Contents

Search

testosterone replacement therapy; androgen therapy

Indications: 1) primary or secondary hypogonadism caused by specific, well-recognized medical conditions in males [30] - Klinefelter's syndrome - hypopituitarism - testicular trauma or injury 2) andropause a) prophylaxis for Alzheimer's disease? [2] (see testosterone & risk of Alzheimer's disease) b) depression? [3] - see testosterone & risk of depression - testosterone associated with a statistically significant but clinically small reduction in depressive symptoms vs placebo - effects greater with higher testosterone doses [45] - testerone improves mood [54] c) osteoporosis [4] - increased bone mineral density & bone strenth at hip & spine in elderly men [39] - see testosterone & risk of osteoporosis d) improves anemia in elderly men - increases blood hemoglobin by 1 g/dL [39] e) recommended for symptomatic men only [13] f) modest improvement in sexual function (0.6 in a 12 point scale) in men > 65 years [31,48] - affects sexual desire & sexual function in some older men with total serum testosterone levels < 275 ng/dL [37] - testosterone improves libido [54] - less effective than phosphodiesterase 5 inhibitors for erectile dysfunction [37] - clinical importance for most patients is unclear [37] g) statistically significant improvement for several measures of muscle performance of uncertain significance [40] h) corrects anemia in elderly men with hypogonadism slightly more often than placebo [51] i) lack of substantial evidence to support its use [30] 3) diminished libido in women* (not FDA-approved use) [8,9,24] * low-dose used for women (Intrinsa, Estratest) * serum testosterone < 100 ng/mL (200 mg/dL [15]) (8 AM) a) 2 8 AM serum testosterone measurements [15] b) free testosterone* in obese patients - total serum testosterone may be affected by a decrease in plasma sex hormone binding globulin (SHBG) [1] c) serum testosterone > 350 mg/dL excludes hypogonadism [1] Contraindications: 1) men a) prostate cancer - avoid in men at high risk of prostate cancer [52] b) severe BPH - palpable prostate abnormalities - obstructive uropathy c) PSA > 3.0 ng/mL d) hematocrit > 50% e) untreated obstructive sleep apnea (may exacerbate) [49] f) severe heart failure g) cirrhosis h) avoid use for improving vitality, energy levels, physical function or cognition i) absence of biochemical evidence of testosterone deficiency [15] j) avoid in men planning for fertility (impairs spermatogenesis) [15] k) does not improve glycemic control in men with diabetes mellitus or prediabetes [55] 2) women [24] a) infertility b) promotion ofcardiovascular health, c) low androgen levels due to hypopituitarism, adrenal insufficiency, or surgical menopause d) DHEA is not recommended [24] 3) inappropriate or ineffective uses - does not improve ejaculation or orgasm (men) [29] - ineffective for age-related hypogonadism [46] - has not been shown to prevent osteoporotic fractures [7] - does not improve sexual dysfunction in men with type 2 diabetes & mildly low testosterone levels [25] - does not improve memory or cognition in cognitively- impaired elderly men [39] - decreased energy, decreased strength, low libido, erectile dysfunction, mood disorders, sleep disorders, poor memory [42] Epidemiology: - 40% of men > 45 years of age [10] - treatment without testing & for ill-defined symptoms common [22] - prescription for age-related hypogonadism common [46] Dosage: 1) testosterone enanthate 125 mg IM weekly is optimal dose [10] 2) transdermal patch 5 mg/day of no benefit to elderly men [11] 3) testosterone undecenoate 80 mg PO BID not effective [14] - does not increase serum testosterone, free testosterone, or bioavailable testosterone 4) transdermal gel a) 50 mg/day doubles serum testosterone [16] b) advantages: 1] steady level of testosterone within 30 minutes of application [15] 2] invisibility of gel c) disadvantages: 1] need to apply daily 2] cost 3] risk of absorption by others who come in