Androgen replacement therapy

{{Short description|Form of hormone therapy}} {{cs1 config|name-list-style=vanc}} {{About|Testosterone Replacement Therapy for cisgender people|transgender applications|Masculinizing hormone therapy}} {{Use mdy dates|date=August 2015}} {{Infobox medical intervention  | image = | caption = | alt = | pronounce = | synonyms = Androgen replacement therapy | ICD10 = | ICD9 = | ICD9unlinked = | MeshID = | LOINC = | other_codes = | MedlinePlus = | eMedicine = }}

'''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.

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.<ref name= "mayo" >{{cite web |year=2012 |title=Testosterone therapy: Key to male vitality? |url=http://www.mayoclinic.com/health/testosterone-therapy/MC00030 | publisher = Mayo Foundation for Medical Education and Research (MFMER) }}</ref><ref name="Sood_2023">{{cite journal | vauthors = Sood A, Hosseinpour A, Sood A, Avula S, Durrani J, Bhatia V, Gupta R | title = Cardiovascular Outcomes of Hypogonadal Men Receiving Testosterone Replacement Therapy: A Meta-analysis of Randomized Controlled Trials | journal = Endocrine Practice | volume = 30| issue = 1| date = October 2023 | pages = 2–10 | pmid = 37797887 | doi = 10.1016/j.eprac.2023.09.012 | s2cid = 263692728 }}</ref><ref name="pmid36181480">{{cite journal | vauthors = Valderrábano RJ, Pencina K, Storer TW, Reid KF, Kibel AS, Burnett AL, Huang G, Dorff T, Privat F, Ghattas-Puylara C, Wilson L, Latham NK, Holmberg M, Bhasin S | display-authors = 6 | title = Testosterone replacement in prostate cancer survivors with testosterone deficiency: Study protocol of a randomized controlled trial | journal = Andrology | volume = 11 | issue = 1 | pages = 93–102 | date = January 2023 | pmid = 36181480 | doi = 10.1111/andr.13299 | pmc = 9771994 }}</ref><ref name="pmid37889486">{{cite journal | vauthors = Pencina KM, Travison TG, Artz AS, Lincoff AM, Nissen SE, Flevaris P, Chan A, Li X, Diegel SA, Wannemuehler K, Bhasin S | display-authors = 6 | title = Efficacy of Testosterone Replacement Therapy in Correcting Anemia in Men With Hypogonadism: A Randomized Clinical Trial | journal = JAMA Network Open | volume = 6 | issue = 10 | pages = e2340030 | date = October 2023 | pmid = 37889486 | pmc = 10611996 | doi = 10.1001/jamanetworkopen.2023.40030 }}</ref><ref name="pmid37177884">{{cite journal | vauthors = Christensen LL, Poulsen HE, Andersen MS, Glintborg D | title = Whole-body oxidative stress reduction during testosterone therapy in aging men: A randomized placebo-controlled trial | journal = Andrology | volume = 12 | issue = 1 | pages = 115–122 | date = January 2024 | pmid = 37177884 | doi = 10.1111/andr.13458 | doi-access = free }}</ref><ref name="pmid35791295">{{cite journal | vauthors = Diaz P, Reddy R, Blachman-Braun R, Zucker I, Dullea A, Gonzalez DC, Kresch E, Ramasamy R | display-authors = 6 | title = Comparison of Intratesticular Testosterone between Men Receiving Nasal, Intramuscular, and Subcutaneous Pellet Testosterone Therapy: Evaluation of Data from Two Single-Center Randomized Clinical Trials | journal = The World Journal of Men's Health | volume = 41 | issue = 2 | pages = 390–395 | date = April 2023 | pmid = 35791295 | pmc = 10042650 | doi = 10.5534/wjmh.210261 }}</ref><ref name="pmid31928918">{{cite journal | vauthors = Corona G, Torres LO, Maggi M | title = Testosterone Therapy: What We Have Learned From Trials | journal = The Journal of Sexual Medicine | volume = 17 | issue = 3 | pages = 447–460 | date = March 2020 | pmid = 31928918 | doi = 10.1016/j.jsxm.2019.11.270 | s2cid = 210191244 | hdl = 2158/1192573 | hdl-access = free }}</ref>

