testosterone replacement therapy; androgen therapy
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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]
Indications
- primary or secondary hypogonadism caused by specific, well-recognized medical conditions in males[30]
- andropause
- prophylaxis for Alzheimer's disease?[2] (see testosterone & risk of Alzheimer's disease)
- 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]
- osteoporosis[4]
- increased bone mineral density & bone strenth at hip & spine in elderly men[39]
- see testosterone & risk of osteoporosis
- improves anemia in elderly men
- increases blood hemoglobin by 1 g/dL[39]
- recommended for symptomatic men only[13]
- 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]
- statistically significant improvement for several measures of muscle performance of uncertain significance[40]
- corrects anemia in elderly men with hypogonadism slightly more often than placebo[51]
- lack of substantial evidence to support its use[30]
- 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)
- 2 8 AM serum testosterone measurements[15]
- free testosterone* in obese patients
- total serum testosterone may be affected by a decrease in plasma sex hormone binding globulin (SHBG)[1]
- serum testosterone > 350 mg/dL excludes hypogonadism[1]
Contraindications
- men
- prostate cancer
- avoid in men at high risk of prostate cancer[52]
- severe BPH
- palpable prostate abnormalities
- obstructive uropathy
- PSA > 3.0 ng/mL
- hematocrit > 50%
- untreated obstructive sleep apnea (may exacerbate)[49]
- severe heart failure
- cirrhosis
- avoid use for improving vitality, energy levels, physical function or cognition
- absence of biochemical evidence of testosterone deficiency[15]
- avoid in men planning for fertility (impairs spermatogenesis)[15]
- does not improve glycemic control in men with diabetes mellitus or prediabetes[55]
- prostate cancer
- women[24]
- infertility
- promotion ofcardiovascular health,
- low androgen levels due to hypopituitarism, adrenal insufficiency, or surgical menopause
- DHEA is not recommended[24]
- 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]
Dosage
- testosterone enanthate 125 mg IM weekly is optimal dose[10]
- transdermal patch 5 mg/day of no benefit to elderly men[11]
- testosterone undecenoate 80 mg PO BID not effective[14]
- does not increase serum testosterone, free testosterone, or bioavailable testosterone
- transdermal gel
- 50 mg/day doubles serum testosterone[16]
- advantages:
- steady level of testosterone within 30 minutes of application[15]
- invisibility of gel
- disadvantages:
- need to apply daily
- cost
- risk of absorption by others who come in contact with the gel[15]
Monitor
- prior to therapy, & at 3, 6 & 12 months
- monitor at least annually thereafter
- monitor
- serum lipid levels, initially & repeat with other lab testing if abnormal
- serum PSA & symptoms of BPH
- hematocrit (keep < 54%)[7][15]
- serum testosterone (total)
- free testosterone if total serum testosterone abnormal
- goal: serum testosterone (or free testosterone) in mid-normal range[15]
- symptoms of sleep apnea
Adverse effects
- see testosterone
- testosterone gel use by older men with mobility problems may increase cardiovascular risk[18][20]
- 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 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]
More general terms
Additional terms
References
- ↑ 1.0 1.1 1.2 Journal Watch 24(6):48, 2004 Institute of Medicine, Testosterone & Aging: Clinical Research Directions http://books.nap.edu/execsumm_pdf/10852.pdf
- ↑ 2.0 2.1 Moffat SD et al, Neurology 62:188, 2004 PMID: https://www.ncbi.nlm.nih.gov/pubmed/14745052
- ↑ 3.0 3.1 Shores MM et al, Arch Gen Psychiatry 61:162, 2004 PMID: https://www.ncbi.nlm.nih.gov/pubmed/14757592
- ↑ 4.0 4.1 Amory JK et al, J Clin Endocrinol Metab 89:503, 2004 PMID: https://www.ncbi.nlm.nih.gov/pubmed/14764753
- ↑ Wang C et al, J Clin Endocrinol Metab 89:534, 2004 PMID: https://www.ncbi.nlm.nih.gov/pubmed/14764758
- ↑ Rhoden EL & Morgentaler A, N Engl J Med 350:482, 2004 PMID: https://www.ncbi.nlm.nih.gov/pubmed/14749457
- ↑ 7.0 7.1 7.2 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 - ↑ 8.0 8.1 Prescriber's Letter 12(1): 2005 Testosterone Replacement for Women; an Update Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=210112&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 9.0 9.1 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: https://www.ncbi.nlm.nih.gov/pubmed/15863529
- ↑ 10.0 10.1 10.2 Internal Medicine News, July 2005, pg 1,22
- ↑ 11.0 11.1 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: https://www.ncbi.nlm.nih.gov/pubmed/17050889
Stewart PM. Aging and fountain-of-youth hormones. N Engl J Med 2006 Oct 19; 355:1724-6 PMID: https://www.ncbi.nlm.nih.gov/pubmed/17050897 - ↑ 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
- ↑ 13.0 13.1 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: https://www.ncbi.nlm.nih.gov/pubmed/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: https://www.ncbi.nlm.nih.gov/pubmed/20525905 corresponding NGC guideline withdrawn Feb 2016 - ↑ 14.0 14.1 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: https://www.ncbi.nlm.nih.gov/pubmed/18167405
- ↑ 15.00 15.01 15.02 15.03 15.04 15.05 15.06 15.07 15.08 15.09 15.10 15.11 Medical Knowledge Self Assessment Program (MKSAP) 15, 16, 17, 18. 19. American College of Physicians, Philadelphia 2009, 2012, 2015, 2018, 2022.
