Androgen replacement therapy

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Androgen replacement therapy
Other namesAndrogen replacement therapy

Testosterone Replacement Therapy (TRT), also known as Androgen replacement therapy (ART), is a form of hormone therapy in which androgens, most 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]

Testosterone has many effects on the body, either when made by the body or when given as a hormone replacement. Testosterone has anabolic effects on muscle and bone, leading to increased muscle mass and bone density. It is also known to stimulate erythropoesis (red blood cell production). It is known to improve penile blood flow to help with erections and also improve sexual drive or desire. [10]

Medical uses

Males

Androgen replacement is the classic treatment of hypogonadism. [11] It is also used in men who have lost the ability to produce androgens due to disease or its treatment. [12] [13]

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. [14] [15] 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." [16]

Other studies have not shown a benefit in diabetes prevention or better diabetes control with testosterone therapy. [17] One study showed testosterone therapy in older men with low testosterone not changing sugar levels or hemoglobin A1c (used as a marker of diabetes control, or for the diagnosis of diabetes) compared to placebo. [18] In another trial from 2024, testosterone therapy for men with hypogonadism and prediabetes did not prevent the progression of prediabetes to diabetes and it did not improve diabetes control compared to placebo. [19]

Females

Androgen replacement is used in postmenopausal women: the indications are to increase sexual desire; and to prevent or treat osteoporosis. [20] 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. [20]

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. [21] The FDA has required that testosterone labels include warning information about the possibility of an increased risk of heart attacks and stroke. [21]

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. [22] The FDA's action followed three peer-reviewed studies of increased cardiovascular events and deaths. [23] Due to an increased rate of adverse cardiovascular events compared to a placebo group, a randomized trial stopped early. [24] Also, in November 2013, a study reported an increase in deaths and heart attacks in older men. [25] Concerns have been raised that testosterone was being widely marketed without the benefit of data on efficacy and safety from large randomized controlled trials. [26] 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. [27] [28] [29] 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. [30] [31]

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. [32] 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. [33] Exogenous testosterone may also cause suppression of spermatogenesis, leading to, in some cases, infertility. [34] 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. [35]

Some studies suggest that ART increases the risk of prostate cancer, although the results are not conclusive. [36] This may be due to many men with risk factors for prostate cancer being excluded from testosterone replacement studies. [10] The PSA (which is a screening blood test for prostate cancer) usually increases with testosterone therapy which may lead to a higher rate of prostate cancer testing, including imaging or biopsies. Although testosterone is theoretically hypothesized to increase prostate size, the effects of testosterone therapy on enlarged prostate or lower urinary tract symptoms (such as urinary urgency, hesitancy or incomplete emptying) is not known. [10]

Testosterone therapy may increase the risk of blood clots, but those with blood clots in the trials were not tested for blood clotting disorders, possibly confounding the findings. [10] Testosterone therapy was found to increase the risk of an irregular heartbeat due to atrial fibrillation in one study (3.5% vs 2.4%), but other studies (including meta analyses) have not found an increased risk. [10]

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. [22]

Society and culture

MMA

Some UFC fighters used TRT until 2014 when the Nevada State Athletic Commission banned its use. [37]

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". [27] [28] [29]

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. [38]

A UK study in 2013 showed that prescriptions for testosterone replacement, particularly transdermal products, almost doubled between 2000 and 2010. [39]