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.<ref name="fem2001">{{cite journal | vauthors = Bachmann G, Bancroft J, Braunstein G, Burger H, Davis S, Dennerstein L, Goldstein I, Guay A, Leiblum S, Lobo R, Notelovitz M, Rosen R, Sarrel P, Sherwin B, Simon J, Simpson E, Shifren J, Spark R, Traish A | display-authors = 6 | title = Female androgen insufficiency: the Princeton consensus statement on definition, classification, and assessment | journal = Fertility and Sterility | volume = 77 | issue = 4 | pages = 660–665 | date = April 2002 | pmid = 11937111 | doi = 10.1016/S0015-0282(02)02969-2 | doi-access = free }}</ref> 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.<ref name="menopause">{{cite journal | vauthors = Sarrel PM | title = Androgen deficiency: menopause and estrogen-related factors | journal = Fertility and Sterility | volume = 77 | pages = S63–S67 | date = April 2002 | issue = Suppl 4 | pmid = 12007905 | doi = 10.1016/S0015-0282(02)02967-9 | doi-access = free }}</ref>

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.<ref name="Bhasin 2025">{{cite journal |last1=Bhasin |first1=Shalender |last2=Snyder |first2=Peter J. |title=Testosterone Treatment in Middle-Aged and Older Men with Hypogonadism |journal=New England Journal of Medicine |date=7 August 2025 |volume=393 |issue=6 |pages=581–591 |doi=10.1056/NEJMra2404637}}</ref>

==Medical uses== {{See also|Testosterone (medication)}}

===Males=== Androgen replacement is the classic treatment of hypogonadism.<ref>{{cite journal | vauthors = Kang DY, Li HJ | title = The effect of testosterone replacement therapy on prostate-specific antigen (PSA) levels in men being treated for hypogonadism: a systematic review and meta-analysis | journal = Medicine | volume = 94 | issue = 3 | article-number = e410 | date = January 2015 | pmid = 25621688 | pmc = 4602637 | doi = 10.1097/MD.0000000000000410 }}</ref> It is also used in men who have lost the ability to produce androgens due to disease or its treatment.<ref>{{cite journal | vauthors = Giwercman A, Lundberg Giwercman Y | title = Hypogonadism in young men treated for cancer | journal = Hormones | volume = 14 | issue = 4 | pages = 590–597 | date = 2015 | pmid = 26859600 | doi = 10.14310/horm.2002.1650 | doi-access = free }} {{open access}}</ref><ref>{{cite journal| vauthors = Ukwenya VO |title=Testosterone propionate ameliorates oxidatve stress and inflammation in nicotine-induced testicular toxicity.|journal=Journal of Experimental and Clinical Anatomy|date= 2019|volume=18|issue=1|pages=74–78|doi=10.4103/jeca.jeca_10_19|s2cid=208531742 |doi-access=free }}</ref> Testosterone replacement in men with hypogonadism has consistently shown to improve sexual function; including increases in libido and sexual activity.<ref name="Bhasin 2025" /> Erectile function was also shown to modestly improve in some studies of testosterone treatment for male hypogonadism, other studies did not show a benefit.<ref name="Bhasin 2025" /> Testosterone treatment in men with hypogonadism was shown to have modest improvements in physical activity, modest improvements in mood (but it did not improve mood in those with major depression), and some studies showed modest improvements in subjective energy levels and self reported physical fitness.<ref name="Bhasin 2025" /> Testosterone therapy was not shown to improve cognitive function in men with hypogonadism.<ref name="Bhasin 2025" /> Testosterone therapy was also shown to raise the hemoglobin (blood count) by 1 point in 33-50% of people, and increase bone density by up to 7% in the spine and hip, but the clinical significance of these changes is unclear.<ref name="Bhasin 2025" />

{{Androgen replacement therapy formulations and dosages used in men}}

====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.<ref>{{cite journal | vauthors = Morales A, Bella AJ, Chun S, Lee J, Assimakopoulos P, Bebb R, Gottesman I, Alarie P, Dugré H, Elliott S | display-authors = 6 | title = A practical guide to diagnosis, management and treatment of testosterone deficiency for Canadian physicians | journal = Canadian Urological Association Journal | volume = 4 | issue = 4 | pages = 269–275 | date = August 2010 | pmid = 20694106 | pmc = 2910774 | doi = 10.5489/cuaj.880 }}</ref><ref>{{cite journal | vauthors = Morimoto S, Jiménez-Trejo F, Cerbón M | title = Sex steroids effects in normal endocrine pancreatic function and diabetes | journal = Current Topics in Medicinal Chemistry | volume = 11 | issue = 13 | pages = 1728–1735 | year = 2011 | pmid = 21463250 | doi = 10.2174/156802611796117540 }}</ref> 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."<ref>{{cite journal | vauthors = Basaria S | title = Male hypogonadism | journal = Lancet | volume = 383 | issue = 9924 | pages = 1250–1263 | date = April 2014 | pmid = 24119423 | doi = 10.1016/S0140-6736(13)61126-5 | s2cid = 30479724 }}</ref>

