Skip to main content
PMC home page
Canadian Family Physician logoLink to Canadian Family Physician
. 2001 Jan;47:91–97.

Andropause. Testosterone replacement therapy for aging men.

J Bain 1
PMCID: PMC2014707  PMID: 11212438

Abstract

OBJECTIVE: To review the rationale for treating symptomatic aging men whose testosterone levels are mildly reduced or low-normal with testosterone replacement therapy. QUALITY OF EVIDENCE: Large-scale multicentre prospective studies on the value of treating andropausal men with hormone therapy do not exist because the whole area of hormone therapy is barely 10 years old. Evidence presented is based on physiologic studies, particularly studies in which treatment has been assessed. These were largely uncontrolled open studies. Studies to date report positive responses to testosterone treatment with very few serious side effects. MAIN MESSAGE: Physicians should consider hypoandrogenism if male patients complain of loss of libido, erectile dysfunction, weakness, fatigue, lethargy, loss of motivation, or mood swings. Less obvious associations with reduced levels of testosterone are anemia and osteoporosis. The main cause of reduced testosterone production is primary gonadal insufficiency, but secondary causes, such as hypothalamic-pituitary disease, should be considered. Evidence shows that most men treated with testosterone will feel better about themselves and their lives. CONCLUSION: Andropause is a term of convenience describing a complex of symptoms in aging men who have low testosterone levels. Physicians should be aware of its existence, should consider ordering tests for men who have symptoms, and should treat carefully selected patients whose serum testosterone levels are low.