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. 1 2 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. 30 (1): 2–10. doi:10.1016/j.eprac.2023.09.012. PMID   37797887. S2CID   263692728.
  3. ↑ Valderrábano RJ, Pencina K, Storer TW, Reid KF, Kibel AS, Burnett AL, et al. (January 2023). "Testosterone replacement in prostate cancer survivors with testosterone deficiency: Study protocol of a randomized controlled trial". Andrology. 11 (1): 93–102. doi:10.1111/andr.13299. PMC   9771994 . PMID   36181480.
  4. ↑ Pencina KM, Travison TG, Artz AS, Lincoff AM, Nissen SE, Flevaris P, et al. (October 2023). "Efficacy of Testosterone Replacement Therapy in Correcting Anemia in Men With Hypogonadism: A Randomized Clinical Trial". JAMA Network Open. 6 (10): e2340030. doi:10.1001/jamanetworkopen.2023.40030. PMC   10611996 . PMID   37889486.
  5. ↑ Christensen LL, Poulsen HE, Andersen MS, Glintborg D (January 2024). "Whole-body oxidative stress reduction during testosterone therapy in aging men: A randomized placebo-controlled trial". Andrology. 12 (1): 115–122. doi: 10.1111/andr.13458 . PMID   37177884.
  6. ↑ Diaz P, Reddy R, Blachman-Braun R, Zucker I, Dullea A, Gonzalez DC, et al. (April 2023). "Comparison of Intratesticular Testosterone between Men Receiving Nasal, Intramuscular, and Subcutaneous Pellet Testosterone Therapy: Evaluation of Data from Two Single-Center Randomized Clinical Trials". The World Journal of Men's Health. 41 (2): 390–395. doi:10.5534/wjmh.210261. PMC   10042650 . PMID   35791295.
  7. ↑ Corona G, Torres LO, Maggi M (March 2020). "Testosterone Therapy: What We Have Learned From Trials". The Journal of Sexual Medicine. 17 (3): 447–460. doi:10.1016/j.jsxm.2019.11.270. hdl: 2158/1192573 . PMID   31928918. S2CID   210191244.
  8. 1 2 Bachmann G, Bancroft J, Braunstein G, Burger H, Davis S, Dennerstein L, et al. (April 2002). "Female androgen insufficiency: the Princeton consensus statement on definition, classification, and assessment". Fertility and Sterility. 77 (4): 660–665. doi: 10.1016/S0015-0282(02)02969-2 . PMID   11937111.
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  10. 1 2 3 4 5 Bhasin S, Snyder PJ (August 7, 2025). "Testosterone Treatment in Middle-Aged and Older Men with Hypogonadism". New England Journal of Medicine. 393 (6): 581–591. doi:10.1056/NEJMra2404637.
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  13. ↑ Ukwenya VO (2019). "Testosterone propionate ameliorates oxidatve stress and inflammation in nicotine-induced testicular toxicity". Journal of Experimental and Clinical Anatomy. 18 (1): 74–78. doi: 10.4103/jeca.jeca_10_19 . S2CID   208531742.
  14. ↑ Morales A, Bella AJ, Chun S, Lee J, Assimakopoulos P, Bebb R, et al. (August 2010). "A practical guide to diagnosis, management and treatment of testosterone deficiency for Canadian physicians". Canadian Urological Association Journal. 4 (4): 269–275. doi:10.5489/cuaj.880. PMC   2910774 . PMID   20694106.
  15. ↑ Morimoto S, Jiménez-Trejo F, Cerbón M (2011). "Sex steroids effects in normal endocrine pancreatic function and diabetes". Current Topics in Medicinal Chemistry. 11 (13): 1728–1735. doi:10.2174/156802611796117540. PMID   21463250.
  16. ↑ Basaria S (April 2014). "Male hypogonadism". Lancet. 383 (9924): 1250–1263. doi:10.1016/S0140-6736(13)61126-5. PMID   24119423. S2CID   30479724.
  17. ↑
  18. ↑ Mohler ER, Ellenberg SS, Lewis CE, Wenger NK, Budoff MJ, Lewis MR, Barrett-Connor E, Swerdloff RS, Stephens-Shields A, Bhasin S, Cauley JA, Crandall JP, Cunningham GR, Ensrud KE, Gill TM, Matsumoto AM, Molitch ME, Pahor M, Preston PE, Hou X, Cifelli D, Snyder PJ (February 1, 2018). "The Effect of Testosterone on Cardiovascular Biomarkers in the Testosterone Trials". The Journal of Clinical Endocrinology & Metabolism. 103 (2): 681–688. doi:10.1210/jc.2017-02243.
  19. ↑ Bhasin S, Lincoff AM, Nissen SE, Wannemuehler K, McDonnell ME, Peters AL, Khan N, Snabes MC, Li X, Li G, Buhr K, Pencina KM, Travison TG (April 1, 2024). "Effect of Testosterone on Progression From Prediabetes to Diabetes in Men With Hypogonadism: A Substudy of the TRAVERSE Randomized Clinical Trial". JAMA Internal Medicine. 184 (4): 353. doi:10.1001/jamainternmed.2023.7862.
  20. 1 2 Davis SR (1999). "The therapeutic use of androgens in women". The Journal of Steroid Biochemistry and Molecular Biology. 69 (1–6): 177–184. doi:10.1016/S0960-0760(99)00054-0. PMID   10418991. S2CID   23520067.
  21. 1 2 Staff (March 3, 2015). "Testosterone Products: Drug Safety Communication - FDA Cautions About Using Testosterone Products for Low Testosterone Due to Aging; Requires Labeling Change to Inform of Possible Increased Risk of Heart Attack And Stroke". FDA . Archived from the original on March 5, 2015. Retrieved March 5, 2015.
  22. 1 2 Staff (January 31, 2014). "FDA evaluating risk of stroke, heart attack and death with FDA-approved testosterone products" (PDF). U.S. Food and Drug Administration. Archived from the original (PDF) on February 15, 2014. Retrieved September 17, 2014.
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  45. ↑ Caminiti G, Volterrani M, Iellamo F, Marazzi G, Massaro R, Miceli M, et al. (September 2009). "Effect of long-acting testosterone treatment on functional exercise capacity, skeletal muscle performance, insulin resistance, and baroreflex sensitivity in elderly patients with chronic heart failure a double-blind, placebo-controlled, randomized study". Journal of the American College of Cardiology. 54 (10): 919–927. doi: 10.1016/j.jacc.2009.04.078 . PMID   19712802.
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