Androgen replacement therapy

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Androgen replacement therapy
Other namesTestosterone 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 supplemented or replaced. It typically involves the administration of testosterone through injections, skin creams, patches, gels, pills, or subcutaneous pellets. ART is often prescribed to counter the effects of male hypogonadism.

Contents

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. [1] [2] [3] [4] [5] [6] [7]

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, and/or more body fat. Dissatisfaction with these changes causes some middle age men to seek ART. Androgen deficiencies in women have also, as of 2001, been recognized as a medical disorder that can be treated with ART. [8] As with men, symptoms associated with androgen deficiency are most prevalent with age, and androgen replacement therapy has been shown to help with symptoms of menopause. [9]

Medical uses

Males

Androgen replacement is the classic treatment of hypogonadism. [10] It is also used in men who have lost the ability to produce androgens due to disease or its treatment. [11] [12]

Androgen replacement therapy formulations and dosages used in men
RouteMedicationMajor brand namesFormDosage
Oral Testosterone a–Tablet400–800 mg/day (in divided doses)
Testosterone undecanoate Andriol, JatenzoCapsule40–80 mg/2–4× day (with meals)
Methyltestosterone bAndroid, Metandren, TestredTablet10–50 mg/day
Fluoxymesterone bHalotestin, Ora-Testryl, UltandrenTablet5–20 mg/day
Metandienone bDianabolTablet5–15 mg/day
Mesterolone bProvironTablet25–150 mg/day
Sublingual Testosterone bTestoralTablet5–10 mg 1–4×/day
Methyltestosterone bMetandren, Oreton MethylTablet10–30 mg/day
Buccal Testosterone StriantTablet30 mg 2×/day
Methyltestosterone bMetandren, Oreton MethylTablet5–25 mg/day
Transdermal Testosterone AndroGel, Testim, TestoGelGel25–125 mg/day
Androderm, AndroPatch, TestoPatchNon-scrotal patch2.5–15 mg/day
TestodermScrotal patch4–6 mg/day
AxironAxillary solution30–120 mg/day
Androstanolone (DHT) AndractimGel100–250 mg/day
Rectal Testosterone Rektandron, TestosteronbSuppository40 mg 2–3×/day
Injection (IM Tooltip intramuscular injection or SC Tooltip subcutaneous injection) Testosterone Andronaq, Sterotate, VirosteroneAqueous suspension10–50 mg 2–3×/week
Testosterone propionate bTestovironOil solution10–50 mg 2–3×/week
Testosterone enanthate DelatestrylOil solution50–250 mg 1x/1–4 weeks
XyostedAuto-injector50–100 mg 1×/week
Testosterone cypionate Depo-TestosteroneOil solution50–250 mg 1x/1–4 weeks
Testosterone isobutyrate Agovirin DepotAqueous suspension50–100 mg 1x/1–2 weeks
Testosterone phenylacetate bPerandren, AndrojectOil solution50–200 mg 1×/3–5 weeks
Mixed testosterone esters Sustanon 100, Sustanon 250Oil solution50–250 mg 1×/2–4 weeks
Testosterone undecanoate Aveed, NebidoOil solution750–1,000 mg 1×/10–14 weeks
Testosterone buciclate a–Aqueous suspension600–1,000 mg 1×/12–20 weeks
Implant Testosterone TestopelPellet150–1,200 mg/3–6 months
Notes: Men produce about 3 to 11 mg of testosterone per day (mean 7 mg/day in young men). Footnotes:a = Never marketed. b = No longer used and/or no longer marketed. Sources: See template.

Diabetes

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. [13] [14] 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." [15]

Females

Androgen replacement is used in postmenopausal women: the indications are to increase sexual desire; and to prevent or treat osteoporosis. [16] Other symptoms of androgen deficiency are similar in both sexes, such as muscle loss and physical fatigue. [8] 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. [16]

