|Synonyms||Androgen antagonists; Androgen blockers; Testosterone blockers|
|Biological target||Androgen receptor|
|Chemical class||Steroidal; Non-steroidal|
Antiandrogens, also known as androgen antagonists or testosterone blockers, are a class of drugs which prevent androgens like testosterone and dihydrotestosterone (DHT) from mediating their biological effects in the body. They act by blocking the androgen receptor (AR) and/or inhibiting or suppressing androgen production. Antiandrogens are one of three types of sex hormone antagonists, the others being antiestrogens and antiprogestogens.
Antiandrogens are used to treat an assortment of androgen-dependent conditions. In males, antiandrogens are used in the treatment of prostate cancer, benign prostatic hyperplasia, androgenic alopecia (pattern hair loss), hypersexuality, paraphilias, and precocious puberty. In women, antiandrogens are used to treat acne, seborrhea, hidradenitis suppurativa, hirsutism, and hyperandrogenism, such as that which occurs in polycystic ovary syndrome (PCOS). Antiandrogens are also used as a component of hormone replacement therapy (HRT) for transgender women.
Side effects of antiandrogens depend on the type of antiandrogen and the specific antiandrogen in question. In any case, common side effects of antiandrogens in men include gynecomastia (breast development) and feminization in general, hot flashes, sexual dysfunction, infertility, and osteoporosis. In women, antiandrogens are much better tolerated, and antiandrogens that act by selectively blocking the AR are associated with minimal side effects. On the other hand, antiandrogens that suppress androgen production can cause hypoestrogenism and associated symptoms like amenorrhea and osteoporosis in women. This is due to the fact that estrogens are produced in the body from androgens and hence their production is suppressed as well.
- 1 Types
- 2 Medical uses
- 3 Side effects
- 4 Mechanism of action
- 5 History
- 6 Research
- 7 See also
- 8 References
There are several different types of antiandrogens. They include the following:
- Androgen receptor antagonists: drugs that bind directly to and block the AR. These drugs include the steroidal antiandrogens cyproterone acetate, megestrol acetate, chlormadinone acetate, spironolactone, oxendolone, and osaterone acetate (veterinary) and the non-steroidal antiandrogens flutamide, bicalutamide, nilutamide, topilutamide, and enzalutamide. Aside from cyproterone acetate and chlormadinone acetate, a few other progestins used in oral contraceptives and/or in menopausal HRT including dienogest, drospirenone, medrogestone, and nomegestrol acetate also have varying degrees of AR antagonistic activity.
- Androgen synthesis inhibitors: drugs that directly inhibit the enzymatic biosynthesis of androgens like testosterone and/or DHT. Examples include the CYP17A1 inhibitors ketoconazole, abiraterone acetate, and seviteronel, the CYP11A1 (P450scc) inhibitor aminoglutethimide, and the 5α-reductase inhibitors finasteride, dutasteride, epristeride, alfatradiol, and saw palmetto extract (Serenoa repens). A number of other antiandrogens, including cyproterone acetate, spironolactone, medrogestone, flutamide, nilutamide, and bifluranol, are also known to weakly inhibit androgen synthesis.
- Antigonadotropins: drugs that suppress the gonadotropin-releasing hormone (GnRH)-induced release of gonadotropins and consequent activation of gonadal androgen production. Examples include GnRH analogues like leuprorelin and cetrorelix, progestogens like chlormadinone acetate, cyproterone acetate, gestonorone caproate, medroxyprogesterone acetate, megestrol acetate, osaterone acetate (veterinary), and oxendolone, and estrogens like estradiol, estradiol esters, conjugated equine estrogens (Premarin), ethinylestradiol, diethylstilbestrol, and bifluranol.
Certain antiandrogens combine multiple of the above mechanisms. An example is the steroidal antiandrogen cyproterone acetate, which is both a potent AR antagonist and a potent progestogen and hence antigonadotropin, as well as a weak androgen synthesis inhibitor.
Although the term antiandrogen is generally used to refer specifically to AR antagonists, it may also be used to describe functional antiandrogens like androgen synthesis inhibitors and antigonadotropins, including even estrogens and progestogens. For example, the progestogen and hence antigonadotropin medroxyprogesterone acetate is sometimes described as a steroidal antiandrogen, even though it is not an antagonist of the AR.
Antiandrogens are used in the treatment of an assortment of androgen-dependent conditions in both men and women. They are used to treat men with prostate cancer, benign prostatic hyperplasia, androgenic alopecia, hypersexuality, and paraphilias, as well as boys with precocious puberty. They have also been used to treat men with priapism. In women, antiandrogens are used to treat acne, seborrhea, hidradenitis suppurativa, hirsutism, and hyperandrogenism. Antiandrogens are also used in transgender women as a component of HRT and as puberty blockers in transgender youth.
Androgens like testosterone and particularly DHT are importantly involved in the development and progression of prostate cancer. They act as growth factors in the prostate gland, stimulating cell division and tissue growth. In accordance, therapeutic modalities that reduce androgen signaling in the prostate gland, referred to collectively as androgen deprivation therapy, are able to significantly slow the course of prostate cancer and extend life in men with the disease. Although antiandrogens are effective in slowing the progression of prostate cancer, they are not generally curative, and with time, the disease adapts and androgen deprivation therapy eventually becomes ineffective. When this occurs, other treatment approaches, such as chemotherapy, are necessary.
The most common methods of androgen deprivation therapy currently employed to treat prostate cancer are castration (with a GnRH analogue or orchiectomy), non-steroidal antiandrogens, and the androgen synthesis inhibitor abiraterone acetate. Castration may be used alone or in combination with one of the other two treatments. When castration is combined with a non-steroidal antiandrogen like bicalutamide, this strategy is referred to as combined androgen blockade (also known as complete or maximal androgen blockade). Enzalutamide and abiraterone acetate are specifically approved for use in combination with castration to treat advanced castration-resistant prostate cancer. Monotherapy with the non-steroidal antiandrogen bicalutamide is also used in the treatment of prostate cancer as an alternative to castration with comparable effectiveness but with a different and potentially advantageous side effect profile.
High-dose estrogens were the first functional antiandrogens to be used in the treatment of prostate cancer and were widely employed, but have largely been abandoned for this indication in favor of newer agents with improved safety profiles. Cyproterone acetate was developed subsequently to them and is the only steroidal antiandrogen that has been widely used in the treatment of prostate cancer, but it has largely been replaced by non-steroidal antiandrogens, which are newer and have greater effectiveness, tolerability, and safety. Bicalutamide, as well as enzalutamide, have largely replaced the earlier non-steroidal antiandrogens flutamide and nilutamide, which are now little used. The earlier androgen synthesis inhibitors aminoglutethimide and ketoconazole have only limitedly been used in the treatment of prostate cancer due to toxicity concerns and have been replaced by abiraterone acetate.
In addition to active treatment of prostate cancer, antiandrogens are effective as prophylaxis (preventatives) in reducing the risk of ever developing prostate cancer. Antiandrogens have only limitedly been assessed for this purpose, but the 5α-reductase inhibitors finasteride and dutasteride and the steroidal AR antagonist spironolactone have been associated with significantly reduced risk of prostate cancer. In addition, it is notable the prostate cancer is extremely rare in transgender women who have been on HRT for an extended period of time.
