely used antiandrogen in Europe and elsewhere in the world for hormone therapy in transgender women.^[101]^[116]^[117] In addition, it is widely used in cisgender women for the treatment of acne and hirsutism.^[118] In the U.S., one of the only countries where CPA has not been approved for medical use,^[119]^[120] the relatively weak agent spironolactone is the antiandrogen most commonly used in transgender and cisgender women instead.^[121]^[122]^[123] Although both CPA and bicalutamide have been associated with hepatotoxicity (while spironolactone is not usually associated with such), bicalutamide has a far lower and only small risk of both elevated liver enzymes and hepatotoxicity (see below);^[124] whereas CPA has been associated with over 100 reports of hepatotoxicity,^[125] five cases of hepatotoxicity, out of millions of patient exposures, have been associated with bicalutamide to date.^[126]^[127]

Male early puberty

Bicalutamide (25–50 mg/day) is useful in combination with the aromatase inhibitor anastrozole as a puberty blocker in the treatment of male precocious puberty.^[17]^[18]^[19] This is potentially a cost-effective alternative to GnRH analogues for the treatment of this condition, as GnRH analogues are very expensive.^[128]^[129] Moreover, the combination is effective in gonadotropin-independent precocious puberty, namely familial male-limited precocious puberty (also known as testotoxicosis), where GnRH analogues notably are not effective.^[18]^[19]^[20] Bicalutamide has been found to be superior to the SAA spironolactone (which has also been used, in combination with the aromatase inhibitor testolactone) for this indication; it has shown greater effectiveness and possesses fewer side effects in comparison.^[18]^[21] For this reason, bicalutamide has replaced spironolactone in the treatment of the condition.^[22]^: 2139

Priapism

Antiandrogens can considerably relieve and prevent priapism (potentially painful penile erections that last more than four hours) via direct blockade of penile ARs.^[23]^[24] In accordance, bicalutamide, at low dosages (50 mg every other day or as little as once or twice weekly), has been found in a series of case reports to completely resolve recurrent priapism in men without producing significant side effects,^[25]^[26]^[29] and is used for this indication off-label.^[27]^[28] In the reported cases, libido, rigid erections, the potential for sexual intercourse, orgasm, and subjective ejaculatory volume have all remained intact or unchanged, and gynecomastia has not developed when bicalutamide is administered at a total dosage of 25 mg/day or less.^[25]^[26]^[29] Some gynecomastia and breast tenderness developed in one patient treated with 50 mg/day, but significantly improved upon the dosage being halved.^[29] The observed tolerability profile of bicalutamide in these subjects has been regarded as significantly more favorable than that of GnRH analogues and estrogens (which are also used in the treatment of this condition).^[25]^[26] However, although successful and well-tolerated, very few cases have been reported.^[130]

Paraphilias and hypersexuality

The antigonadotropic antiandrogens CPA, medroxyprogesterone acetate (MPA), and GnRH analogues have all been widely used to treat paraphilias (e.g., pedophilia) and hypersexuality in men.^[30]^[34] They suppress androgen levels to castrate or near-castrate levels and are highly effective in reducing sexual urges, arousal, and behaviors.^[30] In addition, they are used to treat sex offenders as a means of chemical castration for the purpose of reducing the likelihood of recidivism.^[30]

Although they have not been studied in the treatment of paraphilias and hypersexuality, NSAAs like flutamide and bicalutamide have been suggested as potential medications for these indications and may have superior tolerability and safety relative to antigonadotropic antiandrogens.^[30]^[31]^[32]^[33] As an example, because NSAAs do not reduce estrogen levels, unlike antigonadotropic antiandrogens, they preserve bone mineral density (BMD) and have little or no risk of osteoporosis and associated bone fractures.^[30]^[31]^[131] However, due to unopposed estrogen signaling, a substantial incidence of gynecomastia is associated with NSAAs.^[30] In addition to potential monotherapy use, NSAAs have been advocated for temporarily suppressing sex drive during the start of GnRH agonist treatment via prevention of the increased androgen signaling associated with the initial testosterone flare.^[34]

Though treatment of paraphilias and hypersexuality with selective AR antagonists is a seemingly sound strategy, this may not be true in practice.^[67] Surprisingly, little or no sexual dysfunction, including loss of sex drive and decreased sexual activity, has been observed in clinical studies of NSAA monotherapy.^[67]^[5] The explanation for this is that NSAAs do not lower androgen levels, and metabolites of testosterone like estrogens and neurosteroids may be of critical importance for maintenance of sex drive and function in males.^[68]^[69]^[70]^[71]^[72] In accordance, testosterone is locally aromatized into estradiol widely throughout the brain and estradiol appears to be the mediator of many of the central actions of testosterone.^[84] For these reasons, unlike antigonadotropic antiandrogens, NSAA monotherapy may have limited usefulness in the management of paraphilias and hypersexuality.^[67] The addition of NSAAs to antigonadotropic antiandrogens like GnRH analogues may have some usefulness however, particularly in severe cases.^[34]^[35] In any case, insufficient evidence is available at this time, and further research is thus warranted.^[31]

Available forms

Bicalutamide is available for the treatment of prostate cancer in most developed countries,^[133]^[134]^[135] including over 80 countries worldwide.^[136]^[137] Bicalutamide is available in 50 mg, 80 mg (in Japan),^[138] and 150 mg tablets for oral administration.^[139]^[140] The drug is registered for use as a 150 mg/day monotherapy for the treatment of LAPC in at least 55 countries,^[4] with the U.S. being a notable exception where it is registered only for use at a dosage of 50 mg/day in combination with castration.^[39] No other formulations or routes of administration are available or used.^[139] All formulations of bicalutamide are specifically indicated for the treatment of prostate cancer alone or in combination with surgical or medication castration.^[2] A combined formulation of bicalutamide and the GnRH agonist goserelin in which goserelin is provided as a subcutaneous implant for injection and bicalutamide is included as 50 mg tablets for oral ingestion is marketed in Australia and New Zealand under the brand name ZolaCos CP (Zoladex–Cosudex Combination Pack).^[135]^[141]^[142]^[143]

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^ ^a ^b Rousseau L, Couture M, Dupont A, Labrie F, Couture N (1990). "Effect of combined androgen blockade with an LHRH agonist and flutamide in one severe case of male exhibitionism". The Canadian Journal of Psychiatry. 35 (4): 338–41. doi:10.1177/070674379003500412. PMID 2189544.
^ ^a ^b ^c Vogelzang NJ (September 2012). "Enzalutamide—a major advance in the treatment of metastatic prostate cancer". The New England Journal of Medicine. 367 (13): 1256–7. doi:10.1056/NEJMe1209041. PMID 23013078. The first nonsteroidal antiandrogen agents — flutamide, nilutamide, and bicalutamide2 — were shown to be less effective than castration in cases of metastatic castration-resistant prostate cancer, but bicalutamide is still widely used as a moderately effective secondary hormone therapy because of an excellent safety profile.
^ Cite error: The named reference Regitz-Zagrosek2012 was invoked but never defined (see the help page).
^ Horwich, Alan (11 February 2010). Systemic Treatment of Prostate Cancer. OUP Oxford. pp. 44–. ISBN 978-0-19-956142-1. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
^ ^a ^b ^c ^d Chabner, Bruce A.; Longo, Dan L. (8 November 2010). Cancer Chemotherapy and Biotherapy: Principles and Practice. Lippincott Williams & Wilkins. pp. 679–680. ISBN 978-1-60547-431-1. From a structural standpoint, antiandrogens are classified as steroidal, including cyproterone [acetate] (Androcur) and megestrol [acetate], or nonsteroidal, including flutamide (Eulexin, others), bicalutamide (Casodex), and nilutamide (Nilandron). The steroidal antiandrogens are rarely used. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
^ Weber, Georg F. (22 July 2015). Molecular Therapies of Cancer. Springer. pp. 318–. ISBN 978-3-319-13278-5. Compared to flutamide and nilutamide, bicalutamide has a 2-fold increased affinity for the Androgen Receptor, a longer half-life, and substantially reduced toxicities. Based on a more favorable safety profile relative to flutamide, bicalutamide is indicated for use in combination therapy with a Gonadotropin Releasing Hormone analog for the treatment of advanced metastatic prostate carcinoma. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
^ Kolvenbag GJ, Blackledge GR (January 1996). "Worldwide activity and safety of bicalutamide: a summary review". Urology. 47 (1A Suppl): 70–9, discussion 80–4. doi:10.1016/s0090-4295(96)80012-4. PMID 8560681. Bicalutamide is a new antiandrogen that offers the convenience of once-daily administration, demonstrated activity in prostate cancer, and an excellent safety profile. Because it is effective and offers better tolerability than flutamide, bicalutamide represents a valid first choice for antiandrogen therapy in combination with castration for the treatment of patients with advanced prostate cancer.
^ Kaliks RA, Del Giglio A (2008). "Management of advanced prostate cancer" (PDF). Revista Da Associação Médica Brasileira. 54 (2): 178–82. doi:10.1590/S0104-42302008000200025. PMID 18506331. Archived from the original (PDF) on 10 May 2017. {{cite journal}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
^ Payen, Olivier; Top, Siden; Vessières, Anne; Brulé, Emilie; Lauzier, Agnès; Plamont, Marie-Aude; McGlinchey, Michael J.; Müller-Bunz, Helge; Jaouen, Gérard (2011). "Synthesis and biological activity of ferrocenyl derivatives of the non-steroidal antiandrogens flutamide and bicalutamide" (PDF). Journal of Organometallic Chemistry. 696 (5): 1049–1056. doi:10.1016/j.jorganchem.2010.10.051. Cyproterone acetate was one of the first steroidal antiandrogen clinically used but its side-effects, especially the interaction with the progestin and glucocorticoid receptor, made this drug less popular than the nonsteroidal antiandrogens such as nilutamide [3,4], flutamide [5–7] and bicalutamide [8]. {{cite journal}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
^ ^a ^b Gulley, James Leonard (2011). Prostate Cancer. Demos Medical Publishing. pp. 81–. ISBN 978-1-935281-91-7. Archived from the original on 25 April 2016. {{cite book}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help); Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
^ ^a ^b Moser, Lutz (1 January 2008). Controversies in the Treatment of Prostate Cancer. Karger Medical and Scientific Publishers. pp. 41–42. ISBN 978-3-8055-8524-8. Archived from the original on 16 May 2016. {{cite book}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help); Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
^ ^a ^b Gulley, James L. (20 December 2011). Prostate Cancer. Demos Medical Publishing. pp. 505–. ISBN 978-1-935281-91-7. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
^ ^a ^b ^c ^d ^e Figg, William; Chau, Cindy H.; Small, Eric J. (14 September 2010). Drug Management of Prostate Cancer. Springer Science & Business Media. pp. 56, 71–72, 75, 93. ISBN 978-1-60327-829-4. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
^ Kavoussi, Parviz; Costabile, Raymond A.; Salonia, Andrea (17 October 2012). Clinical Urologic Endocrinology: Principles for Men’s Health. Springer Science & Business Media. pp. 7–. ISBN 978-1-4471-4404-5. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
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^ Munoz J, Wheler JJ, Kurzrock R (2015). "Androgen receptors beyond prostate cancer: an old marker as a new target". Oncotarget. 6 (2): 592–603. doi:10.18632/oncotarget.2831. PMC 4359241. PMID 25595907.
^ Balk SP (September 2002). "Androgen receptor as a target in androgen-independent prostate cancer". Urology. 60 (3 Suppl 1): 132–8, discussion 138–9. doi:10.1016/S0090-4295(02)01593-5. PMID 12231070.
^ Sarosdy MF (1999). "Which is the optimal antiandrogen for use in combined androgen blockade of advanced prostate cancer? The transition from a first- to second-generation antiandrogen". Anticancer Drugs. 10 (9): 791–6. doi:10.1097/00001813-199910000-00001. PMID 10587288.
^ Dasgupta, Prokar; Kirby, Roger S. (27 December 2011). ABC of Prostate Cancer. John Wiley & Sons. pp. 52–. ISBN 978-1-4443-3437-1. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
^ ^a ^b Bruskewitz, Reginald (6 December 2012). Atlas of the Prostate. Springer Science & Business Media. pp. 5, 190. ISBN 978-1-4615-6505-5. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
^ ^a ^b ^c ^d Denis, Louis (6 December 2012). Antiandrogens in Prostate Cancer: A Key to Tailored Endocrine Treatment. Springer Science & Business Media. pp. 128, 158, 203. ISBN 978-3-642-45745-6. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
^ ^a ^b ^c Luo S, Martel C, Chen C, Labrie C, Candas B, Singh SM, Labrie F (December 1997). "Daily dosing with flutamide or Casodex exerts maximal antiandrogenic activity". Urology. 50 (6): 913–9. doi:10.1016/S0090-4295(97)00393-2. PMID 9426723.
^ ^a ^b Gauthier S, Martel C, Labrie F (October 2012). "Steroid derivatives as pure antagonists of the androgen receptor". The Journal of Steroid Biochemistry and Molecular Biology. 132 (1–2): 93–104. doi:10.1016/j.jsbmb.2012.02.006. PMID 22449547.
^ Lupulescu, Aurel (24 October 1990). Hormones and Vitamins in Cancer Treatment. CRC Press. pp. 113–. ISBN 978-0-8493-5973-6. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
^ ^a ^b Petrovich, Zbigniew; Baert, Luc; Brady, Luther W. (6 December 2012). Carcinoma of the Prostate: Innovations in Management. Springer Science & Business Media. pp. 687–. ISBN 978-3-642-60956-5. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
^ Held-Warmkessel, Jeanne (2006). Contemporary Issues in Prostate Cancer: A Nursing Perspective. Jones & Bartlett Learning. pp. 275–. ISBN 978-0-7637-3075-8. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
^ Steckler, Thomas; Kalin, N.H.; Reul, J.M.H.M. (25 February 2005). Handbook of Stress and the Brain Part 2: Stress: Integrative and Clinical Aspects. Elsevier. pp. 442–. ISBN 978-0-08-055331-3. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
^ Hong, Waun Ki; Holland, James F. (2010). Holland-Frei Cancer Medicine 8. PMPH-USA. pp. 939–. ISBN 978-1-60795-014-1. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
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^ Strauss III, Jerome F.; Barbieri, Robert L. (28 August 2013). Yen & Jaffe's Reproductive Endocrinology: Physiology, Pathophysiology, and Clinical Management. Elsevier Health Sciences. pp. 688–. ISBN 978-1-4557-5972-9. Bone density improves in men receiving bicalutamide, most likely secondary to the 146% increase in estradiol and the fact that estradiol is the major mediator of bone density in men. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
^ Fradet Y (February 2004). "Bicalutamide (Casodex) in the treatment of prostate cancer". Expert Review of Anticancer Therapy. 4 (1): 37–48. doi:10.1586/14737140.4.1.37. PMID 14748655. In contrast, the incidence of diarrhea was comparable between the bicalutamide and placebo groups (6.3 vs. 6.4%, respectively) in the EPC program [71].
^ ^a ^b ^c ^d Cite error: The named reference IversenMelezinek2001 was invoked but never defined (see the help page).
^ ^a ^b ^c Wibowo E, Schellhammer P, Wassersug RJ (January 2011). "Role of estrogen in normal male function: clinical implications for patients with prostate cancer on androgen deprivation therapy". The Journal of Urology. 185 (1): 17–23. doi:10.1016/j.juro.2010.08.094. PMID 21074215.
^ ^a ^b ^c Motofei IG, Rowland DL, Popa F, Kreienkamp D, Paunica S (July 2011). "Preliminary study with bicalutamide in heterosexual and homosexual patients with prostate cancer: a possible implication of androgens in male homosexual arousal". BJU International. 108 (1): 110–5. doi:10.1111/j.1464-410X.2010.09764.x. PMID 20955264.
^ ^a ^b Wibowo E, Wassersug RJ (September 2013). "The effect of estrogen on the sexual interest of castrated males: Implications to prostate cancer patients on androgen-deprivation therapy". Critical Reviews in Oncology/Hematology. 87 (3): 224–38. doi:10.1016/j.critrevonc.2013.01.006. PMID 23484454.
^ ^a ^b Chedrese, P. Jorge (13 June 2009). Reproductive Endocrinology: A Molecular Approach. Springer Science & Business Media. pp. 233–. ISBN 978-0-387-88186-7. Archived from the original on 5 September 2017. {{cite book}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help); Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
^ ^a ^b King SR (2008). "Emerging roles for neurosteroids in sexual behavior and function". Journal of Andrology. 29 (5): 524–33. doi:10.2164/jandrol.108.005660. PMID 18567641.
^ Anderson J (March 2003). "The role of antiandrogen monotherapy in the treatment of prostate cancer". BJU International. 91 (5): 455–61. doi:10.1046/j.1464-410X.2003.04026.x. PMID 12603397.
^ Boccardo F (August 2000). "Hormone therapy of prostate cancer: is there a role for antiandrogen monotherapy?". Critical Reviews in Oncology/Hematology. 35 (2): 121–32. doi:10.1016/S1040-8428(00)00051-2. PMID 10936469.
^ Kolvenbag GJ, Iversen P, Newling DW (2001). "Antiandrogen monotherapy: a new form of treatment for patients with prostate cancer". Urology. 58 (2 Suppl 1): 16–23. doi:10.1016/s0090-4295(01)01237-7. PMID 11502439.
^ ^a ^b Blume-Peytavi, Ulrik; Whiting, David A.; Trüeb, Ralph M. (26 June 2008). Hair Growth and Disorders. Springer Science & Business Media. pp. 161–162, 181. ISBN 978-3-540-46911-7. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
^ ^a ^b Zouboulis CC, Degitz K (2004). "Androgen action on human skin -- from basic research to clinical significance". Experimental Dermatology. 13 Suppl 4: 5–10. doi:10.1111/j.1600-0625.2004.00255.x. PMID 15507105.
^ Shalita, Alan R.; Del Rosso, James Q.; Webster, Guy (21 March 2011). Acne Vulgaris. CRC Press. pp. 33–. ISBN 978-1-61631-009-7. Archived from the original on 9 December 2016. {{cite book}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help); Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
^ Zouboulis, Christos C.; Katsambas, Andreas D.; Kligman, Albert M. (28 July 2014). Pathogenesis and Treatment of Acne and Rosacea. Springer. pp. 121–. ISBN 978-3-540-69375-8. Archived from the original on 10 December 2016. {{cite book}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help); Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
^ Marks LS (2004). "5alpha-reductase: history and clinical importance". Reviews in Urology. 6 Suppl 9: S11–21. PMC 1472916. PMID 16985920.
^ Sloane, Ethel (2002). Biology of Women. Cengage Learning. pp. 160–. ISBN 0-7668-1142-5. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
^ Hanno, Philip M; Guzzo, Thomas J.; Malkowicz, S. Bruce; Wein, Alan J. (26 January 2014). Penn Clinical Manual of Urology E-Book: Expert Consult - Online. Elsevier Health Sciences. pp. 782–. ISBN 978-0-323-24466-4. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
^ Harper, Catherine (1 August 2007). Intersex. Berg. pp. 123–. ISBN 978-1-84788-339-1. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
^ ^a ^b ^c ^d ^e ^f Diamanti-Kandarakis E, Tolis G, Duleba AJ (1995). "Androgens and therapeutic aspects of antiandrogens in women". Journal of the Society for Gynocologic Investigation. 2 (4): 577–92. doi:10.1177/107155769500200401. PMID 9420861. Androgen receptors have been detected in many areas including the cortex, pituitary, hypothalamus, preoptic area, septum, amygdala, thalamus, and brain stem.79,80 These receptors appear to be identical to other ARs and may be activated by both testosterone and 5α-DHT. In the cortex and pituitary, androgens do not undergo significant aromatization, and it appears that the effects of androgens on these tissues are mediated by ARs. In contrast, most of the effects of androgens on the hypothalamus and limbic system are thought to be mediated by estrogen receptors rather than AR.78 This concept, the aromatization hypothesis, has been validated in studies of the brain of the female subhuman primate.
^ Katsambas AD, Dessinioti C (2010). "Hormonal therapy for acne: why not as first line therapy? facts and controversies". Clinics in Dermatology. 28 (1): 17–23. doi:10.1016/j.clindermatol.2009.03.006. PMID 20082945.
^ Efficacy and Safety of Myo-Inositol Supplementation in the Treatment of Obese Hirsute PCOS Women: Comparative Evaluation with OCP+Bicalutamide Therapy, 2016, doi:10.1210/endo-meetings.2016.RE.5.SUN-153 {{citation}}: Cite uses deprecated parameter |authors= (help)
^ Bigby, Michael; Herxheimer, Andrew; Naldi, Luigi; et al. (5 June 2014). Evidence-Based Dermatology. Wiley. pp. 1904–. ISBN 978-1-118-35762-0. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
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^ ^a ^b Diamanti-Kandarakis E (September 1999). "Current aspects of antiandrogen therapy in women". Current Pharmaceutical Design. 5 (9): 707–23. PMID 10495361. Several trials demonstrated complete clearing of acne with flutamide [62,77]. Flutamide used in combination with an [oral contraceptive], at a dose of 500mg/d, flutamide caused a dramatic decrease (80%) in total acne, seborrhea and hair loss score after only 3 months of therapy [53]. When used as a monotherapy in lean and obese PCOS, it significantly improves the signs of hyperandrogenism, hirsutism and particularly acne [48]. [...] flutamide 500mg/d combined with an [oral contraceptive] caused an increase in cosmetically acceptable hair density, in sex of seven women suffering from diffuse androgenetic alopecia [53].
^ Cite error: The named reference SinghGauthier2000 was invoked but never defined (see the help page).
^ ^a ^b Iswaran TJ, Imai M, Betton GR, Siddall RA (May 1997). "An overview of animal toxicology studies with bicalutamide (ICI 176,334)". The Journal of Toxicological Sciences. 22 (2): 75–88. doi:10.2131/jts.22.2_75. PMID 9198005.
^ ^a ^b Cite error: The named reference Smith2013 was invoked but never defined (see the help page).
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^ Adam Ostrzenski (2002). Gynecology: Integrating Conventional, Complementary, and Natural Alternative Therapy. Lippincott Williams & Wilkins. pp. 86–. ISBN 978-0-7817-2761-7.
^ Braunstein GD (September 2007). "Clinical practice. Gynecomastia". The New England Journal of Medicine. 357 (12): 1229–37. doi:10.1056/NEJMcp070677. PMID 17881754.
^ Gentilini, Oreste D.; Boccardo, Chiara (2015). "Male Breast Diseases". The Outpatient Breast Clinic: 431–446. doi:10.1007/978-3-319-15907-2_19. {{cite journal}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
^ Kanhai RC, Hage JJ, van Diest PJ, Bloemena E, Mulder JW (January 2000). "Short-term and long-term histologic effects of castration and estrogen treatment on breast tissue of 14 male-to-female transsexuals in comparison with two chemically castrated men". The American Journal of Surgical Pathology. 24 (1): 74–80. doi:10.1097/00000478-200001000-00009. PMID 10632490.
^ ^a ^b Higano CS (February 2003). "Side effects of androgen deprivation therapy: monitoring and minimizing toxicity". Urology. 61 (2 Suppl 1): 32–8. doi:10.1016/S0090-4295(02)02397-X. PMID 12667885.
^ ^a ^b Cite error: The named reference Lehne2013 was invoked but never defined (see the help page).
^ el-Rayes BF, Hussain MH (February 2002). "Hormonal therapy for prostate cancer: past, present and future". Expert Review of Anticancer Therapy. 2 (1): 37–47. doi:10.1586/14737140.2.1.37. PMID 12113064. At 2-year follow-up, loss of spontaneous erections and sexual function occurred in 80 vs. 92% and 78 vs. 88% in the flutamide versus CPA groups, respectively. This group of agents includes flutamide, nilutamide and bicalutamide.
^ ^a ^b ^c ^d Kreukels, Baudewijntje P.C.; Steensma, Thomas D.; de Vries, Annelou L.C. (1 July 2013). Gender Dysphoria and Disorders of Sex Development: Progress in Care and Knowledge. Springer Science & Business Media. pp. 280–. ISBN 978-1-4614-7441-8. Nonsteroidal antiandrogens, such as flutamide (50–75 mg/day) and nilutamide (150 mg/day), are also used, but they increase gonadotropin output with a rise of testosterone and estradiol; the rise of estradiol is a desirable effect in this context. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
^ Jameson, J. Larry; de Kretser, David M.; Marshall, John C.; De Groot, Leslie J. (7 May 2013). Endocrinology Adult and Pediatric: Reproductive Endocrinology. Elsevier Health Sciences. ISBN 978-0-323-22152-8. Archived from the original on 25 July 2014. Nonsteroidal antiandrogens (e.g., flutamide and nilutamide) are also used, but they increase gonadotropin secretion, causing increased secretion of testosterone and estradiol.119 The latter is desirable in this context, as it has feminizing effects. {{cite book}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help); Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
^ Moore E, Wisniewski A, Dobs A (2003). "Endocrine treatment of transsexual people: a review of treatment regimens, outcomes, and adverse effects". The Journal of Clinical Endocrinology & Metabolism. 88 (8): 3467–73. doi:10.1210/jc.2002-021967. PMID 12915619.
^ ""bicalutamide" OR "casodex" "transgender" OR "transsexual" OR "transsexuals" OR "trans women" OR "male-to-female" - Google Scholar". Retrieved 2017-07-06.
^ Elliott S, Latini DM, Walker LM, Wassersug R, Robinson JW (2010). "Androgen deprivation therapy for prostate cancer: recommendations to improve patient and partner quality of life". The Journal of Sexual Medicine. 7 (9): 2996–3010. doi:10.1111/j.1743-6109.2010.01902.x. PMID 20626600.
^ Higano CS (2012). "Sexuality and intimacy after definitive treatment and subsequent androgen deprivation therapy for prostate cancer". Journal of Clinical Oncology. 30 (30): 3720–5. doi:10.1200/JCO.2012.41.8509. PMID 23008326.
^ ^a ^b ^c ^d ^e ^f Asscheman H, Gooren LJ, Peereboom-Wynia JD (1989). "Reduction in undesired sexual hair growth with anandron in male-to-female transsexuals—experiences with a novel androgen receptor blocker". Clinical and Experimental Dermatology. 14 (5): 361–3. doi:10.1111/j.1365-2230.1989.tb02585.x. PMID 2612040.
^ ^a ^b ^c ^d ^e ^f ^g ^h Rao BR, de Voogt HJ, Geldof AA, Gooren LJ, Bouman FG (1988). "Merits and considerations in the use of anti-androgen". Journal of Steroid Biochemistry. 31 (4B): 731–7. doi:10.1016/0022-4731(88)90024-6. PMID 3143862.
^ ^a ^b ^c ^d ^e van Kemenade JF, Cohen-Kettenis PT, Cohen L, Gooren LJ (1989). "Effects of the pure antiandrogen RU 23.903 (anandron) on sexuality, aggression, and mood in male-to-female transsexuals". Archives of Sexual Behavior. 18 (3): 217–28. doi:10.1007/BF01543196. PMID 2751416.
^ ^a ^b ^c Gooren L, Spinder T, Spijkstra JJ, van Kessel H, Smals A, Rao BR, Hoogslag M (1987). "Sex steroids and pulsatile luteinizing hormone release in men. Studies in estrogen-treated agonadal subjects and eugonadal subjects treated with a novel nonsteroidal antiandrogen". The Journal of Clinical Endocrinology & Metabolism. 64 (4): 763–70. doi:10.1210/jcem-64-4-763. PMID 3102546.
^ ^a ^b ^c de Voogt HJ, Rao BR, Geldof AA, Gooren LJ, Bouman FG (1987). "Androgen action blockade does not result in reduction in size but changes histology of the normal human prostate". Prostate. 11 (4): 305–11. doi:10.1002/pros.2990110403. PMID 2960959.
^ Cohen-Kettenis, Peggy T.; Gooren, Louis J.G. (1993). "The Influence of Hormone Treatment on Psychological Functioning of Transsexuals". Journal of Psychology & Human Sexuality. 5 (4): 55–67. doi:10.1300/J056v05n04_04. ISSN 0890-7064. {{cite journal}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
^ Cite error: The named reference Chang2005 was invoked but never defined (see the help page).
^ DeVita, Vincent T.; Lawrence, Theodore S.; Rosenberg, Steven A. (18 March 2016). Prostate and Other Genitourinary Cancers: Cancer: Principles & Practice of Oncology. Wolters Kluwer Health. pp. 1006–. ISBN 978-1-4963-5421-1. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
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^ Ettner, Randi; Monstrey, Stan; Coleman, Eli (27 May 2016). Principles of Transgender Medicine and Surgery. Routledge. pp. 169–. ISBN 978-1-317-51460-2. In Europe, the most widely used drug [in the treatment of male-to-female patients] is cyproterone acetate [...] {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
^ Erickson-Schroth, Laura (12 May 2014). Trans Bodies, Trans Selves: A Resource for the Transgender Community. Oxford University Press. pp. 258–. ISBN 978-0-19-932536-8. Archived from the original on 24 June 2016. Cyproterone [acetate] is widely used outside the United States as the primary testosterone blocker in transgender women. Cyproterone, however, is not authorized for sale in the United States for any condition and has been associated with liver problems. {{cite book}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help); Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
^ Azziz, Ricardo (8 November 2007). Androgen Excess Disorders in Women. Springer Science & Business Media. pp. 382–. ISBN 978-1-59745-179-6. Cyproterone acetate is an effective treatment for hirsutism and acne [in women] and is widely used throughout the world for this indication. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
^ F. William Danby (27 January 2015). Acne: Causes and Practical Management. John Wiley & Sons. pp. 142–. ISBN 978-1-118-23277-4.
^ Loren S Schechter (22 September 2016). Surgical Management of the Transgender Patient. Elsevier Health Sciences. pp. 26–. ISBN 978-0-323-48408-4.
^ H.J.T. Coelingh Benni; H.M. Vemer (15 December 1990). Chronic Hyperandrogenic Anovulation. CRC Press. pp. 152–. ISBN 978-1-85070-322-8. CPA is not available in the United States. Thus, spironolactone is currently used. [...] In our opinion, [spironolactone] has a weak antiandrogenic activity.
^ Tommaso Falcone; William Hurd (26 April 2007). Clinical Reproductive Medicine and Surgery E-Book. Elsevier Health Sciences. pp. 285–. ISBN 978-0-323-07659-3. [Flutamide] is also more effective than spironolactone in treating hirsutism, with reduction in hirsutism scores to almost normal after 6 months of therapy with flutamide versus only a 30% reduction in women treated with spironolactone.151
^ Rowland, David L.; Incrocci, Luca (2 May 2008). Handbook of Sexual and Gender Identity Disorders. John Wiley & Sons. pp. 444–. ISBN 978-0-470-25721-0. Spironolactone is the most commonly prescribed antiandrogen [for feminizing hormone therapy] in the United States. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
^ Thole Z, Manso G, Salgueiro E, Revuelta P, Hidalgo A (2004). "Hepatotoxicity induced by antiandrogens: a review of the literature". Urologia Internationalis. 73 (4): 289–95. doi:10.1159/000081585. PMID 15604569.
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^ Emans, S. Jean; Laufer, Marc R. (5 January 2012). Emans, Laufer, Goldstein's Pediatric and Adolescent Gynecology. Lippincott Williams & Wilkins. pp. 365–. ISBN 978-1-4511-5406-1. Archived from the original on 16 May 2016. Therapy with GnRH analogs is expensive and requires intramuscular injections of depot formulations, the insert of a subcutaneous implant yearly, or, much less commonly, daily subcutaneous injections. {{cite book}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help); Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
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^ m Sternberg, Martin H.; Forget, Bernard G.; Higgs, Douglas R.; Weatherall, David J. (17 August 2009). Disorders of Hemoglobin: Genetics, Pathophysiology, and Clinical Management. Cambridge University Press. pp. 476–. ISBN 978-1-139-48080-2. Archived from the original on 24 August 2017. {{cite book}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help); Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
^ Wadhwa VK, Weston R, Parr NJ (2011). "Bicalutamide monotherapy preserves bone mineral density, muscle strength and has significant health-related quality of life benefits for osteoporotic men with prostate cancer". BJU International. 107 (12): 1923–9. doi:10.1111/j.1464-410X.2010.09726.x. PMID 20950306.
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^ Akaza H (1999). "[A new anti-androgen, bicalutamide (Casodex), for the treatment of prostate cancer—basic clinical aspects]". Gan to Kagaku Ryoho. Cancer & Chemotherapy (in Japanese). 26 (8): 1201–7. PMID 10431591.
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[BagatellBremner2003-1] Bagatelle, Carrie; Bremner, William J. (27 May 2003). Androgens in Health and Disease. Springer Science & Business Media. pp. 25–. ISBN 978-1-59259-388-0. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)

