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testosterone (Delatestryl Testopel, Striant, Intrinsa, Xyosted)

Secreted by Leydig cells of the testes in response to stimulation of LH receptors by LH. The adult testes secrete 7 mg/day of testosterone. Smaller amounts are formed from DHEA secreted by the adrenal cortex. Testosterone is transported in circulation bound to its binding globulin (TEBG). Activity of testosterone is mediated through the androgen receptor. As pharmacologic agent: DEA controlled substance class 3. Testosterone enanthate, cypionate, propionate. Indications: - males: - replacement therapy in hypogonadism & delayed puberty - sarcopenia - andropause (also see testosterone replacement therapy) [11] - symptomatic androgen deficiency [21] - orchitis - cryptorchidism - anorchia - Klinefelter's syndrome (Jatenzo) - LHRH deficiency [24] - medically-related low plasma testosterone [27] - females: - inoperable breast cancer - post-partum pain & engorgement - diminished libido (not FDA-approved use) Contraindications: 1) avoid in patients with prostate cancer 2) BPH, serum PSA > 3 ng/mL 3) hematocrit > 50% 4) obstructive sleep apnea 5) severe heart failure 6) indiscriminant use as an anti-aging drug [18,20]* * testosterone therapy in the absence of testosterone deficiency is not beneficial & is associated with harm [4] Dosage: 1) also see a) testosterone transdermal patch b) testosterone transdermal gel 2) Striant: 30 mg placed in upper gum BID [10] a) tablet will not dissolve completely b) remove old tablet before inserting new one 3) Intrinsa: transdermal testosterone for women (not FDA-approved) 4) undecenoate (oral) 80 mg PO BID [16] {in Europe} not effective 5) maintenance IM, adult men (enanthate): a) 50-400 mg (100 mg/m2) IM every 2-4 weeks b) 125 mg IM weekly is optimal dose [12] 6) children (delayed puberty & hypogonadism): a) 40-50 mg/m2 monthly for 6 months b) 100 mg/m2 monthly during terminal growth phase until growth ceases 7) Testopel subcutaneous pellet: injection every 3-6 months [10] 8) breast carcinoma: 200-400 mg every 3-4 weeks Injection (in oil) - cypionate: 100 mg/mL (10 mL), 200 mg/mL (10 mL) - enanthate: 200 mg/mL (10 mL) - propionate: 100 mg/mL (10 mL) Transdermal system: - Testoderm: 4 mg/day, 6 mg/day - Androderm: pathes 2 & 4 mg/day [22] Androgel 1% & 1.62%: [22] - 2.5 g & 5 g packets (doubles serum testosterone [13]) Striant: 30 mg buccal tablet Testopel subcutaneous pellet [10] Xyosted (testosterone enanthate) - once-weekly self-administration using disposable autoinjector - 50 mg, 75 mg, 100 mg [32] oral testosterone undecanoate (Jatenzo) for Klinefelter's syndrome [33] Pharmacokinetics: 1) metabolized in the liver by cyt P450 3A4 2) metabolized by aromatase to estradiol in peripheral tissues Monitor: 1) serum lipid levels 2) serum PSA 3) hematocrit (keep < 54%) [9] 4) liver function tests periodically [19] Adverse effects: 1) common (> 10%) - menstrual problems (amenorrhea), virilism, edema, acne, priapism, breast soreness 2) less common (1-10%) - GI irritation, nausea/vomiting, hepatic dysfunction, prostatic hypertrophy, prostatic carcinoma, hirsutism (increase in pubic hair growth), impotence, testicular atrophy 3) uncommon (< 1%) - hepatic necrosis, leukopenia, gynecomastia, amenorrhea, hypercalcemia, polycythemia, cholestatic hepatitis, hypersensitivity reactions 4) other a) males - gynecomastia - excessive frequency & duration of penile erections - male pattern baldness - retention of water & electrolytes - suppression of clotting factors - lipoprotein levels generally NOT affected [7] - exogenous testosterone may result in irreversible decline in spermatogenesis, infertility & permanent inability to produce endogenous testosterone [4,29] - fluctuation in mood & libido most common with IM testosterone [34] b) females - amenorrhea - deepening of voice - clitoral enlargement - may diminish HDL cholesterol [9] c) Testoderm, but NOT Androderm associated with elevated serum dihydrotestosterone levels [4] d) sleep apnea [8,12] e) inadvertent exposure to testosterone through contact with a person using AndroGel 1% or Testim 1% f) increased cardiovascular risk - also see testosterone transdermal gel - testosterone supplementation (topical or parenteral) is associated with increased cardiovascular risk in older men after coronary angiography [23] - testosterone may increase risk of myocardial infarction in men [25] g) increased risk of venous thromboembolism [26,31] h) no increased risk of prostate cancer [28] 5) high-dose androgen abuse [30] - myocardial infarction - heart failure - stroke - depression - hostility, aggression - hepatotoxicity - male infertility [30] Drug interactions: 1) increased anticoagulant effect of warfarin 2) cyclosporine 3) any drug that inhibits cyt P450 3A4 may increase levels of testosterone 4) any drug that induces cyt P450 3A4 may diminish levels of testosterone Test interactions: -> may increase PSA Mechanism of action: 1) androgen 2) increases lean body mass, muscle mass, bone mineral density erythrocyte mass, libido 3) may improve depressed mood 4) AndroGel effective [13]

Interactions

molecular events drug interactions drug adverse effects of androgens

Related

androgen excess (hyperandrogenism) androgen insufficiency (hypoandrogenism, testosterone deficiency) androgen receptor; dihydrotestosterone receptor; nuclear receptor subfamily 3 group C member 4 (AR, DHTR, NR3C4) dehydroepiandrosterone; prasterone (DHEA, Aslera, Intrarosa) free testosterone gonadal steroid biosynthesis Leydig cell testosterone in serum testosterone replacement therapy; androgen therapy

Specific

1-testosterone 4-hydroxytestosterone epitestosterone testosterone oral; testosterone undecanoate (Jatenzo) testosterone topical; testosterone transdermal

General

adrenal cortex hormone; corticosteroid androgen or anabolic steroid androstenol ketosteroid

Properties

SIZE: MW = 288 G/M MISC-INFO: elimination route LIVER pregnancy-category X safety in lactation ?