Benign prostatic hyperplasia
The 5α-reductase inhibitors finasteride and dutasteride are used to treat benign prostatic hyperplasia, a condition in which the prostate becomes enlarged and this results in urinary obstruction and discomfort. They are effective because androgens act as growth factors in the prostate gland. The functional antiandrogens oxendolone and gestonorone caproate are also approved in some countries for the treatment of benign prostatic hyperplasia.
5α-Reductase inhibitors like finasteride, dutasteride, and alfatradiol and the topical non-steroidal AR antagonist topilutamide (fluridil) are approved for the treatment of androgenic alopecia, also known as pattern hair loss or baldness. This condition is caused by androgens, so antiandrogens can slow or halt its progression.
Hypersexuality and paraphilias
Androgens increase sex drive, and for this reason, antiandrogens are able to reduce sex drive in men. In accordance, antiandrogens are used in the treatment of hypersexuality (excessively high sex drive) and paraphilias (atypical and sometimes societally unacceptable sexual interests) like pedophilia (sexual attraction to children). They have been used to decrease sex drive in sex offenders so as to reduce the likelihood of recidivism (repeat offenses). Antiandrogens used for these indications include cyproterone acetate, medroxyprogesterone acetate, and GnRH analogues.
Skin and hair conditions
Antiandrogens are used in the treatment of androgen-dependent skin and hair conditions including acne, seborrhea, hidradenitis suppurativa, hirsutism, and androgenic alopecia in women. All of these conditions are dependent on androgens, and for this reason, antiandrogens are effective in treating them. The most commonly used antiandrogens for these indications are cyproterone acetate and spironolactone. Flutamide has also been studied extensively for such uses, but has fallen out of favor due to its association with hepatotoxicity. Bicalutamide, which has minimal risk of hepatotoxicity, has been evaluated for the treatment of hirsutism and found to be effective similarly to flutamide and may be used instead of it. In addition to AR antagonists, oral contraceptives containing ethinylestradiol are effective in treating these conditions, and may be combined with AR antagonists.
Hyperandrogenism is a condition in women in which androgen levels are excessively and abnormally high. It is commonly seen in women with PCOS, and also occurs in women with intersex conditions like congenital adrenal hyperplasia. Hyperandrogenism is associated with virilization – that is, the development of masculine secondary sexual characteristics like male-pattern facial and body hair growth (or hirsutism), voice deepening, increased muscle mass and strength, and broadening of the shoulders, among others. Androgen-dependent skin and hair conditions like acne and androgenic alopecia may also occur in hyperandrogenism, and menstrual disturbances, like amenorrhea, are commonly seen. Although antiandrogens do not treat the underlying cause of hyperandrogenism (e.g., PCOS), they are able to prevent and reverse its manifestation and effects. As with androgen-dependent skin and hair conditions, the most commonly used antiandrogens in the treatment of hyperandrogenism in women are cyproterone acetate and spironolactone. Other antiandrogens, like bicalutamide, may be used alternatively.
Antiandrogens are used to prevent or reverse masculinization and facilitate feminization in transgender women who are undergoing HRT and who have not yet undergone (or who do not plan to undergo) sex reassignment surgery or orchiectomy. Aside from estrogens, the main antiandrogens that have been used for this purpose are cyproterone acetate, spironolactone, and GnRH analogues. Non-steroidal antiandrogens like bicalutamide are also used for this indication. In addition to transgender women, antiandrogens, mainly GnRH analogues, are used as puberty blockers to delay puberty in transgender girls until they are older and ready to begin hormone replacement therapy.
The side effects of antiandrogens vary depending on the type of antiandrogen – namely whether it is a selective AR antagonist or lowers androgen levels – as well as the presence of off-target activity in the antiandrogen in question. For instance, whereas antigonadotropic antiandrogens like GnRH analogues and cyproterone acetate are associated with pronounced sexual dysfunction and osteoporosis in men, selective AR antagonists like bicalutamide are not associated with osteoporosis and have been associated with only minimal sexual dysfunction. These differences are thought to be related to the fact that antigonadotropins suppress androgen levels and by extension levels of bioactive metabolites of androgens like estrogens and neurosteroids whereas selective AR antagonists similarly neutralize the effects of androgens but leave levels of androgens and hence their metabolites intact (and in fact can even increase them as a result of their progonadotropic effects). As another example, the steroidal antiandrogens cyproterone acetate and spironolactone possess off-target actions including progestogenic, antimineralocorticoid, and/or glucocorticoid activity in addition to their antiandrogen activity, and these off-target activities can result in additional side effects.
In males, the major side effects of antiandrogens are demasculinization and feminization. These side effects include breast pain/tenderness and gynecomastia, reduced body hair growth/density, decreased muscle mass and strength, feminine changes in fat mass and distribution, and reduced penile length and testicular size. In addition, antiandrogens can cause infertility, osteoporosis, hot flashes, sexual dysfunction (including loss of libido and erectile dysfunction), depression, fatigue, anemia, and decreased semen/ejaculate volume in males. Conversely, the side effects of selective AR antagonists in women are minimal. However, antigonadotropic antiandrogens like cyproterone acetate can produce hypoestrogenism, amenorrhea, and osteoporosis in women, among other side effects.
A number of antiandrogens have been associated with hepatotoxicity. These include, to varying extents, cyproterone acetate, flutamide, nilutamide, bicalutamide, aminoglutethimide, and ketoconazole. In contrast, spironolactone, enzalutamide, and other antiandrogens are not associated with hepatotoxicity. However, although they do not pose a risk of hepatotoxicity, spironolactone has a risk of hyperkalemia and enzalutamide has a risk of seizures.
In women who are pregnant, antiandrogens can interfere with the androgen-mediated sexual differentiation of the genitalia and brain of male fetuses. This manifests primarily as ambiguous genitalia – that is, undervirilized or feminized genitalia which, anatomically, are a cross between a penis and a vagina – and theoretically also as femininity and homosexuality. As such, antiandrogens are teratogens, and women who are pregnant should never be treated with an antiandrogen. Moreover, women who can or may become pregnant are strongly recommended to take an antiandrogen only in combination with proper contraception.
Mechanism of action
Androgen receptor antagonists
AR antagonists act by directly binding to and competitively displacing androgens like testosterone and DHT from the AR, thereby preventing them from activating the receptor and mediating their biological effects. AR antagonists are classified into two types, based on chemical structure: steroidal and non-steroidal. Steroidal AR antagonists are structurally related to steroid hormones like testosterone and progesterone, whereas non-steroidal AR antagonists are not steroids and are structurally distinct. Steroidal AR antagonists tend to have off-target hormonal actions due to their structural similarity to other steroid hormones. In contrast, non-steroidal AR antagonists are selective for the AR and have no off-target hormonal activity. For this reason, they are sometimes described as "pure" antiandrogens.
