EXECUTIVE SUMMARY

Results of a comprehensive meta-analysis indicate that testosterone can improve sexual well-being for postmenopausal women. According to the analysis, benefits includeed improved sexual desire, function, and pleasure, and fewer concerns about sex.

• Testosterone contributes to female libido and helps maintain normal metabolic function, muscle strength, cognitive function, and mood. Levels decline naturally over a woman’s lifespan, and can decline after surgical menopause.

• Although evidence indicates testosterone therapy can improve sexual function in women, available formulations have been designed for men, with little evidence available regarding safety or adverse side effects in women.


Results of a comprehensive meta-analysis indicate that testosterone can improve sexual well-being for postmenopausal women.1 According to the analysis, benefits include improved sexual desire, function, and pleasure, and fewer concerns about sex.

Testosterone contributes to female libido and and helps maintain normal metabolic function, muscle strength, cognitive function, and mood. Levels decline naturally over a woman’s lifespan, and can decline after surgical menopause. Although evidence indicates that testosterone therapy can improve sexual function in women, available formulations have been designed for men, with little evidence available regarding safety or adverse side effects in women. Susan Davis, MBBS, FRACP, PhD, FAHMS, professor at Monash University in Melbourne, Australia, and senior author of the meta-analysis, said her research group’s results suggested it is time to develop specific testosterone treatment tailored to postmenopausal women.

“Nearly a third of women experience low sexual desire at midlife, with associated distress, but no approved testosterone formulation or product exists for them in any country and there are no internationally agreed guidelines for testosterone use by women,” said Davis in a press statement. “Considering the benefits we found for women’s sex lives and personal well-being, new guidelines and new formulations are urgently needed.” (The statement can be found online at: https://bit.ly/2NzkIHu.)

Take a Closer Look

Investigators reviewed 46 reports of 36 randomized controlled trials conducted between January 1990 and December 2018. The trials included 8,480 participants ages 18-75 years, with about 95% identified as postmenopausal. The trials compared testosterone treatment to a placebo or to an alternative hormone treatment such as estrogen, with or without progestogen.

The analysis examined the effect of treatments on sexual function, as well as measures of heart, cognitive, and musculoskeletal health. Also studied were serious side effects, such as increased risk of heart disease or breast cancer; effect on mood and well-being; measures of breast health, such as mammographic density; metabolic effects; and lipid profiles. Investigators also looked for reports of development of androgenic effects, such as increased hair growth.

In 15 studies, including 3,766 naturally and surgically postmenopausal women, consistent beneficial effects were seen for all measures of sexual function. Testosterone treatment increased frequency of satisfactory sexual events, and increased sexual desire, pleasure, arousal, orgasm, responsiveness to sexual stimuli, and self-image. Women treated with testosterone also showed reduced measures of sexual concerns and sexually associated distress.1

“The beneficial effects for postmenopausal women shown in our study extend beyond simply increasing the number of times a month they have sex,” said Davis. “Some women who have regular sexual encounters report dissatisfaction with their sexual function, so increasing their frequency of a positive sexual experience from never, or occasionally, to once or twice a month can improve self-image and reduce sexual concerns, and may improve overall well-being.”

The meta-analysis uncovered no beneficial effects on cognitive measures, bone mineral density, body composition, or muscle strength. No benefits were seen for depressive mood irrespective of menopausal status or in psychological well-being. Researchers noted that the number of women included in these studies was small, requiring further research.

Testosterone use had no serious adverse effects on postmenopausal women in terms of glucose or insulin in the blood, blood pressure, or measures of breast health, researchers reported. Limited data were available for breast cancer risk, and further research is needed to clarify the effects, researchers stated.

In studies of non-oral testosterone, researchers determined no effects on lipid profiles or metabolic variables such as cholesterol. However, use of oral testosterone increased LDL cholesterol, and reduced HDL cholesterol, overall cholesterol, and triglycerides. Postmenopausal women treated with testosterone were not more likely to experience a serious cardiovascular event, they reported.1

More Research Needed

In postmenopausal women, testosterone has been used with concurrent estrogen, estrogen plus progestogen, or on its own.2-6 With the increasing use of compounded therapies that include testosterone, more research is needed. No current therapy including testosterone carries an approved indication from the FDA. A comment published with the meta-analysis indicates that adequate long-term studies can address benefits and risks of testosterone treatment in specific clinical conditions relevant to healthy female longevity.7

Two drugs carry indications for hypoactive sexual desire dysfunction. In 2015, the FDA approved flibanserin. Originally developed as an antidepressant, flibanserin works by increasing levels of dopamine and norepinephrine, while decreasing levels of serotonin. This drug interaction is intended to increase chemicals that help promote sexual desire and decrease one that can suppress desire. In June 2019, the FDA approved bremelanotide for treatment of hypoactive sexual desire dysfunction. Bremelanotide, a melanocortin 4 receptor agonist drug candidate, is a synthetic peptide analog of the naturally occurring hormone alpha-MSH (melanocyte-stimulating hormone).

REFERENCES

  1. Islam RM, Bell RJ, Green S, et al. Safety and efficacy of testosterone for women: A systematic review and meta-analysis of randomised controlled trial data. Lancet Diabetes Endocrinol 2019;doi:10.1016/S2213-858730189-5.
  2. Simon J, Braunstein G, Nachtigall L, et al. Testosterone patch increases sexual activity and desire in surgically menopausal women with hypoactive sexual desire disorder. J Clin Endocrinol Metab 2005;90:5226-5233.
  3. Braunstein GD, Sundwall DA, Katz M, et al. Safety and efficacy of a testosterone patch for the treatment of hypoactive sexual desire disorder in surgically menopausal women: A randomized, placebo-controlled trial. Arch Intern Med 2005;165:1582-1589.
  4. Shifren J, Davis SR, Moreau M, et al. Testosterone patch for the treatment of hypoactive sexual desire disorder in naturally menopausal women: Results from the INTIMATE NM1 study. Menopause 2006;13:770-779.
  5. Panay N, Al-Azzawi F, Bouchard C, et al. Testosterone treatment of HSDD in naturally menopausal women: The ADORE study. Climacteric 2010;13:121-131.
  6. Davis SR, Moreau M, Kroll R, et al. Testosterone for low libido in menopausal women not taking estrogen therapy. N Engl J Med 2008;359:2005-2017.
  7. Nappi RE. Testosterone for women: Green light for sex, amber light for health? Lancet Diabetes Endocrinol 2019;doi:10.1016/S2213-858730251-7.