Evidence-Based Reviews

Persistent depression? Low libido? Androgen decline may be to blame

Current Psychiatry. 2004 May;3(5):24-42

References

1. Pope HG, Jr, Cohane GH, Kanayama G, et al. Testosterone gel supplementation for men with refractory depression: a randomized, placebo-controlled trial. Am J Psychiatry 2003;160:105-11.

2. Ehrenreich H, Halaris A, Ruether E, et al. Psychoendocrine sequelae of chronic testosterone deficiency. J Psychiatric Res 1999;33:379-87.

3. Schweiger U, Deuschle M, Weber B, et al. Testosterone, gonadotropin, and cortisol secretion in male patients with major depression. Psychosom Med 1999;61:292-6.

4. Seidman SN, Walsh BT. Testosterone and depression in aging men. Am J Geriatr Psychiatry 1999;7:18-33.

5. Mulchahey JJ, Ekhator NN, Zhang H, et al. Cerebrospinal fluid and plasma testosterone levels in post-traumatic stress disorder and tobacco dependence. Psychoneuroendocrinology 2001;26:273-85.

6. Shores MM, Sloan KL, Matsumoto AM, et al. Increased incidence of diagnosed depressive illness in hypogonadal older men. Arch Gen Psychiatry 2004;61:162-7.

7. Bachman G, Bancroft J, Braunstein G, et al. Female androgen insufficiency: the Princeton consensus statement on definition, classification, and assessment. Fertil Steril 2002;77:660-5.

8. Pope HG, Jr, Kouri EM, Hudson JI. Effects of supraphysiologic doses of testosterone on mood and aggression in normal men. A randomized controlled trial. Arch Gen Psychiatry 2000;57:133-40.

9. Matsumoto AM. The testis. In: Felig P, Frohman LA (eds). Endocrinology and metabolism (4th ed). New York: McGraw-Hill, 2001;635-705.

10. O’Carroll R, Shapiro C, Bancroft J. Androgens, behavior and nocturnal erection in hypogonadal men: the effects of varying the replacement dose. Clin Endocrinol 1985;23:527-38.

11. Wang C, Swerdloff R, Iranmanesh A, et al. and the Testosterone Gel Study Group. Transdermal testosterone gel improves sexual function, mood, muscle strength, and body composition parameters in hypogonadal men. J Clin Endocrinol Metab 2000;85:2839-53.

12. Seidman SN, Rabkin JG. Testosterone replacement therapy for hypogonadal men with SSRI-refractory depression. J Affect Disord 1998;48(2-3):157-61.

13. Goldstat R, Briganti E, Tran J, et al. Transdermal testosterone therapy improves well-being, mood, and sexual function in premenopausal women. Menopause 2003;10:390-8.

14. Smith KW, Feldman HA, McKinlay JB. Construction and field validation of self-administered screener for testosterone deficiency (hypogonadism) in ageing men. Clin Endocrinol 2000;53:703-11.

15. Harmon SM, Metter EJ, Tobin JD, et al. Longitudinal effects of aging on serum total and free testosterone levels in healthy men. J Clin Endocrinol Metab 2001;86:724-31.

16. Prasad AS, Fitzgerald JT, Hess JW, et al. Zinc deficiency in elderly patients. Nutrition 1993;9:218-24.

17. Maes M, D’Haese PC, Scharpe S, et al. Hypozincemia in depression. J Affect Disord 1994;31:135-40.

18. Prasad AS, Mantzoros CS, Beck FW, et al. Zinc status and serum testosterone levels of healthy adults. Nutrition 1996;12:344-8.

19. Weisser H, Tunn S, Behnke B, Krieg M. Effects of the sabal serrulata extract IDS 89 and its subfractions on 5 alpha-reductase activity in human benign prostatic hyperplasia. Prostate 1996;28:300-6.

20. Forbes GB, Porta CR, Herr BE, Griggs RC. Sequence of changes in body composition induced by testosterone and reversal of changes after drug is stopped. JAMA 1992;267(3):397-9.

21. Meikle AW. Transdermal testosterone. Drugs 1998;55:259.-

22. Parasrampuria J, Schwartz K, Petesch R. Quality control of dehydroepiandrosterone dietary supplement products. JAMA 1998;280:1565.-

23. Hak AE, Witteman JC, de Jong FH, et al. Low levels of endogenous androgens increase the risk of atherosclerosis in elderly men: the Rotterdam study. J Clin Endocrinol Metab 2002;87:3632-9.

Potential adverse effects

Short-term testosterone replacement is generally low-risk. Acne is the most common adverse effect (Table 3).

The incidence of adverse events increases as testosterone concentrations are elevated above the normal range. For example, about 5% of men experience a manic or hypomanic arousal within 2 to 6 weeks of induced supraphysiologic testosterone levels.⁸

Gonadal suppression. Exogenous testosterone (or high-dose DHEA) suppresses endogenous gonadal function in men and premenopausal women. When a sustained course of exogenous androgens is discontinued, gonadal suppression usually does not reverse completely for several months or longer.

Prostatic hypertrophy, commonly considered to be testosterone driven, may be a risk of testosterone replacement therapy. Emergent urinary retention during testosterone replacement therapy has been reported, so use caution when giving testosterone to men with prostatic hypertrophy.

Barring evidence to the contrary, testosterone therapy is contraindicated in patients with prostate cancer. Baseline and post-treatment prostate-specific antigen measures are recommended.

Other risks in men. Men occasionally develop gynecomastia during testosterone replacement, perhaps because of testosterone aromatization to estradiol. Beyond increased hematocrit levels and associated problems, testosterone’s cardiovascular risks are unclear. Testosterone deficiency also has been linked to increased atherosclerosis risk in older men.²³

Risks in women. Overtreating women with testosterone (DHEA) can promote hirsutism (including facial hair), loss of hair on scalp, voice lowering, clitoromegaly, breast regression, and muscle hypertrophy.

Related resources

Daly RC, Su T-P, Schmidt PJ, et al. Cerebrospinal fluid and behavioral changes after methyltestosterone administration. Arch Gen Psychiatry 2001;58:172-7.
Davis S. Testosterone deficiency in women.J Reprod Med2 001; 46(3 suppl):291-6.
Rohr UD. The impact of testosterone imbalance on depression and women’s health. Maturitas 2002;41(1 suppl):S25-S46.
Mantzoros CS, Georgiadis EI. Contribution of dihydrotestosterone to male sexual behaviour. BMJ 1995;310:1289-91.

Drug brand names

Methyltestosterone (oral) • Android, Methitest, Testred, Virilon
Testosterone (buccal) • Striant
Testosterone (gel) • AndroGel, Testim
Testosterone (transdermal) • Androderm, Testoderm
Testosterone enanthate (IM injection) • Delatestryl

Disclosure

Dr. Geracioti reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.