contact with the gel [15] Monitor: 1) prior to therapy, & at 3, 6 & 12 months 2) monitor at least annually thereafter 3) monitor a) serum lipid levels, initially & repeat with other lab testing if abnormal b) serum PSA & symptoms of BPH - alert when serum PSA increases by > 0.4 ng/mL within the 1st 6 months of use or > 1.4 ng/mL annually [15] c) hematocrit (keep < 54%) [7,15] d) serum testosterone (total) - free testosterone if total serum testosterone abnormal - goal: serum testosterone (or free testosterone) in mid-normal range [15] low-normal range (400-500 ng/dL) [7] e) symptoms of sleep apnea Adverse effects: - see testosterone - not associated with increased risks of myocardial infarction, stroke, or cardiovascular death (Androgen Society) [58] - testosterone gel use by older men with mobility problems may increase cardiovascular risk [18,20] - use of testerone gel appears to be safe for middle-age & older men over a period of 2 years [50] - testosterone may increase risk of myocardial infarction in men [21] - possible increased risk of myocardial infarction & stroke [28] - increases non-calcified coronary atherosclerosis [39] - short therapy durations (median, 2 months) associated with increased risk for 5 year mortality (RR=1.11) & cardiovascular events (RR=1.26) [34] - longer therapy durations (median, 35 months) associated with diminished risk for 5 year mortality (RR=0.67) & cardiovascular events (RR=0.84) [34] - diminishes risk of cardiovascular events in elerly men with androgen deficiency 17 vs 24 per 1000 person-years [39] - no increased risk of prostate cancer [26,27,52] - lower risk for prostate cancer diagnosis [34] - avoid in men at high-risk of prostate cancer [52] - oligospermia & infertility [15,32]* - exogenous testosterone may result in irreversible decline in spermatogenesis, infertility & permanent inability to produce endogenous testosterone - assess desire for fertility prior to initiation of testosterone replacement therapy [15,32] - increased risk of venous thromboembolism during 1st 6 months of therapy (RR=1.63) [38,47] - fluctuation in mood & libido most common with IM testosterone [49] - increased risk of fractures 3.5% vs 2.5% [53] - incidents of major osteoporotic fracture too low to assess risk by fracture site [53] Mechanism of action: - prevents deterioration in muscle strength - improves sexual desire, & erectile function [56] - may increase walking distance in less impaired elderly [56] - does not increase energy [56] - slightly improves mood & depressive symptoms [56] - does not improve cognitive function [56,57] - increases blood hemoglobin [56] - increases bone mineral density [56] (no reduction in fractures) - mixed results on cardiovascular risk [56] - not associated with increased risk of prostate cancer [56] - improves symptom-related quality of life [16]* - does not improve self-reported function, fatigue or walking speed [19] * editorialist notes results mixed, endorsement overly enthusiastic [16] Notes: - testosterone television advertisement has led to increased testing & initiation of therapy [41]

Related

testosterone (Delatestryl Testopel, Striant, Intrinsa, Xyosted)

General

hormonal therapy

References

  1. Journal Watch 24(6):48, 2004 Institute of Medicine, Testosterone & Aging: Clinical Research Directions http://books.nap.edu/execsumm_pdf/10852.pdf
  2. Moffat SD et al, Neurology 62:188, 2004 PMID: 14745052
  3. Shores MM et al, Arch Gen Psychiatry 61:162, 2004 PMID: 14757592
  4. Amory JK et al, J Clin Endocrinol Metab 89:503, 2004 PMID: 14764753
  5. Wang C et al, J Clin Endocrinol Metab 89:534, 2004 PMID: 14764758
  6. Rhoden EL & Morgentaler A, N Engl J Med 350:482, 2004 PMID: 14749457
  7. Geriatrics Review Syllabus, American Geriatrics Society, 5th edition, 2002-2004 - Geriatric Review Syllabus, 8th edition (GRS8) Durso SC and Sullivan GN (eds) American Geriatrics Society, 2013 - Geriatric Review Syllabus, 11th edition (GRS11) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2022