Although they are described as antiandrogens and indeed show only such effects generally, most or all steroidal AR antagonists are actually not silent antagonists of the AR but rather are weak partial agonists and are able to activate the receptor in the absence of more potent AR agonists like testosterone and DHT. This may have clinical implications in the specific context of prostate cancer treatment. As an example, steroidal AR antagonists are able to increase prostate weight and accelerate prostate cancer cell growth in the absence of more potent AR agonists, and spironolactone has been found to accelerate progression of prostate cancer in case reports. In addition, whereas cyproterone acetate produces ambiguous genitalia via feminization in male fetuses when administered to pregnant animals, it has been found to produce masculinization of the genitalia of female fetuses of pregnant animals. In contrast to steroidal AR antagonists, non-steroidal AR antagonists are silent antagonists of the AR and do not activate the receptor. This may be why they have greater efficacy than steroidal AR antagonists in the treatment of prostate cancer and is an important reason as to why they have largely replaced them for this indication in medicine.
AR antagonists may not bind to or block membrane androgen receptors (mARs), which are distinct from the classical nuclear AR. However, the mARs do not appear to be involved in virilization. This is evidenced by the perfectly female phenotype of women with complete androgen insensitivity syndrome. These women have a 46,XY karyotype (i.e., are genetically "male") and high levels of androgens but possess a defective AR and for this reason never virilize. They are described as highly feminine, both physically and mentally/behaviorally.
N-Terminal domain antagonists
N-Terminal domain AR antagonists are a new type of AR antagonist which, unlike all currently marketed AR antagonists, bind to the N-terminal domain (NTD) of the AR rather than the ligand-binding domain (LBD). Whereas conventional AR antagonists bind to the LBD of the AR and competitively displace androgens, thereby preventing them from activating the receptor, AR NTD antagonists bind covalently to the NTD of the AR and prevent protein–protein interactions subsequent to activation that are required for transcriptional activity. As such, they are non-competitive and irreversible antagonists of the AR. Examples of AR NTD antagonists include bisphenol A diglycidyl ether (BADGE) and its derivatives EPI-001 and EPI-506. These drugs are currently under development for the treatment of prostate cancer, and it is thought that they may have greater efficacy as antiandrogens relative to conventional AR antagonists. In accordance with this notion, AR NTD antagonists are active against splice variants of the AR, which conventional AR antagonists are not, and AR NTD antagonists are immune to gain-of-function mutations in the AR LBD that convert AR antagonists into AR agonists and which commonly occur in prostate cancer.
Androgen synthesis inhibitors
Androgen synthesis inhibitors are enzyme inhibitors which prevent the biosynthesis of androgens. This process occurs mainly in the gonads and adrenal glands. These drugs include aminoglutethimide, ketoconazole, and abiraterone acetate. Aminoglutethimide inhibits cholesterol side-chain cleavage enzyme, also known as P450scc or CYP11A1, which is responsible for the conversion of cholesterol into pregnenolone and by extension the production of all steroid hormones, including the androgens. Ketoconazole and abiraterone acetate are inhibitors of the enzyme CYP17A1, also known as 17α-hydroxylase/17,20-lyase, which is responsible for the conversion of pregnane steroids into androgens, as well as the conversion of mineralocorticoids into glucocorticoids. Because these drugs all prevent the formation of glucocorticoids in addition to androgens, they must be combined with a glucocorticoid like prednisone to avoid adrenal insufficiency. A newer drug which is currently under development for the treatment of prostate cancer, seviteronel, is selective for inhibition of the 17,20-lyase functionality of CYP17A1, and for this reason, unlike earlier drugs, does not require concomitant treatment with a glucocorticoid.
5α-Reductase inhibitors such as finasteride and dutasteride are inhibitors of 5α-reductase, an enzyme that is responsible for the formation of DHT from testosterone. DHT is between 2.5- and 10-fold more potent than testosterone as an androgen and is produced in a tissue-selective manner based on expression of 5α-reductase. Tissues in which DHT is formed at a high rate include the prostate gland, skin, and hair follicles. In accordance, DHT is involved in the pathophysiology of benign prostatic hyperplasia, androgenic alopecia, and hirsutism, and 5α-reductase inhibitors are used to treat these conditions. Because 5α-reductase inhibitors selectively prevent the formation of DHT and do not affect testosterone levels, and because DHT is important as an endgenous androgen only in select tissues, 5α-reductase inhibitors have minimal side effects in both men and women, unlike other antiandrogens.
Antigonadotropins are drugs which suppress the GnRH-mediated secretion of gonadotropins from the pituitary gland. Gonadotropins include luteinizing hormone (LH) and follicle-stimulating hormone (FSH) and are peptide hormones that signal the gonads to produce sex hormones. By suppressing gonadotropin secretion, antigonadotropins suppress gonadal sex hormone production and by extension circulating androgen levels. GnRH analogues, including both GnRH agonists and GnRH antagonists, are powerful antigonadotropins that are able to suppress androgen levels by 95% in men. In addition, estrogens and progestogens are antigonadotropins via exertion of negative feedback on the hypothalamic-pituitary-gonadal axis, and high-dose estrogens are able to suppress androgen levels to castrate levels in men similarly to GnRH analogues, while high-dose progestogens are able to suppress androgen levels by up to approximately 70 to 80% in men.
Examples of GnRH agonists include leuprorelin (leuprolide) and goserelin, while an example of a GnRH antagonist is cetrorelix. Estrogens that are or that have been used as antigonadotropins include estradiol, estradiol esters like estradiol valerate, estradiol undecylate, and polyestradiol phosphate, conjugated equine estrogens, ethinylestradiol, diethylstilbestrol (no longer widely used), and bifluranol. Progestogens that are used as antigonadotropins include chlormadinone acetate, cyproterone acetate, gestonorone caproate, medroxyprogesterone acetate, megestrol acetate, and oxendolone.
In addition to their antigonadotropic effects, estrogens are also functional antiandrogens by decreasing free concentrations of androgens via increasing the hepatic production of sex hormone-binding globulin (SHBG) and by extension circulating SHBG levels. Combined oral contraceptives containing ethinylestradiol have been found to increase circulating SHBG levels by 2- to 4-fold in women and to reduce free testosterone concentrations by 40 to 80%. However, combined oral contraceptives containing the particularly androgenic progestin levonorgestrel have been found to increase SHBG levels by only 50 to 100%, which is likely due to the fact that activation of the AR in the liver has the opposite effect of estrogen and suppresses production of SHBG. Levonorgestrel and certain other 19-nortestosterone progestins used in combined oral contraceptives like norethisterone also directly bind to and displace androgens from SHBG, which may additionally antagonize the functional antiandrogenic effects of ethinylestradiol. In men, a study found that treatment with a relatively low dosage of 20 μg/day ethinylestradiol for 5 weeks increased circulating SHBG levels by 150% and, due to the accompanying decrease free testosterone levels, increased total circulating levels of testosterone by 50% (via reduced negative feedback by androgens on the hypothalamic-pituitary-gonadal axis).
Ovandrotone albumin (Fecundin, Ovastim) and Androvax (androstenedione albumin) are immunogens and vaccines against androstenedione that are used in veterinary medicine to improve fecundity (reproductive rate) in ewes (adult female sheep). The generation of antibodies against androstenedione by these agents is thought to decrease circulating levels of androstenedione and its metabolites (e.g., testosterone and estrogens), which in turn increases the activity of the hypothalamic-pituitary-gonadal axis via reduced negative feedback and increases the rate of ovulation, resulting in greater fertility and fecundity.
