Do testosterone injections increase libido for elderly hypogonadal patients?

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Clinical Inquiries

Do testosterone injections increase libido for elderly hypogonadal patients?

J Fam Pract. 2007 April;56(4):301-302

By

Krupa Shah, MD

Cathy Montoya, MLS

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References

1. Tamimi RM, Hankinson SE, Chen WY, Rosner B, Colditz GA. Combined estrogen and testosterone use and risk of breast cancer in postmenopausal women. Arch Intern Med 2006;166:1483-1489.

2. Laumann EO, Paik A, Rosen RD. Sexual dysfunction in the United States: prevalence and predictors. JAMA 1999;281:537-544.

3. Feldman HA, Longcope C, Derby CA, et al. Age trends in the level of serum testosterone and other hormones in middle-aged men: longitudinal results from the Massachusetts Male Aging Study. J Clin Endocrinol Metab 2002;87:589-598.

4. Harman SM, Metter EJ, Tobin JD, Pearson J, Blackman MR. Longitudinal effects of aging on serum total and free testosterone levels in healthy men. Baltimore Longitudinal Study of Aging. J Clin Endocrinol Metab 2001;86:724-731.

5. Amory JK, Watts NB, Easley KA, et al. Exogenous testosterone or testosterone with finasteride increases bone mineral density in older men with low serum testosterone. J Clin Endocrinol Metab 2004;89:503-510.

6. Snyder PJ, Peachey H, Hannoush P, et al. Effect of testosterone treatment on body composition and muscle strength in men over 65 years of age. J Clin Endocrinol Metab 1999;84:2647-2653.

7. Cavallini G, Caracciolo S, Vitali G, Modenini F, Biagiotti G. Carnitine versus androgen administration in the treatment of sexual dysfunction, depressed mood, and fatigue associated with male aging. Urology 2004;63:641-646.

8. Page ST, Amory JK, Bowman FD, et al. Exogenous testosterone (T) alone or with finasteride increases physical performance, grip strength, and lean body mass in older men with low serum T. J Clin Endocrinol Metab 2005;90:1502-1510.

9. Sih R, Morley JE, Kaiser FE, Perry HM, 3rd, Patrick P, Ross C. Testosterone replacement in older hypogonadal men: a 12-month randomized controlled trial. J Clin Endocrinol Metab 1997;82:1661-1667.

10. Bachmann GA, Leiblum SR, Sandler B, et al. Correlates of sexual desire in post-menopausal women. Maturitas 1985;7:211-216.

11. McCoy NL, Davidson JM. A longitudinal study of the effects of menopause on sexuality. Maturitas 1985;7:203-210.

12. Davis SR, McCloud P, Strauss BJ, Burger H. Testosterone enhances estradiol’s effects on postmenopausal bone density and sexuality. Maturitas 1995;21:227-236.

13. Sarrel P, Dobay B, Wiita B. Estrogen and estrogen-androgen replacement in postmenopausal women dissatisfied with estrogen-only therapy. Sexual behavior and neuroendocrine responses. J Reprod Med 1998;43:847-856.

14. Sherwin BB, Gelfand MM, Brender W. Androgen enhances sexual motivation in females: a prospective, crossover study of sex steroid administration in the surgical menopause. Psychosom Med 1985;47:339-351.

15. Gelfand MM, Wiita B. Androgen and estrogen-androgen hormone replacement therapy: a review of the safety literature, 1941 to 1996. Clin Ther 1997;19:383-404.

16. AACE Menopause Guidelines Revision Task Force. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the diagnosis and treatment of menopause. Endocr Pract 2006;12:315-337.

17. Bhasin S, Cunningham GR, Hayes FJ, et al. Testosterone therapy in adult men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2006;91:1995-2010.

18. Liverman CT, Blazer DG (eds). Testosterone and Aging: Clinical Research Directions. Washington, DC: National Academies Press, 2004.

EVIDENCE-BASED ANSWER

Yes, testosterone therapy is effective in improving libido for elderly hypogonadal males (strength of recommendation [SOR]: B, based on small randomized controlled trials [RCTs]). Testosterone combined with estrogen can also improve libido for postmenopausal women, but it’s not approved by the US Food and Drug Administration (FDA) for this purpose (SOR: B, based on small RCTs).