Full Text

The Full Text of this article is available as a PDF (57.0 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Araneo B. A., Dowell T., Diegel M., Daynes R. A. Dihydrotestosterone exerts a depressive influence on the production of interleukin-4 (IL-4), IL-5, and gamma-interferon, but not IL-2 by activated murine T cells. Blood. 1991 Aug 1;78(3):688–699. [PubMed] [Google Scholar]
  2. Bagatell C. J., Bremner W. J. Androgens in men--uses and abuses. N Engl J Med. 1996 Mar 14;334(11):707–714. doi: 10.1056/NEJM199603143341107. [DOI] [PubMed] [Google Scholar]
  3. Bagatell C. J., Heiman J. R., Rivier J. E., Bremner W. J. Effects of endogenous testosterone and estradiol on sexual behavior in normal young men. J Clin Endocrinol Metab. 1994 Mar;78(3):711–716. doi: 10.1210/jcem.78.3.8126146. [DOI] [PubMed] [Google Scholar]
  4. Bardin C. W., Swerdloff R. S., Santen R. J. Androgens: risks and benefits. J Clin Endocrinol Metab. 1991 Jul;73(1):4–7. doi: 10.1210/jcem-73-1-4. [DOI] [PubMed] [Google Scholar]
  5. Barrett-Connor E. Lower endogenous androgen levels and dyslipidemia in men with non-insulin-dependent diabetes mellitus. Ann Intern Med. 1992 Nov 15;117(10):807–811. doi: 10.7326/0003-4819-117-10-807. [DOI] [PubMed] [Google Scholar]
  6. Barrett-Connor E., Von Mühlen D. G., Kritz-Silverstein D. Bioavailable testosterone and depressed mood in older men: the Rancho Bernardo Study. J Clin Endocrinol Metab. 1999 Feb;84(2):573–577. doi: 10.1210/jcem.84.2.5495. [DOI] [PubMed] [Google Scholar]
  7. Behre H. M., Bohmeyer J., Nieschlag E. Prostate volume in testosterone-treated and untreated hypogonadal men in comparison to age-matched normal controls. Clin Endocrinol (Oxf) 1994 Mar;40(3):341–349. doi: 10.1111/j.1365-2265.1994.tb03929.x. [DOI] [PubMed] [Google Scholar]
  8. Behre H. M., Kliesch S., Leifke E., Link T. M., Nieschlag E. Long-term effect of testosterone therapy on bone mineral density in hypogonadal men. J Clin Endocrinol Metab. 1997 Aug;82(8):2386–2390. doi: 10.1210/jcem.82.8.4163. [DOI] [PubMed] [Google Scholar]
  9. Berglund L., Carlström K., Stege R., Gottlieb C., Eriksson M., Angelin B., Henriksson P. Hormonal regulation of serum lipoprotein (a) levels: effects of parenteral administration of estrogen or testosterone in males. J Clin Endocrinol Metab. 1996 Jul;81(7):2633–2637. doi: 10.1210/jcem.81.7.8675589. [DOI] [PubMed] [Google Scholar]
  10. Bhasin S., Bagatell C. J., Bremner W. J., Plymate S. R., Tenover J. L., Korenman S. G., Nieschlag E. Issues in testosterone replacement in older men. J Clin Endocrinol Metab. 1998 Oct;83(10):3435–3448. doi: 10.1210/jcem.83.10.5060-1. [DOI] [PubMed] [Google Scholar]
  11. Bilezikian J. P. Osteoporosis in men. J Clin Endocrinol Metab. 1999 Oct;84(10):3431–3434. doi: 10.1210/jcem.84.10.6060. [DOI] [PubMed] [Google Scholar]
  12. Brodsky I. G., Balagopal P., Nair K. S. Effects of testosterone replacement on muscle mass and muscle protein synthesis in hypogonadal men--a clinical research center study. J Clin Endocrinol Metab. 1996 Oct;81(10):3469–3475. doi: 10.1210/jcem.81.10.8855787. [DOI] [PubMed] [Google Scholar]
  13. Chan J. M., Stampfer M. J., Giovannucci E., Gann P. H., Ma J., Wilkinson P., Hennekens C. H., Pollak M. Plasma insulin-like growth factor-I and prostate cancer risk: a prospective study. Science. 1998 Jan 23;279(5350):563–566. doi: 10.1126/science.279.5350.563. [DOI] [PubMed] [Google Scholar]
  14. Cutolo M., Balleari E., Giusti M., Intra E., Accardo S. Androgen replacement therapy in male patients with rheumatoid arthritis. Arthritis Rheum. 1991 Jan;34(1):1–5. doi: 10.1002/art.1780340102. [DOI] [PubMed] [Google Scholar]
  15. Ebeling P. R. Osteoporosis in men. New insights into aetiology, pathogenesis, prevention and management. Drugs Aging. 1998 Dec;13(6):421–434. doi: 10.2165/00002512-199813060-00002. [DOI] [PubMed] [Google Scholar]
  16. Friedl K. E., Hannan C. J., Jr, Jones R. E., Plymate S. R. High-density lipoprotein cholesterol is not decreased if an aromatizable androgen is administered. Metabolism. 1990 Jan;39(1):69–74. doi: 10.1016/0026-0495(90)90150-b. [DOI] [PubMed] [Google Scholar]