[LemkeWilliams2008-2] ^ ^a ^b ^c ^d ^e ^f ^g Lemke, Thomas L.; Williams, David A. (2008). Foye's Principles of Medicinal Chemistry. Lippincott Williams & Wilkins. pp. 121, 1288, 1290. ISBN 978-0-7817-6879-5. Archived from the original on 8 September 2017. {{cite book}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help); Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)

[pmid15882477-3] Klotz L, Schellhammer P (March 2005). "Combined androgen blockade: the case for bicalutamide". Clinical Prostate Cancer. 3 (4): 215–9. doi:10.3816/cgc.2005.n.002. PMID 15882477.

[Cockshott2004-4] Cockshott ID (2004). "Bicalutamide: clinical pharmacokinetics and metabolism". Clinical Pharmacokinetics. 43 (13): 855–878. doi:10.2165/00003088-200443130-00003. PMID 15509184. These data indicate that direct glucuronidation is the main metabolic pathway for the rapidly cleared (S)-bicalutamide, whereas hydroxylation followed by glucuronidation is a major metabolic pathway for the slowly cleared (R)-bicalutamide.

[Wellington2006-5] Wellington K, Keam SJ (2006). "Bicalutamide 150mg: a review of its use in the treatment of locally advanced prostate cancer" (PDF). Drugs. 66 (6): 837–50. doi:10.2165/00003495-200666060-00007. PMID 16706554. Archived from the original (PDF) on 28 August 2016. {{cite journal}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)

[pmid9301693-6] Schellhammer PF, Sharifi R, Block NL, Soloway MS, Venner PM, Patterson AL, Sarosdy MF, Vogelzang NJ, Schellenger JJ, Kolvenbag GJ (September 1997). "Clinical benefits of bicalutamide compared with flutamide in combined androgen blockade for patients with advanced prostatic carcinoma: final report of a double-blind, randomized, multicenter trial. Casodex Combination Study Group". Urology. 50 (3): 330–6. doi:10.1016/S0090-4295(97)00279-3. PMID 9301693.

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[pmid24455796-8] Erem C (2013). "Update on idiopathic hirsutism: diagnosis and treatment". Acta Clinica Belgica. 68 (4): 268–74. doi:10.2143/ACB.3267. PMID 24455796.

[AscensoMarques2009-9] Ascenso A, Marques HC (January 2009). "Acne in the adult". Mini Reviews in Medicinal Chemistry. 9 (1): 1–10. doi:10.2174/138955709787001730. PMID 19149656.

[pmid27512185-10] Kaur S, Verma P, Sangwan A, Dayal S, Jain VK (2016). "Etiopathogenesis and Therapeutic Approach to Adult Onset Acne". Indian Journal of Dermatology. 61 (4): 403–7. doi:10.4103/0019-5154.185703. PMC 4966398. PMID 27512185.{{cite journal}}: CS1 maint: unflagged free DOI (link)

[LottiMaggi2015-11] Lotti, Francesco; Maggi, Mario (2015). "Hormonal Treatment for Skin Androgen-Related Disorders". European Handbook of Dermatological Treatments: 1451–1464. doi:10.1007/978-3-662-45139-7_142. {{cite journal}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)

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[BourgeoisAuriche2016-13] Bourgeois AL, Auriche P, Palmaro A, Montastruc JL, Bagheri H (February 2016). "Risk of hormonotherapy in transgender people: Literature review and data from the French Database of Pharmacovigilance". Annales d'Endocrinologie. 77 (1): 14–21. doi:10.1016/j.ando.2015.12.001. PMID 26830952. Drugs for cross-gender hormonal replacement therapy used in the male to female (MtoF) transsexual population. [...] Non-steroidal anti-androgens Bicalutamide, flutamide, nilutamide

[pmid22299206-14] Ho CK (December 2011). "Testosterone testing in adult males". The Malaysian Journal of Pathology. 33 (2): 71–81. PMID 22299206. Anti-androgens such as flutamide, bicalutamide and cyproterone acetate are also used in patients with prostate cancer and sometimes in male-to-female transgender individuals [...]

[WierckxGooren2014-15] Wierckx K, Gooren L, T'Sjoen G (May 2014). "Clinical review: Breast development in trans women receiving cross-sex hormones". The Journal of Sexual Medicine. 11 (5): 1240–7. doi:10.1111/jsm.12487. PMID 24618412. Other agents with anti-androgenic properties used [in the treatment of transgender women] are nonsteroidal androgen receptor blockers, such as flutamide and bicalutamide [...]

[Deutsch2016-16] Deutsch, Madeline (17 June 2016), Guidelines for the Primary and Gender-Affirming Care of Transgender and Gender Nonbinary People (PDF) (2nd ed.), University of California, San Francisco: Center of Excellence for Transgender Health, p. 28 {{citation}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)

[KliegmanStanton2015-17] Kliegman, Robert M.; Stanton, Bonita; St. Geme, Joseph; Schor, Nina F (17 April 2015). Nelson Textbook of Pediatrics. Elsevier Health Sciences. pp. 2661–. ISBN 978-0-323-26352-8. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)

[KreherPescovitz2006-18] Kreher NC, Pescovitz OH, Delameter P, Tiulpakov A, Hochberg Z (September 2006). "Treatment of familial male-limited precocious puberty with bicalutamide and anastrozole". The Journal of Pediatrics. 149 (3): 416–20. doi:10.1016/j.jpeds.2006.04.027. PMID 16939760.

[ReiterMauras2010-19] Reiter EO, Mauras N, McCormick K, Kulshreshtha B, Amrhein J, De Luca F, O'Brien S, Armstrong J, Melezinkova H (October 2010). "Bicalutamide plus anastrozole for the treatment of gonadotropin-independent precocious puberty in boys with testotoxicosis: a phase II, open-label pilot study (BATT)". Journal of Pediatric Endocrinology & Metabolism. 23 (10): 999–1009. doi:10.1515/jpem.2010.161. PMID 21158211.

[Styne2016-20] Styne, Dennis M. (25 April 2016). "Disorders of Puberty". Pediatric Endocrinology: A Clinical Handbook. Springer. pp. 197–. ISBN 978-3-319-18371-8. Antiandrogens are used [...] in conditions such as premature Leydig cell and germ cell maturation in boys to decrease androgen effects if the source of androgens cannot be removed. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)

[LenzShulman2010-21] Lenz AM, Shulman D, Eugster EA, Rahhal S, Fuqua JS, Pescovitz OH, Lewis KA (September 2010). "Bicalutamide and third-generation aromatase inhibitors in testotoxicosis". Pediatrics. 126 (3): e728-33. doi:10.1542/peds.2010-0596. PMC 4096839. PMID 20713483.

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[LeveyKutlu2011-23] Levey HR, Kutlu O, Bivalacqua TJ (2012). "Medical management of ischemic stuttering priapism: a contemporary review of the literature". Asian Journal of Andrology. 14 (1): 156–63. doi:10.1038/aja.2011.114. PMC 3753435. PMID 22057380.