Other studies have not shown a benefit in diabetes prevention or better diabetes control with testosterone therapy.<ref name="Bhasin 2025" /> 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.<ref name="Mohler 2018">{{cite journal |last1=Mohler |first1=Emile R |last2=Ellenberg |first2=Susan S |last3=Lewis |first3=Cora E |last4=Wenger |first4=Nanette K |last5=Budoff |first5=Matthew J |last6=Lewis |first6=Michael R |last7=Barrett-Connor |first7=Elizabeth |last8=Swerdloff |first8=Ronald S |last9=Stephens-Shields |first9=Alisa |last10=Bhasin |first10=Shalender |last11=Cauley |first11=Jane A |last12=Crandall |first12=Jill P |last13=Cunningham |first13=Glenn R |last14=Ensrud |first14=Kristine E |last15=Gill |first15=Thomas M |last16=Matsumoto |first16=Alvin M |last17=Molitch |first17=Mark E |last18=Pahor |first18=Marco |last19=Preston |first19=Peter E |last20=Hou |first20=Xiaoling |last21=Cifelli |first21=Denise |last22=Snyder |first22=Peter J |title=The Effect of Testosterone on Cardiovascular Biomarkers in the Testosterone Trials |journal=The Journal of Clinical Endocrinology & Metabolism |date=1 February 2018 |volume=103 |issue=2 |pages=681–688 |doi=10.1210/jc.2017-02243|pmc=5800829 }}</ref> 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.<ref name="S Bhasin 2024">{{cite journal |last1=Bhasin |first1=Shalender |last2=Lincoff |first2=A. Michael |last3=Nissen |first3=Steven E. |last4=Wannemuehler |first4=Kathleen |last5=McDonnell |first5=Marie E. |last6=Peters |first6=Anne L. |last7=Khan |first7=Nader |last8=Snabes |first8=Michael C. |last9=Li |first9=Xue |last10=Li |first10=Geng |last11=Buhr |first11=Kevin |last12=Pencina |first12=Karol M. |last13=Travison |first13=Thomas G. |title=Effect of Testosterone on Progression From Prediabetes to Diabetes in Men With Hypogonadism: A Substudy of the TRAVERSE Randomized Clinical Trial |journal=JAMA Internal Medicine |date=1 April 2024 |volume=184 |issue=4 |page=353 |doi=10.1001/jamainternmed.2023.7862|pmc=10845044 }}</ref>

===Females=== Androgen replacement is used in postmenopausal women: the indications are to increase sexual desire; and to prevent or treat osteoporosis.<ref name="pmid10418991">{{cite journal | vauthors = Davis SR | title = The therapeutic use of androgens in women | journal = The Journal of Steroid Biochemistry and Molecular Biology | volume = 69 | issue = 1–6 | pages = 177–184 | date = 1999 | pmid = 10418991 | doi = 10.1016/S0960-0760(99)00054-0 | s2cid = 23520067 }}</ref> Other symptoms of androgen deficiency are similar in both sexes, such as muscle loss and physical fatigue.<ref name="fem2001"/> 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.<ref name="pmid10418991"/>

{{Androgen replacement therapy formulations and dosages used in women}}

==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.<ref name=FDA2015>{{cite web |author=Staff |title=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 |url=https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm436280.htm |archive-url=https://web.archive.org/web/20150305015556/http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm436280.htm |archive-date=March 5, 2015 |date=March 3, 2015 |work=FDA |access-date=March 5, 2015 }}</ref> The FDA has required that testosterone labels include warning information about the possibility of an increased risk of heart attacks and stroke.<ref name=FDA2015/>