  17. Glueck C. J., Glueck H. I., Stroop D., Speirs J., Hamer T., Tracy T. Endogenous testosterone, fibrinolysis, and coronary heart disease risk in hyperlipidemic men. J Lab Clin Med. 1993 Oct;122(4):412–420. [PubMed] [Google Scholar]
  18. Gooren L. J. A ten-year safety study of the oral androgen testosterone undecanoate. J Androl. 1994 May-Jun;15(3):212–215. [PubMed] [Google Scholar]
  19. Gray A., Feldman H. A., McKinlay J. B., Longcope C. Age, disease, and changing sex hormone levels in middle-aged men: results of the Massachusetts Male Aging Study. J Clin Endocrinol Metab. 1991 Nov;73(5):1016–1025. doi: 10.1210/jcem-73-5-1016. [DOI] [PubMed] [Google Scholar]
  20. Grinspoon S., Corcoran C., Stanley T., Baaj A., Basgoz N., Klibanski A. Effects of hypogonadism and testosterone administration on depression indices in HIV-infected men. J Clin Endocrinol Metab. 2000 Jan;85(1):60–65. doi: 10.1210/jcem.85.1.6224. [DOI] [PubMed] [Google Scholar]
  21. Haffner S. M., Mykkänen L., Valdez R. A., Katz M. S. Relationship of sex hormones to lipids and lipoproteins in nondiabetic men. J Clin Endocrinol Metab. 1993 Dec;77(6):1610–1615. doi: 10.1210/jcem.77.6.8263149. [DOI] [PubMed] [Google Scholar]
  22. Hajjar R. R., Kaiser F. E., Morley J. E. Outcomes of long-term testosterone replacement in older hypogonadal males: a retrospective analysis. J Clin Endocrinol Metab. 1997 Nov;82(11):3793–3796. doi: 10.1210/jcem.82.11.4387. [DOI] [PubMed] [Google Scholar]
  23. Jin B., Turner L., Walters W. A., Handelsman D. J. The effects of chronic high dose androgen or estrogen treatment on the human prostate [corrected]. J Clin Endocrinol Metab. 1996 Dec;81(12):4290–4295. doi: 10.1210/jcem.81.12.8954029. [DOI] [PubMed] [Google Scholar]
  24. Jones G., Nguyen T., Sambrook P. N., Kelly P. J., Gilbert C., Eisman J. A. Symptomatic fracture incidence in elderly men and women: the Dubbo Osteoporosis Epidemiology Study (DOES). Osteoporos Int. 1994 Sep;4(5):277–282. doi: 10.1007/BF01623352. [DOI] [PubMed] [Google Scholar]
  25. Katznelson L., Finkelstein J. S., Schoenfeld D. A., Rosenthal D. I., Anderson E. J., Klibanski A. Increase in bone density and lean body mass during testosterone administration in men with acquired hypogonadism. J Clin Endocrinol Metab. 1996 Dec;81(12):4358–4365. doi: 10.1210/jcem.81.12.8954042. [DOI] [PubMed] [Google Scholar]
  26. Li Z. G., Danis V. A., Brooks P. M. Effect of gonadal steroids on the production of IL-1 and IL-6 by blood mononuclear cells in vitro. Clin Exp Rheumatol. 1993 Mar-Apr;11(2):157–162. [PubMed] [Google Scholar]
  27. Matsumoto A. M., Sandblom R. E., Schoene R. B., Lee K. A., Giblin E. C., Pierson D. J., Bremner W. J. Testosterone replacement in hypogonadal men: effects on obstructive sleep apnoea, respiratory drives, and sleep. Clin Endocrinol (Oxf) 1985 Jun;22(6):713–721. doi: 10.1111/j.1365-2265.1985.tb00161.x. [DOI] [PubMed] [Google Scholar]
  28. Morales A., Bain J., Ruijs A., Chapdelaine A., Tremblay R. R. Clinical practice guidelines for screening and monitoring male patients receiving testosterone supplementation therapy. Int J Impot Res. 1996 Jun;8(2):95–97. [PubMed] [Google Scholar]
  29. Morley J. E., Perry H. M., 3rd, Kaiser F. E., Kraenzle D., Jensen J., Houston K., Mattammal M., Perry H. M., Jr Effects of testosterone replacement therapy in old hypogonadal males: a preliminary study. J Am Geriatr Soc. 1993 Feb;41(2):149–152. doi: 10.1111/j.1532-5415.1993.tb02049.x. [DOI] [PubMed] [Google Scholar]
  30. Mårin P., Holmäng S., Jönsson L., Sjöström L., Kvist H., Holm G., Lindstedt G., Björntorp P. The effects of testosterone treatment on body composition and metabolism in middle-aged obese men. Int J Obes Relat Metab Disord. 1992 Dec;16(12):991–997. [PubMed] [Google Scholar]
  31. Nahoul K., Roger M. Age-related decline of plasma bioavailable testosterone in adult men. J Steroid Biochem. 1990 Feb;35(2):293–299. doi: 10.1016/0022-4731(90)90287-3. [DOI] [PubMed] [Google Scholar]