Androgen replacement therapy formulations and dosages used in women
RouteMedicationMajor brand namesFormDosage
Oral Testosterone undecanoate Andriol, JatenzoCapsule40–80 mg 1x/1–2 days
Methyltestosterone Metandren, EstratestTablet0.5–10 mg/day
Fluoxymesterone HalotestinTablet1–2.5 mg 1x/1–2 days
Normethandrone aGinecosideTablet5 mg/day
Tibolone LivialTablet1.25–2.5 mg/day
Prasterone (DHEA) b–Tablet10–100 mg/day
Sublingual Methyltestosterone MetandrenTablet0.25 mg/day
Transdermal Testosterone IntrinsaPatch150–300 μg/day
AndroGelGel, cream1–10 mg/day
Vaginal Prasterone (DHEA) IntrarosaInsert6.5 mg/day
Injection Testosterone propionate aTestovironOil solution25 mg 1x/1–2 weeks
Testosterone enanthate Delatestryl, Primodian DepotOil solution25–100 mg 1x/4–6 weeks
Testosterone cypionate Depo-Testosterone, Depo-TestadiolOil solution25–100 mg 1x/4–6 weeks
Testosterone isobutyrate aFemandren M, FolivirinAqueous suspension25–50 mg 1x/4–6 weeks
Mixed testosterone esters ClimacteronaOil solution150 mg 1x/4–8 weeks
Omnadren, SustanonOil solution50–100 mg 1x/4–6 weeks
Nandrolone decanoate Deca-DurabolinOil solution25–50 mg 1x/6–12 weeks
Prasterone enanthate aGynodian DepotOil solution200 mg 1x/4–6 weeks
Implant Testosterone TestopelPellet50–100 mg 1x/3–6 months
Notes: Premenopausal women produce about 230 ± 70 μg testosterone per day (6.4 ± 2.0 mg testosterone per 4 weeks), with a range of 130 to 330 μg per day (3.6–9.2 mg per 4 weeks). Footnotes:a = Mostly discontinued or unavailable. b = Over-the-counter. Sources: See template.

Adverse effects

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. [17] The FDA has required that testosterone labels include warning information about the possibility of an increased risk of heart attacks and stroke. [17]

Heart disease

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. [18] The FDA's action followed three peer-reviewed studies of increased cardiovascular events and deaths. [19] Due to an increased rate of adverse cardiovascular events compared to a placebo group, a randomized trial stopped early. [20] Also, in November 2013, a study reported an increase in deaths and heart attacks in older men. [21] Concerns have been raised that testosterone was being widely marketed without the benefit of data on efficacy and safety from large randomized controlled trials. [22] 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. [23] [24] [25] However, when given to men with hypogonadism in the short- and medium-term, testosterone replacement therapy does not increase the risk of cardiovascular events (including strokes and heart attacks and other heart diseases). [2] The long-term safety of the therapy is not known yet. [26] [27]

Other

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. [28] A 2014 review said there was some evidence men with certain comorbidities may be at risk of adverse effects including sleep apnoea, metabolic syndrome and cardiovascular disease. [29] Exogenous testosterone may also cause suppression of spermatogenesis, leading to, in some cases, infertility. [30] 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. [31]

Some studies argue that ART increases the risk of prostate cancer, although the results are not conclusive. [32]

Methods of administration

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, capsule, cream or gel; or depot injections given into fat or muscle. [18]

Society and culture

MMA

Some UFC fighters used TRT until 2014 when the Nevada State Athletic Commission banned its use. [33]

Regulation

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". [23] [24] [25]

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. [34]

A UK study in 2013 showed that prescriptions for testosterone replacement, particularly transdermal products, almost doubled between 2000 and 2010. [35]

Research

Testosterone is being investigated as therapy for the following conditions:

See also

Related Research Articles

<span class="mw-page-title-main">Testosterone</span> Primary male sex hormone

Testosterone is the primary male sex hormone and androgen in males. In humans, testosterone plays a key role in the development of male reproductive tissues such as testicles and prostate, as well as promoting secondary sexual characteristics such as increased muscle and bone mass, and the growth of body hair. It is associated with increased aggression, sex drive, dominance, courtship display, and a wide range of behavioral characteristics. In addition, testosterone in both sexes is involved in health and well-being, where it has a significant effect on overall mood, cognition, social and sexual behavior, metabolism and energy output, the cardiovascular system, and in the prevention of osteoporosis. Insufficient levels of testosterone in men may lead to abnormalities including frailty, accumulation of adipose fat tissue within the body, anxiety and depression, sexual performance issues, and bone loss.