Antigonadotropins like estrogens and progestogens were both first introduced in the 1930s. AR antagonists were first discovered in the early 1960s. The steroidal antiandrogen cyproterone acetate was discovered in 1961 and introduced in 1973 and is often described as the first antiandrogen to have been marketed. However, spironolactone was introduced in 1959, and although its antiandrogen effects were not recognized or taken advantage of until later and were originally an unintended off-target action of the drug, it may be more appropriate to regard it as the first antiandrogen to have been introduced. In addition to spironolactone, chlormadinone acetate and megestrol acetate are steroidal antiandrogens that are weaker than cyproterone acetate but were also introduced earlier, in the 1960s. Other early steroidal antiandrogens that were developed around this time but were never marketed include benorterone (SKF-7690; 17α-methyl-B-nortestosterone), BOMT (Ro 7-2340), cyproterone (SH-80881), and trimethyltrienolone (R-2956).
The non-steroidal antiandrogen flutamide was first reported in 1967. It was introduced in 1983 and was the first non-steroidal antiandrogen to be marketed. Another early non-steroidal antiandrogen, DIMP (Ro 7-8117), which is structurally related to thalidomide and is a relatively weak antiandrogen, was first described in 1973 and was never marketed. Flutamide was followed by nilutamide in 1989 and bicalutamide in 1995. In addition to these three drugs, which have been regarded as first-generation non-steroidal antiandrogens, the second-generation non-steroidal antiandrogen enzalutamide was introduced in 2012. It differs from the earlier non-steroidal antiandrogens namely in that it is much more efficacious in comparison.
The androgen synthesis inhibitors aminoglutethimide and ketoconazole were first marketed in 1960 and 1977, respectively, and the newer drug abiraterone acetate was introduced in 2011. GnRH analogues were first introduced in the 1980s. The 5α-reductase inhibitors finasteride and dutasteride were introduced in 1992 and 2002, respectively.
There has been much interest and effort in the development of topical AR antagonists to treat androgen-dependent conditions like acne and androgenic alopecia in males. Unfortunately, whereas systemic administration of antiandrogens is very effective in treating these conditions, topical administration has disappointingly been found generally to possess limited and only modest effectiveness, even when high-affinity steroidal AR antagonists like cyproterone acetate and spironolactone have been employed. Moreover, in the specific case of acne treatment, topical AR antagonists have been found to be greatly inferior in effectiveness compared to established treatments like benzoyl peroxide and antibiotics.
A variety of AR antagonists have been developed for topical use but have not completed development and hence have never been marketed. These include the steroidal AR antagonists cortexolone 17α-propionate, cyproterone, rosterolone, and topterone and the non-steroidal AR antagonists cioteronel, inocoterone acetate, RU-22930, RU-58642, and RU-58841. However, one topical AR antagonist, topilutamide (fluridil), has been introduced in a few European countries for the treatment of androgenic alopecia in men. In addition, a topical 5α-reductase inhibitor and weak estrogen, alfatradiol, has also been introduced in some European countries for the same indication, although its effectiveness is controversial. Spironolactone has been marketed in Italy in the form of a topical cream under the brand name Spiroderm for the treatment of acne and hirsutism, but this formulation was discontinued and hence is no longer available.
- Anabolic-androgenic steroid
- Androgen insensitivity syndrome
- Antiandrogens in the environment
- Selective androgen receptor modulator
- Mowszowicz I (1989). "Antiandrogens. Mechanisms and paradoxical effects". Ann. Endocrinol. (Paris). 50 (3): 50(3):189–99. PMID 2530930.
- Judi Lindsley Nath (2006). Using Medical Terminology: A Practical Approach. Lippincott Williams & Wilkins. pp. 977–. ISBN 978-0-7817-4868-1.
- Gillatt D (2006). "Antiandrogen treatments in locally advanced prostate cancer: are they all the same?". J Cancer Res Clin Oncol. 1: S17–26. doi:10.1007/s00432-006-0133-5. PMID 16845534.
- Singh SM, Gauthier S, Labrie F (2000). "Androgen receptor antagonists (antiandrogens): structure-activity relationships". Curr. Med. Chem. 7 (2): 211–47. doi:10.2174/0929867003375371. PMID 10637363.
- Shen, Howard C.; Taplin, Mary-Ellen; Balk, Steven P. (2010). "Androgen Receptor Antagonists". Drug Management of Prostate Cancer: 71–81. doi:10.1007/978-1-60327-829-4_6.
- Raudrant D, Rabe T (2003). "Progestogens with antiandrogenic properties". Drugs. 63 (5): 463–92. doi:10.2165/00003495-200363050-00003. PMID 12600226.
- Schneider HP (2003). "Androgens and antiandrogens". Ann. N. Y. Acad. Sci. 997: 292–306. doi:10.1196/annals.1290.033. PMID 14644837.
- Jerome F. Strauss, III; Robert L. Barbieri (13 September 2013). Yen and Jaffe's Reproductive Endocrinology. Elsevier Health Sciences. pp. 90–. ISBN 978-1-4557-2758-2.
- William Figg; Cindy H. Chau; Eric J. Small (14 September 2010). Drug Management of Prostate Cancer. Springer Science & Business Media. pp. 71–72, 75, 93. ISBN 978-1-60327-829-4.
- Aggarwal S, Thareja S, Verma A, Bhardwaj TR, Kumar M (2010). "An overview on 5alpha-reductase inhibitors". Steroids. 75 (2): 109–53. doi:10.1016/j.steroids.2009.10.005. PMID 19879888.
- Peter B. Farmer; John M. Walker (6 December 2012). The Molecular Basis of Cancer. Springer Science & Business Media. pp. 232–. ISBN 978-1-4684-7313-1.
- Thomas L. Lemke; David A. Williams (24 January 2012). Foye's Principles of Medicinal Chemistry. Lippincott Williams & Wilkins. pp. 228–231, 1371–1372. ISBN 978-1-60913-345-0.
- de Lignières B, Silberstein S (April 2000). "Pharmacodynamics of oestrogens and progestogens". Cephalalgia : an International Journal of Headache. 20 (3): 200–7. doi:10.1046/j.1468-2982.2000.00042.x. PMID 10997774.
- William Ledger; William D. Schlaff; Thierry G. Vancaillie (11 December 2014). Chronic Pelvic Pain. Cambridge University Press. pp. 55–. ISBN 978-1-316-21414-5.
- Louise Hanna; Tom Crosby; Fergus Macbeth (19 November 2015). Practical Clinical Oncology. Cambridge University Press. pp. 37–. ISBN 978-1-107-68362-4.
- Georg F. Weber (22 July 2015). Molecular Therapies of Cancer. Springer. pp. 314, 316. ISBN 978-3-319-13278-5.
- Nicholas Vogelzang (2006). Comprehensive Textbook of Genitourinary Oncology. Lippincott Williams & Wilkins. pp. 316–. ISBN 978-0-7817-4984-8.
- Sciarra F, Toscano V, Concolino G, Di Silverio F (1990). "Antiandrogens: clinical applications". J. Steroid Biochem. Mol. Biol. 37 (3): 349–62. doi:10.1016/0960-0760(90)90484-3. PMID 2147859.
- Broderick GA, Kadioglu A, Bivalacqua TJ, Ghanem H, Nehra A, Shamloul R (2010). "Priapism: pathogenesis, epidemiology, and management". J Sex Med. 7 (1 Pt 2): 476–500. doi:10.1111/j.1743-6109.2009.01625.x. PMID 20092449.