- ↑ 16.0 16.1 16.2 16.3 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: https://www.ncbi.nlm.nih.gov/pubmed/20061435
- ↑ 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#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=270301&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 18.0 18.1 Basaria S et al, Adverse Events Associated with Testosterone Administration N Engl J Med 2010; 363:109-122. PMID: https://www.ncbi.nlm.nih.gov/pubmed/20592293
Bremner WJ. Testosterone deficiency and replacement in older men. N Engl J Med 2010; 363:189-191. PMID: https://www.ncbi.nlm.nih.gov/pubmed/20647215 - ↑ 19.0 19.1 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: https://www.ncbi.nlm.nih.gov/pubmed/21697501
- ↑ 20.0 20.1 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
- ↑ 21.0 21.1 Finkle WD et al. Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men. PLoS ONE 2014 Jan 29; 9:e85805 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24489673 <Internet> http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0085805
- ↑ 22.0 22.1 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. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24423353 <Internet> http://press.endocrine.org/doi/abs/10.1210/jc.2013-3570
- ↑ 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: https://www.ncbi.nlm.nih.gov/pubmed/21711483
- ↑ 24.0 24.1 24.2 24.3 Wierman ME et al Androgen Therapy in Women: A Reappraisal: An Endocrine Society Clinical Practice Guideline. J of Clin Endocrinol& Metabob. 2014 99(10): <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25279570 <Internet> http://press.endocrine.org/doi/full/10.1210/jc.2014-2
- ↑ 25.0 25.1 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: https://www.ncbi.nlm.nih.gov/pubmed/24978674
- ↑ 26.0 26.1 Swerdloff R, Anawalt BD Testosterone-Replacement Therapy. N Engl J Med 2014; 371:2032-2034. November 20, 2014 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25409377 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMclde1406595
- ↑ 27.0 27.1 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: https://www.ncbi.nlm.nih.gov/pubmed/24980615
- ↑ 28.0 28.1 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
- ↑ 29.0 29.1 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: https://www.ncbi.nlm.nih.gov/pubmed/26158605
- ↑ 30.0 30.1 30.2 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26287846 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMp1506632
- ↑ 31.0 31.1 Snyder PJ, Bhasin S, Cunningham GR Effects of Testosterone Treatment in Older Men. N Engl J Med 2016; 374:611-624. February 18, 2016 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26886521 PMCID: PMC5209754 Free PMC article <Internet> 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. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26886526 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMe1600196 - ↑ 32.0 32.1 32.2 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: https://www.ncbi.nlm.nih.gov/pubmed/24094422
- ↑ 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: https://www.ncbi.nlm.nih.gov/pubmed/20525906
- ↑ 34.0 34.1 34.2 34.3 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27165609 <Internet> 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27165608 <Internet> http://www.thelancet.com/journals/landia/article/PIIS2213-8587%2816%2930008-0/abstract - ↑ 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: https://www.ncbi.nlm.nih.gov/pubmed/25044637 Free Article
- ↑ 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24193080 <Internet> 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24193077 <Internet> http://jama.jamanetwork.com/article.aspx?articleid=1764030 - ↑ 37.0 37.1 37.2 37.3 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: https://www.ncbi.nlm.nih.gov/pubmed/27355400
- ↑ 38.0 38.1 Martinez C, Suissa S, Rietbrock S et al Testosterone treatment and risk of venous thromboembolism: population based case-control study. BMJ 2016;355:i5968 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27903495 <Internet> http://www.bmj.com/content/355/bmj.i5968
- ↑ 39.0 39.1 39.2 39.3 39.4 39.5 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28241355 <Internet> 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28241356 <Internet> http://jamanetwork.com/journals/jama/fullarticle/2603930