In February 2025, the FDA removed the black box warning on prescription testosterone products regarding increased risk of adverse cardiovascular outcomes, following the results of the TRAVERSE trial which demonstrated no increased risk compared to placebo in men with hypogonadism. The FDA now requires labeling to include TRAVERSE trial data, and continues to monitor other potential risks such as increased blood pressure.<ref name="FDA2025">{{cite web|url=https://www.fda.gov/drugs/drug-safety-and-availability/fda-issues-class-wide-labeling-changes-testosterone-products|title=FDA issues class-wide labeling changes for testosterone products |date=28 February 2025|website=U.S. Food and Drug Administration|accessdate=8 October 2025}}</ref>

===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.<ref name="FDA-20140131" /> The FDA's action followed three peer-reviewed studies of increased cardiovascular events and deaths.<ref>{{cite journal | vauthors = Finkle WD, Greenland S, Ridgeway GK, Adams JL, Frasco MA, Cook MB, Fraumeni JF, Hoover RN | display-authors = 6 | title = Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men | journal = PLOS ONE | volume = 9 | issue = 1 | article-number = e85805 | date = January 2014 | pmid = 24489673 | pmc = 3905977 | doi = 10.1371/journal.pone.0085805 | doi-access = free | bibcode = 2014PLoSO...985805F }}</ref> Due to an increased rate of adverse cardiovascular events compared to a placebo group, a randomized trial stopped early.<ref>{{cite journal | vauthors = Basaria S, Coviello AD, Travison TG, Storer TW, Farwell WR, Jette AM, Eder R, Tennstedt S, Ulloor J, Zhang A, Choong K, Lakshman KM, Mazer NA, Miciek R, Krasnoff J, Elmi A, Knapp PE, Brooks B, Appleman E, Aggarwal S, Bhasin G, Hede-Brierley L, Bhatia A, Collins L, LeBrasseur N, Fiore LD, Bhasin S | display-authors = 6 | title = Adverse events associated with testosterone administration | journal = The New England Journal of Medicine | volume = 363 | issue = 2 | pages = 109–122 | date = July 2010 | pmid = 20592293 | pmc = 3440621 | doi = 10.1056/NEJMoa1000485 }}</ref> Also, in November 2013, a study reported an increase in deaths and heart attacks in older men.<ref>{{cite journal | vauthors = Vigen R, O'Donnell CI, Barón AE, Grunwald GK, Maddox TM, Bradley SM, Barqawi A, Woning G, Wierman ME, Plomondon ME, Rumsfeld JS, Ho PM | display-authors = 6 | title = Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels | journal = JAMA | volume = 310 | issue = 17 | pages = 1829–1836 | date = November 2013 | pmid = 24193080 | doi = 10.1001/jama.2013.280386 | doi-access = }}</ref> Concerns have been raised that testosterone was being widely marketed without the benefit of data on efficacy and safety from large randomized controlled trials.<ref name="PH-20140305">{{cite web | vauthors = McCullough M |title=As testosterone use grows, questions on risks await answers |url=http://articles.philly.com/2014-04-04/news/48838961_1_testosterone-low-t-male-hormone-replacement |archive-url=https://web.archive.org/web/20140407050949/http://articles.philly.com/2014-04-04/news/48838961_1_testosterone-low-t-male-hormone-replacement |archive-date=April 7, 2014 |date=April 4, 2014 |work=Philly.com |access-date=March 19, 2015 }}</ref> 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.<ref name="NYT-20140917">{{cite news | vauthors = Tavernise S |title=F.D.A. Panel Backs Limits on Testosterone Drugs |url=https://www.nytimes.com/2014/09/18/health/testosterone-drugs-fda.html |date=September 17, 2014 |work=The New York Times |access-date=September 18, 2014 }}</ref><ref name="CNN-20140905">{{cite news |author=Staff |title=FDA Panel To Review Testosterone Therapy Appropriateness and Safety |url=http://ireport.cnn.com/docs/DOC-1167887 |date=September 5, 2014 |work=CNN News |access-date=September 14, 2014 |archive-url=https://web.archive.org/web/20160304062101/http://ireport.cnn.com/docs/DOC-1167887 |archive-date=March 4, 2016 }}</ref><ref name="FDA-20140903">{{cite web |author=Staff |title=Joint Meeting for Bone, Reproductive and Urologic Drugs Advisory Committee (BRUDAC) and the Drug Safety And Risk Management Advisory Committee (DSARM AC) - FDA background documents for the discussion of two major issues in testosterone replacement therapy (TRT): 1. The appropriate indicated population for TRT, and 2. The potential for adverse cardiovascular outcomes associated with use of TRT |url=https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/ReproductiveHealthDrugsAdvisoryCommittee/UCM412536.pdf |archive-url=https://web.archive.org/web/20140906043632/http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/ReproductiveHealthDrugsAdvisoryCommittee/UCM412536.pdf |archive-date=September 6, 2014 |date=September 17, 2014 |work=Food and Drug Administration |access-date=September 14, 2014 }}</ref> However, when given to men with hypogonadism in the short- and medium-term (over a median of 33 months in the TRAVERSE trial), testosterone replacement therapy does not increase the risk of cardiovascular events (including strokes and heart attacks).<ref name="Bhasin 2025" /><ref name="Bhasin 2022">{{cite journal |last1=Bhasin |first1=Shalender |last2=Lincoff |first2=A. Michael |last3=Basaria |first3=Shehzad |title=Effects of long-term testosterone treatment on cardiovascular outcomes in men with hypogonadism: Rationale and design of the TRAVERSE study |journal=American Heart Journal |date=March 2022 |volume=245 |pages=41–50 |doi=10.1016/j.ahj.2021.11.016|doi-access=free }}</ref><ref name="Sood_2023" /> The long-term safety of the therapy is not known yet.<ref>{{Cite journal |date=6 February 2023 |title=Research provides reassurance about the safety of testosterone treatment |url=https://evidence.nihr.ac.uk/alert/research-provides-reassurance-about-safety-testosterone-treatment/ |journal=NIHR Evidence |type=Plain English summary |publisher=National Institute for Health and Care Research|doi=10.3310/nihrevidence_56696 |s2cid=257851823 |url-access=subscription |doi-access=free }}</ref><ref>{{cite journal | vauthors = Hudson J, Cruickshank M, Quinton R, Aucott L, Aceves-Martins M, Gillies K, Bhasin S, Snyder PJ, Ellenberg SS, Grossmann M, Travison TG, Gianatti EJ, van der Schouw YT, Emmelot-Vonk MH, Giltay EJ, Hackett G, Ramachandran S, Svartberg J, Hildreth KL, Groti Antonic K, Brock GB, Tenover JL, Tan HM, Kong CH, Tan WS, Marks LS, Ross RJ, Schwartz RS, Manson P, Roberts S, Andersen MS, Magnussen LV, Hernández R, Oliver N, Wu F, Dhillo WS, Bhattacharya S, Brazzelli M, Jayasena CN | display-authors = 6 | title = Adverse cardiovascular events and mortality in men during testosterone treatment: an individual patient and aggregate data meta-analysis | journal = The Lancet. Healthy Longevity | volume = 3 | issue = 6 | pages = e381–e393 | date = June 2022 | pmid = 35711614 | pmc = 9184259 | doi = 10.1016/S2666-7568(22)00096-4 }}</ref>