- Martin H. Steinberg; Bernard G. Forget; Douglas R. Higgs; David J. Weatherall (17 August 2009). Disorders of Hemoglobin: Genetics, Pathophysiology, and Clinical Management. Cambridge University Press. pp. 476–. ISBN 978-1-139-48080-2.
- Essah PA, Wickham EP, Nunley JR, Nestler JE (2006). "Dermatology of androgen-related disorders". Clin. Dermatol. 24 (4): 289–98. doi:10.1016/j.clindermatol.2006.04.004. PMID 16828411.
- Rabe, T.; Grunwald, K.; Feldmann, K.; Runnebaum, B. (2009). "Treatment of hyperandrogenism in women". Gynecological Endocrinology. 10 (sup3): 1–44. doi:10.3109/09513599609045658. ISSN 0951-3590.
- Bockting W, Coleman E, De Cuypere G (2011). "Care of transsexual persons". N. Engl. J. Med. 364 (26): 2559–60; author reply 2560. doi:10.1056/NEJMc1104884#SA1. PMID 21714669.
- Vance SR, Ehrensaft D, Rosenthal SM (2014). "Psychological and medical care of gender nonconforming youth". Pediatrics. 134 (6): 1184–92. doi:10.1542/peds.2014-0772. PMID 25404716.
- Wadosky KM, Koochekpour S (2016). "Therapeutic Rationales, Progresses, Failures, and Future Directions for Advanced Prostate Cancer". Int. J. Biol. Sci. 12 (4): 409–26. doi:10.7150/ijbs.14090. PMC . PMID 27019626.
- Massard C, Fizazi K (2011). "Targeting continued androgen receptor signaling in prostate cancer". Clin. Cancer Res. 17 (12): 3876–83. doi:10.1158/1078-0432.CCR-10-2815. PMID 21680543.
- Msaouel P, Diamanti E, Tzanela M, Koutsilieris M (2007). "Luteinising hormone-releasing hormone antagonists in prostate cancer therapy". Expert Opin Emerg Drugs. 12 (2): 285–99. doi:10.1517/14728188.8.131.525. PMID 17604502.
- Akaza H (Jan 2011). "Combined androgen blockade for prostate cancer: review of efficacy, safety, and cost-effectiveness". Cancer Science. 102 (1): 51–6. doi:10.1111/j.1349-7006.2010.01774.x. PMID 21091846.
- Mateo J, Smith A, Ong M, de Bono JS (2014). "Novel drugs targeting the androgen receptor pathway in prostate cancer". Cancer Metastasis Rev. 33 (2–3): 567–79. doi:10.1007/s10555-013-9472-2. PMID 24390422.
- Iversen P, Melezinek I, Schmidt A (2001). "Nonsteroidal antiandrogens: a therapeutic option for patients with advanced prostate cancer who wish to retain sexual interest and function". BJU Int. 87 (1): 47–56. doi:10.1046/j.1464-410x.2001.00988.x. PMID 11121992.
- Kolvenbag GJ, Iversen P, Newling DW (August 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.
- Mcleod DG (2003). "Hormonal therapy: historical perspective to future directions". Urology. 61 (2 Suppl 1): 3–7. PMID 12667881.
- Smith HJ, Williams H (10 October 2005). Smith and Williams' Introduction to the Principles of Drug Design and Action, Fourth Edition. CRC Press. pp. 489–. ISBN 978-0-203-30415-0.
- Chabner BA, Longo DL (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.
- 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.
- Chang S (10 March 2010), Bicalutamide BPCA Drug Use Review in the Pediatric Population (PDF), U.S. Department of Health and Human Service, retrieved 20 July 2016
- Gulley JL (2011). Prostate Cancer. Demos Medical Publishing. pp. 81–. ISBN 978-1-935281-91-7.
- Moser L (1 January 2008). Controversies in the Treatment of Prostate Cancer. Karger Medical and Scientific Publishers. pp. 41–42. ISBN 978-3-8055-8524-8.
- Prostate Cancer. Demos Medical Publishing. 20 December 2011. pp. 505–. ISBN 978-1-935281-91-7.
- Rittmaster RS (2011). "Chemoprevention of prostate cancer". Acta Oncol. 50 Suppl 1: 127–36. doi:10.3109/0284186X.2010.527367. PMID 21604953.
- Mackenzie IS, Morant SV, Wei L, Thompson AM, MacDonald TM (2016). "Spironolactone use and risk of incident cancers: a retrospective, matched cohort study". Br J Clin Pharmacol. doi:10.1111/bcp.13152. PMID 27735065.
- Hembree WC, Cohen-Kettenis P, Delemarre-van de Waal HA, Gooren LJ, Meyer WJ, Spack NP, Tangpricha V, Montori VM (2009). "Endocrine treatment of transsexual persons: an Endocrine Society clinical practice guideline". J. Clin. Endocrinol. Metab. 94 (9): 3132–54. doi:10.1210/jc.2009-0345. PMID 19509099.
- Gooren L, Morgentaler A (2014). "Prostate cancer incidence in orchidectomised male-to-female transsexual persons treated with oestrogens". Andrologia. 46 (10): 1156–60. doi:10.1111/and.12208. PMID 24329588.
- Turo R, Jallad S, Prescott S, Cross WR (2013). "Metastatic prostate cancer in transsexual diagnosed after three decades of estrogen therapy". Can Urol Assoc J. 7 (7–8): E544–6. doi:10.5489/cuaj.175. PMC . PMID 24032068.
- Dörsam J, Altwein J (2009). "5alpha-Reductase inhibitor treatment of prostatic diseases: background and practical implications". Prostate Cancer Prostatic Dis. 12 (2): 130–6. doi:10.1038/pcan.2008.56. PMID 19030020.
- Ishizuka O, Nishizawa O, Hirao Y, Ohshima S (2002). "Evidence-based meta-analysis of pharmacotherapy for benign prostatic hypertrophy". Int. J. Urol. 9 (11): 607–12. doi:10.1046/j.1442-2042.2002.00539.x. PMID 12534901.
- G. Raspé; W. Brosig (22 October 2013). International Symposium on the Treatment of Carcinoma of the Prostate, Berlin, November 13 to 15, 1969: Life Science Monographs. Elsevier. pp. 165–. ISBN 978-1-4831-8711-2.
- Ralph M. Trüeb; Won-Soo Lee (13 February 2014). Male Alopecia: Guide to Successful Management. Springer Science & Business Media. pp. 91–93. ISBN 978-3-319-03233-7.
- Jean L. Bolognia; Joseph L. Jorizzo; Ronald P. Rapini. Dermatology. Gulf Professional Publishing. pp. 1072–. ISBN 9789997638991.
- Richard E. Jones; Kristin H. Lopez (28 September 2013). Human Reproductive Biology. Academic Press. pp. 77–. ISBN 978-0-12-382185-0.
- Bradford JM (2001). "The neurobiology, neuropharmacology, and pharmacological treatment of the paraphilias and compulsive sexual behaviour". Can J Psychiatry. 46 (1): 26–34. PMID 11221487.
- Guay DR (2009). "Drug treatment of paraphilic and nonparaphilic sexual disorders". Clin Ther. 31 (1): 1–31. doi:10.1016/j.clinthera.2009.01.009. PMID 19243704.
