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===Other===
===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]].<ref>{{cite journal | vauthors = Pastuszak AW, Pearlman AM, Lai WS, Godoy G, Sathyamoorthy K, Liu JS, Miles BJ, Lipshultz LI, Khera M | display-authors = 6 | title = Testosterone replacement therapy in patients with prostate cancer after radical prostatectomy | journal = The Journal of Urology | volume = 190 | issue = 2 | pages = 639–644 | date = August 2013 | pmid = 23395803 | pmc = 4544840 | doi = 10.1016/j.juro.2013.02.002 }}</ref> Adverse effects may also include bone fractures (especially after falls), [[acne]] and oily skin, significant hair loss and 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]].<ref>{{cite journal | vauthors = Grech A, Breck J, Heidelbaugh J | title = Adverse effects of testosterone replacement therapy: an update on the evidence and controversy | journal = Therapeutic Advances in Drug Safety | volume = 5 | issue = 5 | pages = 190–200 | date = October 2014 | pmid = 25360240 | pmc = 4212439 | doi = 10.1177/2042098614548680 }}</ref><!-- These adverse effects are not mentioned in the source cited. --><ref name="Snyder 2024">{{cite journal |last1=Snyder |first1=Peter J. |last2=Bauer |first2=Douglas C. |last3=Ellenberg |first3=Susan S. |last4=Cauley |first4=Jane A. |last5=Buhr |first5=Kevin A. |last6=Bhasin |first6=Shalender |last7=Miller |first7=Michael G. |last8=Khan |first8=Nader S. |last9=Li |first9=Xue |last10=Nissen |first10=Steven E. |title=Testosterone Treatment and Fractures in Men with Hypogonadism |journal=New England Journal of Medicine |date=18 January 2024 |volume=390 |issue=3 |pages=203–211 |doi=10.1056/NEJMoa2308836}}</ref> Exogenous testosterone may also cause suppression of [[spermatogenesis]], leading to, in some cases, infertility.<ref name="pmid1977002">{{cite journal | vauthors = | title = Contraceptive efficacy of testosterone-induced azoospermia in normal men. World Health Organization Task Force on methods for the regulation of male fertility | journal = Lancet | volume = 336 | issue = 8721 | pages = 955–959 | date = October 1990 | pmid = 1977002 | doi = 10.1016/0140-6736(90)92416-F | s2cid = 25825354 }}</ref> 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.<ref>{{cite book | veditors = Liverman CT, Blazer DG | location = Washington (DC) |url= https://www.ncbi.nlm.nih.gov/books/NBK216164/#ddd00024/ |title=Introduction - Testosterone and Aging | chapter = Introduction | via = NCBI Bookshelf |publisher=National Academies Press (US) |year=2004 }}</ref>
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]].<ref>{{cite journal | vauthors = Pastuszak AW, Pearlman AM, Lai WS, Godoy G, Sathyamoorthy K, Liu JS, Miles BJ, Lipshultz LI, Khera M | display-authors = 6 | title = Testosterone replacement therapy in patients with prostate cancer after radical prostatectomy | journal = The Journal of Urology | volume = 190 | issue = 2 | pages = 639–644 | date = August 2013 | pmid = 23395803 | pmc = 4544840 | doi = 10.1016/j.juro.2013.02.002 }}</ref> 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.<ref>{{cite journal | vauthors = Grech A, Breck J, Heidelbaugh J | title = Adverse effects of testosterone replacement therapy: an update on the evidence and controversy | journal = Therapeutic Advances in Drug Safety | volume = 5 | issue = 5 | pages = 190–200 | date = October 2014 | pmid = 25360240 | pmc = 4212439 | doi = 10.1177/2042098614548680 }}</ref> Exogenous testosterone may also cause suppression of [[spermatogenesis]], leading to, in some cases, infertility.<ref name="pmid1977002">{{cite journal | vauthors = | title = Contraceptive efficacy of testosterone-induced azoospermia in normal men. World Health Organization Task Force on methods for the regulation of male fertility | journal = Lancet | volume = 336 | issue = 8721 | pages = 955–959 | date = October 1990 | pmid = 1977002 | doi = 10.1016/0140-6736(90)92416-F | s2cid = 25825354 }}</ref> 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.<ref>{{cite book | veditors = Liverman CT, Blazer DG | location = Washington (DC) |url= https://www.ncbi.nlm.nih.gov/books/NBK216164/#ddd00024/ |title=Introduction - Testosterone and Aging | chapter = Introduction | via = NCBI Bookshelf |publisher=National Academies Press (US) |year=2004 }}</ref>


Some studies argue that ART increases the risk of prostate cancer, although the results are not conclusive.<ref name="pmid16281043">{{cite journal | vauthors = Barqawi A, Crawford ED | title = Testosterone replacement therapy and the risk of prostate cancer. Is there a link? | journal = International Journal of Impotence Research | volume = 18 | issue = 4 | pages = 323–8 | date = 2006 | pmid = 16281043 | doi = 10.1038/sj.ijir.3901418 | s2cid = 46230482 | url = https://www.medscape.com/viewarticle/540617 }}</ref>
Some studies argue that ART increases the risk of prostate cancer, although the results are not conclusive.<ref name="pmid16281043">{{cite journal | vauthors = Barqawi A, Crawford ED | title = Testosterone replacement therapy and the risk of prostate cancer. Is there a link? | journal = International Journal of Impotence Research | volume = 18 | issue = 4 | pages = 323–8 | date = 2006 | pmid = 16281043 | doi = 10.1038/sj.ijir.3901418 | s2cid = 46230482 | url = https://www.medscape.com/viewarticle/540617 }}</ref>{{medcn}}


==Methods of administration==
==Methods of administration==

Revision as of 11:32, 20 January 2024

This article is about Androgen replacement therapy for cisgender people. For transgender applications, see Masculinizing hormone therapy.