[BroderickKadioglu2010-24] Broderick GA, Kadioglu A, Bivalacqua TJ, Ghanem H, Nehra A, Shamloul R (2010). "Priapism: pathogenesis, epidemiology, and management". The Journal of Sexual Medicine. 7 (1 Pt 2): 476–500. doi:10.1111/j.1743-6109.2009.01625.x. PMID 20092449.

[ChowPayne2008-25] Chow K, Payne S (2008). "The pharmacological management of intermittent priapismic states". BJU International. 102 (11): 1515–21. doi:10.1111/j.1464-410X.2008.07951.x. PMID 18793304.

[DahmRao2002-26] Dahm P, Rao DS, Donatucci CF (2002). "Antiandrogens in the treatment of priapism". Urology. 59 (1): 138. doi:10.1016/S0090-4295(01)01492-3. PMID 11796309.

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[Skidmore-Roth2013-28] Skidmore-Roth, Linda (17 April 2013). Mosby's 2014 Nursing Drug Reference – Elsevieron VitalSource. Elsevier Health Sciences. pp. 193–194. ISBN 978-0-323-22267-9. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)

[YuanDeSouza2008-29] Yuan J, Desouza R, Westney OL, Wang R (2008). "Insights of priapism mechanism and rationale treatment for recurrent priapism". Asian Journal of Andrology. 10 (1): 88–101. doi:10.1111/j.1745-7262.2008.00314.x. PMID 18087648.

[pmid21956411-30] ^ ^a ^b ^c ^d ^e ^f ^g Gooren LJ (2011). "Clinical review: Ethical and medical considerations of androgen deprivation treatment of sex offenders". The Journal of Clinical Endocrinology & Metabolism. 96 (12): 3628–37. doi:10.1210/jc.2011-1540. PMID 21956411.

[pmid19297634-31] Giltay EJ, Gooren LJ (2009). "Potential side effects of androgen deprivation treatment in sex offenders". The Journal of the American Academy of Psychiatry and the Law. 37 (1): 53–8. PMID 19297634.

[pmid27032060-32] Khan O, Mashru A (2016). "The efficacy, safety and ethics of the use of testosterone-suppressing agents in the management of sex offending". Current Opinion in Endocrinology, Diabetes and Obesity. 23 (3): 271–8. doi:10.1097/MED.0000000000000257. PMID 27032060.

[APA1999-33] Dangerous Sex Offenders: A Task Force Report of the American Psychiatric Association. American Psychiatric Pub. 1999. pp. 111–. ISBN 978-0-89042-280-9.

[pmid22005210-34] Houts FW, Taller I, Tucker DE, Berlin FS (2011). "Androgen deprivation treatment of sexual behavior". Advances in Psychosomatic Medicine. 31: 149–63. doi:10.1159/000330196. PMID 22005210.

[pmid2189544-35] Rousseau L, Couture M, Dupont A, Labrie F, Couture N (1990). "Effect of combined androgen blockade with an LHRH agonist and flutamide in one severe case of male exhibitionism". The Canadian Journal of Psychiatry. 35 (4): 338–41. doi:10.1177/070674379003500412. PMID 2189544.

[Vogelzang2012-36] Vogelzang NJ (September 2012). "Enzalutamide—a major advance in the treatment of metastatic prostate cancer". The New England Journal of Medicine. 367 (13): 1256–7. doi:10.1056/NEJMe1209041. PMID 23013078. The first nonsteroidal antiandrogen agents — flutamide, nilutamide, and bicalutamide2 — were shown to be less effective than castration in cases of metastatic castration-resistant prostate cancer, but bicalutamide is still widely used as a moderately effective secondary hormone therapy because of an excellent safety profile.

[Regitz-Zagrosek2012-37] Cite error: The named reference Regitz-Zagrosek2012 was invoked but never defined (see the help page).

[Horwich2010-38] Horwich, Alan (11 February 2010). Systemic Treatment of Prostate Cancer. OUP Oxford. pp. 44–. ISBN 978-0-19-956142-1. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)

[ChabnerLongo2010-39] Chabner, Bruce A.; Longo, Dan L. (8 November 2010). Cancer Chemotherapy and Biotherapy: Principles and Practice. Lippincott Williams & Wilkins. pp. 679–680. ISBN 978-1-60547-431-1. From a structural standpoint, antiandrogens are classified as steroidal, including cyproterone [acetate] (Androcur) and megestrol [acetate], or nonsteroidal, including flutamide (Eulexin, others), bicalutamide (Casodex), and nilutamide (Nilandron). The steroidal antiandrogens are rarely used. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)

[Weber2015-40] Weber, Georg F. (22 July 2015). Molecular Therapies of Cancer. Springer. pp. 318–. ISBN 978-3-319-13278-5. Compared to flutamide and nilutamide, bicalutamide has a 2-fold increased affinity for the Androgen Receptor, a longer half-life, and substantially reduced toxicities. Based on a more favorable safety profile relative to flutamide, bicalutamide is indicated for use in combination therapy with a Gonadotropin Releasing Hormone analog for the treatment of advanced metastatic prostate carcinoma. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)

[Kolvenbag1996-41] Kolvenbag GJ, Blackledge GR (January 1996). "Worldwide activity and safety of bicalutamide: a summary review". Urology. 47 (1A Suppl): 70–9, discussion 80–4. doi:10.1016/s0090-4295(96)80012-4. PMID 8560681. Bicalutamide is a new antiandrogen that offers the convenience of once-daily administration, demonstrated activity in prostate cancer, and an excellent safety profile. Because it is effective and offers better tolerability than flutamide, bicalutamide represents a valid first choice for antiandrogen therapy in combination with castration for the treatment of patients with advanced prostate cancer.

[KaliksDel_Giglio2008-42] Kaliks RA, Del Giglio A (2008). "Management of advanced prostate cancer" (PDF). Revista Da Associação Médica Brasileira. 54 (2): 178–82. doi:10.1590/S0104-42302008000200025. PMID 18506331. Archived from the original (PDF) on 10 May 2017. {{cite journal}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)

[PayenTop2011-43] Payen, Olivier; Top, Siden; Vessières, Anne; Brulé, Emilie; Lauzier, Agnès; Plamont, Marie-Aude; McGlinchey, Michael J.; Müller-Bunz, Helge; Jaouen, Gérard (2011). "Synthesis and biological activity of ferrocenyl derivatives of the non-steroidal antiandrogens flutamide and bicalutamide" (PDF). Journal of Organometallic Chemistry. 696 (5): 1049–1056. doi:10.1016/j.jorganchem.2010.10.051. Cyproterone acetate was one of the first steroidal antiandrogen clinically used but its side-effects, especially the interaction with the progestin and glucocorticoid receptor, made this drug less popular than the nonsteroidal antiandrogens such as nilutamide [3,4], flutamide [5–7] and bicalutamide [8]. {{cite journal}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)

[Gulley2011-44] Gulley, James Leonard (2011). Prostate Cancer. Demos Medical Publishing. pp. 81–. ISBN 978-1-935281-91-7. Archived from the original on 25 April 2016. {{cite book}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help); Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)

[Moser2008-45] Moser, Lutz (1 January 2008). Controversies in the Treatment of Prostate Cancer. Karger Medical and Scientific Publishers. pp. 41–42. ISBN 978-3-8055-8524-8. Archived from the original on 16 May 2016. {{cite book}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help); Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)

[Demnos2011-46] Gulley, James L. (20 December 2011). Prostate Cancer. Demos Medical Publishing. pp. 505–. ISBN 978-1-935281-91-7. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)

[FiggChau2010-47] Figg, William; Chau, Cindy H.; Small, Eric J. (14 September 2010). Drug Management of Prostate Cancer. Springer Science & Business Media. pp. 56, 71–72, 75, 93. ISBN 978-1-60327-829-4. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)

[KavoussiCostabile2012-48] Kavoussi, Parviz; Costabile, Raymond A.; Salonia, Andrea (17 October 2012). Clinical Urologic Endocrinology: Principles for Men’s Health. Springer Science & Business Media. pp. 7–. ISBN 978-1-4471-4404-5. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)

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[pmid25595907-50] Munoz J, Wheler JJ, Kurzrock R (2015). "Androgen receptors beyond prostate cancer: an old marker as a new target". Oncotarget. 6 (2): 592–603. doi:10.18632/oncotarget.2831. PMC 4359241. PMID 25595907.

[pmid12231070-51] Balk SP (September 2002). "Androgen receptor as a target in androgen-independent prostate cancer". Urology. 60 (3 Suppl 1): 132–8, discussion 138–9. doi:10.1016/S0090-4295(02)01593-5. PMID 12231070.

[pmid10587288-52] Sarosdy MF (1999). "Which is the optimal antiandrogen for use in combined androgen blockade of advanced prostate cancer? The transition from a first- to second-generation antiandrogen". Anticancer Drugs. 10 (9): 791–6. doi:10.1097/00001813-199910000-00001. PMID 10587288.

[DasguptaKirby2011-53] Dasgupta, Prokar; Kirby, Roger S. (27 December 2011). ABC of Prostate Cancer. John Wiley & Sons. pp. 52–. ISBN 978-1-4443-3437-1. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)

[Bruskewitz2012-54] Bruskewitz, Reginald (6 December 2012). Atlas of the Prostate. Springer Science & Business Media. pp. 5, 190. ISBN 978-1-4615-6505-5. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)

[Denis2012-55] Denis, Louis (6 December 2012). Antiandrogens in Prostate Cancer: A Key to Tailored Endocrine Treatment. Springer Science & Business Media. pp. 128, 158, 203. ISBN 978-3-642-45745-6. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)

[LuoMartel1997-56] Luo S, Martel C, Chen C, Labrie C, Candas B, Singh SM, Labrie F (December 1997). "Daily dosing with flutamide or Casodex exerts maximal antiandrogenic activity". Urology. 50 (6): 913–9. doi:10.1016/S0090-4295(97)00393-2. PMID 9426723.

[GauthierMartel2012-57] Gauthier S, Martel C, Labrie F (October 2012). "Steroid derivatives as pure antagonists of the androgen receptor". The Journal of Steroid Biochemistry and Molecular Biology. 132 (1–2): 93–104. doi:10.1016/j.jsbmb.2012.02.006. PMID 22449547.

[Lupulescu1990-58] Lupulescu, Aurel (24 October 1990). Hormones and Vitamins in Cancer Treatment. CRC Press. pp. 113–. ISBN 978-0-8493-5973-6. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)

[PetrovichBaert2012-59] Petrovich, Zbigniew; Baert, Luc; Brady, Luther W. (6 December 2012). Carcinoma of the Prostate: Innovations in Management. Springer Science & Business Media. pp. 687–. ISBN 978-3-642-60956-5. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)

[Held-Warmkessel2006-60] Held-Warmkessel, Jeanne (2006). Contemporary Issues in Prostate Cancer: A Nursing Perspective. Jones & Bartlett Learning. pp. 275–. ISBN 978-0-7637-3075-8. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)

[StecklerKalin2005-61] Steckler, Thomas; Kalin, N.H.; Reul, J.M.H.M. (25 February 2005). Handbook of Stress and the Brain Part 2: Stress: Integrative and Clinical Aspects. Elsevier. pp. 442–. ISBN 978-0-08-055331-3. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)

[HongHolland2010-62] Hong, Waun Ki; Holland, James F. (2010). Holland-Frei Cancer Medicine 8. PMPH-USA. pp. 939–. ISBN 978-1-60795-014-1. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)

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[IIIBarbieri2013a-65] Strauss III, Jerome F.; Barbieri, Robert L. (28 August 2013). Yen & Jaffe's Reproductive Endocrinology: Physiology, Pathophysiology, and Clinical Management. Elsevier Health Sciences. pp. 688–. ISBN 978-1-4557-5972-9. Bone density improves in men receiving bicalutamide, most likely secondary to the 146% increase in estradiol and the fact that estradiol is the major mediator of bone density in men. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)

[pmid14748655-66] Fradet Y (February 2004). "Bicalutamide (Casodex) in the treatment of prostate cancer". Expert Review of Anticancer Therapy. 4 (1): 37–48. doi:10.1586/14737140.4.1.37. PMID 14748655. In contrast, the incidence of diarrhea was comparable between the bicalutamide and placebo groups (6.3 vs. 6.4%, respectively) in the EPC program [71].

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[MotofeiRowland2011-69] Motofei IG, Rowland DL, Popa F, Kreienkamp D, Paunica S (July 2011). "Preliminary study with bicalutamide in heterosexual and homosexual patients with prostate cancer: a possible implication of androgens in male homosexual arousal". BJU International. 108 (1): 110–5. doi:10.1111/j.1464-410X.2010.09764.x. PMID 20955264.

[pmid23484454-70] Wibowo E, Wassersug RJ (September 2013). "The effect of estrogen on the sexual interest of castrated males: Implications to prostate cancer patients on androgen-deprivation therapy". Critical Reviews in Oncology/Hematology. 87 (3): 224–38. doi:10.1016/j.critrevonc.2013.01.006. PMID 23484454.

[Chedrese2009-71] Chedrese, P. Jorge (13 June 2009). Reproductive Endocrinology: A Molecular Approach. Springer Science & Business Media. pp. 233–. ISBN 978-0-387-88186-7. Archived from the original on 5 September 2017. {{cite book}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help); Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)

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[Anderson2003-73] Anderson J (March 2003). "The role of antiandrogen monotherapy in the treatment of prostate cancer". BJU International. 91 (5): 455–61. doi:10.1046/j.1464-410X.2003.04026.x. PMID 12603397.

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[pmid11502439-75] Kolvenbag GJ, Iversen P, Newling DW (2001). "Antiandrogen monotherapy: a new form of treatment for patients with prostate cancer". Urology. 58 (2 Suppl 1): 16–23. doi:10.1016/s0090-4295(01)01237-7. PMID 11502439.

[Blume-PeytaviWhiting2008-76] Blume-Peytavi, Ulrik; Whiting, David A.; Trüeb, Ralph M. (26 June 2008). Hair Growth and Disorders. Springer Science & Business Media. pp. 161–162, 181. ISBN 978-3-540-46911-7. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)

[pmid15507105-77] Zouboulis CC, Degitz K (2004). "Androgen action on human skin -- from basic research to clinical significance". Experimental Dermatology. 13 Suppl 4: 5–10. doi:10.1111/j.1600-0625.2004.00255.x. PMID 15507105.

[ShalitaRosso2011-78] Shalita, Alan R.; Del Rosso, James Q.; Webster, Guy (21 March 2011). Acne Vulgaris. CRC Press. pp. 33–. ISBN 978-1-61631-009-7. Archived from the original on 9 December 2016. {{cite book}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help); Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)

[ZouboulisKatsambas2014-79] Zouboulis, Christos C.; Katsambas, Andreas D.; Kligman, Albert M. (28 July 2014). Pathogenesis and Treatment of Acne and Rosacea. Springer. pp. 121–. ISBN 978-3-540-69375-8. Archived from the original on 10 December 2016. {{cite book}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help); Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)

[pmid16985920-80] Marks LS (2004). "5alpha-reductase: history and clinical importance". Reviews in Urology. 6 Suppl 9: S11–21. PMC 1472916. PMID 16985920.

[Sloane2002-81] Sloane, Ethel (2002). Biology of Women. Cengage Learning. pp. 160–. ISBN 0-7668-1142-5. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)

[HannoGuzzo2014-82] Hanno, Philip M; Guzzo, Thomas J.; Malkowicz, S. Bruce; Wein, Alan J. (26 January 2014). Penn Clinical Manual of Urology E-Book: Expert Consult - Online. Elsevier Health Sciences. pp. 782–. ISBN 978-0-323-24466-4. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)

[Harper2007-83] Harper, Catherine (1 August 2007). Intersex. Berg. pp. 123–. ISBN 978-1-84788-339-1. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)

[pmid9420861-84] ^ ^a ^b ^c ^d ^e ^f Diamanti-Kandarakis E, Tolis G, Duleba AJ (1995). "Androgens and therapeutic aspects of antiandrogens in women". Journal of the Society for Gynocologic Investigation. 2 (4): 577–92. doi:10.1177/107155769500200401. PMID 9420861. Androgen receptors have been detected in many areas including the cortex, pituitary, hypothalamus, preoptic area, septum, amygdala, thalamus, and brain stem.79,80 These receptors appear to be identical to other ARs and may be activated by both testosterone and 5α-DHT. In the cortex and pituitary, androgens do not undergo significant aromatization, and it appears that the effects of androgens on these tissues are mediated by ARs. In contrast, most of the effects of androgens on the hypothalamus and limbic system are thought to be mediated by estrogen receptors rather than AR.78 This concept, the aromatization hypothesis, has been validated in studies of the brain of the female subhuman primate.

[pmid20082945-85] Katsambas AD, Dessinioti C (2010). "Hormonal therapy for acne: why not as first line therapy? facts and controversies". Clinics in Dermatology. 28 (1): 17–23. doi:10.1016/j.clindermatol.2009.03.006. PMID 20082945.

[MorettiGuccione2016-86] Efficacy and Safety of Myo-Inositol Supplementation in the Treatment of Obese Hirsute PCOS Women: Comparative Evaluation with OCP+Bicalutamide Therapy, 2016, doi:10.1210/endo-meetings.2016.RE.5.SUN-153 {{citation}}: Cite uses deprecated parameter |authors= (help)

[BigbyHerxheimer2014-87] Bigby, Michael; Herxheimer, Andrew; Naldi, Luigi; et al. (5 June 2014). Evidence-Based Dermatology. Wiley. pp. 1904–. ISBN 978-1-118-35762-0. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)

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[Diamanti-Kandarakis_1999-89] Diamanti-Kandarakis E (September 1999). "Current aspects of antiandrogen therapy in women". Current Pharmaceutical Design. 5 (9): 707–23. PMID 10495361. Several trials demonstrated complete clearing of acne with flutamide [62,77]. Flutamide used in combination with an [oral contraceptive], at a dose of 500mg/d, flutamide caused a dramatic decrease (80%) in total acne, seborrhea and hair loss score after only 3 months of therapy [53]. When used as a monotherapy in lean and obese PCOS, it significantly improves the signs of hyperandrogenism, hirsutism and particularly acne [48]. [...] flutamide 500mg/d combined with an [oral contraceptive] caused an increase in cosmetically acceptable hair density, in sex of seven women suffering from diffuse androgenetic alopecia [53].

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[Higano2003-98] Higano CS (February 2003). "Side effects of androgen deprivation therapy: monitoring and minimizing toxicity". Urology. 61 (2 Suppl 1): 32–8. doi:10.1016/S0090-4295(02)02397-X. PMID 12667885.

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[El-RayesHussain2014-100] -Rayes BF, Hussain MH (February 2002). "Hormonal therapy for prostate cancer: past, present and future". Expert Review of Anticancer Therapy. 2 (1): 37–47. doi:10.1586/14737140.2.1.37. PMID 12113064. At 2-year follow-up, loss of spontaneous erections and sexual function occurred in 80 vs. 92% and 78 vs. 88% in the flutamide versus CPA groups, respectively. This group of agents includes flutamide, nilutamide and bicalutamide.