- William Lamont Marshall; D.R. Laws; Howard E. Barbaree (21 November 2013). Handbook of Sexual Assault: Issues, Theories, and Treatment of the Offender. Springer Science & Business Media. pp. 297–. ISBN 978-1-4899-0915-2.
- Albert J. Stunkard; Andrew Baum (1989). Eating, Sleeping, and Sex. Psychology Press. pp. 209–. ISBN 978-0-8058-0280-1.
- Amy Phenix; Harry M. Hoberman (7 December 2015). Sexual Offending: Predisposing Antecedents, Assessments and Management. Springer. pp. 759–. ISBN 978-1-4939-2416-5.
- 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 . PMID 22057380.
- 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.
- 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.
- 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.
- 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.
- Robert Baran; Howard I. Maibach (1 October 1998). Textbook of Cosmetic Dermatology. CRC Press. pp. 388–. ISBN 978-1-85317-478-0.
- Howard I. Maibach; Farzam Gorouhi (2011). Evidence Based Dermatology. PMPH-USA. pp. 526–. ISBN 978-1-60795-039-4.
- Hywel Williams; Michael Bigby; Thomas Diepgen; Andrew Herxheimer; Luigi Naldi; Berthold Rzany (22 January 2009). Evidence-Based Dermatology. John Wiley & Sons. pp. 529–. ISBN 978-1-4443-0017-8.
- Erem C (2013). "Update on idiopathic hirsutism: diagnosis and treatment". Acta Clin Belg. 68 (4): 268–74. doi:10.2143/ACB.3267. PMID 24455796.
- Kenneth L. Becker (2001). Principles and Practice of Endocrinology and Metabolism. Lippincott Williams & Wilkins. pp. 1004, 1196. ISBN 978-0-7817-1750-2.
- Camacho; Hossein Gharib; Glen W. Sizemore (2012). Evidence-Based Endocrinology. Lippincott Williams & Wilkins. pp. 199–. ISBN 978-1-4511-1091-3.
- G. Plewig; A.M. Kligman (6 December 2012). ACNE and ROSACEA. Springer Science & Business Media. pp. 687–. ISBN 978-3-642-59715-2.
- Brian K. Alldredge; Robin L. Corelli; Michael E. Ernst (1 February 2012). Koda-Kimble and Young's Applied Therapeutics: The Clinical Use of Drugs. Lippincott Williams & Wilkins. pp. 952–. ISBN 978-1-60913-713-7.
- John A. Thomas (12 March 1997). Endocrine Toxicology, Second Edition. CRC Press. pp. 152–. ISBN 978-1-4398-1048-4.
- Anderson J (2003). "The role of antiandrogen monotherapy in the treatment of prostate cancer". BJU Int. 91 (5): 455–61. doi:10.1046/j.1464-410x.2003.04026.x. PMID 12603397.
- Terrence Priestman (26 May 2012). Cancer Chemotherapy in Clinical Practice. Springer Science & Business Media. pp. 97–. ISBN 978-0-85729-727-3.
- Higano CS (2003). "Side effects of androgen deprivation therapy: monitoring and minimizing toxicity". Urology. 61 (2 Suppl 1): 32–8. PMID 12667885.
- Jerry Shapiro (12 November 2012). Hair Disorders: Current Concepts in Pathophysiology, Diagnosis and Management, An Issue of Dermatologic Clinics. Elsevier Health Sciences. pp. 187–. ISBN 1-4557-7169-4.
- W. Futterweit (6 December 2012). Polycystic Ovarian Disease. Springer Science & Business Media. pp. 282–. ISBN 978-1-4613-8289-8.
- Katsambas AD, Dessinioti C (2010). "Hormonal therapy for acne: why not as first line therapy? facts and controversies". Clin. Dermatol. 28 (1): 17–23. doi:10.1016/j.clindermatol.2009.03.006. PMID 20082945.
- Thole Z, Manso G, Salgueiro E, Revuelta P, Hidalgo A (2004). "Hepatotoxicity induced by antiandrogens: a review of the literature". Urol. Int. 73 (4): 289–95. doi:10.1159/000081585. PMID 15604569.
- Keating GM (March 2015). "Enzalutamide: a review of its use in chemotherapy-naïve metastatic castration-resistant prostate cancer". Drugs & Aging. 32 (3): 243–9. doi:10.1007/s40266-015-0248-y. PMID 25711765.
- Phyllis Carolyn Leppert; Jeffrey F. Peipert (2004). Primary Care for Women. Lippincott Williams & Wilkins. pp. 277–. ISBN 978-0-7817-3790-6.
- Spencer A. Rathus; Jeffrey S. Nevid; Lois Fichner-Rathus (2005). Human sexuality in a world of diversity. Pearson Allyn and Bacon. p. 313. ISBN 978-0-205-40615-9.
- Poyet P, Labrie F (October 1985). "Comparison of the antiandrogenic/androgenic activities of flutamide, cyproterone acetate and megestrol acetate". Molecular and Cellular Endocrinology. 42 (3): 283–8. doi:10.1016/0303-7207(85)90059-0. PMID 3930312.
- Luthy IA, Begin DJ, Labrie F (1988). "Androgenic activity of synthetic progestins and spironolactone in androgen-sensitive mouse mammary carcinoma (Shionogi) cells in culture". Journal of Steroid Biochemistry. 31 (5): 845–52. doi:10.1016/0022-4731(88)90295-6. PMID 2462135.
- Sundar S, Dickinson PD (2012). "Spironolactone, a possible selective androgen receptor modulator, should be used with caution in patients with metastatic carcinoma of the prostate". BMJ Case Rep. 2012: bcr1120115238. doi:10.1136/bcr.11.2011.5238. PMC . PMID 22665559.
- Flynn T, Guancial EA, Kilari M, Kilari D (2016). "Case Report: Spironolactone Withdrawal Associated With a Dramatic Response in a Patient With Metastatic Castrate-Resistant Prostate Cancer". Clin Genitourin Cancer. doi:10.1016/j.clgc.2016.08.006. PMID 27641657.
- James VH, Pasqualini JR (22 October 2013). Hormonal Steroids: Proceedings of the Sixth International Congress on Hormonal Steroids. Elsevier Science. pp. 391–. ISBN 978-1-4831-9067-9.
- Bennett NC, Gardiner RA, Hooper JD, Johnson DW, Gobe GC (2010). "Molecular cell biology of androgen receptor signalling". Int. J. Biochem. Cell Biol. 42 (6): 813–27. doi:10.1016/j.biocel.2009.11.013. PMID 19931639.
- Wang C, Liu Y, Cao JM (2014). "G protein-coupled receptors: extranuclear mediators for the non-genomic actions of steroids". Int J Mol Sci. 15 (9): 15412–25. doi:10.3390/ijms150915412. PMC . PMID 25257522.
- Lang F, Alevizopoulos K, Stournaras C (2013). "Targeting membrane androgen receptors in tumors". Expert Opin. Ther. Targets. 17 (8): 951–63. doi:10.1517/14728222.2013.806491. PMID 23746222.
- Ora Hirsch Pescovitz; Erica A. Eugster (2004). Pediatric Endocrinology: Mechanisms, Manifestations, and Management. Lippincott Williams & Wilkins. pp. 248–. ISBN 978-0-7817-4059-3.
