Androgen replacement therapy
|Androgen replacement therapy|
Androgen replacement therapy (ART), often referred to as testosterone replacement therapy (TRT), is a form of hormone therapy in which androgens, often testosterone, are replaced. ART is often prescribed to counter the effects of male hypogonadism. It typically involves the administration of testosterone through injections, skin creams, patches, gels, or subcutaneous pellets.
ART is also prescribed to lessen the effects or delay the onset of normal male aging. However, this is controversial and is the subject of ongoing clinical trials. As men enter middle age they may notice changes caused by a relative decline in testosterone: fewer erections, fatigue, thinning skin, declining muscle mass and strength, more body fat. Dissatisfaction with these changes causes some middle age men to seek ART.
The risks of diabetes and of testosterone deficiency in men over 45 (i.e., hypogonadism, specifically hypoandrogenism) are strongly correlated. Testosterone replacement therapies have been shown to improve blood glucose management. Still, "it is prudent not to start testosterone therapy in men with diabetes solely for the purpose of improving metabolic control if they show no signs and symptoms of hypogonadism."
Androgen replacement is also used in postmenopausal women, for instance to increase sexual desire and to prevent or treat osteoporosis. The androgens used for androgen replacement in women include testosterone (and esters), prasterone (dehydroepiandrosterone; DHEA) (and the ester prasterone enanthate), methyltestosterone, nandrolone decanoate, and tibolone, among others.
|Route||Medication||Form(s)||Major brand name(s)||Dose range||Frequency|
|Oral||Testosterone undecanoatea||Capsule||Andriol||40–80 mg||Every 1–2 days|
|Oral||Methyltestosteroneb||Tablet||Metandren; Estratest||0.5–10 mg||Daily|
|Oral||Prasterone (dehydroepiandrosterone)c||Tablet||N/A||25–100 mg||Daily|
|Transdermal||Testosteronea||Patch||Intrinsa||150–300 μg/day||Every 3–4 days|
|Transdermal||Testosterone||Cream; Gel||AndroGel||5–10 mg||Daily|
|Vaginal||Testosteroned||Cream; Gel||N/A||Unspecified||Every 1–3 days|
|Vaginal||Prasterone (dehydroepiandrosterone)||Insert||Intrarosa||6.5 mg||Daily|
|Intramuscular||Testosterone enanthateb||Oil||Delatestryl; Ditate-DS||25–100 mg||Every 4–6 weeks|
|Intramuscular||Testosterone cypionateb||Oil||Depo-Testosterone; Depo-Testadiol||25–100 mg||Every 4–6 weeks|
|Intramuscular||Testosterone enanthate benzilic acid hydrazoneb,e||Oil||Climacteron||150 mg||Every 4–8 weeks|
|Intramuscular||Nandrolone decanoate||Oil||Deca-Durabolin||25–50 mg||Every 6–12 weeks|
|Intramuscular||Prasterone enanthatea,b||Oil||Gynodian Depot||200 mg||Every 4–6 weeks|
|Subcutaneous||Testosterone||Implant||Testopel||50–100 mg||Every 3–6 months|
|Footnotes: a = Not available or no longer available in the United States. b = Alone and/or in combination with an estrogen. c = Over-the-counter. d = Compounded only. e = Discontinued. Miscellaneous: Direct link to table. Sources: General:  Specific: |
The Food and Drug Administration (FDA) stated in 2015 that neither the benefits nor the safety of testosterone have been established for low testosterone levels due to aging. The FDA has required that testosterone labels include warning information about the possibility of an increased risk of heart attacks and stroke.
On January 31, 2014, reports of strokes, heart attacks, and deaths in men taking testosterone-replacement led the FDA to announce that it would be investigating this issue. The FDA's action followed three peer-reviewed studies of increased cardiovascular events and deaths. Due to an increased rate of adverse cardiovascular events compared to a placebo group, a randomized trial stopped early. Also, in November 2013, a study reported an increase in deaths and heart attacks in older men. Even after a correction was published, the "Androgen Study Group", a group with many members who have relationships with drug companies in the testosterone market, requested JAMA to retract the article as misleading due to substantial residual errors. Concerns have been raised that testosterone was being widely marketed ahead of large randomized controlled trials. As a result of the "potential for adverse cardiovascular outcomes", the FDA announced, in September 2014, a review of the appropriateness and safety of testosterone replacement therapy.
Other significant adverse effects of testosterone supplementation include acceleration of pre-existing prostate cancer growth in individuals who have undergone androgen deprivation; increased hematocrit, which can require venipuncture in order to treat; and, exacerbation of sleep apnea. Adverse effects may also include minor side-effects such as acne and oily skin, as well as, significant hair loss and/or thinning of the hair, which may be prevented with 5-alpha reductase inhibitors ordinarily used for the treatment of benign prostatic hyperplasia, such as finasteride. Exogenous testosterone may also cause suppression of spermatogenesis, leading to, in some cases, infertility. It is recommended that physicians screen for prostate cancer with a digital rectal exam and prostate-specific antigen (PSA) level before starting therapy, and monitor PSA and hematocrit levels closely during therapy.
Some studies argue that ART increases the risk of prostate cancer, although the results are not conclusive.
Society and culture
As of September 2014, testosterone replacement therapy has been under review for appropriateness and safety by the Food and Drug Administration due to the "potential for adverse cardiovascular outcomes".
Frequency of use
In the United States usage increased from 0.5% in 2002 to 3.2% in 2013 and have since decreased to 1.7% in 2016.
There are several artificial androgens, many of which are manipulations of the testosterone molecule referred to as anabolic-androgenic steroids. Androgen replacement is administered by patch, tablet, pill, cream or gel; or depot injections given into fat or muscle.
In addition, a number of other effects of testosterone have led to research into possible therapeutic roles in:
- Erectile dysfunction
- Diabetes mellitus
- Chronic heart failure
- Dementia, but the evidence base is small and the balance of benefit needs to be clarified
- Transgender hormone therapy for transgender men
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Despite the lack of clinical trials and quality-control standards, custom-compounded testosterone creams, ointments, and gel forms are popular formulations for improving women's sexual desire.68-70 For women, an appropriate dosage of compounded 1% testosterone gel, cream, or ointment is 0.5 g/day, which should deliver 5 mg of testosterone daily, one tenth the generally prescribed dosage for men.39 The product can be applied directly to any skin surface (but commonly the clitoris, labia, thigh, arm, or abdomen) several times weekly.
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Topical vaginal testosterone is often used in premenopausal women as a first step in the treatment of sexual dysfunction and vaginal lichen planus. Topical testosteorne preparations can be compounded in 1% to 2% formulations and should be applied up to 3 times per week.
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Testosterone can also be compounded as a cream containing 1 mg/mL, with 1 mL applied to the abdomen daily. Vaginal testosterone is an option for postmenopausal women who cannot use systemic or vaginal estrogen due to breast cancer. Testosterone 150–300 mcg/day vaginally appears to reduce vaginal dryness and dyspareunia without increasing systemic estrogen levels.
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At present, bioidentical testosterone can be obtained only froma compounding pharmacy, where 4 to 6 mg of bioidentical testosterone is generally formulated alone or together with the biestrogen or triestrogen formulation. Testosterone cream applied to the genital region can be used as an alternative delivery method. Common prescriptions are anywhere from 1 to 10 mg/g of cream.
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