[KreukelsSteensma2013-101] Kreukels, Baudewijntje P.C.; Steensma, Thomas D.; de Vries, Annelou L.C. (1 July 2013). Gender Dysphoria and Disorders of Sex Development: Progress in Care and Knowledge. Springer Science & Business Media. pp. 280–. ISBN 978-1-4614-7441-8. Nonsteroidal antiandrogens, such as flutamide (50–75 mg/day) and nilutamide (150 mg/day), are also used, but they increase gonadotropin output with a rise of testosterone and estradiol; the rise of estradiol is a desirable effect in this context. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)

[JamesonKretser2013-102] Jameson, J. Larry; de Kretser, David M.; Marshall, John C.; De Groot, Leslie J. (7 May 2013). Endocrinology Adult and Pediatric: Reproductive Endocrinology. Elsevier Health Sciences. ISBN 978-0-323-22152-8. Archived from the original on 25 July 2014. Nonsteroidal antiandrogens (e.g., flutamide and nilutamide) are also used, but they increase gonadotropin secretion, causing increased secretion of testosterone and estradiol.119 The latter is desirable in this context, as it has feminizing effects. {{cite book}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help); Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)

[pmid12915619-103] Moore E, Wisniewski A, Dobs A (2003). "Endocrine treatment of transsexual people: a review of treatment regimens, outcomes, and adverse effects". The Journal of Clinical Endocrinology & Metabolism. 88 (8): 3467–73. doi:10.1210/jc.2002-021967. PMID 12915619.

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[AsschemanGooren1989-107] ^ ^a ^b ^c ^d ^e ^f Asscheman H, Gooren LJ, Peereboom-Wynia JD (1989). "Reduction in undesired sexual hair growth with anandron in male-to-female transsexuals—experiences with a novel androgen receptor blocker". Clinical and Experimental Dermatology. 14 (5): 361–3. doi:10.1111/j.1365-2230.1989.tb02585.x. PMID 2612040.

[Raode_Voogt1988-108] ^ ^a ^b ^c ^d ^e ^f ^g ^h Rao BR, de Voogt HJ, Geldof AA, Gooren LJ, Bouman FG (1988). "Merits and considerations in the use of anti-androgen". Journal of Steroid Biochemistry. 31 (4B): 731–7. doi:10.1016/0022-4731(88)90024-6. PMID 3143862.

[van_KemenadeCohen-Kettenis1989-109] van Kemenade JF, Cohen-Kettenis PT, Cohen L, Gooren LJ (1989). "Effects of the pure antiandrogen RU 23.903 (anandron) on sexuality, aggression, and mood in male-to-female transsexuals". Archives of Sexual Behavior. 18 (3): 217–28. doi:10.1007/BF01543196. PMID 2751416.

[GoorenSpinder1987-110] Gooren L, Spinder T, Spijkstra JJ, van Kessel H, Smals A, Rao BR, Hoogslag M (1987). "Sex steroids and pulsatile luteinizing hormone release in men. Studies in estrogen-treated agonadal subjects and eugonadal subjects treated with a novel nonsteroidal antiandrogen". The Journal of Clinical Endocrinology & Metabolism. 64 (4): 763–70. doi:10.1210/jcem-64-4-763. PMID 3102546.

[De_VoogtRao1987-111] Voogt HJ, Rao BR, Geldof AA, Gooren LJ, Bouman FG (1987). "Androgen action blockade does not result in reduction in size but changes histology of the normal human prostate". Prostate. 11 (4): 305–11. doi:10.1002/pros.2990110403. PMID 2960959.

[Cohen-KettenisGooren1993-112] Cohen-Kettenis, Peggy T.; Gooren, Louis J.G. (1993). "The Influence of Hormone Treatment on Psychological Functioning of Transsexuals". Journal of Psychology & Human Sexuality. 5 (4): 55–67. doi:10.1300/J056v05n04_04. ISSN 0890-7064. {{cite journal}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)

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[DeVitaLawrence2016-114] DeVita, Vincent T.; Lawrence, Theodore S.; Rosenberg, Steven A. (18 March 2016). Prostate and Other Genitourinary Cancers: Cancer: Principles & Practice of Oncology. Wolters Kluwer Health. pp. 1006–. ISBN 978-1-4963-5421-1. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)

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[EttnerMonstrey2016-116] Ettner, Randi; Monstrey, Stan; Coleman, Eli (27 May 2016). Principles of Transgender Medicine and Surgery. Routledge. pp. 169–. ISBN 978-1-317-51460-2. In Europe, the most widely used drug [in the treatment of male-to-female patients] is cyproterone acetate [...] {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)

[Erickson-Schroth2014-117] Erickson-Schroth, Laura (12 May 2014). Trans Bodies, Trans Selves: A Resource for the Transgender Community. Oxford University Press. pp. 258–. ISBN 978-0-19-932536-8. Archived from the original on 24 June 2016. Cyproterone [acetate] is widely used outside the United States as the primary testosterone blocker in transgender women. Cyproterone, however, is not authorized for sale in the United States for any condition and has been associated with liver problems. {{cite book}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help); Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)

[Azziz2007-118] Azziz, Ricardo (8 November 2007). Androgen Excess Disorders in Women. Springer Science & Business Media. pp. 382–. ISBN 978-1-59745-179-6. Cyproterone acetate is an effective treatment for hirsutism and acne [in women] and is widely used throughout the world for this indication. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)

[Danby2015-119] F. William Danby (27 January 2015). Acne: Causes and Practical Management. John Wiley & Sons. pp. 142–. ISBN 978-1-118-23277-4.

[Schechter2016-120] Loren S Schechter (22 September 2016). Surgical Management of the Transgender Patient. Elsevier Health Sciences. pp. 26–. ISBN 978-0-323-48408-4.

[BenniVemer1990-121] H.J.T. Coelingh Benni; H.M. Vemer (15 December 1990). Chronic Hyperandrogenic Anovulation. CRC Press. pp. 152–. ISBN 978-1-85070-322-8. CPA is not available in the United States. Thus, spironolactone is currently used. [...] In our opinion, [spironolactone] has a weak antiandrogenic activity.

[FalconeHurd2007-122] Tommaso Falcone; William Hurd (26 April 2007). Clinical Reproductive Medicine and Surgery E-Book. Elsevier Health Sciences. pp. 285–. ISBN 978-0-323-07659-3. [Flutamide] is also more effective than spironolactone in treating hirsutism, with reduction in hirsutism scores to almost normal after 6 months of therapy with flutamide versus only a 30% reduction in women treated with spironolactone.151

[RowlandIncrocci2008-123] Rowland, David L.; Incrocci, Luca (2 May 2008). Handbook of Sexual and Gender Identity Disorders. John Wiley & Sons. pp. 444–. ISBN 978-0-470-25721-0. Spironolactone is the most commonly prescribed antiandrogen [for feminizing hormone therapy] in the United States. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)

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[HHS2010-127] Chang, Stephen (10 March 2010), Bicalutamide BPCA Drug Use Review in the Pediatric Population (PDF), U.S. Department of Health and Human Service, archived from the original (PDF) on 24 October 2016, retrieved 20 July 2016 {{citation}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help); Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)

[EmansLaufer2012-128] Emans, S. Jean; Laufer, Marc R. (5 January 2012). Emans, Laufer, Goldstein's Pediatric and Adolescent Gynecology. Lippincott Williams & Wilkins. pp. 365–. ISBN 978-1-4511-5406-1. Archived from the original on 16 May 2016. Therapy with GnRH analogs is expensive and requires intramuscular injections of depot formulations, the insert of a subcutaneous implant yearly, or, much less commonly, daily subcutaneous injections. {{cite book}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help); Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)

[Hillard2013-129] Hillard, Paula J. Adams (29 March 2013). Practical Pediatric and Adolescent Gynecology. John Wiley & Sons. pp. 182–. ISBN 978-1-118-53857-9. Treatment is expensive, with costs typicall in the range of $10,000–$15,000 per year. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)

[SteinbergForget2009-130] Sternberg, Martin H.; Forget, Bernard G.; Higgs, Douglas R.; Weatherall, David J. (17 August 2009). Disorders of Hemoglobin: Genetics, Pathophysiology, and Clinical Management. Cambridge University Press. pp. 476–. ISBN 978-1-139-48080-2. Archived from the original on 24 August 2017. {{cite book}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help); Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)

[pmid20950306-131] Wadhwa VK, Weston R, Parr NJ (2011). "Bicalutamide monotherapy preserves bone mineral density, muscle strength and has significant health-related quality of life benefits for osteoporotic men with prostate cancer". BJU International. 107 (12): 1923–9. doi:10.1111/j.1464-410X.2010.09726.x. PMID 20950306.

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[Ak1999-136] Akaza H (1999). "[A new anti-androgen, bicalutamide (Casodex), for the treatment of prostate cancer—basic clinical aspects]". Gan to Kagaku Ryoho. Cancer & Chemotherapy (in Japanese). 26 (8): 1201–7. PMID 10431591.