  32. Nankin H. R., Calkins J. H. Decreased bioavailable testosterone in aging normal and impotent men. J Clin Endocrinol Metab. 1986 Dec;63(6):1418–1420. doi: 10.1210/jcem-63-6-1418. [DOI] [PubMed] [Google Scholar]
  33. Nomura A., Heilbrun L. K., Stemmermann G. N., Judd H. L. Prediagnostic serum hormones and the risk of prostate cancer. Cancer Res. 1988 Jun 15;48(12):3515–3517. [PubMed] [Google Scholar]
  34. Orwoll E. S., Klein R. F. Osteoporosis in men. Endocr Rev. 1995 Feb;16(1):87–116. doi: 10.1210/edrv-16-1-87. [DOI] [PubMed] [Google Scholar]
  35. Phillips G. B., Pinkernell B. H., Jing T. Y. The association of hypotestosteronemia with coronary artery disease in men. Arterioscler Thromb. 1994 May;14(5):701–706. doi: 10.1161/01.atv.14.5.701. [DOI] [PubMed] [Google Scholar]
  36. Schow D. A., Redmon B., Pryor J. L. Male menopause. How to define it, how to treat it. Postgrad Med. 1997 Mar;101(3):62-4, 67-8, 71-4 passim. doi: 10.3810/pgm.1997.03.181. [DOI] [PubMed] [Google Scholar]
  37. Sih R., Morley J. E., Kaiser F. E., Perry H. M., 3rd, Patrick P., Ross C. Testosterone replacement in older hypogonadal men: a 12-month randomized controlled trial. J Clin Endocrinol Metab. 1997 Jun;82(6):1661–1667. doi: 10.1210/jcem.82.6.3988. [DOI] [PubMed] [Google Scholar]
  38. Snyder P. J., Peachey H., Hannoush P., Berlin J. A., Loh L., Holmes J. H., Dlewati A., Staley J., Santanna J., Kapoor S. C. Effect of testosterone treatment on bone mineral density in men over 65 years of age. J Clin Endocrinol Metab. 1999 Jun;84(6):1966–1972. doi: 10.1210/jcem.84.6.5741. [DOI] [PubMed] [Google Scholar]
  39. Sorva R., Kuusi T., Taskinen M. R., Perheentupa J., Nikkilä E. A. Testosterone substitution increases the activity of lipoprotein lipase and hepatic lipase in hypogonadal males. Atherosclerosis. 1988 Feb;69(2-3):191–197. doi: 10.1016/0021-9150(88)90014-7. [DOI] [PubMed] [Google Scholar]
  40. Tenover J. L. Testosterone and the aging male. J Androl. 1997 Mar-Apr;18(2):103–106. [PubMed] [Google Scholar]
  41. Tenover J. S. Effects of testosterone supplementation in the aging male. J Clin Endocrinol Metab. 1992 Oct;75(4):1092–1098. doi: 10.1210/jcem.75.4.1400877. [DOI] [PubMed] [Google Scholar]
  42. Umstot E. S., Baxter J. E., Andersen R. N. A theoretically sound and practicable equilibrium dialysis method for measuring percentage of free testosterone. J Steroid Biochem. 1985 May;22(5):639–648. doi: 10.1016/0022-4731(85)90218-3. [DOI] [PubMed] [Google Scholar]
  43. Vermeulen A. Clinical review 24: Androgens in the aging male. J Clin Endocrinol Metab. 1991 Aug;73(2):221–224. doi: 10.1210/jcem-73-2-221. [DOI] [PubMed] [Google Scholar]
  44. Vermeulen A., Kaufman J. M. Ageing of the hypothalamo-pituitary-testicular axis in men. Horm Res. 1995;43(1-3):25–28. doi: 10.1159/000184233. [DOI] [PubMed] [Google Scholar]
  45. Wang C., Alexander G., Berman N., Salehian B., Davidson T., McDonald V., Steiner B., Hull L., Callegari C., Swerdloff R. S. Testosterone replacement therapy improves mood in hypogonadal men--a clinical research center study. J Clin Endocrinol Metab. 1996 Oct;81(10):3578–3583. doi: 10.1210/jcem.81.10.8855804. [DOI] [PubMed] [Google Scholar]
  46. Wheeler M. J. The determination of bio-available testosterone. Ann Clin Biochem. 1995 Jul;32(Pt 4):345–357. doi: 10.1177/000456329503200401. [DOI] [PubMed] [Google Scholar]
  47. Wishart J. M., Need A. G., Horowitz M., Morris H. A., Nordin B. E. Effect of age on bone density and bone turnover in men. Clin Endocrinol (Oxf) 1995 Feb;42(2):141–146. doi: 10.1111/j.1365-2265.1995.tb01854.x. [DOI] [PubMed] [Google Scholar]
  48. Zgliczynski S., Ossowski M., Slowinska-Srzednicka J., Brzezinska A., Zgliczynski W., Soszynski P., Chotkowska E., Srzednicki M., Sadowski Z. Effect of testosterone replacement therapy on lipids and lipoproteins in hypogonadal and elderly men. Atherosclerosis. 1996 Mar;121(1):35–43. doi: 10.1016/0021-9150(95)05673-4. [DOI] [PubMed] [Google Scholar]

Articles from Canadian Family Physician are provided here courtesy of College of Family Physicians of Canada

RESOURCES