Database Correlations

PUBCHEM correlations

References

  1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
  2. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
  3. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  4. Medical Knowledge Self Assessment Program (MKSAP) 11, 17, 19. American College of Physicians, Philadelphia 1998, 2015, 2022
  5. Prescriber's Letter 7(6):36 2000
  6. Geriatric Dosage Handbook, 6th edition, Selma et al eds, Lexi-Comp, Cleveland, 2001
  7. Journal Watch 21(22):178, 2001 Snyder et al Am J Med 111:255, 2001 Whitsel et al Am J Med 11:261, 2001 Hoffman AR, Am J Med 11:322, 2001
  8. Solomon DH, in: UCLA Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 12-15, 2001
  9. Geriatrics Review Syllabus, American Geriatrics Society, 5th edition, 2002-2004
  10. Prescriber's Letter 10(8):46 2003
  11. Journal Watch 24(6):48, 2004
  12. Internal Medicine News, July 2005, pg 1,22
  13. The Use of Testosterone for 'Male Menopause' Prescriber's Letter 11(4):22 2004 Detail-Document#: 200407 (subscription needed) http://www.prescribersletter.com - Journal Watch 24(13):102-103, 2004 Wang C, Cunningham G, Dobs A, Iranmanesh A, Matsumoto AM, Snyder PJ, Weber T, Berman N, Hull L, Swerdloff RS. Long-term testosterone gel (AndroGel) treatment maintains beneficial effects on sexual function and mood, lean and fat mass, and bone mineral density in hypogonadal men. J Clin Endocrinol Metab. 2004 May;89(5):2085-98. PMID: 15126525
  14. Prescriber's Letter 12(1): 2005 Testosterone Replacement for Women; an Update Detail-Document#: 210112 (subscription needed) http://www.prescribersletter.com
  15. The role of testosterone therapy in postmenopausal women: position statement of The North American Menopause Society http://www.menopause.org/aboutmeno/PStestosterone.pdf - corresponding NGC guideline withdrawn 12/10
  16. 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
  17. FDA MedWatch Testosterone gel products (AndroGel 1% and Testim 1%) http://www.fda.gov/medwatch/safety/2009/safety09.htm#testosterone
  18. Prescriber's Letter 17(7): 2010 COMMENTARY: The Use of Testosterone and the Aging Male GUIDELINES: Testosterone Therapy in Men with Androgen Deficiency Detail-Document#: 260713 (subscription needed) http://www.prescribersletter.com - Wu FCW et al. Identification of late-onset hypogonadism in middle-aged and elderly men. N Engl J Med 2010 Jul 8; 363:123 PMID: 20554979 - Krasnoff JB et al Free testosterone levels are associated with mobility limitation and physical performance in community-dwelling men: the Framingham Offspring Study. J Clin Endocrinol Metab. 2010 Jun;95(6):2790-9 PMID: 20382680
  19. Prescriber's Letter 17(7): 2010 Recommended Lab Monitoring for Common Medications Liver Function Test Scheduling Detail-Document#: 260704 (subscription needed) http://www.prescribersletter.com
  20. Basaria S et al, Adverse Events Associated with Testosterone Administration N Engl J Med June 30, 2010 PMID: 20592293
  21. Bhasin S et al. Testosterone therapy in men with androgen deficiency syndromes: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2010 Jun; 95:2536. PMID: 20525905 http://content.nejm.org/cgi/content/full/NEJMoa1000485
  22. Prescriber's Letter 18(12): 2011 Comparison of Testosterone Products Detail-Document#: 271209 (subscription needed) http://www.prescribersletter.com
  23. 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
  24. Deprecated Reference
  25. 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
  26. FDA MedWatch. June 19. 2014 FDA adding general warning to testosterone products about potential for venous blood clots. http://www.fda.gov/Drugs/DrugSafety/ucm401746.htm
  27. Herman AO, Sofair A, Chavey WE Physician's First Watch, Sept 19, 2014 David G. Fairchild, MD, MPH, Editor-in-Chief Massachusetts Medical Society http://www.jwatch.org
  28. 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
  29. 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
  30. Brooks M FDA Adds New Warnings to All Testosterone Product Labels. Medscape. Oct 25, 2016 http://www.medscape.com/viewarticle/870932 - FDA Safety Alert. Oct 25, 2016 Testosterone and Other Anabolic Androgenic Steroids (AAS): FDA Statement - Risks Associated With Abuse and Dependence. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm526151.htm
  31. 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
  32. Brooks M FDA Clears First Autoinjectable Testosterone, Xyosted. Medscape - Oct 02, 2018. https://www.medscape.com/viewarticle/902818
  33. FDA News Release. March 27, 2019 FDA approves new oral testosterone capsule for treatment of men with certain forms of hypogonadism. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm634585.htm
  34. NEJM Knowledge+ Endocrinology

Substructure-of

methyltestosterone (Android, Testred, Metandren, Oretan, Virilon)

Component-of

benzoate/estradiol/testosterone estradiol/testosterone tibolone