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@@ Line 1: / Line 1: @@
-[[Bicalutamide]] is mainly used in and is only [[approved drug|approved]] for the following indications:<ref name="BagatellBremner2003" />
+[[Bicalutamide]] is mainly used in and is only [[approved drug|approved]] for the following indications:<ref name="BagatellBremner2003">{{cite book |first1=Carrie |last1=Bagatelle |first2=William J. |last2=Bremner | name-list-format = vanc |title=Androgens in Health and Disease |url=https://books.google.com/books?id=vDcBCAAAQBAJ&pg=PA25 |date=27 May 2003 |publisher=Springer Science & Business Media |isbn=978-1-59259-388-0 |pages=25–}}</ref>
 * [[Metastatic prostate cancer]] (mPC) in men in combination with a [[gonadotropin-releasing hormone]] (GnRH) [[gonadotropin-releasing hormone analogue|analogue]] or [[orchiectomy]] at moderate doses<ref name="LemkeWilliams2008" /><ref name="pmid15882477" />
+* [[Locally advanced prostate cancer]] (LAPC) in men as a monotherapy in high doses<ref name="LemkeWilliams2008" /><ref name="Cockshott2004">{{cite journal |vauthors=Cockshott ID |title=Bicalutamide: clinical pharmacokinetics and metabolism |journal=Clinical Pharmacokinetics |volume=43 |issue=13 |pages=855–878 |date=2004 |pmid=15509184 |doi=10.2165/00003088-200443130-00003 |quote=These data indicate that direct glucuronidation is the main metabolic pathway for the rapidly cleared (''S'')-bicalutamide, whereas hydroxylation followed by glucuronidation is a major metabolic pathway for the slowly cleared (''R'')-bicalutamide.}}</ref><ref name=Wellington2006>{{cite journal |vauthors=Wellington K, Keam SJ |title=Bicalutamide 150mg: a review of its use in the treatment of locally advanced prostate cancer |journal=Drugs |volume=66 |issue=6 |pages=837–50 |year=2006 |pmid=16706554 |doi=10.2165/00003495-200666060-00007 |url=http://www.antialabs.com/reference/21018026.pdf |deadurl=no |archiveurl=https://web.archive.org/web/20160828024232/http://www.antialabs.com/reference/21018026.pdf |archivedate=28 August 2016 |df=dmy-all}}</ref><ref name="pmid9301693" />
-* [[Locally advanced prostate cancer]] (LAPC) in men as a monotherapy in high doses<ref name="LemkeWilliams2008" /><ref name="Cockshott2004" /><ref name="Wellington2006" /><ref name="pmid9301693" />
 It can also be and is used to a lesser extent for the following [[off-label use|off-label]] (non-approved) indications:
@@ Line 8: / Line 8: @@
 * [[Hormone replacement therapy (transgender)|Hormone therapy]] for [[transgender women]] in combination with [[estrogen]] or alone<ref name="Gooren2011" /><ref name="BourgeoisAuriche2016" /><ref name="pmid22299206" /><ref name="WierckxGooren2014" /><ref name="Deutsch2016" />
 * [[Precocious puberty]] in boys in moderate doses, especially due to [[familial male-limited precocious puberty]] (testotoxicosis)<ref name="KliegmanStanton2015" /><ref name="KreherPescovitz2006" /><ref name="ReiterMauras2010" /><ref name="Styne2016" /><ref name="LenzShulman2010" /><ref name="JamesonGroot2015" />
-* [[Priapism]] in men at low to very low doses<ref name="LeveyKutlu2011" /><ref name="BroderickKadioglu2010" /><ref name="ChowPayne2008" /><ref name="DahmRao2002" /><ref name="Dart2004" /><ref name="Skidmore-Roth2013" /><ref name="YuanDeSouza2008" />
+* [[Priapism]] in men at low to very low doses<ref name="LeveyKutlu2011" /><ref name="BroderickKadioglu2010" /><ref name="ChowPayne2008" /><ref name="DahmRao2002" /><ref name="Dart2004" /><ref name="Skidmore-Roth2013">{{cite book |first=Linda |last=Skidmore-Roth | name-list-format = vanc |title=Mosby's 2014 Nursing Drug Reference – Elsevieron VitalSource |url=https://books.google.com/books?id=ISYiAQAAQBAJ&pg=PA194 |date=17 April 2013 |publisher=Elsevier Health Sciences |isbn=978-0-323-22267-9 |pages=193–194}}</ref><ref name=YuanDeSouza2008>{{cite journal |vauthors=Yuan J, Desouza R, Westney OL, Wang R |title=Insights of priapism mechanism and rationale treatment for recurrent priapism |journal=Asian Journal of Andrology |volume=10 |issue=1 |pages=88–101 |year=2008 |pmid=18087648 |doi=10.1111/j.1745-7262.2008.00314.x}}</ref>
 It has been suggested for but has uncertain effectiveness in the following indications:
@@ Line 14: / Line 14: @@
 ==Prostate cancer==
-Bicalutamide is used primarily in the treatment of early and advanced prostate cancer.<ref name="BagatellBremner2003" /> It is approved at a dosage of 50&nbsp;mg/day as a [[combination therapy]] with a {{abbr|GnRH|gonadotropin-releasing hormone}} or orchiectomy (that is, surgical or medical castration) in the treatment of [[Prostate cancer staging#Whitmore-Jewett staging|stage D2]] {{abbr|mPC|metastatic prostate cancer}},<ref name="LemkeWilliams2008" /><ref name="pmid15882477">{{cite journal |vauthors=Klotz L, Schellhammer P |title=Combined androgen blockade: the case for bicalutamide |journal=Clinical Prostate Cancer |volume=3 |issue=4 |pages=215–9 |date=March 2005 |pmid=15882477 |doi=10.3816/cgc.2005.n.002}}</ref> and as a [[monotherapy]] at a dosage of 150&nbsp;mg/day for the treatment of [[Prostate cancer staging#Whitmore-Jewett staging|stage C or D1]] {{abbr|LAPC|locally advanced prostate cancer}}.<ref name="LemkeWilliams2008" /><ref name="Cockshott2004" /><ref name="Wellington2006" /><ref name="pmid9301693">{{cite journal |vauthors=Schellhammer PF, Sharifi R, Block NL, Soloway MS, Venner PM, Patterson AL, Sarosdy MF, Vogelzang NJ, Schellenger JJ, Kolvenbag GJ |title=Clinical benefits of bicalutamide compared with flutamide in combined androgen blockade for patients with advanced prostatic carcinoma: final report of a double-blind, randomized, multicenter trial. Casodex Combination Study Group |journal=Urology |volume=50 |issue=3 |pages=330–6 |date=September 1997 |pmid=9301693 |doi=10.1016/S0090-4295(97)00279-3}}</ref> Although effective in {{abbr|mPC|metastatic prostate cancer}} and {{abbr|LAPC|locally advanced prostate cancer}}, bicalutamide is no longer indicated for the treatment of [[localized prostate cancer]] (LPC) due to negative findings in the Early Prostate Cancer (EPC) trial.<ref name="Wellington2006" /> Prior to the introduction of the newer {{abbr|NSAA|nonsteroidal antiandrogen}} [[enzalutamide]] in 2012,<ref name="Vogelzang2012" /> bicalutamide was considered to be the [[standard-of-care]] antiandrogen in the treatment of prostate cancer, and still remains widely used for this indication.<ref name="Regitz-Zagrosek2012" /><ref name="Vogelzang2012" /><ref name="Horwich2010" /> Compared to earlier antiandrogens like the [[steroidal antiandrogen]] (SAA) [[cyproterone acetate]] (CPA) and the {{abbr|NSAAs|nonsteroidal antiandrogens}} [[flutamide]] and [[nilutamide]], bicalutamide shows an improved profile of [[effectiveness]], tolerability, and [[pharmacovigilance|safety]],<ref name="ChabnerLongo2010">{{cite book |first1=Bruce A. |last1=Chabner |first2=Dan L. |last2=Longo | name-list-format = vanc |title=Cancer Chemotherapy and Biotherapy: Principles and Practice |url=https://books.google.com/books?id=WL4arNFsQa8C&pg=PA680 |date=8 November 2010 |publisher=Lippincott Williams & Wilkins |isbn=978-1-60547-431-1 |pages=679–680 |quote=From a structural standpoint, antiandrogens are classified as steroidal, including cyproterone [acetate] (Androcur) and megestrol [acetate], or nonsteroidal, including flutamide (Eulexin, others), bicalutamide (Casodex), and nilutamide (Nilandron). The steroidal antiandrogens are rarely used.}}</ref><ref name="Vogelzang2012">{{cite journal |vauthors=Vogelzang NJ |title=Enzalutamide—a major advance in the treatment of metastatic prostate cancer |journal=The New England Journal of Medicine |volume=367 |issue=13 |pages=1256–7 |date=September 2012 |pmid=23013078 |doi=10.1056/NEJMe1209041 |quote=The first nonsteroidal antiandrogen agents — flutamide, nilutamide, and bicalutamide2 — were shown to be less effective than castration in cases of metastatic castration-resistant prostate cancer, but bicalutamide is still widely used as a moderately effective secondary hormone therapy because of an excellent safety profile.}}</ref><ref name="Weber2015">{{cite book |first=Georg F. |last=Weber | name-list-format = vanc |title=Molecular Therapies of Cancer |url=https://books.google.com/books?id=dhs_CgAAQBAJ&pg=PA318 |date=22 July 2015 |publisher=Springer |isbn=978-3-319-13278-5 |pages=318– |quote=Compared to flutamide and nilutamide, bicalutamide has a 2-fold increased affinity for the Androgen Receptor, a longer half-life, and substantially reduced toxicities. Based on a more favorable safety profile relative to flutamide, bicalutamide is indicated for use in combination therapy with a Gonadotropin Releasing Hormone analog for the treatment of advanced metastatic prostate carcinoma.}}</ref><ref name="Kolvenbag1996">{{cite journal |vauthors=Kolvenbag GJ, Blackledge GR |title=Worldwide activity and safety of bicalutamide: a summary review |journal=Urology |volume=47 |issue=1A Suppl |pages=70–9; discussion 80–4 |date=January 1996 |pmid=8560681 |doi= 10.1016/s0090-4295(96)80012-4|quote=Bicalutamide is a new antiandrogen that offers the convenience of once-daily administration, demonstrated activity in prostate cancer, and an excellent safety profile. Because it is effective and offers better tolerability than flutamide, bicalutamide represents a valid first choice for antiandrogen therapy in combination with castration for the treatment of patients with advanced prostate cancer.}}</ref> and for this reason has largely replaced them in the treatment of prostate cancer.<ref name="LemkeWilliams2008">{{cite book |first1=Thomas L. |last1=Lemke |first2=David A. |last2=Williams|name-list-format=vanc |title=Foye's Principles of Medicinal Chemistry |url=https://books.google.com/books?id=R0W1ErpsQpkC&pg=PA1288 |year=2008 |publisher=Lippincott Williams & Wilkins |isbn=978-0-7817-6879-5 |pages=121, 1288, 1290 |deadurl=no |archiveurl=https://web.archive.org/web/20170908145128/https://books.google.com/books?id=R0W1ErpsQpkC |archivedate=8 September 2017 |df=dmy-all}}</ref><ref name="KaliksDel Giglio2008">{{cite journal |vauthors=Kaliks RA, Del Giglio A |title=Management of advanced prostate cancer |journal=Revista Da Associação Médica Brasileira |volume=54 |issue=2 |pages=178–82 |year=2008 |pmid=18506331 |doi=10.1590/S0104-42302008000200025 |url=http://www.scielo.br/pdf/ramb/v54n2/a25v54n2.pdf |deadurl=no |archiveurl=https://web.archive.org/web/20170510112152/http://www.scielo.br/pdf/ramb/v54n2/a25v54n2.pdf |archivedate=10 May 2017 |df=dmy-all}}</ref><ref name="PayenTop2011">{{cite journal |last1=Payen |first1=Olivier |last2=Top |first2=Siden |last3=Vessières |first3=Anne |last4=Brulé |first4=Emilie |last5=Lauzier |first5=Agnès |last6=Plamont |first6=Marie-Aude |last7=McGlinchey |first7=Michael J. |last8=Müller-Bunz |first8=Helge |last9=Jaouen |first9=Gérard | name-list-format = vanc |title=Synthesis and biological activity of ferrocenyl derivatives of the non-steroidal antiandrogens flutamide and bicalutamide |journal=Journal of Organometallic Chemistry |volume=696 |issue=5 |year=2011 |pages=1049–1056 |doi=10.1016/j.jorganchem.2010.10.051 |url=http://www.academia.edu/download/42912839/1-s2.0-S0022328X10006765-main.pdf |quote=Cyproterone acetate was one of the first steroidal antiandrogen clinically used but its side-effects, especially the interaction with the progestin and glucocorticoid receptor, made this drug less popular than the nonsteroidal antiandrogens such as nilutamide [3,4], flutamide [5–7] and bicalutamide [8].}}</ref><ref name="ChabnerLongo2010" /><ref name="Gulley2011">{{cite book |first1=James Leonard |last1=Gulley |name-list-format=vanc |title=Prostate Cancer |url=https://books.google.com/books?id=WJkjgbRJe3EC&pg=PT81 |year=2011 |publisher=Demos Medical Publishing |isbn=978-1-935281-91-7 |pages=81– |deadurl=no |archiveurl=https://web.archive.org/web/20160425141102/https://books.google.com/books?id=WJkjgbRJe3EC&pg=PT81 |archivedate=25 April 2016 |df=dmy-all}}</ref><ref name="Moser2008">{{cite book |first1=Lutz |last1=Moser |name-list-format=vanc |title=Controversies in the Treatment of Prostate Cancer |url=https://books.google.com/books?id=4J4OCRyHWRYC&pg=PA41 |date=1 January 2008 |publisher=Karger Medical and Scientific Publishers |isbn=978-3-8055-8524-8 |pages=41–42 |deadurl=no |archiveurl=https://web.archive.org/web/20160516112448/https://books.google.com/books?id=4J4OCRyHWRYC&pg=PA41 |archivedate=16 May 2016 |df=dmy-all}}</ref><ref name="Demnos2011">{{cite book |first=James L. |last=Gulley | name-list-format = vanc |title=Prostate Cancer |url=https://books.google.com/books?id=WJkjgbRJe3EC&pg=PA505 |date=20 December 2011 |publisher=Demos Medical Publishing |isbn=978-1-935281-91-7 |pages=505–}}</ref>
+Bicalutamide is used primarily in the treatment of early and advanced prostate cancer.<ref name="BagatellBremner2003" /> It is approved at a dosage of 50&nbsp;mg/day as a [[combination therapy]] with a {{abbr|GnRH|gonadotropin-releasing hormone}} or orchiectomy (that is, surgical or medical castration) in the treatment of [[Prostate cancer staging#Whitmore-Jewett staging|stage D2]] {{abbr|mPC|metastatic prostate cancer}},<ref name="LemkeWilliams2008" /><ref name="pmid15882477">{{cite journal |vauthors=Klotz L, Schellhammer P |title=Combined androgen blockade: the case for bicalutamide |journal=Clinical Prostate Cancer |volume=3 |issue=4 |pages=215–9 |date=March 2005 |pmid=15882477 |doi=10.3816/cgc.2005.n.002}}</ref> and as a [[monotherapy]] at a dosage of 150&nbsp;mg/day for the treatment of [[Prostate cancer staging#Whitmore-Jewett staging|stage C or D1]] {{abbr|LAPC|locally advanced prostate cancer}}.<ref name="LemkeWilliams2008" /><ref name="Cockshott2004" /><ref name="Wellington2006" /><ref name="pmid9301693">{{cite journal |vauthors=Schellhammer PF, Sharifi R, Block NL, Soloway MS, Venner PM, Patterson AL, Sarosdy MF, Vogelzang NJ, Schellenger JJ, Kolvenbag GJ |title=Clinical benefits of bicalutamide compared with flutamide in combined androgen blockade for patients with advanced prostatic carcinoma: final report of a double-blind, randomized, multicenter trial. Casodex Combination Study Group |journal=Urology |volume=50 |issue=3 |pages=330–6 |date=September 1997 |pmid=9301693 |doi=10.1016/S0090-4295(97)00279-3}}</ref> Although effective in {{abbr|mPC|metastatic prostate cancer}} and {{abbr|LAPC|locally advanced prostate cancer}}, bicalutamide is no longer indicated for the treatment of [[localized prostate cancer]] (LPC) due to negative findings in the Early Prostate Cancer (EPC) trial.<ref name="Wellington2006" /> Prior to the introduction of the newer {{abbr|NSAA|nonsteroidal antiandrogen}} [[enzalutamide]] in 2012,<ref name="Vogelzang2012" /> bicalutamide was considered to be the [[standard-of-care]] antiandrogen in the treatment of prostate cancer, and still remains widely used for this indication.<ref name="Regitz-Zagrosek2012" /><ref name="Vogelzang2012" /><ref name="Horwich2010">{{cite book |first=Alan |last=Horwich | name-list-format = vanc |title=Systemic Treatment of Prostate Cancer |url=https://books.google.com/books?id=MR-vVpipynUC&pg=PT44 |date=11 February 2010 |publisher=OUP Oxford |isbn=978-0-19-956142-1 |pages=44–}}</ref> Compared to earlier antiandrogens like the [[steroidal antiandrogen]] (SAA) [[cyproterone acetate]] (CPA) and the {{abbr|NSAAs|nonsteroidal antiandrogens}} [[flutamide]] and [[nilutamide]], bicalutamide shows an improved profile of [[effectiveness]], tolerability, and [[pharmacovigilance|safety]],<ref name="ChabnerLongo2010">{{cite book |first1=Bruce A. |last1=Chabner |first2=Dan L. |last2=Longo | name-list-format = vanc |title=Cancer Chemotherapy and Biotherapy: Principles and Practice |url=https://books.google.com/books?id=WL4arNFsQa8C&pg=PA680 |date=8 November 2010 |publisher=Lippincott Williams & Wilkins |isbn=978-1-60547-431-1 |pages=679–680 |quote=From a structural standpoint, antiandrogens are classified as steroidal, including cyproterone [acetate] (Androcur) and megestrol [acetate], or nonsteroidal, including flutamide (Eulexin, others), bicalutamide (Casodex), and nilutamide (Nilandron). The steroidal antiandrogens are rarely used.}}</ref><ref name="Vogelzang2012">{{cite journal |vauthors=Vogelzang NJ |title=Enzalutamide—a major advance in the treatment of metastatic prostate cancer |journal=The New England Journal of Medicine |volume=367 |issue=13 |pages=1256–7 |date=September 2012 |pmid=23013078 |doi=10.1056/NEJMe1209041 |quote=The first nonsteroidal antiandrogen agents — flutamide, nilutamide, and bicalutamide2 — were shown to be less effective than castration in cases of metastatic castration-resistant prostate cancer, but bicalutamide is still widely used as a moderately effective secondary hormone therapy because of an excellent safety profile.}}</ref><ref name="Weber2015">{{cite book |first=Georg F. |last=Weber | name-list-format = vanc |title=Molecular Therapies of Cancer |url=https://books.google.com/books?id=dhs_CgAAQBAJ&pg=PA318 |date=22 July 2015 |publisher=Springer |isbn=978-3-319-13278-5 |pages=318– |quote=Compared to flutamide and nilutamide, bicalutamide has a 2-fold increased affinity for the Androgen Receptor, a longer half-life, and substantially reduced toxicities. Based on a more favorable safety profile relative to flutamide, bicalutamide is indicated for use in combination therapy with a Gonadotropin Releasing Hormone analog for the treatment of advanced metastatic prostate carcinoma.}}</ref><ref name="Kolvenbag1996">{{cite journal |vauthors=Kolvenbag GJ, Blackledge GR |title=Worldwide activity and safety of bicalutamide: a summary review |journal=Urology |volume=47 |issue=1A Suppl |pages=70–9; discussion 80–4 |date=January 1996 |pmid=8560681 |doi= 10.1016/s0090-4295(96)80012-4|quote=Bicalutamide is a new antiandrogen that offers the convenience of once-daily administration, demonstrated activity in prostate cancer, and an excellent safety profile. Because it is effective and offers better tolerability than flutamide, bicalutamide represents a valid first choice for antiandrogen therapy in combination with castration for the treatment of patients with advanced prostate cancer.}}</ref> and for this reason has largely replaced them in the treatment of prostate cancer.<ref name="LemkeWilliams2008">{{cite book |first1=Thomas L. |last1=Lemke |first2=David A. |last2=Williams|name-list-format=vanc |title=Foye's Principles of Medicinal Chemistry |url=https://books.google.com/books?id=R0W1ErpsQpkC&pg=PA1288 |year=2008 |publisher=Lippincott Williams & Wilkins |isbn=978-0-7817-6879-5 |pages=121, 1288, 1290 |deadurl=no |archiveurl=https://web.archive.org/web/20170908145128/https://books.google.com/books?id=R0W1ErpsQpkC |archivedate=8 September 2017 |df=dmy-all}}</ref><ref name="KaliksDel Giglio2008">{{cite journal |vauthors=Kaliks RA, Del Giglio A |title=Management of advanced prostate cancer |journal=Revista Da Associação Médica Brasileira |volume=54 |issue=2 |pages=178–82 |year=2008 |pmid=18506331 |doi=10.1590/S0104-42302008000200025 |url=http://www.scielo.br/pdf/ramb/v54n2/a25v54n2.pdf |deadurl=no |archiveurl=https://web.archive.org/web/20170510112152/http://www.scielo.br/pdf/ramb/v54n2/a25v54n2.pdf |archivedate=10 May 2017 |df=dmy-all}}</ref><ref name="PayenTop2011">{{cite journal |last1=Payen |first1=Olivier |last2=Top |first2=Siden |last3=Vessières |first3=Anne |last4=Brulé |first4=Emilie |last5=Lauzier |first5=Agnès |last6=Plamont |first6=Marie-Aude |last7=McGlinchey |first7=Michael J. |last8=Müller-Bunz |first8=Helge |last9=Jaouen |first9=Gérard | name-list-format = vanc |title=Synthesis and biological activity of ferrocenyl derivatives of the non-steroidal antiandrogens flutamide and bicalutamide |journal=Journal of Organometallic Chemistry |volume=696 |issue=5 |year=2011 |pages=1049–1056 |doi=10.1016/j.jorganchem.2010.10.051 |url=http://www.academia.edu/download/42912839/1-s2.0-S0022328X10006765-main.pdf |quote=Cyproterone acetate was one of the first steroidal antiandrogen clinically used but its side-effects, especially the interaction with the progestin and glucocorticoid receptor, made this drug less popular than the nonsteroidal antiandrogens such as nilutamide [3,4], flutamide [5–7] and bicalutamide [8].}}</ref><ref name="ChabnerLongo2010" /><ref name="Gulley2011">{{cite book |first1=James Leonard |last1=Gulley |name-list-format=vanc |title=Prostate Cancer |url=https://books.google.com/books?id=WJkjgbRJe3EC&pg=PT81 |year=2011 |publisher=Demos Medical Publishing |isbn=978-1-935281-91-7 |pages=81– |deadurl=no |archiveurl=https://web.archive.org/web/20160425141102/https://books.google.com/books?id=WJkjgbRJe3EC&pg=PT81 |archivedate=25 April 2016 |df=dmy-all}}</ref><ref name="Moser2008">{{cite book |first1=Lutz |last1=Moser |name-list-format=vanc |title=Controversies in the Treatment of Prostate Cancer |url=https://books.google.com/books?id=4J4OCRyHWRYC&pg=PA41 |date=1 January 2008 |publisher=Karger Medical and Scientific Publishers |isbn=978-3-8055-8524-8 |pages=41–42 |deadurl=no |archiveurl=https://web.archive.org/web/20160516112448/https://books.google.com/books?id=4J4OCRyHWRYC&pg=PA41 |archivedate=16 May 2016 |df=dmy-all}}</ref><ref name="Demnos2011">{{cite book |first=James L. |last=Gulley | name-list-format = vanc |title=Prostate Cancer |url=https://books.google.com/books?id=WJkjgbRJe3EC&pg=PA505 |date=20 December 2011 |publisher=Demos Medical Publishing |isbn=978-1-935281-91-7 |pages=505–}}</ref>