  8. Prescriber's Letter 12(1): 2005 Testosterone Replacement for Women; an Update Detail-Document#: 210112 (subscription needed) http://www.prescribersletter.com
  9. Journal Watch 25(12):93-94, 2005 Buster JE, Kingsberg SA, Aguirre O, Brown C, Breaux JG, Buch A, Rodenberg CA, Wekselman K, Casson P. Testosterone patch for low sexual desire in surgically menopausal women: a randomized trial. Obstet Gynecol. 2005 May;105(5 Pt 1):944-52. PMID: 15863529
  10. Internal Medicine News, July 2005, pg 1,22
  11. Nair KS et al DHEA in elderly women and DHEA or testosterone in elderly men. N Engl J Med 2006 Oct 19; 355:1647-59 PMID: 17050889 - Stewart PM. Aging and fountain-of-youth hormones. N Engl J Med 2006 Oct 19; 355:1724-6 PMID: 17050897
  12. Guidelines on testosterone therapy in adult men with androgen deficiency syndromes (Endocrine Society) http://www.endo-society.org/quickcontent/clinicalpractice/clinical-guidelines/upload/AndrogensMenGuideline053006.pdf
  13. Bhasin S et al, Testosterone therapy in adult men with androgen deficiency syndromes: An endocrine society clinical practice guideline. J Clin Endocrin Metab 2006; 91:1995 PMID: 16720669 - Bhasin S, Cunningham GR, Hayes FJ et al Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010 Jun;95(6):2536-59 PMID: 20525905 corresponding NGC guideline withdrawn Feb 2016
  14. Emmelot-Vonk MH et al, Effect of testosterone supplementation on functional mobility, cognition, and other parameters in older men: A randomized controlled trial. JAMA 2008, 299:39 PMID: 18167405
  15. Medical Knowledge Self Assessment Program (MKSAP) 15, 16, 17, 18. 19. American College of Physicians, Philadelphia 2009, 2012, 2015, 2018, 2022.
  16. Srinivas-Shankar U et al. Effects of testosterone on muscle strength, physical function, body composition, and quality of life in intermediate-frail and frail elderly men: A randomized, double-blind, placebo- controlled study. J Clin Endocrinol Metab 2010 Feb; 95:639. PMID: 20061435
  17. Prescriber's Letter 18(3): 2011 CHART: Comparison of Testosterone Products COMMENTARY: The Use of Testosterone and the Aging Male GUIDELINES: Testosterone Therapy in Adult Men with Androgen Deficiency Syndromes: An Endocrine Society Clinical Practice Guideline (2010) Detail-Document#: 270301 (subscription needed) http://www.prescribersletter.com
  18. Basaria S et al, Adverse Events Associated with Testosterone Administration N Engl J Med 2010; 363:109-122. PMID: 20592293 - Bremner WJ. Testosterone deficiency and replacement in older men. N Engl J Med 2010; 363:189-191. PMID: 20647215
  19. Travison TG et al Clinical meaningfulness of the changes in muscle performance and physical function associated with testosterone administration in older men with mobility limitation. J Gerontol A Biol Sci Med Sci. 2011 Oct;66(10):1090-9. PMID: 21697501
  20. FDA MedWatch. Jan 31, 2014 Testosterone Products: Drug Safety Communication - FDA Investigating Risk of Cardiovascular Events. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm384225.htm
  21. Finkle WD et al. Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men. PLoS ONE 2014 Jan 29; 9:e85805 PMID: 24489673 http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0085805
  22. Layton JB et al. Testosterone lab testing and initiation in the United Kingdom and the United States, 2000 to 2011. J Clin Endocrinol Metab 2014 Mar; 99:835. PMID: 24423353 http://press.endocrine.org/doi/abs/10.1210/jc.2013-3570
  23. Corona G, Rastrelli G, Forti G, Maggi M. Update in testosterone therapy for men. J Sex Med. 2011 Mar;8(3):639-54; quiz 655. Review. PMID: 21711483
  24. Wierman ME et al Androgen Therapy in Women: A Reappraisal: An Endocrine Society Clinical Practice Guideline. J of Clin Endocrinol& Metabob. 2014 99(10): PMID: 25279570 http://press.endocrine.org/doi/full/10.1210/jc.2014-2
  25. Gianatti EJ et al. Effect of testosterone treatment on constitutional and sexual symptoms in men with type 2 diabetes in a randomized, placebo- controlled clinical trial. J Clin Endocrinol Metab 2014 Oct; 99:3821 PMID: 24978674