Clinical Commentary

Offer testosterone replacement—and candid talk about risks and alternatives
Robert K. Persons, DO, FAAFP
Eglin Air Force Base Family Medicine Residency, Eglin Air Force Base, Fla

Sexual dysfunction is a relatively frequent complaint from elderly patients, and its multifactorial nature must be investigated. If you discover low or hypogonadal testosterone levels in a male patient, offer replacement therapy. Be sure, too, to discuss the risks and the alternatives (including psychological aspects of care and partner communication). If your patient is a postmenopausal woman who is interested in combination estrogen and testosterone therapy, you should counsel her on the estimated 17% increased risk of breast cancer per year of use.¹

Evidence summary

Sexual dysfunction includes desire, arousal, orgasmic, and sex pain disorders. In the US, 43% of women and 31% of men experience sexual dysfunction. Since sexual dysfunction increases with age, the prevalence will likely increase with the aging American population.²

Testosterone helps men, but long-term risks are unclear

FAST TRACK

Testosterone by any route improves libido and sexual function

Several cross-sectional and longitudinal studies^3,4 demonstrate that serum total and free testosterone concentrations in men decline with age. Although the decline is gradual, by the eighth decade 30% of men have total testosterone values in the hypogonadal range and 50% have low free testosterone values.⁴

In randomized, placebo-controlled trials^5,6 of older men with low testosterone concentrations, testosterone administration was associated with a sustained increase in testosterone levels over 1 to 3 years. Regardless of the route of administration (gel, transdermal patch, or intramuscular injection), testosterone replacement results in improved libido and sexual function for men with low testosterone levels.^6-8 The caveat, though, is that testosterone trials of older men are characterized by very small sample sizes (n=10–50), disparate outcome measures, and the inclusion of men who were not uniformly testosterone-deficient and were asymptomatic.

In addition, these studies did not have sufficient power to detect either meaningful gains in patient-important outcomes or changes in prostate or cardiovascular event rates.^5,6,8,9 Thus, the long-term benefit/risk ratio of testosterone replacement therapy for aging hypogonadal men is unknown.

Less evidence for women

Up to 50% of postmenopausal women experience sexual dysfunction,¹⁰ and a low testosterone level is correlated with a decreased coital frequency.¹¹ Some studies suggest that testosterone at supraphysiological doses—by injections, implants, or pill (in combination with estrogen)—improves libido and sexual function.^12-14

The downside is that these studies are very small and have several methodological shortcomings. The pharmacokinetics of testosterone formulations for women are unclear, and the assays for the measurement of total and free testosterone concentrations in women lack accuracy and sensitivity. Long-term safety studies on breast cancer and cardiovascular events are lacking.

Testosterone’s major adverse effects include virilization (oily skin, acne, hirsutism, alopecia, deep voice), liver toxicity, polycythemia, breast carcinoma, and unfavorable changes in cardiovascular risk markers such as reduction in high-density lipoprotein cholesterol or insulin sensitivity.^5-8,12-15

Recommendations from others

FAST TRACK

The goal should be a testosterone level in the midnormal range

American Association of Clinical Endocrinologists guidelines for menopause¹⁶ recommends against the general use of testosterone therapy at menopause, except for women with continuing symptoms during adequate estrogen therapy.

The Endocrine Society¹⁷ recommends that clinicians consider offering testosterone therapy on an individualized basis to older men with low testosterone levels and significant symptoms of testosterone androgen deficiency. Before administration, it’s important to discuss the uncertainties, risks, and benefits of testosterone therapy in older men.

The Endocrine Society also recommends against starting testosterone therapy for patients with breast or prostate cancer, a palpable prostate nodule or induration or prostate-specific antigen >3 ng/mL without further urological evaluation, erythrocytosis (hematocrit >50%), hyperviscosity, untreated obstructive sleep apnea, severe lower urinary tract symptoms with an International Prostate Symptom Score (IPSS) >19, or class III or IV heart failure. When testosterone therapy is instituted, the goal should be to achieve testosterone levels in the midnormal range. This guideline recommends evaluating the patient 3 months after treatment initiation and then annually to assess whether he or she has responded to treatment and whether the patient is suffering any adverse effects.¹⁷

The Institute of Medicine examined the effectiveness and safety of testosterone therapy for older men. The report¹⁸ states that its use is appropriate only for those conditions approved by the FDA (primary and secondary hypogonadism among men), and that it is inappropriate to use testosterone replacement therapy to prevent possible future disease for otherwise healthy older men. The committee found no compelling evidence of major adverse effects resulting from testosterone therapy.¹⁸

Evidence-based answers from the Family Physicians Inquiries Network