Handelsman DJ Testosterone and Male Aging. Faltering Hope for Rejuvenation. JAMA. 2017;317(7):699-701 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28241336 <Internet> 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28241231 <Internet> 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28241237 <Internet> 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28241244 <Internet> 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28241252 <Internet> http://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2604136 - ↑ 40.0 40.1 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27754805 <Internet> http://press.endocrine.org/doi/10.1210/jc.2016-2771
- ↑ 41.0 41.1 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28324090 <Internet> http://jamanetwork.com/journals/jama/article-abstract/2612615
Kravitz RL Direct-to-Consumer Advertising of Androgen Replacement Therapy. JAMA. 2017;317(11):1124-1125 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28324072 <Internet> http://jamanetwork.com/journals/jama/article-abstract/2612596 - ↑ 42.0 42.1 Fugh-Berman A Treating Aging With Testosterone. Am Fam Physician. 2017 Oct 1;96(7):428-430 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29094915 https://www.medscape.com/viewarticle/886851.
- ↑ 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: https://www.ncbi.nlm.nih.gov/pubmed/29550857 https://jamanetwork.com/journals/jama/fullarticle/2675569
- ↑ 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: https://www.ncbi.nlm.nih.gov/pubmed/2956236 https://academic.oup.com/jcem/article/103/5/1715/4939465
- ↑ 45.0 45.1 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: https://www.ncbi.nlm.nih.gov/pubmed/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: https://www.ncbi.nlm.nih.gov/pubmed/30428087 - ↑ 46.0 46.1 46.2 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
- ↑ 47.0 47.1 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: https://www.ncbi.nlm.nih.gov/pubmed/31710339 https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2754091
- ↑ 48.0 48.1 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: https://www.ncbi.nlm.nih.gov/pubmed/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: https://www.ncbi.nlm.nih.gov/pubmed/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:http://dx.doi.org/ 10.7326/P19-0017 PMID: https://www.ncbi.nlm.nih.gov/pubmed/31905404
Adlin EV Age-Related Low Testosterone. Ann Intern Med. 2020. Jan 7 PMID: https://www.ncbi.nlm.nih.gov/pubmed/31905380 https://annals.org/aim/article-abstract/2758508/age-related-low-testosterone - ↑ 49.0 49.1 49.2 NEJM Knowledge+ Endocrinology
- ↑ 50.0 50.1 Lincoff AM et al. Cardiovascular safety of testosterone-replacement therapy. N Engl J Med 2023 Jun 16; [e-pub]. PMID: https://www.ncbi.nlm.nih.gov/pubmed/37326322 https://www.nejm.org/doi/10.1056/NEJMoa2215025
- ↑ 51.0 51.1 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: https://www.ncbi.nlm.nih.gov/pubmed/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: https://www.ncbi.nlm.nih.gov/pubmed/37889494 Free article https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2811123 - ↑ 52.0 52.1 52.2 52.3 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: https://www.ncbi.nlm.nih.gov/pubmed/38150256 PMCID: PMC10753401 Free PMC article https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2813293
- ↑ 53.0 53.1 53.2 Snyder PJ et al. Testosterone treatment and fractures in men with hypogonadism. N Engl J Med 2024 Jan 18; 390:203. PMID: https://www.ncbi.nlm.nih.gov/pubmed/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: https://www.ncbi.nlm.nih.gov/pubmed/38231628 https://www.nejm.org/doi/10.1056/NEJMe2313787 - ↑ 54.0 54.1 54.2 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: https://www.ncbi.nlm.nih.gov/pubmed/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: https://www.ncbi.nlm.nih.gov/pubmed/38205962 https://academic.oup.com/jcem/advance-article-abstract/doi/10.1210/clinem/dgae026/7516050 - ↑ 55.0 55.1 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: https://www.ncbi.nlm.nih.gov/pubmed/38315466 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2814401
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