===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> 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.{{Citation needed|date=September 2025}}

Some studies suggest 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 | url-access = subscription }}</ref> This may be due to many men with risk factors for prostate cancer being excluded from testosterone replacement studies.<ref name="Bhasin 2025" /> 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.<ref name="Bhasin 2025" />

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.<ref name="Bhasin 2025" /> 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.<ref name="Bhasin 2025" />

==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.<ref name="FDA-20140131">{{cite web |author=Staff |title=FDA evaluating risk of stroke, heart attack and death with FDA-approved testosterone products |url=https://www.fda.gov/downloads/Drugs/DrugSafety/UCM383909.pdf |archive-url=https://web.archive.org/web/20140215045935/http://www.fda.gov/downloads/Drugs/DrugSafety/UCM383909.pdf |archive-date=February 15, 2014 |publisher=U.S. Food and Drug Administration |date=January 31, 2014 |access-date=September 17, 2014 }}</ref>

==Society and culture==

===MMA=== Some UFC fighters used TRT until 2014 when the Nevada State Athletic Commission banned its use.<ref name="AP News">{{cite web |title=Nevada commission bans testosterone replacement |url=https://apnews.com/article/bfbd566f68c6468490b223b2cb0afe6f |website=AP News |date=27 February 2014}}</ref>

===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".<ref name="NYT-20140917" /><ref name="CNN-20140905" /><ref name="FDA-20140903" />

===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.<ref>{{cite journal | vauthors = Baillargeon J, Kuo YF, Westra JR, Urban RJ, Goodwin JS | title = Testosterone Prescribing in the United States, 2002-2016 | journal = JAMA | volume = 320 | issue = 2 | pages = 200–202 | date = July 2018 | pmid = 29998328 | pmc = 6396809 | doi = 10.1001/jama.2018.7999 }}</ref>