  26. Swerdloff R, Anawalt BD Testosterone-Replacement Therapy. N Engl J Med 2014; 371:2032-2034. November 20, 2014 PMID: 25409377 http://www.nejm.org/doi/full/10.1056/NEJMclde1406595
  27. Haider A et al. Incidence of prostate cancer in hypogonadal men receiving testosterone therapy: Observations from 5-year median followup of 3 registries. J Urol 2015 Jan; 193:80 PMID: 24980615
  28. FDA Safety Alert. 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. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm436280.htm
  29. Paduch DA et al. Testosterone replacement in androgen-deficient men with ejaculatory dysfunction: A randomized controlled trial. J Clin Endocrinol Metab 2015 Aug; 100:2956 PMID: 26158605
  30. Nguyen CP, Hirsch MS, Moeny D et al Perspective. Testosterone and "Age-Related Hypogonadism" - FDA Concerns. N Engl J Med 2015; 373:689-691. August 20, 2015 PMID: 26287846 http://www.nejm.org/doi/full/10.1056/NEJMp1506632
  31. Snyder PJ, Bhasin S, Cunningham GR Effects of Testosterone Treatment in Older Men. N Engl J Med 2016; 374:611-624. February 18, 2016 PMID: 26886521 PMCID: PMC5209754 Free PMC article http://www.nejm.org/doi/full/10.1056/NEJMoa1506119 - Orwoll ES. Establishing a framework - does testosterone supplementation help older men? N Engl J Med 2016 Feb 18; 374:682. PMID: 26886526 http://www.nejm.org/doi/full/10.1056/NEJMe1600196
  32. Samplaski MK, Loai Y, Wong K et al Testosterone use in the male infertility population: prescribing patterns and effects on semen and hormonal parameters. Fertil Steril. 2014 Jan;101(1):64-9. PMID: 24094422
  33. Fernandez-Balsells MM, Murad MH, Lane M et al Clinical review 1: Adverse effects of testosterone therapy in adult men: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2010 Jun;95(6):2560-75. Review. PMID: 20525906
  34. Wallis CJ, Lo K, Lee Y et al Survival and cardiovascular events in men treated with testosterone replacement therapy: an intention-to-treat observational cohort study. Lancet Diabetes & Endocrinology. May 7, 2016 PMID: 27165609 http://www.thelancet.com/journals/landia/article/PIIS2213-8587%2816%2900112-1/abstract - Lauer MS Testosterone replacement therapy: intent matters. Lancet Diabetes & Endocrinology. May 7, 2016 PMID: 27165608 http://www.thelancet.com/journals/landia/article/PIIS2213-8587%2816%2930008-0/abstract
  35. Corona G, Rastrelli G, Maseroli E et al Low testosterone syndrome protects subjects with high cardiovascular risk burden from major adverse cardiovascular events. Andrology. 2014 Sep;2(5):741-7. PMID: 25044637 Free Article
  36. Vigen R et al Association of Testosterone Therapy With Mortality, Myocardial Infarction, and Stroke in Men With Low Testosterone Levels. JAMA. 2013;310(17):1829-1836 PMID: 24193080 http://jama.jamanetwork.com/article.aspx?articleid=1764051 - Cappola AR Testosterone Therapy and Risk of Cardiovascular Disease in Men JAMA. 2013;310(17):1805-1806 PMID: 24193077 http://jama.jamanetwork.com/article.aspx?articleid=1764030
  37. Cunningham GR, Stephens-Shields AJ, Rosen RC et al. Testosterone treatment and sexual function in older men with low testosterone levels. J Clin Endocrinol Metab 2016 Aug; 101:3096. PMID: 27355400
  38. Martinez C, Suissa S, Rietbrock S et al Testosterone treatment and risk of venous thromboembolism: population based case-control study. BMJ 2016;355:i5968 PMID: 27903495 http://www.bmj.com/content/355/bmj.i5968