Hormone therapy or hormonal therapy is the use of hormones in medical treatment. Treatment with hormone antagonists may also be referred to as hormonal therapy or antihormone therapy. The most general classes of hormone therapy are oncologic hormone therapy, hormone replacement therapy, androgen replacement therapy (ART), oral contraceptive pills, and Gender-affirming hormone therapy.

<span class="mw-page-title-main">Dihydrotestosterone</span> Human hormone

Dihydrotestosterone is an endogenous androgen sex steroid and hormone primarily involved in the growth and repair of the prostate and the penis, as well as the production of sebum and body hair composition.

<span class="mw-page-title-main">Methyltestosterone</span> Chemical compound

Methyltestosterone, sold under the brand names Android, Metandren, and Testred among others, is an androgen and anabolic steroid (AAS) medication which is used in the treatment of low testosterone levels in men, delayed puberty in boys, at low doses as a component of menopausal hormone therapy for menopausal symptoms like hot flashes, osteoporosis, and low sexual desire in women, and to treat breast cancer in women. It is taken by mouth or held in the cheek or under the tongue.

Hypogonadism means diminished functional activity of the gonads—the testicles or the ovaries—that may result in diminished production of sex hormones. Low androgen levels are referred to as hypoandrogenism and low estrogen as hypoestrogenism. These are responsible for the observed signs and symptoms in both males and females.

Late-onset hypogonadism (LOH) or testosterone deficiency syndrome (TDS) is a term for a condition in older men characterized by measurably low testosterone levels and clinical symptoms mostly of a sexual nature, including decreased desire for mating, fewer spontaneous erections, and erectile dysfunction. It is the result of a gradual drop in testosterone; a steady decline in testosterone levels of about 1% per year can happen and is well documented in both men and women.

Hypoestrogenism, or estrogen deficiency, refers to a lower than normal level of estrogen. It is an umbrella term used to describe estrogen deficiency in various conditions. Estrogen deficiency is also associated with an increased risk of cardiovascular disease, and has been linked to diseases like urinary tract infections and osteoporosis.

<span class="mw-page-title-main">Testosterone cypionate</span> Chemical compound

Testosterone cypionate, sold under the brand name Depo-Testosterone among others, is an androgen and anabolic steroid (AAS) medication which is used mainly in the treatment of low testosterone levels in men, including hormone therapy for transgender men. It is given by injection into muscle or subcutaneously, once every one to four weeks, depending on clinical indication.

<span class="mw-page-title-main">Polyestradiol phosphate</span> Chemical compound

Polyestradiol phosphate (PEP), sold under the brand name Estradurin, is an estrogen medication which is used primarily in the treatment of prostate cancer in men. It is also used in women to treat breast cancer, as a component of hormone therapy to treat low estrogen levels and menopausal symptoms, and as a component of feminizing hormone therapy for transgender women. It is given by injection into muscle once every four weeks.

<span class="mw-page-title-main">Enclomifene</span> Chemical compound

Enclomifene (INNTooltip International Nonproprietary Name), or enclomiphene (USANTooltip United States Adopted Name), a nonsteroidal selective estrogen receptor modulator of the triphenylethylene group, acts by antagonizing the estrogen receptor (ER) in the pituitary gland, which reduces negative feedback by estrogen on the hypothalamic-pituitary-gonadal axis, thereby increasing gonadotropin secretion and hence gonadal production of testosterone. It is one of the two stereoisomers of clomifene, which itself is a mixture of 38% zuclomifene and 62% enclomifene. Enclomifene is the (E)-stereoisomer of clomifene, while zuclomifene is the (Z)-stereoisomer. Whereas zuclomifene is more estrogenic, enclomifene is more antiestrogenic. In accordance, unlike enclomifene, zuclomifene is antigonadotropic due to activation of the ER and reduces testosterone levels in men. As such, isomerically pure enclomifene is more favorable than clomifene as a progonadotropin for the treatment of male hypogonadism.

<span class="mw-page-title-main">Selective androgen receptor modulator</span> Class of pharmaceutical drugs

Selective androgen receptor modulators (SARMs) are a class of drugs that selectively activate the androgen receptor in specific tissues, promoting muscle and bone growth while having less effect on male reproductive tissues like the prostate gland.