- Giuseppe Buonocore; Rodolfo Bracci; Michael Weindling (28 January 2012). Neonatology: A Practical Approach to Neonatal Diseases. Springer Science & Business Media. pp. 1012–. ISBN 978-88-470-1405-3.
- Rebecca M. Jordan-Young (7 January 2011). Brain Storm. Harvard University Press. pp. 82–. ISBN 978-0-674-05879-8.
- Judith E. Owen Blakemore; Sheri A. Berenbaum; Lynn S. Liben (13 May 2013). Gender Development. Psychology Press. pp. 115–. ISBN 978-1-135-07932-1.
- Mario Maggi (30 January 2012). Hormonal Therapy for Male Sexual Dysfunction. John Wiley & Sons. pp. 6–. ISBN 978-0-470-65760-7.
- Imamura, Yusuke; Sadar, Marianne D (2016). "Androgen receptor targeted therapies in castration-resistant prostate cancer: Bench to clinic". International Journal of Urology. 23 (8): 654–665. doi:10.1111/iju.13137. ISSN 0919-8172.
- De Mol, Eva; Fenwick, R. Bryn; Phang, Christopher T. W.; Buzón, Victor; Szulc, Elzbieta; de la Fuente, Alex; Escobedo, Albert; García, Jesús; Bertoncini, Carlos W.; Estébanez-Perpiñá, Eva; McEwan, Iain J.; Riera, Antoni; Salvatella, Xavier (2016). "EPI-001, A Compound Active against Castration-Resistant Prostate Cancer, Targets Transactivation Unit 5 of the Androgen Receptor". ACS Chemical Biology. 11 (9): 2499–2505. doi:10.1021/acschembio.6b00182. ISSN 1554-8929.
- Martinez-Ariza G, Hulme C (2015). "Recent advances in allosteric androgen receptor inhibitors for the potential treatment of castration-resistant prostate cancer". Pharm Pat Anal. 4 (5): 387–402. doi:10.4155/ppa.15.20. PMID 26389532.
- Witjes FJ, Debruyne FM, Fernandez del Moral P, Geboers AD (May 1989). "Ketoconazole high dose in management of hormonally pretreated patients with progressive metastatic prostate cancer. Dutch South-Eastern Urological Cooperative Group". Urology. 33 (5): 411–5. doi:10.1016/0090-4295(89)90037-X. PMID 2652864.
- Jeanne Held-Warmkessel (2006). Contemporary Issues in Prostate Cancer: A Nursing Perspective. Jones & Bartlett Learning. pp. 275–. ISBN 978-0-7637-3075-8.
- Bird IM, Abbott DH (2016). "The hunt for a selective 17,20 lyase inhibitor; learning lessons from nature". J. Steroid Biochem. Mol. Biol. 163: 136–46. doi:10.1016/j.jsbmb.2016.04.021. PMC . PMID 27154414.
- Flores E, Bratoeff E, Cabeza M, Ramirez E, Quiroz A, Heuze I (May 2003). "Steroid 5alpha-reductase inhibitors". Mini-Reviews in Medicinal Chemistry. 3 (3): 225–37. doi:10.2174/1389557033488196. PMID 12570838.
- Ashraf Mozayani; Lionel Raymon (18 September 2011). Handbook of Drug Interactions: A Clinical and Forensic Guide. Springer Science & Business Media. pp. 656–. ISBN 978-1-61779-222-9.
- N. V. Bhagavan (2002). Medical Biochemistry. Academic Press. pp. 787–. ISBN 978-0-12-095440-7.
- Hirshburg JM, Kelsey PA, Therrien CA, Gavino AC, Reichenberg JS (2016). "Adverse Effects and Safety of 5-alpha Reductase Inhibitors (Finasteride, Dutasteride): A Systematic Review". J Clin Aesthet Dermatol. 9 (7): 56–62. PMC . PMID 27672412.
- Urotext (1 January 2001). Urotext-Luts: Urology. Urotext. pp. 71–. ISBN 978-1-903737-03-3.
- Neumann F (1978). "The physiological action of progesterone and the pharmacological effects of progestogens--a short review". Postgraduate Medical Journal. 54 Suppl 2: 11–24. PMID 368741.
- Jacobi GH, Altwein JE, Kurth KH, Basting R, Hohenfellner R (1980). "Treatment of advanced prostatic cancer with parenteral cyproterone acetate: a phase III randomised trial". Br J Urol. 52 (3): 208–15. doi:10.1111/j.1464-410x.1980.tb02961.x. PMID 7000222.
- Wein AJ, Kavoussi LR, Novick AC, Partin AW, Peters CA (25 August 2011). Campbell-Walsh Urology: Expert Consult Premium Edition: Enhanced Online Features and Print, 4-Volume Set. Elsevier Health Sciences. pp. 2938–. ISBN 978-1-4160-6911-9.
- Kjeld JM, Puah CM, Kaufman B, Loizou S, Vlotides J, Gwee HM, Kahn F, Sood R, Joplin GF (1979). "Effects of norgestrel and ethinyloestradiol ingestion on serum levels of sex hormones and gonadotrophins in men". Clinical Endocrinology. 11 (5): 497–504. doi:10.1111/j.1365-2265.1979.tb03102.x. PMID 519881.
- Norman G, Dean ME, Langley RE, Hodges ZC, Ritchie G, Parmar MK, Sydes MR, Abel P, Eastwood AJ (2008). "Parenteral oestrogen in the treatment of prostate cancer: a systematic review". Br. J. Cancer. 98 (4): 697–707. doi:10.1038/sj.bjc.6604230. PMC . PMID 18268497.
- Dekanski JB (1980). "Anti-prostatic activity of bifluranol, a fluorinated bibenzyl". Br. J. Pharmacol. 71 (1): 11–6. doi:10.1111/j.1476-5381.1980.tb10903.x. PMC . PMID 6258683.
- Sander S, Nissen-Meyer R, Aakvaag A (1978). "On gestagen treatment of advanced prostatic carcinoma". Scand. J. Urol. Nephrol. 12 (2): 119–21. doi:10.3109/00365597809179977. PMID 694436.
- Robert Alan Prentky; Ann Wolbert Burgess (31 July 2000). Forensic Management of Sexual Offenders. Springer Science & Business Media. pp. 219–. ISBN 978-0-306-46278-8.
- Sudo K, Yamazaki I, Masuoka M, Nakayama R (1979). "Anti-androgen TSAA-291. IV. Effects of the anti-androgen TSAA-291 (16 beta-ethyl-17 beta-hydroxy-4-oestren-3-one) on the secretion of gonadotrophins". Acta Endocrinol Suppl (Copenh). 229: 53–66. PMID 294107.
- Eberhard Nieschlag; Hermann M. Behre; Susan Nieschlag (26 July 2012). Testosterone: Action, Deficiency, Substitution. Cambridge University Press. pp. 62–. ISBN 978-1-107-01290-5.
- IARC Working Group on the Evaluation of Carcinogenic Risks to Humans; World Health Organization; International Agency for Research on Cancer (2007). Combined Estrogen-progestogen Contraceptives and Combined Estrogen-progestogen Menopausal Therapy. World Health Organization. pp. 157–. ISBN 978-92-832-1291-1.