  39. Budoff MJ, Ellenberg SS, Lewis CE et al Testosterone Treatment and Coronary Artery Plaque Volume in Older Men With Low Testosterone. JAMA. 2017;317(7):708-716 PMID: 28241355 http://jamanetwork.com/journals/jama/fullarticle/2603929 - Resnick SM, Matsumoto AM, Stephens-Shields AJ et al Testosterone Treatment and Cognitive Function in Older Men With Low Testosterone and Age-Associated Memory Impairment. JAMA. 2017;317(7):717-727 PMID: 28241356 http://jamanetwork.com/journals/jama/fullarticle/2603930 - Handelsman DJ Testosterone and Male Aging. Faltering Hope for Rejuvenation. JAMA. 2017;317(7):699-701 PMID: 28241336 http://jamanetwork.com/journals/jama/article-abstract/2603909 - Snyder PJ, Kopperdahl DL, Stephens-Shields AJ et al Effect of Testosterone Treatment on Volumetric Bone Density and Strength in Older Men With Low TestosteroneA Controlled Clinical Trial. JAMA Intern Med. Published online February 21, 2017 PMID: 28241231 http://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2604138 - Roy CN, Snyder PJ, Stephens-Shields AJ et al Association of Testosterone Levels With Anemia in Older Men. A Controlled Clinical Trial. JAMA Intern Med. Published online February 21, 2017 PMID: 28241237 http://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2604139 - Cheetham TC, An J, Jacobsen SJ et al Association of Testosterone Replacement With Cardiovascular Outcomes Among Men With Androgen Deficiency. JAMA Intern Med. Published online February 21, 2017 PMID: 28241244 http://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2604140 - Orwoll E Further Elucidation of the Potential Benefits of Testosterone Therapy in Older Men. JAMA Intern Med. Published online February 21, 2017 PMID: 28241252 http://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2604136
  40. Storer TW et al. Effects of testosterone supplementation for 3 years on muscle performance and physical function in older men. J Clin Endocrinol Metab 2017 Feb 1; 102:583 PMID: 27754805 http://press.endocrine.org/doi/10.1210/jc.2016-2771
  41. Layton JB, Kim Y, Alexander GC et al Association Between Direct-to-Consumer Advertising and Testosterone Testing and Initiation in the United States, 2009-2013. JAMA. 2017;317(11):1159-1166 PMID: 28324090 http://jamanetwork.com/journals/jama/article-abstract/2612615 - Kravitz RL Direct-to-Consumer Advertising of Androgen Replacement Therapy. JAMA. 2017;317(11):1124-1125 PMID: 28324072 http://jamanetwork.com/journals/jama/article-abstract/2612596
  42. Fugh-Berman A Treating Aging With Testosterone. Am Fam Physician. 2017 Oct 1;96(7):428-430 PMID: 29094915 https://www.medscape.com/viewarticle/886851.
  43. Sargis RM, Davis AM Evaluation and Treatment of Male Hypogonadism. Testosterone Therapy in Men With Hypogonadism: An Endocrine Society Clinical Practice Guideline. JAMA. Published online March 17, 2018. PMID: 29550857 https://jamanetwork.com/journals/jama/fullarticle/2675569
  44. Bhasin S, Brito JP, Cunningham GR et al. Testosterone therapy in men with hypogonadism: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2018 May 1; 103:1715 PMID: 2956236 https://academic.oup.com/jcem/article/103/5/1715/4939465
  45. Walther A, Breidenstein J, Miller R. Association of testosterone treatment with alleviation of depressive symptoms in men: A systematic review and meta-analysis. JAMA Psychiatry 2018 Nov 14; PMID: 30427999 - Bhasin S, Seidman S. Testosterone treatment of depressive disorders in men: Too much smoke, not enough high-quality evidence. JAMA Psychiatry 2018 Nov 14; PMID: 30428087
  46. Morden NE, Woloshin S, Brooks CG, Schwartz LM. Trends in testosterone prescribing for age-related hypogonadism in men with and without heart disease. JAMA Intern Med. Published online December 28, 2018. https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2719423
  47. Walker RF, Zakai NA, MacLehose RF et al Association of Testosterone Therapy With Risk of Venous Thromboembolism Among Men With and Without Hypogonadism. JAMA Intern Med. Published online November 11, 2019 PMID: 31710339 https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2754091