 ===Role of antiandrogens in prostate cancer===
@@ Line 23: / Line 23: @@
 In the past, surgical [[adrenalectomy]] and early androgen biosynthesis inhibitors like [[ketoconazole]] and [[aminoglutethimide]] were successfully employed in the treatment of castration-resistant prostate cancer.<ref name="Bruskewitz2012" /><ref name="FiggChau2010" /><ref name="Lupulescu1990">{{cite book |first=Aurel |last=Lupulescu | name-list-format = vanc |title=Hormones and Vitamins in Cancer Treatment |url=https://books.google.com/books?id=VddUa-2cp-YC&pg=PA113 |date=24 October 1990 |publisher=CRC Press |isbn=978-0-8493-5973-6 |pages=113–}}</ref><ref name="PetrovichBaert2012">{{cite book |first1=Zbigniew |last1=Petrovich |first2=Luc |last2=Baert |first3=Luther W. |last3=Brady | name-list-format = vanc |title=Carcinoma of the Prostate: Innovations in Management |url=https://books.google.com/books?id=K6G1BwAAQBAJ&pg=PT687 |date=6 December 2012 |publisher=Springer Science & Business Media |isbn=978-3-642-60956-5 |pages=687–}}</ref> However, adrenalectomy is an invasive procedure with high [[morbidity]], ketoconazole and aminoglutethimide have relatively high toxicity, and both treatment modalities require supplementation with [[corticosteroid]]s, making them in many ways unideal.<ref name="FiggChau2010" /><ref name="Held-Warmkessel2006">{{cite book |first=Jeanne |last=Held-Warmkessel | name-list-format = vanc |title=Contemporary Issues in Prostate Cancer: A Nursing Perspective |url=https://books.google.com/books?id=dZe4ZSVDdBsC&pg=PA275 |year=2006 |publisher=Jones & Bartlett Learning |isbn=978-0-7637-3075-8 |pages=275–}}</ref><ref name="StecklerKalin2005">{{cite book |first1=Thomas |last1=Steckler |first2=N.H. |last2=Kalin |first3=J.M.H.M. |last3=Reul | name-list-format = vanc |title=Handbook of Stress and the Brain Part 2: Stress: Integrative and Clinical Aspects |url=https://books.google.com/books?id=MtlcFuGKgnMC&pg=PA442 |date=25 February 2005 |publisher=Elsevier |isbn=978-0-08-055331-3 |pages=442–}}</ref><ref name="HongHolland2010">{{cite book |first1=Waun Ki |last1=Hong |first2=James F. |last2=Holland | name-list-format = vanc |title=Holland-Frei Cancer Medicine 8 |url=https://books.google.com/books?id=R0FbhLsWHBEC&pg=PA939 |year=2010 |publisher=PMPH-USA |isbn=978-1-60795-014-1 |pages=939–}}</ref> The development of {{abbr|CAB|combined androgen blockade}} with {{abbr|NSAAs|nonsteroidal antiandrogens}} like bicalutamide and enzalutamide and with newer and more tolerable androgen biosynthesis inhibitors like abiraterone acetate has since allowed for non-invasive, convenient, and well-tolerated therapies that have replaced the earlier modalities.<ref name="PetrovichBaert2012" /><ref name="WeinKavoussi2011" />
-Subsequent clinical research has found that monotherapy with higher dosages of {{abbr|NSAAs|nonsteroidal antiandrogens}} than those used in {{abbr|CAB|combined androgen blockade}} is roughly equivalent to castration in extending life in men with prostate cancer.<ref name="ChabnerLongo2010" /><ref name="FiggChau2010" /><ref name="MydloGodec2015" /><ref name="IIIBarbieri2013a" /> Moreover, {{abbr|NSAA|nonsteroidal antiandrogen}} monotherapy is overall better tolerated and associated with greater [[quality of life]] than is castration,<ref name="pmid14748655">{{cite journal |vauthors=Fradet Y |title=Bicalutamide (Casodex) in the treatment of prostate cancer |journal=Expert Review of Anticancer Therapy |volume=4 |issue=1 |pages=37–48 |date=February 2004 |pmid=14748655 |doi=10.1586/14737140.4.1.37 |quote=In contrast, the incidence of diarrhea was comparable between the bicalutamide and placebo groups (6.3 vs. 6.4%, respectively) in the EPC program [71].}}</ref><ref name="IversenMelezinek2001" /><ref name="WibowoSchellhammer2011" /><ref name="MotofeiRowland2011" /> which is thought to be related to the fact that testosterone levels do not decrease with {{abbr|NSAA|nonsteroidal antiandrogen}} monotherapy and hence by extension that levels of [[biological activity|biologically active]] and beneficial [[metabolite]]s of testosterone such as estrogens and [[neurosteroid]]s are preserved.<ref name="WibowoSchellhammer2011" /><ref name="MotofeiRowland2011" /><ref name="pmid23484454" /><ref name="Chedrese2009" /><ref name="King2008" /> For these reasons, {{abbr|NSAA|nonsteroidal antiandrogen}} monotherapy has become an important alternative to castration and {{abbr|CAB|combined androgen blockade}} in the treatment of prostate cancer.<ref name="Anderson2003" /><ref name="Boccardo2000" /><ref name="pmid11502439" />
+Subsequent clinical research has found that monotherapy with higher dosages of {{abbr|NSAAs|nonsteroidal antiandrogens}} than those used in {{abbr|CAB|combined androgen blockade}} is roughly equivalent to castration in extending life in men with prostate cancer.<ref name="ChabnerLongo2010" /><ref name="FiggChau2010" /><ref name="MydloGodec2015" /><ref name="IIIBarbieri2013a">{{cite book |first1=Jerome F. |last1=Strauss III |first2=Robert L. |last2=Barbieri | name-list-format = vanc |title=Yen & Jaffe's Reproductive Endocrinology: Physiology, Pathophysiology, and Clinical Management |url=https://books.google.com/books?id=TTCwAAAAQBAJ&pg=PA688 |date=28 August 2013 |publisher=Elsevier Health Sciences |isbn=978-1-4557-5972-9 |pages=688– |quote=Bone density improves in men receiving bicalutamide, most likely secondary to the 146% increase in estradiol and the fact that estradiol is the major mediator of bone density in men.}}</ref> Moreover, {{abbr|NSAA|nonsteroidal antiandrogen}} monotherapy is overall better tolerated and associated with greater [[quality of life]] than is castration,<ref name="pmid14748655">{{cite journal |vauthors=Fradet Y |title=Bicalutamide (Casodex) in the treatment of prostate cancer |journal=Expert Review of Anticancer Therapy |volume=4 |issue=1 |pages=37–48 |date=February 2004 |pmid=14748655 |doi=10.1586/14737140.4.1.37 |quote=In contrast, the incidence of diarrhea was comparable between the bicalutamide and placebo groups (6.3 vs. 6.4%, respectively) in the EPC program [71].}}</ref><ref name="IversenMelezinek2001" /><ref name="WibowoSchellhammer2011">{{cite journal |vauthors=Wibowo E, Schellhammer P, Wassersug RJ |title=Role of estrogen in normal male function: clinical implications for patients with prostate cancer on androgen deprivation therapy |journal=The Journal of Urology |volume=185 |issue=1 |pages=17–23 |date=January 2011 |pmid=21074215 |doi=10.1016/j.juro.2010.08.094}}</ref><ref name="MotofeiRowland2011">{{cite journal |vauthors=Motofei IG, Rowland DL, Popa F, Kreienkamp D, Paunica S |title=Preliminary study with bicalutamide in heterosexual and homosexual patients with prostate cancer: a possible implication of androgens in male homosexual arousal |journal=BJU International |volume=108 |issue=1 |pages=110–5 |date=July 2011 |pmid=20955264 |doi=10.1111/j.1464-410X.2010.09764.x}}</ref> which is thought to be related to the fact that testosterone levels do not decrease with {{abbr|NSAA|nonsteroidal antiandrogen}} monotherapy and hence by extension that levels of [[biological activity|biologically active]] and beneficial [[metabolite]]s of testosterone such as estrogens and [[neurosteroid]]s are preserved.<ref name="WibowoSchellhammer2011" /><ref name="MotofeiRowland2011" /><ref name="pmid23484454">{{cite journal |vauthors=Wibowo E, Wassersug RJ |title=The effect of estrogen on the sexual interest of castrated males: Implications to prostate cancer patients on androgen-deprivation therapy |journal=Critical Reviews in Oncology/Hematology |volume=87 |issue=3 |pages=224–38 |date=September 2013 |pmid=23484454 |doi=10.1016/j.critrevonc.2013.01.006}}</ref><ref name="Chedrese2009">{{cite book |first=P. Jorge |last=Chedrese | name-list-format = vanc |title=Reproductive Endocrinology: A Molecular Approach |url=https://books.google.com/books?id=3FJXUN6Vh44C&pg=PA233 |date=13 June 2009 |publisher=Springer Science & Business Media |isbn=978-0-387-88186-7 |pages=233– |deadurl=no |archiveurl=https://web.archive.org/web/20170905040216/https://books.google.com/books?id=3FJXUN6Vh44C |archivedate=5 September 2017 |df=dmy-all}}</ref><ref name="King2008">{{cite journal |vauthors=King SR |title=Emerging roles for neurosteroids in sexual behavior and function |journal=Journal of Andrology |volume=29 |issue=5 |pages=524–33 |year=2008 |pmid=18567641 |doi=10.2164/jandrol.108.005660}}</ref> For these reasons, {{abbr|NSAA|nonsteroidal antiandrogen}} monotherapy has become an important alternative to castration and {{abbr|CAB|combined androgen blockade}} in the treatment of prostate cancer.<ref name="Anderson2003">{{cite journal |vauthors=Anderson J |title=The role of antiandrogen monotherapy in the treatment of prostate cancer |journal=BJU International |volume=91 |issue=5 |pages=455–61 |date=March 2003 |pmid=12603397 |doi=10.1046/j.1464-410X.2003.04026.x}}</ref><ref name="Boccardo2000">{{cite journal |vauthors=Boccardo F |title=Hormone therapy of prostate cancer: is there a role for antiandrogen monotherapy? |journal=Critical Reviews in Oncology/Hematology |volume=35 |issue=2 |pages=121–32 |date=August 2000 |pmid=10936469 |doi=10.1016/S1040-8428(00)00051-2}}</ref><ref name="pmid11502439">{{cite journal |vauthors=Kolvenbag GJ, Iversen P, Newling DW |title=Antiandrogen monotherapy: a new form of treatment for patients with prostate cancer |journal=Urology |volume=58 |issue=2 Suppl 1 |pages=16–23 |year=2001 |pmid=11502439 |doi=10.1016/s0090-4295(01)01237-7 |url=}}</ref>
 ==Skin and hair conditions==
@@ Line 34: / Line 34: @@
 In addition to hirsutism, bicalutamide can also be used in the treatment of acne in women.<ref name="AscensoMarques2009">{{cite journal |vauthors=Ascenso A, Marques HC |title=Acne in the adult |journal=Mini Reviews in Medicinal Chemistry |volume=9 |issue=1 |pages=1–10 |date=January 2009 |pmid=19149656 |doi=10.2174/138955709787001730}}</ref><ref name="pmid27512185">{{cite journal |vauthors=Kaur S, Verma P, Sangwan A, Dayal S, Jain VK |title=Etiopathogenesis and Therapeutic Approach to Adult Onset Acne |journal=Indian Journal of Dermatology |volume=61 |issue=4 |pages=403–7 |year=2016 |pmid=27512185 |pmc=4966398 |doi=10.4103/0019-5154.185703 |url=}}</ref> Several studies have observed complete clearing of acne with flutamide in women, and similar benefits would be expected with bicalutamide.<ref name="Diamanti-Kandarakis_1999">{{cite journal |vauthors=Diamanti-Kandarakis E |title=Current aspects of antiandrogen therapy in women |journal=Current Pharmaceutical Design |volume=5 |issue=9 |pages=707–23 |date=September 1999 |pmid=10495361 |doi= |url=https://books.google.com/books?id=9rfNZL6oEO0C&pg=PA717 |quote=Several trials demonstrated complete clearing of acne with flutamide [62,77]. Flutamide used in combination with an [oral contraceptive], at a dose of 500mg/d, flutamide caused a dramatic decrease (80%) in total acne, seborrhea and hair loss score after only 3 months of therapy [53]. When used as a monotherapy in lean and obese PCOS, it significantly improves the signs of hyperandrogenism, hirsutism and particularly acne [48]. [...] flutamide 500mg/d combined with an [oral contraceptive] caused an increase in cosmetically acceptable hair density, in sex of seven women suffering from diffuse androgenetic alopecia [53].}}</ref>{{rp|712–717}} Bicalutamide may also treat other androgen-dependent skin and hair conditions like seborrhea and pattern hair loss.<ref name="LottiMaggi2015">{{cite journal |last1=Lotti |first1=Francesco |last2=Maggi |first2=Mario | name-list-format = vanc |title=Hormonal Treatment for Skin Androgen-Related Disorders |year=2015 |pages=1451–1464 |doi=10.1007/978-3-662-45139-7_142 |journal=European Handbook of Dermatological Treatments}}</ref> Flutamide has been found to produce a decrease of hirsutism score to normal and an 80% or greater decrease in scores of acne, seborrhea, and androgen-dependent hair loss.<ref name="SinghGauthier2000" /> Moreover, in combination with an [[oral contraceptive]], flutamide treatment resulted in an increase in cosmetically acceptable scalp hair density in 6 of 7 women suffering from pattern hair loss.<ref name="Diamanti-Kandarakis_1999" />
-Antiandrogens like flutamide and bicalutamide are male-specific [[teratogen]]s which can feminize male [[fetus]]es due to their antiandrogen effects (see [[Bicalutamide#Pregnancy and breastfeeding|below]]),<ref name="pmid9420861" /><ref name="IswaranImai1997" /><ref name="Smith2013" /> and for this reason, are not recommended by the {{abbr|FDA|Food and Drug Administration}} for use in women.<ref name="AHFS2016" /> Because of this risk, it is strongly recommended that antiandrogens only be used to treat women who are of reproductive age in conjunction with adequate contraception.<ref name="pmid9420861" /><ref name="IswaranImai1997" /><ref name="Smith2013" /> Oral contraceptives, which contain an estrogen and a [[progestin]], are typically used for this purpose.<ref name="pmid9420861" /> Moreover, oral contraceptives themselves are functional antiandrogens and are independently effective in the treatment of androgen-dependent skin and hair conditions, and hence can significantly augment the effectiveness of antiandrogens in the treatment of such conditions.<ref name="pmid9420861" /><ref name="Ostrzenski2002">{{cite book |author=Adam Ostrzenski |title=Gynecology: Integrating Conventional, Complementary, and Natural Alternative Therapy |url=https://books.google.com/books?id=TYlZsGdwqrQC&pg=PA86 |year=2002 |publisher=Lippincott Williams & Wilkins |isbn=978-0-7817-2761-7 |pages=86–}}</ref>
+Antiandrogens like flutamide and bicalutamide are male-specific [[teratogen]]s which can feminize male [[fetus]]es due to their antiandrogen effects (see [[Bicalutamide#Pregnancy and breastfeeding|below]]),<ref name="pmid9420861" /><ref name="IswaranImai1997">{{cite journal |vauthors=Iswaran TJ, Imai M, Betton GR, Siddall RA |title=An overview of animal toxicology studies with bicalutamide (ICI 176,334) |journal=The Journal of Toxicological Sciences |volume=22 |issue=2 |pages=75–88 |date=May 1997 |pmid=9198005 |doi=10.2131/jts.22.2_75}}</ref><ref name="Smith2013" /> and for this reason, are not recommended by the {{abbr|FDA|Food and Drug Administration}} for use in women.<ref name="AHFS2016" /> Because of this risk, it is strongly recommended that antiandrogens only be used to treat women who are of reproductive age in conjunction with adequate contraception.<ref name="pmid9420861" /><ref name="IswaranImai1997" /><ref name="Smith2013" /> Oral contraceptives, which contain an estrogen and a [[progestin]], are typically used for this purpose.<ref name="pmid9420861" /> Moreover, oral contraceptives themselves are functional antiandrogens and are independently effective in the treatment of androgen-dependent skin and hair conditions, and hence can significantly augment the effectiveness of antiandrogens in the treatment of such conditions.<ref name="pmid9420861" /><ref name="Ostrzenski2002">{{cite book |author=Adam Ostrzenski |title=Gynecology: Integrating Conventional, Complementary, and Natural Alternative Therapy |url=https://books.google.com/books?id=TYlZsGdwqrQC&pg=PA86 |year=2002 |publisher=Lippincott Williams & Wilkins |isbn=978-0-7817-2761-7 |pages=86–}}</ref>
 ==Transgender hormone therapy==
 {{See also|Hormone replacement therapy (male-to-female)|Nilutamide#Transgender hormone therapy}}
-Bicalutamide is used as a component of [[hormone replacement therapy (male-to-female)|hormone replacement therapy]] (HRT) for transgender women.<ref name="Gooren2011" /><ref name="BourgeoisAuriche2016">{{cite journal |vauthors=Bourgeois AL, Auriche P, Palmaro A, Montastruc JL, Bagheri H |title=Risk of hormonotherapy in transgender people: Literature review and data from the French Database of Pharmacovigilance |journal=Annales d'Endocrinologie |volume=77 |issue=1 |pages=14–21 |date=February 2016 |pmid=26830952 |doi=10.1016/j.ando.2015.12.001 |quote="Drugs for cross-gender hormonal replacement therapy used in the male to female (MtoF) transsexual population. [...] Non-steroidal anti-androgens Bicalutamide, flutamide, nilutamide"}}</ref><ref name="pmid22299206">{{cite journal |vauthors=Ho CK |title=Testosterone testing in adult males |journal=The Malaysian Journal of Pathology |volume=33 |issue=2 |pages=71–81 |date=December 2011 |pmid=22299206 |doi= |quote="Anti-androgens such as flutamide, bicalutamide and cyproterone acetate are also used in patients with prostate cancer and sometimes in male-to-female transgender individuals [...]"}}</ref><ref name="WierckxGooren2014">{{cite journal |vauthors=Wierckx K, Gooren L, T'Sjoen G |title=Clinical review: Breast development in trans women receiving cross-sex hormones |journal=The Journal of Sexual Medicine |volume=11 |issue=5 |pages=1240–7 |date=May 2014 |pmid=24618412 |doi=10.1111/jsm.12487 |quote=Other agents with anti-androgenic properties used [in the treatment of transgender women] are nonsteroidal androgen receptor blockers, such as flutamide and bicalutamide [...]}}</ref><ref name="Deutsch2016">{{citation |last=Deutsch |first=Madeline | name-list-format = vanc |title=Guidelines for the Primary and Gender-Affirming Care of Transgender and Gender Nonbinary People |date=17 June 2016 |edition=2nd |publisher=Center of Excellence for Transgender Health |location=University of California, San Francisco |page=28 |url=http://transhealth.ucsf.edu/pdf/Transgender-PGACG-6-17-16.pdf}}</ref> Beneficial or desired effects consist of [[demasculinization]] and [[feminization (biology)|feminization]], and include [[breast development]],<ref name="Braunstein2007">{{cite journal |vauthors=Braunstein GD |title=Clinical practice. Gynecomastia |journal=The New England Journal of Medicine |volume=357 |issue=12 |pages=1229–37 |date=September 2007 |pmid=17881754 |doi=10.1056/NEJMcp070677}}</ref><ref name="GentiliniBoccardo2015">{{cite journal |last1=Gentilini |first1=Oreste D. |last2=Boccardo |first2=Chiara | name-list-format = vanc |title=Male Breast Diseases |year=2015 |pages=431–446 |doi=10.1007/978-3-319-15907-2_19 |journal=The Outpatient Breast Clinic}}</ref><ref name="KanhaiHage2000">{{cite journal |vauthors=Kanhai RC, Hage JJ, van Diest PJ, Bloemena E, Mulder JW |title=Short-term and long-term histologic effects of castration and estrogen treatment on breast tissue of 14 male-to-female transsexuals in comparison with two chemically castrated men |journal=The American Journal of Surgical Pathology |volume=24 |issue=1 |pages=74–80 |date=January 2000 |pmid=10632490 |doi=10.1097/00000478-200001000-00009}}</ref> reduced [[body hair|male-pattern hair]],<ref name="Higano2003" /> [[muscle atrophy|decreased muscle mass]],<ref name="Lehne2013" /> [[gynoid fat distribution|feminine]] changes in [[fat distribution]], lowered [[libido]],<ref name="Lehne2013" /> and loss of [[spontaneous erection]]s.<ref name="El-RayesHussain2014">{{cite journal |vauthors=el-Rayes BF, Hussain MH |title=Hormonal therapy for prostate cancer: past, present and future |journal=Expert Review of Anticancer Therapy |volume=2 |issue=1 |pages=37–47 |date=February 2002 |pmid=12113064 |doi=10.1586/14737140.2.1.37 |quote=At 2-year follow-up, loss of spontaneous erections and sexual function occurred in 80 vs. 92% and 78 vs. 88% in the flutamide versus CPA groups, respectively. This group of agents includes flutamide, nilutamide and bicalutamide.}}</ref> It is also noteworthy that, when used as a monotherapy, bicalutamide significantly increases [[estradiol]] levels in biological males and hence can have indirect estrogenic effects in transgender women; this is a property that can be considered to be desirable in transgender women, as it can produce or contribute to feminization.<ref name="KreukelsSteensma2013">{{cite book |first1=Baudewijntje P.C. |last1=Kreukels |first2=Thomas D. |last2=Steensma |first3=Annelou L.C. |last3=de Vries | name-list-format = vanc |title=Gender Dysphoria and Disorders of Sex Development: Progress in Care and Knowledge |url=https://books.google.com/books?id=YQ5GAAAAQBAJ&pg=PA280 |date=1 July 2013 |publisher=Springer Science & Business Media |isbn=978-1-4614-7441-8 |pages=280– |quote=Nonsteroidal antiandrogens, such as flutamide (50–75 mg/day) and nilutamide (150 mg/day), are also used, but they increase gonadotropin output with a rise of testosterone and estradiol; the rise of estradiol is a desirable effect in this context.}}</ref><ref name="JamesonKretser2013">{{cite book |first1=J. Larry |last1=Jameson |first2=David M. |last2=de Kretser |first3=John C. |last3=Marshall |first4=Leslie J. |last4=De Groot | name-list-format = vanc |title=Endocrinology Adult and Pediatric: Reproductive Endocrinology |url=https://books.google.com/books?id=Np8xxP6pcdUC&pg=RA1-PT476 |date=7 May 2013 |publisher=Elsevier Health Sciences |isbn=978-0-323-22152-8 |pages= |quote=Nonsteroidal antiandrogens (e.g., flutamide and nilutamide) are also used, but they increase gonadotropin secretion, causing increased secretion of testosterone and estradiol.119 The latter is desirable in this context, as it has feminizing effects. |deadurl=no |archiveurl=https://web.archive.org/web/20140725230829/http://books.google.com/books?id=Np8xxP6pcdUC&pg=RA1-PT476 |archivedate=25 July 2014 |df=dmy-all}}</ref>