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.

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

See also: Testosterone (medication)

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
Route Medication Major brand names Form Dosage
Oral Testosteronea – Tablet 400–800 mg/day (in divided doses)
Testosterone undecanoate Andriol, Jatenzo Capsule 40–80 mg/2–4× day (with meals)
Methyltestosteroneb Android, Metandren, Testred Tablet 10–50 mg/day
Fluoxymesteroneb Halotestin, Ora-Testryl, Ultandren Tablet 5–20 mg/day
Metandienoneb Dianabol Tablet 5–15 mg/day
Mesteroloneb Proviron Tablet 25–150 mg/day
Sublingual Testosteroneb Testoral Tablet 5–10 mg 1–4×/day
Methyltestosteroneb Metandren, Oreton Methyl Tablet 10–30 mg/day
Buccal Testosterone Striant Tablet 30 mg 2×/day
Methyltestosteroneb Metandren, Oreton Methyl Tablet 5–25 mg/day
Transdermal Testosterone AndroGel, Testim, TestoGel Gel 25–125 mg/day
Androderm, AndroPatch, TestoPatch Non-scrotal patch 2.5–15 mg/day
Testoderm Scrotal patch 4–6 mg/day
Axiron Axillary solution 30–120 mg/day
Androstanolone (DHT) Andractim Gel 100–250 mg/day
Rectal Testosterone Rektandron, Testosteronb Suppository 40 mg 2–3×/day
Injection (IMTooltip intramuscular injection or SCTooltip subcutaneous injection) Testosterone Andronaq, Sterotate, Virosterone Aqueous suspension 10–50 mg 2–3×/week
Testosterone propionateb Testoviron Oil solution 10–50 mg 2–3×/week
Testosterone enanthate Delatestryl Oil solution 50–250 mg 1x/1–4 weeks
Xyosted Auto-injector 50–100 mg 1×/week
Testosterone cypionate Depo-Testosterone Oil solution 50–250 mg 1x/1–4 weeks
Testosterone isobutyrate Agovirin Depot Aqueous suspension 50–100 mg 1x/1–2 weeks
Testosterone phenylacetateb Perandren, Androject Oil solution 50–200 mg 1×/3–5 weeks
Mixed testosterone esters Sustanon 100, Sustanon 250 Oil solution 50–250 mg 1×/2–4 weeks
Testosterone undecanoate Aveed, Nebido Oil solution 750–1,000 mg 1×/10–14 weeks
Testosterone buciclatea – Aqueous suspension 600–1,000 mg 1×/12–20 weeks
Implant Testosterone Testopel Pellet 150–1,200 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
Route Medication Major brand names Form Dosage
Oral Testosterone undecanoate Andriol, Jatenzo Capsule 40–80 mg 1x/1–2 days
Methyltestosterone Metandren, Estratest Tablet 0.5–10 mg/day
Fluoxymesterone Halotestin Tablet 1–2.5 mg 1x/1–2 days
Normethandronea Ginecoside Tablet 5 mg/day
Tibolone Livial Tablet 1.25–2.5 mg/day
Prasterone (DHEA)b – Tablet 10–100 mg/day
Sublingual Methyltestosterone Metandren Tablet 0.25 mg/day
Transdermal Testosterone Intrinsa Patch 150–300 μg/day
AndroGel Gel, cream 1–10 mg/day
Vaginal Prasterone (DHEA) Intrarosa Insert 6.5 mg/day
Injection Testosterone propionatea Testoviron Oil solution 25 mg 1x/1–2 weeks
Testosterone enanthate Delatestryl, Primodian Depot Oil solution 25–100 mg 1x/4–6 weeks
Testosterone cypionate Depo-Testosterone, Depo-Testadiol Oil solution 25–100 mg 1x/4–6 weeks
Testosterone isobutyratea Femandren M, Folivirin Aqueous suspension 25–50 mg 1x/4–6 weeks
Mixed testosterone esters Climacterona Oil solution 150 mg 1x/4–8 weeks
Omnadren, Sustanon Oil solution 50–100 mg 1x/4–6 weeks
Nandrolone decanoate Deca-Durabolin Oil solution 25–50 mg 1x/6–12 weeks
Prasterone enanthatea Gynodian Depot Oil solution 200 mg 1x/4–6 weeks
Implant Testosterone Testopel Pellet 50–100 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

See also: Testosterone § 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] 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,[22][23] requested JAMA to retract the article as misleading due to substantial residual errors.[24] Concerns have been raised that testosterone was being widely marketed without the benefit of data on efficacy and safety from large randomized controlled trials.[25] 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.[26][27][28] 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.[29][30]

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.[31] 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.[32] Exogenous testosterone may also cause suppression of spermatogenesis, leading to, in some cases, infertility.[33] 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.[34]

Some studies argue that ART increases the risk of prostate cancer, although the results are not conclusive.[35][medical citation needed]

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.[36]

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".[26][27][28]

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.[37]

A UK study in 2013 showed that prescriptions for testosterone replacement, particularly transdermal products, almost doubled between 2000 and 2010.[38]

Research

Testosterone is being investigated as therapy for the following conditions:

See also

References

  1. ^ "Testosterone therapy: Key to male vitality?". Mayo Foundation for Medical Education and Research (MFMER). 2012.
  2. ^ a b Sood A, Hosseinpour A, Sood A, Avula S, Durrani J, Bhatia V, Gupta R (October 2023). "Cardiovascular Outcomes of Hypogonadal Men Receiving Testosterone Replacement Therapy: A Meta-analysis of Randomized Controlled Trials". Endocrine Practice. doi:10.1016/j.eprac.2023.09.012. PMID 37797887. S2CID 263692728.
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