Masculinizing hormone therapy, also known as transmasculine hormone therapy or female-to-male hormone therapy, is a form of hormone therapy and gender affirming therapy which is used to change the secondary sexual characteristics of transgender people from feminine or androgynous to masculine. It is a common type of transgender hormone therapy, and is predominantly used to treat transgender men and other transmasculine individuals who were assigned female at birth. Some intersex people also receive this form of therapy, either starting in childhood to confirm the assigned sex or later if the assignment proves to be incorrect.

Feminizing hormone therapy, also known as transfeminine hormone therapy, is hormone therapy and sex reassignment therapy to change the secondary sex characteristics of transgender people from masculine or androgynous to feminine. It is a common type of transgender hormone therapy and is used to treat transgender women and non-binary transfeminine individuals. Some, in particular intersex people, but also some non-transgender people, take this form of therapy according to their personal needs and preferences.

<span class="mw-page-title-main">Enzalutamide</span> Antiandrogen medication used in treatment of prostate cancer

Enzalutamide, sold under the brand name Xtandi, is a nonsteroidal antiandrogen (NSAA) medication which is used in the treatment of prostate cancer. It is indicated for use in conjunction with castration in the treatment of metastatic castration-resistant prostate cancer (mCRPC), nonmetastatic castration-resistant prostate cancer, and metastatic castration-sensitive prostate cancer (mCSPC). It is taken by mouth.

<span class="mw-page-title-main">Enobosarm</span> Investigational selective androgen receptor modulator

Enobosarm, also formerly known as ostarine and by the developmental code names GTx-024, MK-2866, and S-22, is a selective androgen receptor modulator (SARM) which is under development for the treatment of androgen receptor-positive breast cancer in women and for improvement of body composition in people taking GLP-1 receptor agonists like semaglutide. It was also under development for a variety of other indications, including treatment of cachexia, Duchenne muscular dystrophy, muscle atrophy or sarcopenia, and stress urinary incontinence, but development for all other uses has been discontinued. Enobosarm was evaluated for the treatment of muscle wasting related to cancer in late-stage clinical trials, and the drug improved lean body mass in these trials, but it was not effective in improving muscle strength. As a result, enobosarm was not approved and development for this use was terminated. Enobosarm is taken by mouth.

<span class="mw-page-title-main">Testosterone undecanoate</span> Chemical compound

Testosterone undecanoate, sold under the brand name Nebido among others, is an androgen and anabolic steroid (AAS) medication that is used mainly in the treatment of low testosterone levels in men, It is taken by mouth or given by injection into muscle.

Androgen deficiency is a medical condition characterized by insufficient androgenic activity in the body. Androgen deficiency most commonly affects women, and is also called Female androgen insufficiency syndrome (FAIS), although it can happen in both sexes. Androgenic activity is mediated by androgens, and is dependent on various factors including androgen receptor abundance, sensitivity and function. Androgen deficiency is associated with lack of energy and motivation, depression, lack of desire (libido), and in more severe cases changes in secondary sex characteristics.

Testosterone and the cardiovascular system are the effects that the male hormone testosterone has on the cardiovascular system.

<span class="mw-page-title-main">Testosterone (medication)</span> Medication and naturally occurring steroid hormone

Testosterone (T) is a medication and naturally occurring steroid hormone. It is used to treat male hypogonadism, gender dysphoria, and certain types of breast cancer. It may also be used to increase athletic ability in the form of doping. It is unclear if the use of testosterone for low levels due to aging is beneficial or harmful. Testosterone can be used as a gel or transdermal patch that is applied to the skin topically, intramuscular injection (IM), buccally, or as an oral tablet.

<span class="mw-page-title-main">Androstanolone</span> Androgenic and anabolic steroid medication

Androstanolone, or stanolone, also known as dihydrotestosterone (DHT) and sold under the brand name Andractim among others, is an androgen and anabolic steroid (AAS) medication and hormone which is used mainly in the treatment of low testosterone levels in men. It is also used to treat breast development and small penis in males. Compared to testosterone, androstanolone (DHT) is less likely to aromatize into estrogen, and therefore it shows less pronounced estrogenic side effects, such as gynecomastia and water retention. On the other hand, androstanolone (DHT) show more significant androgenic side effects, such as acne, hair loss and prostate enlargement.

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