- Coss CC, Jones A, Parke DN, Narayanan R, Barrett CM, Kearbey JD, Veverka KA, Miller DD, Morton RA, Steiner MS, Dalton JT (2012). "Preclinical characterization of a novel diphenyl benzamide selective ERα agonist for hormone therapy in prostate cancer". Endocrinology. 153 (3): 1070–81. doi:10.1210/en.2011-1608. PMID 22294742.
- Krishna; Usha R. (1 January 2000). Adolescent Gynecology (pb). Orient Blackswan. pp. 121–. ISBN 978-81-250-1793-6.
- Marcus Filshie; John Guillebaud (22 October 2013). Contraception: Science and Practice. Elsevier Science. pp. 26–. ISBN 978-1-4831-6366-6.
- J.M. Sreenan; M.G. Diskin (6 December 2012). Embryonic Mortality in Farm Animals. Springer Science & Business Media. pp. 172–. ISBN 978-94-009-5038-2.
- Satish Kumar Jindal; M. C. Sharma (2010). Biotechnology in Animal Health and Production. New India Publishing. pp. 77–. ISBN 978-93-80235-35-6.
- Marc A. Fritz; Leon Speroff (28 March 2012). Clinical Gynecologic Endocrinology and Infertility. Lippincott Williams & Wilkins. pp. 750–751, 963. ISBN 978-1-4511-4847-3.
- Advances in Drug Research. Academic Press. 12 August 1997. pp. 34–. ISBN 978-0-08-052628-7.
- Bodh I. Jugdutt (19 February 2014). Aging and Heart Failure: Mechanisms and Management. Springer Science & Business Media. pp. 175–. ISBN 978-1-4939-0268-2.
- Camille Georges Wermuth (2 May 2011). The Practice of Murl=https://books.google.com/books?id=Qmt1_DQkCpEC&pg=PA34. Academic Press. pp. 34–. ISBN 978-0-08-056877-5.
- Ricardo Azziz (8 November 2007). Androgen Excess Disorders in Women. Springer Science & Business Media. pp. 382–. ISBN 978-1-59745-179-6.
- Benno Clemens Runnebaum; Thomas Rabe; Ludwig Kiesel (6 December 2012). Female Contraception: Update and Trends. Springer Science & Business Media. pp. 136–. ISBN 978-3-642-73790-9.
- C.E. Orfanos; W. Montagna; G. Stüttgen (6 December 2012). Hair Research: Status and Future Aspects; Proceedings of the First International Congress on Hair Research, Hamburg, March 13th–16, 1979. Springer Science & Business Media. pp. 587–. ISBN 978-3-642-81650-5.
- Lara Marks (2010). Sexual Chemistry: A History of the Contraceptive Pill. Yale University Press. pp. 76–78. ISBN 978-0-300-16791-7.
- J. Horsky; J. Presl (6 December 2012). Ovarian Function and its Disorders: Diagnosis and Therapy. Springer Science & Business Media. pp. 112–. ISBN 978-94-009-8195-9.
- Vitamins and Hormones. Academic Press. 18 May 1976. pp. 682–. ISBN 978-0-08-086630-7.
- David E. Neal (6 December 2012). Tumours in Urology. Springer Science & Business Media. pp. 233–. ISBN 978-1-4471-2086-5.
- Eckhard Ottow; Hilmar Weinmann (8 September 2008). Nuclear Receptors as Drug Targets. John Wiley & Sons. pp. 255–. ISBN 978-3-527-62330-3.
- Radhey Lal Singhal; John A. Thomas (1 January 1976). Cellular Mechanisms Modulating Gonadal Action. University Park Press. p. 239. ISBN 978-0-8391-0776-7.
- Liu, Bo; Su, Lei; Geng, Jingkun; Liu, Junjie; Zhao, Guisen (2010). "Developments in Nonsteroidal Antiandrogens Targeting the Androgen Receptor". ChemMedChem. 5 (10): 1651–1661. doi:10.1002/cmdc.201000259. ISSN 1860-7179.
- Heyns, W.; G., Verhoeven; De Moor, P. (1976). "Androgen binding in rat uterus cytosol. Study of the specificity". Journal of Steroid Biochemistry. 7 (5): 335–343. doi:10.1016/0022-4731(76)90092-3. ISSN 0022-4731.
- Annual Reports in Medicinal Chemistry. Academic Press. 16 September 1986. pp. 182–. ISBN 978-0-08-058365-5.
- Boris, A.; Scott, J. W.; DeMartino, L.; Cox, D. C. (1973). "ENDOCRINE PROFILE OF A NONSTEROIDAL ANTIANDROGEN N-(3,5-DIMETHYL-4-ISOXAZOLYLMETHYL)PHTHALIMIDE (DIMP)". European Journal of Endocrinology. 72 (3): 604–614. doi:10.1530/acta.0.0720604. ISSN 0804-4643.
- Jean-Pierre Bégué; Daniele Bonnet-Delpon (2 June 2008). Bioorganic and Medicinal Chemistry of Fluorine. John Wiley & Sons. pp. 327–. ISBN 978-0-470-28187-1.
- Menon MP, Higano CS (2013). "Enzalutamide, a second generation androgen receptor antagonist: development and clinical applications in prostate cancer". Curr Oncol Rep. 15 (2): 69–75. doi:10.1007/s11912-013-0293-9. PMID 23341368.
- Tran C, Ouk S, Clegg NJ, Chen Y, Watson PA, Arora V, Wongvipat J, Smith-Jones PM, Yoo D, Kwon A, Wasielewska T, Welsbie D, Chen CD, Higano CS, Beer TM, Hung DT, Scher HI, Jung ME, Sawyers CL (2009). "Development of a second-generation antiandrogen for treatment of advanced prostate cancer". Science. 324 (5928): 787–90. doi:10.1126/science.1168175. PMC . PMID 19359544.
- Walter Sneader (23 June 2005). Drug Discovery: A History. John Wiley & Sons. pp. 367–. ISBN 978-0-471-89979-2.
- David E. Golan (2008). Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy. Lippincott Williams & Wilkins. pp. 624–. ISBN 978-0-7817-8355-2.
- Prostate Cancer. Demos Medical Publishing. 20 December 2011. pp. 518–. ISBN 978-1-935281-91-7.
- Winsor Bowsher; Adam Carter (15 April 2008). Challenges in Prostate Cancer. John Wiley & Sons. pp. 138–. ISBN 978-1-4051-7177-9.
- Gautam Allahbadia; Rina Agrawal; Rubina Merchant (2007). Polycystic Ovary Syndrome. Anshan. pp. 184–. ISBN 978-1-904798-74-3.
- Frontiers in Medicinal Chemistry. Bentham Science Publishers. 2010. pp. 329–. ISBN 978-1-60805-208-0.
- Richard A. Helms; David J. Quan (2006). Textbook of Therapeutics: Drug and Disease Management. Lippincott Williams & Wilkins. pp. 211–. ISBN 978-0-7817-5734-8.
- NADIR R. FARID; Evanthia Diamanti-Kandarakis (27 February 2009). Diagnosis and Management of Polycystic Ovary Syndrome. Springer Science & Business Media. pp. 235–. ISBN 978-0-387-09718-3.