+Bicalutamide is used as a component of [[hormone replacement therapy (male-to-female)|hormone replacement therapy]] (HRT) for transgender women.<ref name="Gooren2011" /><ref name="BourgeoisAuriche2016">{{cite journal |vauthors=Bourgeois AL, Auriche P, Palmaro A, Montastruc JL, Bagheri H |title=Risk of hormonotherapy in transgender people: Literature review and data from the French Database of Pharmacovigilance |journal=Annales d'Endocrinologie |volume=77 |issue=1 |pages=14–21 |date=February 2016 |pmid=26830952 |doi=10.1016/j.ando.2015.12.001 |quote="Drugs for cross-gender hormonal replacement therapy used in the male to female (MtoF) transsexual population. [...] Non-steroidal anti-androgens Bicalutamide, flutamide, nilutamide"}}</ref><ref name="pmid22299206">{{cite journal |vauthors=Ho CK |title=Testosterone testing in adult males |journal=The Malaysian Journal of Pathology |volume=33 |issue=2 |pages=71–81 |date=December 2011 |pmid=22299206 |doi= |quote="Anti-androgens such as flutamide, bicalutamide and cyproterone acetate are also used in patients with prostate cancer and sometimes in male-to-female transgender individuals [...]"}}</ref><ref name="WierckxGooren2014">{{cite journal |vauthors=Wierckx K, Gooren L, T'Sjoen G |title=Clinical review: Breast development in trans women receiving cross-sex hormones |journal=The Journal of Sexual Medicine |volume=11 |issue=5 |pages=1240–7 |date=May 2014 |pmid=24618412 |doi=10.1111/jsm.12487 |quote=Other agents with anti-androgenic properties used [in the treatment of transgender women] are nonsteroidal androgen receptor blockers, such as flutamide and bicalutamide [...]}}</ref><ref name="Deutsch2016">{{citation |last=Deutsch |first=Madeline | name-list-format = vanc |title=Guidelines for the Primary and Gender-Affirming Care of Transgender and Gender Nonbinary People |date=17 June 2016 |edition=2nd |publisher=Center of Excellence for Transgender Health |location=University of California, San Francisco |page=28 |url=http://transhealth.ucsf.edu/pdf/Transgender-PGACG-6-17-16.pdf}}</ref> Beneficial or desired effects consist of [[demasculinization]] and [[feminization (biology)|feminization]], and include [[breast development]],<ref name="Braunstein2007">{{cite journal |vauthors=Braunstein GD |title=Clinical practice. Gynecomastia |journal=The New England Journal of Medicine |volume=357 |issue=12 |pages=1229–37 |date=September 2007 |pmid=17881754 |doi=10.1056/NEJMcp070677}}</ref><ref name="GentiliniBoccardo2015">{{cite journal |last1=Gentilini |first1=Oreste D. |last2=Boccardo |first2=Chiara | name-list-format = vanc |title=Male Breast Diseases |year=2015 |pages=431–446 |doi=10.1007/978-3-319-15907-2_19 |journal=The Outpatient Breast Clinic}}</ref><ref name="KanhaiHage2000">{{cite journal |vauthors=Kanhai RC, Hage JJ, van Diest PJ, Bloemena E, Mulder JW |title=Short-term and long-term histologic effects of castration and estrogen treatment on breast tissue of 14 male-to-female transsexuals in comparison with two chemically castrated men |journal=The American Journal of Surgical Pathology |volume=24 |issue=1 |pages=74–80 |date=January 2000 |pmid=10632490 |doi=10.1097/00000478-200001000-00009}}</ref> reduced [[body hair|male-pattern hair]],<ref name="Higano2003">{{cite journal |vauthors=Higano CS |title=Side effects of androgen deprivation therapy: monitoring and minimizing toxicity |journal=Urology |volume=61 |issue=2 Suppl 1 |pages=32–8 |date=February 2003 |pmid=12667885 |doi=10.1016/S0090-4295(02)02397-X}}</ref> [[muscle atrophy|decreased muscle mass]],<ref name="Lehne2013" /> [[gynoid fat distribution|feminine]] changes in [[fat distribution]], lowered [[libido]],<ref name="Lehne2013" /> and loss of [[spontaneous erection]]s.<ref name="El-RayesHussain2014">{{cite journal |vauthors=el-Rayes BF, Hussain MH |title=Hormonal therapy for prostate cancer: past, present and future |journal=Expert Review of Anticancer Therapy |volume=2 |issue=1 |pages=37–47 |date=February 2002 |pmid=12113064 |doi=10.1586/14737140.2.1.37 |quote=At 2-year follow-up, loss of spontaneous erections and sexual function occurred in 80 vs. 92% and 78 vs. 88% in the flutamide versus CPA groups, respectively. This group of agents includes flutamide, nilutamide and bicalutamide.}}</ref> It is also noteworthy that, when used as a monotherapy, bicalutamide significantly increases [[estradiol]] levels in biological males and hence can have indirect estrogenic effects in transgender women; this is a property that can be considered to be desirable in transgender women, as it can produce or contribute to feminization.<ref name="KreukelsSteensma2013">{{cite book |first1=Baudewijntje P.C. |last1=Kreukels |first2=Thomas D. |last2=Steensma |first3=Annelou L.C. |last3=de Vries | name-list-format = vanc |title=Gender Dysphoria and Disorders of Sex Development: Progress in Care and Knowledge |url=https://books.google.com/books?id=YQ5GAAAAQBAJ&pg=PA280 |date=1 July 2013 |publisher=Springer Science & Business Media |isbn=978-1-4614-7441-8 |pages=280– |quote=Nonsteroidal antiandrogens, such as flutamide (50–75 mg/day) and nilutamide (150 mg/day), are also used, but they increase gonadotropin output with a rise of testosterone and estradiol; the rise of estradiol is a desirable effect in this context.}}</ref><ref name="JamesonKretser2013">{{cite book |first1=J. Larry |last1=Jameson |first2=David M. |last2=de Kretser |first3=John C. |last3=Marshall |first4=Leslie J. |last4=De Groot | name-list-format = vanc |title=Endocrinology Adult and Pediatric: Reproductive Endocrinology |url=https://books.google.com/books?id=Np8xxP6pcdUC&pg=RA1-PT476 |date=7 May 2013 |publisher=Elsevier Health Sciences |isbn=978-0-323-22152-8 |pages= |quote=Nonsteroidal antiandrogens (e.g., flutamide and nilutamide) are also used, but they increase gonadotropin secretion, causing increased secretion of testosterone and estradiol.119 The latter is desirable in this context, as it has feminizing effects. |deadurl=no |archiveurl=https://web.archive.org/web/20140725230829/http://books.google.com/books?id=Np8xxP6pcdUC&pg=RA1-PT476 |archivedate=25 July 2014 |df=dmy-all}}</ref>
-Unlike the {{abbr|SAAs|steroidal antiandrogens}} {{abbr|CPA|cyproterone acetate}} and [[spironolactone]], as well as {{abbr|GnRH|gonadotropin-releasing hormone}} analogues,<ref name="pmid12915619">{{cite journal |vauthors=Moore E, Wisniewski A, Dobs A |title=Endocrine treatment of transsexual people: a review of treatment regimens, outcomes, and adverse effects |journal=The Journal of Clinical Endocrinology & Metabolism |volume=88 |issue=8 |pages=3467–73 |year=2003 |pmid=12915619 |doi=10.1210/jc.2002-021967 |url=}}</ref> no clinical studies assessing bicalutamide as an antiandrogen in the hormonal therapy of transgender women appear to have been conducted to date.<ref name="GoogleScholar">{{cite web |title="bicalutamide" OR "casodex" "transgender" OR "transsexual" OR "transsexuals" OR "trans women" OR "male-to-female" - Google Scholar |accessdate=2017-07-06 |url=https://scholar.google.com/scholar?as_sdt=1,5&q=%22bicalutamide%22+OR+%22casodex%22+%22transgender%22+OR+%22transsexual%22+OR+%22transsexuals%22+OR+%22trans+women%22+OR+%22male-to-female%22&hl=en}}</ref> In any case, bicalutamide is clinically effective as an antiandrogen in women with hirsutism<ref name="WilliamsBigby2009" /><ref name="pmid24455796" /> and in boys with precocious puberty,<ref name="KliegmanStanton2015" /><ref name="KreherPescovitz2006" /><ref name="ReiterMauras2010" /><ref name="JamesonGroot2015" /> and demasculinization and feminization are well-documented effects of bicalutamide in men treated with it for prostate cancer ([[#Side effects|see below]]).<ref name="Higano2003" /><ref name="pmid20626600" /><ref name="pmid23008326" /> In addition, nilutamide, a closely related antiandrogen that possesses essentially the same mechanism of action as bicalutamide, has been evaluated in transgender women in at least five small clinical studies.<ref name="KreukelsSteensma2013" /><ref name="AsschemanGooren1989">{{cite journal |vauthors=Asscheman H, Gooren LJ, Peereboom-Wynia JD |title=Reduction in undesired sexual hair growth with anandron in male-to-female transsexuals—experiences with a novel androgen receptor blocker |journal=Clinical and Experimental Dermatology |volume=14 |issue=5 |pages=361–3 |year=1989 |pmid=2612040 |doi=10.1111/j.1365-2230.1989.tb02585.x}}</ref><ref name="Raode Voogt1988">{{cite journal |vauthors=Rao BR, de Voogt HJ, Geldof AA, Gooren LJ, Bouman FG |title=Merits and considerations in the use of anti-androgen |journal=Journal of Steroid Biochemistry |volume=31 |issue=4B |pages=731–7 |year=1988 |pmid=3143862 |doi=10.1016/0022-4731(88)90024-6}}</ref><ref name="van KemenadeCohen-Kettenis1989">{{cite journal |vauthors=van Kemenade JF, Cohen-Kettenis PT, Cohen L, Gooren LJ |title=Effects of the pure antiandrogen RU 23.903 (anandron) on sexuality, aggression, and mood in male-to-female transsexuals |journal=Archives of Sexual Behavior |volume=18 |issue=3 |pages=217–28 |year=1989 |pmid=2751416 |doi=10.1007/BF01543196}}</ref><ref name="GoorenSpinder1987">{{cite journal |vauthors=Gooren L, Spinder T, Spijkstra JJ, van Kessel H, Smals A, Rao BR, Hoogslag M |title=Sex steroids and pulsatile luteinizing hormone release in men. Studies in estrogen-treated agonadal subjects and eugonadal subjects treated with a novel nonsteroidal antiandrogen |journal=The Journal of Clinical Endocrinology & Metabolism |volume=64 |issue=4 |pages=763–70 |year=1987 |pmid=3102546 |doi=10.1210/jcem-64-4-763}}</ref><ref name="De VoogtRao1987">{{cite journal |vauthors=de Voogt HJ, Rao BR, Geldof AA, Gooren LJ, Bouman FG |title=Androgen action blockade does not result in reduction in size but changes histology of the normal human prostate |journal=Prostate |volume=11 |issue=4 |pages=305–11 |year=1987 |pmid=2960959 |doi=10.1002/pros.2990110403}}</ref> It was given at a high dosage of 300&nbsp;mg/day, the same dosage in which it has been used as a monotherapy in the treatment of prostate cancer.<ref name="KreukelsSteensma2013" /><ref name="AsschemanGooren1989" /><ref name="Raode Voogt1988" /><ref name="van KemenadeCohen-Kettenis1989" /><ref name="GoorenSpinder1987" /><ref name="De VoogtRao1987" /> The corresponding monotherapy dosage of bicalutamide in the treatment of prostate cancer is 150&nbsp;mg/day.<ref name="LemkeWilliams2008" /><ref name="Cockshott2004" /><ref name="Wellington2006" />
+Unlike the {{abbr|SAAs|steroidal antiandrogens}} {{abbr|CPA|cyproterone acetate}} and [[spironolactone]], as well as {{abbr|GnRH|gonadotropin-releasing hormone}} analogues,<ref name="pmid12915619">{{cite journal |vauthors=Moore E, Wisniewski A, Dobs A |title=Endocrine treatment of transsexual people: a review of treatment regimens, outcomes, and adverse effects |journal=The Journal of Clinical Endocrinology & Metabolism |volume=88 |issue=8 |pages=3467–73 |year=2003 |pmid=12915619 |doi=10.1210/jc.2002-021967 |url=}}</ref> no clinical studies assessing bicalutamide as an antiandrogen in the hormonal therapy of transgender women appear to have been conducted to date.<ref name="GoogleScholar">{{cite web |title="bicalutamide" OR "casodex" "transgender" OR "transsexual" OR "transsexuals" OR "trans women" OR "male-to-female" - Google Scholar |accessdate=2017-07-06 |url=https://scholar.google.com/scholar?as_sdt=1,5&q=%22bicalutamide%22+OR+%22casodex%22+%22transgender%22+OR+%22transsexual%22+OR+%22transsexuals%22+OR+%22trans+women%22+OR+%22male-to-female%22&hl=en}}</ref> In any case, bicalutamide is clinically effective as an antiandrogen in women with hirsutism<ref name="WilliamsBigby2009" /><ref name="pmid24455796" /> and in boys with precocious puberty,<ref name="KliegmanStanton2015" /><ref name="KreherPescovitz2006" /><ref name="ReiterMauras2010" /><ref name="JamesonGroot2015" /> and demasculinization and feminization are well-documented effects of bicalutamide in men treated with it for prostate cancer ([[#Side effects|see below]]).<ref name="Higano2003" /><ref name="pmid20626600">{{cite journal |vauthors=Elliott S, Latini DM, Walker LM, Wassersug R, Robinson JW |title=Androgen deprivation therapy for prostate cancer: recommendations to improve patient and partner quality of life |journal=The Journal of Sexual Medicine |volume=7 |issue=9 |pages=2996–3010 |year=2010 |pmid=20626600 |doi=10.1111/j.1743-6109.2010.01902.x |url=}}</ref><ref name="pmid23008326">{{cite journal |vauthors=Higano CS |title=Sexuality and intimacy after definitive treatment and subsequent androgen deprivation therapy for prostate cancer |journal=Journal of Clinical Oncology |volume=30 |issue=30 |pages=3720–5 |year=2012 |pmid=23008326 |doi=10.1200/JCO.2012.41.8509 |url=}}</ref> In addition, nilutamide, a closely related antiandrogen that possesses essentially the same mechanism of action as bicalutamide, has been evaluated in transgender women in at least five small clinical studies.<ref name="KreukelsSteensma2013" /><ref name="AsschemanGooren1989">{{cite journal |vauthors=Asscheman H, Gooren LJ, Peereboom-Wynia JD |title=Reduction in undesired sexual hair growth with anandron in male-to-female transsexuals—experiences with a novel androgen receptor blocker |journal=Clinical and Experimental Dermatology |volume=14 |issue=5 |pages=361–3 |year=1989 |pmid=2612040 |doi=10.1111/j.1365-2230.1989.tb02585.x}}</ref><ref name="Raode Voogt1988">{{cite journal |vauthors=Rao BR, de Voogt HJ, Geldof AA, Gooren LJ, Bouman FG |title=Merits and considerations in the use of anti-androgen |journal=Journal of Steroid Biochemistry |volume=31 |issue=4B |pages=731–7 |year=1988 |pmid=3143862 |doi=10.1016/0022-4731(88)90024-6}}</ref><ref name="van KemenadeCohen-Kettenis1989">{{cite journal |vauthors=van Kemenade JF, Cohen-Kettenis PT, Cohen L, Gooren LJ |title=Effects of the pure antiandrogen RU 23.903 (anandron) on sexuality, aggression, and mood in male-to-female transsexuals |journal=Archives of Sexual Behavior |volume=18 |issue=3 |pages=217–28 |year=1989 |pmid=2751416 |doi=10.1007/BF01543196}}</ref><ref name="GoorenSpinder1987">{{cite journal |vauthors=Gooren L, Spinder T, Spijkstra JJ, van Kessel H, Smals A, Rao BR, Hoogslag M |title=Sex steroids and pulsatile luteinizing hormone release in men. Studies in estrogen-treated agonadal subjects and eugonadal subjects treated with a novel nonsteroidal antiandrogen |journal=The Journal of Clinical Endocrinology & Metabolism |volume=64 |issue=4 |pages=763–70 |year=1987 |pmid=3102546 |doi=10.1210/jcem-64-4-763}}</ref><ref name="De VoogtRao1987">{{cite journal |vauthors=de Voogt HJ, Rao BR, Geldof AA, Gooren LJ, Bouman FG |title=Androgen action blockade does not result in reduction in size but changes histology of the normal human prostate |journal=Prostate |volume=11 |issue=4 |pages=305–11 |year=1987 |pmid=2960959 |doi=10.1002/pros.2990110403}}</ref> It was given at a high dosage of 300&nbsp;mg/day, the same dosage in which it has been used as a monotherapy in the treatment of prostate cancer.<ref name="KreukelsSteensma2013" /><ref name="AsschemanGooren1989" /><ref name="Raode Voogt1988" /><ref name="van KemenadeCohen-Kettenis1989" /><ref name="GoorenSpinder1987" /><ref name="De VoogtRao1987" /> The corresponding monotherapy dosage of bicalutamide in the treatment of prostate cancer is 150&nbsp;mg/day.<ref name="LemkeWilliams2008" /><ref name="Cockshott2004" /><ref name="Wellington2006" />
 In the clinical studies of nilutamide for transgender hormone therapy, the drug, without being combined with estrogen, induced observable signs of clinical feminization in young transgender women (age range 19–33&nbsp;years) within 8 weeks,<ref name="Raode Voogt1988" /> including breast development, decreased male-pattern hair,<ref name="AsschemanGooren1989" /> decreased spontaneous erections and [[sex drive]],<ref name="van KemenadeCohen-Kettenis1989" /> and positive psychological and emotional changes.<ref name="van KemenadeCohen-Kettenis1989" /><ref name="Cohen-KettenisGooren1993">{{cite journal |last1=Cohen-Kettenis |first1=Peggy T. |last2=Gooren |first2=Louis J.G. | name-list-format = vanc |title=The Influence of Hormone Treatment on Psychological Functioning of Transsexuals |journal=Journal of Psychology & Human Sexuality |volume=5 |issue=4 |year=1993 |pages=55–67 |issn=0890-7064 |doi=10.1300/J056v05n04_04}}</ref> Signs of breast development occurred in all subjects within 6&nbsp;weeks and were associated with increased [[nipple sensitivity]];<ref name="De VoogtRao1987" /><ref name="Raode Voogt1988" /><ref name="van KemenadeCohen-Kettenis1989" /> along with decreased hair growth, these changes were the earliest signs of feminization.<ref name="Raode Voogt1988" /> The drug more than doubled [[luteinizing hormone]] (LH) and testosterone levels and tripled estradiol levels (see [[#Influences on hormone levels|below]]),<ref name="AsschemanGooren1989" /><ref name="Raode Voogt1988" /><ref name="GoorenSpinder1987" /> and the addition of [[ethinylestradiol]], a potent estrogen, to nilutamide therapy after 8 weeks of treatment abolished the increase in {{abbr|LH|luteinizing hormone}}, testosterone, and estradiol levels and dramatically suppressed testosterone levels, into the castrate range.<ref name="AsschemanGooren1989" /><ref name="Raode Voogt1988" /> On the basis of these results, both nilutamide alone, and particularly the combination of nilutamide and an estrogen, were regarded as effective in terms of producing antiandrogen effects and feminization in transgender women.<ref name="AsschemanGooren1989" /><ref name="Raode Voogt1988" />
@@ Line 51: / Line 51: @@
 {{Quotation|''In many countries, cyproterone acetate, a synthetic progestagen with strong anti-androgen activity is commonly used [as an antiandrogen in feminizing hormone therapy for transgender women]. Cyproterone [acetate] has been associated with uncommon episodes of fulminant hepatitis.[12] Bicalutamide, a direct anti-androgen used for the treatment of prostate cancer, also has a small but not fully quantified risk of liver function abnormalities (including several cases of fulminant hepatitis); while such risks are acceptable when considering the benefits of bicalutamide in the management of prostate cancer, such risks are less justified in the context of gender-affirming treatment.[13] No evidence at present exists to inform such an analysis.''<ref name="Deutsch2016" />}}