A UK study in 2013 showed that prescriptions for testosterone replacement, particularly transdermal products, almost doubled between 2000 and 2010.<ref>{{cite journal | vauthors = Gan EH, Pattman S, Pearce HS, Quinton R | title = A UK epidemic of testosterone prescribing, 2001-2010 | journal = Clinical Endocrinology | volume = 79 | issue = 4 | pages = 564–570 | date = October 2013 | pmid = 23480258 | doi = 10.1111/cen.12178 | s2cid = 4952458 | url = https://eprint.ncl.ac.uk/fulltext.aspx?url=191970/48129080-E74C-433C-A3CD-1006D2FB2DAA.pdf&pub_id=191970 }}</ref>

==Research== Testosterone is being investigated as therapy for the following conditions: * Erectile dysfunction<ref name="ReferenceA">{{cite journal | vauthors = Walther A, Mahler F, Debelak R, Ehlert U | title = Psychobiological Protective Factors Modifying the Association Between Age and Sexual Health in Men: Findings From the Men's Health 40+ Study | journal = American Journal of Men's Health | volume = 11 | issue = 3 | pages = 737–747 | date = May 2017 | pmid = 28413941 | pmc = 5675228 | doi = 10.1177/1557988316689238 }}</ref><ref name="ReferenceB">{{cite journal | vauthors = Finkelstein JS, Lee H, Leder BZ, Burnett-Bowie SA, Goldstein DW, Hahn CW, Hirsch SC, Linker A, Perros N, Servais AB, Taylor AP, Webb ML, Youngner JM, Yu EW | display-authors = 6 | title = Gonadal steroid-dependent effects on bone turnover and bone mineral density in men | journal = The Journal of Clinical Investigation | volume = 126 | issue = 3 | pages = 1114–1125 | date = March 2016 | pmid = 26901812 | pmc = 4767351 | doi = 10.1172/JCI84137 }}</ref> * Osteoporosis<ref name="pmid19535658">{{cite journal | vauthors = Farley JF, Blalock SJ | title = Trends and determinants of prescription medication use for treatment of osteoporosis | journal = American Journal of Health-System Pharmacy | volume = 66 | issue = 13 | pages = 1191–1201 | date = July 2009 | pmid = 19535658 | doi = 10.2146/ajhp080248 }}</ref> * Diabetes mellitus<ref name="pmid18772488">{{cite journal | vauthors = Traish AM, Saad F, Guay A | title = The dark side of testosterone deficiency: II. Type 2 diabetes and insulin resistance | journal = Journal of Andrology | volume = 30 | issue = 1 | pages = 23–32 | year = 2009 | pmid = 18772488 | doi = 10.2164/jandrol.108.005751 | s2cid = 29463129 }}</ref><ref>{{cite journal | vauthors = Boyanov MA, Boneva Z, Christov VG | title = Testosterone supplementation in men with type 2 diabetes, visceral obesity and partial androgen deficiency | journal = The Aging Male | volume = 6 | issue = 1 | pages = 1–7 | date = March 2003 | pmid = 12809074 | doi = 10.1080/tam.6.1.1.7 | s2cid = 7328751 | doi-access = free }}</ref> * Chronic heart failure<ref name="pmid19712802">{{cite journal | vauthors = Caminiti G, Volterrani M, Iellamo F, Marazzi G, Massaro R, Miceli M, Mammi C, Piepoli M, Fini M, Rosano GM | display-authors = 6 | title = 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 = Journal of the American College of Cardiology | volume = 54 | issue = 10 | pages = 919–927 | date = September 2009 | pmid = 19712802 | doi = 10.1016/j.jacc.2009.04.078 | doi-access = free }}</ref> * Dementia, but the evidence base is small and the balance of benefit needs to be clarified<ref name="pmid19011295">{{cite journal | vauthors = Cherrier M | title = Testosterone effects on cognition in health and disease | journal = Frontiers of Hormone Research | volume = 37 | pages = 150–162 | year = 2009 | pmid = 19011295 | doi = 10.1159/000176051 | isbn = 978-3-8055-8622-1 }}</ref>

== References == {{Reflist}}

Category:Endocrine procedures Category:Androgens Category:Medical treatments