  48. Qaseem A, Horwitch CA, Vijan S et al Testosterone Treatment in Adult Men With Age-Related Low Testosterone: A Clinical Guideline From the American College of Physicians. Ann Intern Med. 2020. Jan 7 PMID: 31905405 https://annals.org/aim/fullarticle/2758507/testosterone-treatment-adult-men-age-related-low-testosterone-clinical-guideline - Diem SJ, Greer NL, MacDonald R et al Efficacy and Safety of Testosterone Treatment in Men: An Evidence Report for a Clinical Practice Guideline by the American College of Physicians. Ann Intern Med. 2020. Jan 7 PMID: 31905375 https://annals.org/aim/article-abstract/2758506/efficacy-safety-testosterone-treatment-men-evidence-report-clinical-practice-guideline - [No authors listed] Testosterone Treatment in Adult Men With Age-Related Low Testosterone. Ann Intern Med. 2020 Jan 7. doi: 10.7326/P19-0017 PMID: 31905404 - Adlin EV Age-Related Low Testosterone. Ann Intern Med. 2020. Jan 7 PMID: 31905380 https://annals.org/aim/article-abstract/2758508/age-related-low-testosterone
  49. NEJM Knowledge+ Endocrinology
  50. Lincoff AM et al. Cardiovascular safety of testosterone-replacement therapy. N Engl J Med 2023 Jun 16; [e-pub]. PMID: 37326322 https://www.nejm.org/doi/10.1056/NEJMoa2215025
  51. Pencina KM et al. Efficacy of testosterone replacement therapy in correcting anemia in men with hypogonadism: A randomized clinical trial. JAMA Netw Open 2023 Oct 27; 6:e2340030. PMID: 37889486 PMCID: PMC10611996 Free PMC article https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2811115 - Alibhai SMH. Testosterone replacement in men with hypogonadism and effects on anemia - Blood, sex, and aging. JAMA Netw Open 2023 Oct 27; 6:e2339969 PMID: 37889494 Free article https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2811123
  52. Bhasin S et al. Prostate safety events during testosterone replacement therapy in men with hypogonadism: A randomized clinical trial. JAMA Netw Open 2023 Dec; 6:e2348692. PMID: 38150256 PMCID: PMC10753401 Free PMC article https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2813293
  53. Snyder PJ et al. Testosterone treatment and fractures in men with hypogonadism. N Engl J Med 2024 Jan 18; 390:203. PMID: 38231621 https://www.nejm.org/doi/10.1056/NEJMoa2308836 - Grossmann M, Anawalt BD. Breaking news - Testosterone treatment and fractures in older men. N Engl J Med 2024 Jan 18; 390:267. PMID: 38231628 https://www.nejm.org/doi/10.1056/NEJMe2313787
  54. Pencina KM et al. Effect of testosterone replacement therapy on sexual function and hypogonadal symptoms in men with hypogonadism. J Clin Endocrinol Metab 2024 Jan 18; 109:569. PMID: 37589949 https://academic.oup.com/jcem/article-abstract/109/2/569/7244351 - Bhasin S et al. Depressive syndromes in men with hypogonadism in the TRAVERSE trial: Response to testosterone-replacement therapy. J Clin Endocrinol Metab 2024 Jan 11; [e-pub]. PMID: 38205962 https://academic.oup.com/jcem/advance-article-abstract/doi/10.1210/clinem/dgae026/7516050
  55. Bhasin S et al. Effect of testosterone on progression from prediabetes to diabetes in men with hypogonadism: A substudy of the TRAVERSE randomized clinical trial. JAMA Intern Med 2024 Feb 5; e237862; [e-pub]. PMID: 38315466 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2814401 - Mody L, Covinsky KE. Testosterone replacement therapy and diabetes in men with hypogonadism. JAMA Intern Med 2024 Feb 5; [e-pub] PMID: 38315460 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2814405
  56. Snyder PJ, Bhasin S, Cunningham GR et al Lessons From the Testosterone Trials. Endocr Rev. 2018 Jun 1;39(3):369-386. doi: 10.1210/er.2017-00234. PMID: 29522088 PMCID: PMC628728 Free PMC article.
  57. Huang G, Wharton W, Bhasin S et al Effects of long-term testosterone administration on cognition in older men with low or low-to-normal testosterone concentrations: a prespecified secondary analysis of data from the randomised, double-blind, placebo-controlled TEAAM trial. Lancet Diabetes Endocrinol. 2016 Aug;4(8):657-665. PMID: 27377542 Clinical Trial.
  58. Morgentaler A, Dhindsa S, Dobs AS et al Androgen Society Position Paper on Cardiovascular Risk With Testosterone Therapy. Mayo Clin Proc. 2024 Oct 9:S0025-6196(24)00408-7. PMID: 39436329 Review. https://www.mayoclinicproceedings.org/article/S0025-6196(24)00408-7/fulltext