-In spite of its risk of hepatotoxicity, {{abbr|CPA|cyproterone acetate}} is the most widely used antiandrogen in Europe and elsewhere in the world for hormone therapy in transgender women.<ref name="KreukelsSteensma2013" /><ref name="EttnerMonstrey2016">{{cite book |first1=Randi |last1=Ettner |first2=Stan |last2=Monstrey |first3=Eli |last3=Coleman | name-list-format = vanc |title=Principles of Transgender Medicine and Surgery |url=https://books.google.com/books?id=LwszDAAAQBAJ&pg=PA169 |date=27 May 2016 |publisher=Routledge |isbn=978-1-317-51460-2 |pages=169– |quote=In Europe, the most widely used drug [in the treatment of male-to-female patients] is cyproterone acetate [...]}}</ref><ref name="Erickson-Schroth2014">{{cite book |first=Laura |last=Erickson-Schroth|name-list-format=vanc |title=Trans Bodies, Trans Selves: A Resource for the Transgender Community |url=https://books.google.com/books?id=oZeAAwAAQBAJ&pg=PA258 |date=12 May 2014 |publisher=Oxford University Press |isbn=978-0-19-932536-8 |pages=258– |quote=Cyproterone [acetate] is widely used outside the United States as the primary testosterone blocker in transgender women. Cyproterone, however, is not authorized for sale in the United States for any condition and has been associated with liver problems. |deadurl=no |archiveurl=https://web.archive.org/web/20160624162616/https://books.google.com/books?id=oZeAAwAAQBAJ |archivedate=24 June 2016 |df=dmy-all}}</ref> In addition, it is widely used in [[cisgender women]] for the treatment of acne and hirsutism.<ref name="Azziz2007">{{cite book |first=Ricardo |last=Azziz | name-list-format = vanc |title=Androgen Excess Disorders in Women |url=https://books.google.com/books?id=Ch-BsGAOtucC&pg=PA382 |date=8 November 2007 |publisher=Springer Science & Business Media |isbn=978-1-59745-179-6 |pages=382– |quote=Cyproterone acetate is an effective treatment for hirsutism and acne [in women] and is widely used throughout the world for this indication.}}</ref> In the {{abbr|U.S.|United States}}, one of the only countries where {{abbr|CPA|cyproterone acetate}} has not been approved for medical use,<ref name="Danby2015">{{cite book |author=F. William Danby |title=Acne: Causes and Practical Management |url=https://books.google.com/books?id=Z1yFBQAAQBAJ&pg=PA142 |date=27 January 2015 |publisher=John Wiley & Sons |isbn=978-1-118-23277-4 |pages=142–}}</ref><ref name="Schechter2016">{{cite book |author=Loren S Schechter |title=Surgical Management of the Transgender Patient |url=https://books.google.com/books?id=eGkgDQAAQBAJ&pg=PP26 |date=22 September 2016 |publisher=Elsevier Health Sciences |isbn=978-0-323-48408-4 |pages=26–}}</ref> the relatively weak agent spironolactone is the antiandrogen most commonly used in transgender and cisgender women instead.<ref name="BenniVemer1990">{{cite book |author1=H.J.T. Coelingh Benni |author2=H.M. Vemer |title=Chronic Hyperandrogenic Anovulation |url=https://books.google.com/books?id=q6zqFrCLUoIC&pg=PA152 |date=15 December 1990 |publisher=CRC Press |isbn=978-1-85070-322-8 |pages=152– |quote=CPA is not available in the United States. Thus, spironolactone is currently used. [...] In our opinion, [spironolactone] has a weak antiandrogenic activity.}}</ref><ref name="FalconeHurd2007">{{cite book |author1=Tommaso Falcone |author2=William Hurd |title=Clinical Reproductive Medicine and Surgery E-Book |url=https://books.google.com/books?id=YAejBQAAQBAJ&pg=PT285 |date=26 April 2007 |publisher=Elsevier Health Sciences |isbn=978-0-323-07659-3 |pages=285– |quote=[Flutamide] is also more effective than spironolactone in treating hirsutism, with reduction in hirsutism scores to almost normal after 6 months of therapy with flutamide versus only a 30% reduction in women treated with spironolactone.151}}</ref><ref name="RowlandIncrocci2008">{{cite book |first1=David L. |last1=Rowland |first2=Luca |last2=Incrocci | name-list-format = vanc |title=Handbook of Sexual and Gender Identity Disorders |url=https://books.google.com/books?id=1stVkph8Ay8C&pg=PA444 |date=2 May 2008 |publisher=John Wiley & Sons |isbn=978-0-470-25721-0 |pages=444– |quote=Spironolactone is the most commonly prescribed antiandrogen [for feminizing hormone therapy] in the United States.}}</ref> Although both {{abbr|CPA|cyproterone acetate}} and bicalutamide have been associated with hepatotoxicity (while spironolactone is not usually associated with such), bicalutamide has a far lower and only small risk of both elevated liver enzymes and hepatotoxicity (see [[Bicalutamide#Liver toxicity|below]]);<ref name="pmid15604569">{{cite journal |vauthors=Thole Z, Manso G, Salgueiro E, Revuelta P, Hidalgo A |title=Hepatotoxicity induced by antiandrogens: a review of the literature |journal=Urologia Internationalis |volume=73 |issue=4 |pages=289–95 |year=2004 |pmid=15604569 |doi=10.1159/000081585 |url=}}</ref> whereas {{abbr|CPA|cyproterone acetate}} has been associated with over 100&nbsp;reports of hepatotoxicity,<ref name="Kaplowitz2002" /> five cases of hepatotoxicity, out of millions of patient exposures, have been associated with bicalutamide to date.<ref name="YunKim2016" /><ref name="HHS2010" />
+In spite of its risk of hepatotoxicity, {{abbr|CPA|cyproterone acetate}} is the most widely used antiandrogen in Europe and elsewhere in the world for hormone therapy in transgender women.<ref name="KreukelsSteensma2013" /><ref name="EttnerMonstrey2016">{{cite book |first1=Randi |last1=Ettner |first2=Stan |last2=Monstrey |first3=Eli |last3=Coleman | name-list-format = vanc |title=Principles of Transgender Medicine and Surgery |url=https://books.google.com/books?id=LwszDAAAQBAJ&pg=PA169 |date=27 May 2016 |publisher=Routledge |isbn=978-1-317-51460-2 |pages=169– |quote=In Europe, the most widely used drug [in the treatment of male-to-female patients] is cyproterone acetate [...]}}</ref><ref name="Erickson-Schroth2014">{{cite book |first=Laura |last=Erickson-Schroth|name-list-format=vanc |title=Trans Bodies, Trans Selves: A Resource for the Transgender Community |url=https://books.google.com/books?id=oZeAAwAAQBAJ&pg=PA258 |date=12 May 2014 |publisher=Oxford University Press |isbn=978-0-19-932536-8 |pages=258– |quote=Cyproterone [acetate] is widely used outside the United States as the primary testosterone blocker in transgender women. Cyproterone, however, is not authorized for sale in the United States for any condition and has been associated with liver problems. |deadurl=no |archiveurl=https://web.archive.org/web/20160624162616/https://books.google.com/books?id=oZeAAwAAQBAJ |archivedate=24 June 2016 |df=dmy-all}}</ref> In addition, it is widely used in [[cisgender women]] for the treatment of acne and hirsutism.<ref name="Azziz2007">{{cite book |first=Ricardo |last=Azziz | name-list-format = vanc |title=Androgen Excess Disorders in Women |url=https://books.google.com/books?id=Ch-BsGAOtucC&pg=PA382 |date=8 November 2007 |publisher=Springer Science & Business Media |isbn=978-1-59745-179-6 |pages=382– |quote=Cyproterone acetate is an effective treatment for hirsutism and acne [in women] and is widely used throughout the world for this indication.}}</ref> In the {{abbr|U.S.|United States}}, one of the only countries where {{abbr|CPA|cyproterone acetate}} has not been approved for medical use,<ref name="Danby2015">{{cite book |author=F. William Danby |title=Acne: Causes and Practical Management |url=https://books.google.com/books?id=Z1yFBQAAQBAJ&pg=PA142 |date=27 January 2015 |publisher=John Wiley & Sons |isbn=978-1-118-23277-4 |pages=142–}}</ref><ref name="Schechter2016">{{cite book |author=Loren S Schechter |title=Surgical Management of the Transgender Patient |url=https://books.google.com/books?id=eGkgDQAAQBAJ&pg=PP26 |date=22 September 2016 |publisher=Elsevier Health Sciences |isbn=978-0-323-48408-4 |pages=26–}}</ref> the relatively weak agent spironolactone is the antiandrogen most commonly used in transgender and cisgender women instead.<ref name="BenniVemer1990">{{cite book |author1=H.J.T. Coelingh Benni |author2=H.M. Vemer |title=Chronic Hyperandrogenic Anovulation |url=https://books.google.com/books?id=q6zqFrCLUoIC&pg=PA152 |date=15 December 1990 |publisher=CRC Press |isbn=978-1-85070-322-8 |pages=152– |quote=CPA is not available in the United States. Thus, spironolactone is currently used. [...] In our opinion, [spironolactone] has a weak antiandrogenic activity.}}</ref><ref name="FalconeHurd2007">{{cite book |author1=Tommaso Falcone |author2=William Hurd |title=Clinical Reproductive Medicine and Surgery E-Book |url=https://books.google.com/books?id=YAejBQAAQBAJ&pg=PT285 |date=26 April 2007 |publisher=Elsevier Health Sciences |isbn=978-0-323-07659-3 |pages=285– |quote=[Flutamide] is also more effective than spironolactone in treating hirsutism, with reduction in hirsutism scores to almost normal after 6 months of therapy with flutamide versus only a 30% reduction in women treated with spironolactone.151}}</ref><ref name="RowlandIncrocci2008">{{cite book |first1=David L. |last1=Rowland |first2=Luca |last2=Incrocci | name-list-format = vanc |title=Handbook of Sexual and Gender Identity Disorders |url=https://books.google.com/books?id=1stVkph8Ay8C&pg=PA444 |date=2 May 2008 |publisher=John Wiley & Sons |isbn=978-0-470-25721-0 |pages=444– |quote=Spironolactone is the most commonly prescribed antiandrogen [for feminizing hormone therapy] in the United States.}}</ref> Although both {{abbr|CPA|cyproterone acetate}} and bicalutamide have been associated with hepatotoxicity (while spironolactone is not usually associated with such), bicalutamide has a far lower and only small risk of both elevated liver enzymes and hepatotoxicity (see [[Bicalutamide#Liver toxicity|below]]);<ref name="pmid15604569">{{cite journal |vauthors=Thole Z, Manso G, Salgueiro E, Revuelta P, Hidalgo A |title=Hepatotoxicity induced by antiandrogens: a review of the literature |journal=Urologia Internationalis |volume=73 |issue=4 |pages=289–95 |year=2004 |pmid=15604569 |doi=10.1159/000081585 |url=}}</ref> whereas {{abbr|CPA|cyproterone acetate}} has been associated with over 100&nbsp;reports of hepatotoxicity,<ref name="Kaplowitz2002" /> five cases of hepatotoxicity, out of millions of patient exposures, have been associated with bicalutamide to date.<ref name="YunKim2016">{{cite journal |vauthors=Yun GY, Kim SH, Kim SW, Joo JS, Kim JS, Lee ES, Lee BS, Kang SH, Moon HS, Sung JK, Lee HY, Kim KH |title=Atypical onset of bicalutamide-induced liver injury |journal=World Journal of Gastroenterology |volume=22 |issue=15 |pages=4062–5 |date=April 2016 |pmid=27099451 |pmc=4823258 |doi=10.3748/wjg.v22.i15.4062}}</ref><ref name=HHS2010>{{citation |title=Bicalutamide BPCA Drug Use Review in the Pediatric Population |first=Stephen |last=Chang | name-list-format = vanc |publisher=[[United States Department of Health and Human Services|U.S. Department of Health and Human Service]] |date=10 March 2010 |accessdate=20 July 2016 |url=http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/PediatricAdvisoryCommittee/UCM214400.pdf |deadurl=no |archiveurl=https://web.archive.org/web/20161024181831/http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/PediatricAdvisoryCommittee/UCM214400.pdf |archivedate=24 October 2016 |df=dmy-all}}</ref>
 ==Male early puberty==
@@ Line 69: / Line 69: @@
 [[File:Bicalutamide Teva 50 mg tablets.jpg|thumb|right|230px|Bicalutamide [[Teva Pharmaceutical Industries|Teva]] 50 mg tablets.<ref>{{cite web |url=https://www.tevagenerics.com/product/bicalutamide-tablets-usp |title=Bicalutamide Tablets, USP |publisher=Teva Pharmaceuticals USA, Inc. |deadurl=no |archiveurl=https://web.archive.org/web/20160917110946/https://www.tevagenerics.com/product/bicalutamide-tablets-usp |archivedate=17 September 2016 |df=dmy-all}}</ref>]]
-Bicalutamide is available for the treatment of prostate cancer in most developed countries,<ref name="IndexNominum2000">{{cite book |editor=Swiss Pharmaceutical Society |title=Index Nominum 2000: International Drug Directory |url=https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA123 |date=January 2000 |publisher=Taylor & Francis |isbn=978-3-88763-075-1 |pages=123– |deadurl=no |archiveurl=https://web.archive.org/web/20160424054101/https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA123 |archivedate=24 April 2016 |df=dmy-all}}</ref><ref name="Drugs.com-2" /><ref name="Martindale2011">{{cite book |first=Sean C. |last=Sweetman  | name-list-format = vanc |title=Martindale: The Complete Drug Reference |url=https://books.google.com/books?id=r_qfcQAACAAJ |year=2011 |publisher=Pharmaceutical Press |isbn=978-0-85369-933-0 |pages=750–751}}</ref> including over 80&nbsp;countries worldwide.<ref name="Ak1999" /><ref name="AstraZeneca1999" /> Bicalutamide is available in 50&nbsp;mg, 80&nbsp;mg (in Japan),<ref name="SuzukiKamiya2008" /> and 150&nbsp;mg tablets for [[oral administration]].<ref name="WhiteBradnam2015">{{cite book |first1=Rebecca |last1=White |first2=Vicky |last2=Bradnam | name-list-format = vanc |title=Handbook of Drug Administration via Enteral Feeding Tubes |edition=3rd |url=https://books.google.com/books?id=yyikBwAAQBAJ&pg=PA133 |date=11 March 2015 |publisher=Pharmaceutical Press |isbn=978-0-85711-162-3 |pages=133–}}</ref><ref name="MortonHall2001">{{cite book |first1=Ian |last1=Morton |first2=Judith |last2=Hall | name-list-format = vanc |title=The Avery Complete Guide to Medicines |url=https://books.google.com/books?id=0MlN61X5ogkC&focus=searchwithinvolume&q=bicalutamide |year=2001 |publisher=Avery |isbn=978-1-58333-105-7 |pages=105–106}}</ref> The drug is registered for use as a 150&nbsp;mg/day monotherapy for the treatment of {{abbr|LAPC|locally advanced prostate cancer}} in at least 55 countries,<ref name="Cockshott2004" /> with the {{abbr|U.S.|United States}} being a notable exception where it is registered only for use at a dosage of 50&nbsp;mg/day in combination with castration.<ref name="ChabnerLongo2010" /> No other [[pharmaceutical formulation|formulations]] or [[routes of administration]] are available or used.<ref name="WhiteBradnam2015" /> All formulations of bicalutamide are specifically indicated for the treatment of prostate cancer alone or in combination with surgical or medication castration.<ref name="LemkeWilliams2008" /> A [[combination drug|combined formulation]] of bicalutamide and the [[GnRH agonist|{{abbr|GnRH|gonadotropin-releasing hormone}} agonist]] [[goserelin]] in which goserelin is provided as a [[subcutaneous tissue|subcutaneous]] [[implant (medicine)|implant]] for [[injection (medicine)|injection]] and bicalutamide is included as 50&nbsp;mg tablets for oral ingestion is marketed in Australia and [[New Zealand]] under the brand name ZolaCos CP (Zoladex–Cosudex Combination Pack).<ref name="Martindale2011" /><ref name="Drugs.com-3">{{cite web |title=Zolacos CP |url=https://www.drugs.com/international/zolacos-cp.html |work=Drugs.com |deadurl=no |archiveurl=https://web.archive.org/web/20160920130215/https://www.drugs.com/international/zolacos-cp.html |archivedate=20 September 2016 |df=dmy-all}}</ref><ref name="ZolacosCPLabelAu">{{cite web |title=Zolacos CP | archive-url = https://web.archive.org/web/20160917215734/https://www.betterhealth.vic.gov.au/~/media/bhc/files/medicine%20guides%20library/07/cmi7435.pdf |url=https://www.betterhealth.vic.gov.au/~/media/bhc/files/medicine%20guides%20library/07/cmi7435.pdf |archive-date=17 September 2016 | dead-url = yes |publisher=MIMS/myDr |date=April 2007}}</ref><ref name="ZolacosCPLabelNZ">{{cite web |url=http://www.medsafe.govt.nz/profs/datasheet/z/ZolaCosCP.pdf |title=ZOLACOS CP |work=New Zealand Data Sheet |date=25 July 2016 |deadurl=no |archiveurl=https://web.archive.org/web/20160919034509/http://www.medsafe.govt.nz/profs/datasheet/z/ZolaCosCP.pdf |archivedate=19 September 2016 |df=dmy-all}}</ref>
+Bicalutamide is available for the treatment of prostate cancer in most developed countries,<ref name="IndexNominum2000">{{cite book |editor=Swiss Pharmaceutical Society |title=Index Nominum 2000: International Drug Directory |url=https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA123 |date=January 2000 |publisher=Taylor & Francis |isbn=978-3-88763-075-1 |pages=123– |deadurl=no |archiveurl=https://web.archive.org/web/20160424054101/https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA123 |archivedate=24 April 2016 |df=dmy-all}}</ref><ref name="Drugs.com-2">{{cite web |title=Bicalutamide – International Drug Names |url=https://www.drugs.com/international/bicalutamide.html |publisher=Drugs.com |accessdate=13 August 2016 |deadurl=no |archiveurl=https://web.archive.org/web/20160918143637/https://www.drugs.com/international/bicalutamide.html |archivedate=18 September 2016 |df=dmy-all}}</ref><ref name="Martindale2011">{{cite book |first=Sean C. |last=Sweetman  | name-list-format = vanc |title=Martindale: The Complete Drug Reference |url=https://books.google.com/books?id=r_qfcQAACAAJ |year=2011 |publisher=Pharmaceutical Press |isbn=978-0-85369-933-0 |pages=750–751}}</ref> including over 80&nbsp;countries worldwide.<ref name=Ak1999>{{cite journal |vauthors=Akaza H |title=[A new anti-androgen, bicalutamide (Casodex), for the treatment of prostate cancer—basic clinical aspects] |language=Japanese |journal=Gan to Kagaku Ryoho. Cancer & Chemotherapy |volume=26 |issue=8 |pages=1201–7 |year=1999 |pmid=10431591 |doi= |url=}}</ref><ref name="AstraZeneca1999">{{cite web |title=1999 Annual Report and Form 20-F |url=https://ddd.uab.cat/pub/infanu/40172/iaASTZENa1999ieng.pdf |publisher=AstraZeneca |accessdate=1 July 2017}}</ref> Bicalutamide is available in 50&nbsp;mg, 80&nbsp;mg (in Japan),<ref name="SuzukiKamiya2008">{{cite journal |vauthors=Suzuki H, Kamiya N, Imamoto T, Kawamura K, Yano M, Takano M, Utsumi T, Naya Y, Ichikawa T |title=Current topics and perspectives relating to hormone therapy for prostate cancer |journal=International Journal of Clinical Oncology |volume=13 |issue=5 |pages=401–10 |date=October 2008 |pmid=18946750 |doi=10.1007/s10147-008-0830-y}}</ref> and 150&nbsp;mg tablets for [[oral administration]].<ref name="WhiteBradnam2015">{{cite book |first1=Rebecca |last1=White |first2=Vicky |last2=Bradnam | name-list-format = vanc |title=Handbook of Drug Administration via Enteral Feeding Tubes |edition=3rd |url=https://books.google.com/books?id=yyikBwAAQBAJ&pg=PA133 |date=11 March 2015 |publisher=Pharmaceutical Press |isbn=978-0-85711-162-3 |pages=133–}}</ref><ref name="MortonHall2001">{{cite book |first1=Ian |last1=Morton |first2=Judith |last2=Hall | name-list-format = vanc |title=The Avery Complete Guide to Medicines |url=https://books.google.com/books?id=0MlN61X5ogkC&focus=searchwithinvolume&q=bicalutamide |year=2001 |publisher=Avery |isbn=978-1-58333-105-7 |pages=105–106}}</ref> The drug is registered for use as a 150&nbsp;mg/day monotherapy for the treatment of {{abbr|LAPC|locally advanced prostate cancer}} in at least 55 countries,<ref name="Cockshott2004" /> with the {{abbr|U.S.|United States}} being a notable exception where it is registered only for use at a dosage of 50&nbsp;mg/day in combination with castration.<ref name="ChabnerLongo2010" /> No other [[pharmaceutical formulation|formulations]] or [[routes of administration]] are available or used.<ref name="WhiteBradnam2015" /> All formulations of bicalutamide are specifically indicated for the treatment of prostate cancer alone or in combination with surgical or medication castration.<ref name="LemkeWilliams2008" /> A [[combination drug|combined formulation]] of bicalutamide and the [[GnRH agonist|{{abbr|GnRH|gonadotropin-releasing hormone}} agonist]] [[goserelin]] in which goserelin is provided as a [[subcutaneous tissue|subcutaneous]] [[implant (medicine)|implant]] for [[injection (medicine)|injection]] and bicalutamide is included as 50&nbsp;mg tablets for oral ingestion is marketed in Australia and [[New Zealand]] under the brand name ZolaCos CP (Zoladex–Cosudex Combination Pack).<ref name="Martindale2011" /><ref name="Drugs.com-3">{{cite web |title=Zolacos CP |url=https://www.drugs.com/international/zolacos-cp.html |work=Drugs.com |deadurl=no |archiveurl=https://web.archive.org/web/20160920130215/https://www.drugs.com/international/zolacos-cp.html |archivedate=20 September 2016 |df=dmy-all}}</ref><ref name="ZolacosCPLabelAu">{{cite web |title=Zolacos CP | archive-url = https://web.archive.org/web/20160917215734/https://www.betterhealth.vic.gov.au/~/media/bhc/files/medicine%20guides%20library/07/cmi7435.pdf |url=https://www.betterhealth.vic.gov.au/~/media/bhc/files/medicine%20guides%20library/07/cmi7435.pdf |archive-date=17 September 2016 | dead-url = yes |publisher=MIMS/myDr |date=April 2007}}</ref><ref name="ZolacosCPLabelNZ">{{cite web |url=http://www.medsafe.govt.nz/profs/datasheet/z/ZolaCosCP.pdf |title=ZOLACOS CP |work=New Zealand Data Sheet |date=25 July 2016 |deadurl=no |archiveurl=https://web.archive.org/web/20160919034509/http://www.medsafe.govt.nz/profs/datasheet/z/ZolaCosCP.pdf |archivedate=19 September 2016 |df=dmy-all}}</ref>
 ==References==