Although estrogen remains the central female hormone most frequently used in both wellness and disease prevention, much less controversy surrounds the use of testosterone in women, though the evidence either supporting or discouraging its use is scarce. Nicknamed ‘‘the hormone of desire’’ and promoted in the popular media as the rescuer from the plight of decreasing libido in aging women, testosterone has gained rapid acceptance in the prevention and wellness arenas at a time when controversy and confusion surround estrogen and progesterone therapies.

Testosterone is produced by the ovaries and adrenals in young women in low doses (free testosterone levels range between 2–8 pg/mL). The bulk of the present research on the use of testosterone has been conducted on women with surgical menopause, hypopituitarianism, anorexia nervosa, and primary adrenal insufficiency; patients with HIV and low body weight;[1] and patients with steroid- and oral contraceptive–induced suppression of endogenous androgens. Although there has been little if any formal study on testosterone use in normal aging in women, we know that adequate levels of testosterone play an important role in helping women maintain a healthy body composition.

Women begin to gain body fat 10 years before they experience menopause, and many women gain weight when taking birth control pills, but doctors frequently overlook the role that testosterone can play in helping to ameliorate this weight gain. Testosterone therapy results in an increase in fat-free body mass and mitigates central fat deposition associated with estrogen use.[2] In a double-blind placebo-controlled small study of androgen-deficient women, testosterone replacement demonstrably increased thigh muscle mass as measured by CT scanning.[3]

Loss of libido in the aging female is the most common complaint that leads physicians to consider testosterone deficiency as a possible cause and the main consideration for treatment with testosterone. Multiple factors directly affect sexual inclination. Poor relationship status, self-image issues, multiple medications and their side effects, other stress factors, aging, and concurrent chronic or acute illnesses are some of the most frequently encountered deterrents of sex drive. Many of these factors cannot be altered, and all factors should be taken into account.  While circulating testosterone levels do not definitively diagnose low testosterone as the cause for loss of libido, it may be helpful to keep in mind that premenopausal women have a range of 20 to 75 ng/dL total testosterone while postmenopausal women can present with values as low as 5 to 10 ng/dL.  The seminal study on impaired sexual function improvement with supplemental testosterone comes from a double-blind, placebo-controlled study in the New England Journal of Medicine. Seventy-five women 31 to 56 years old after undergoing oophorectomy (removal of ovaries) and hysterectomy were randomly assigned to receive placebo, conjugated estrogen and either 150 mcg or 300 mcg doses of transdermal testosterone. The women who received the higher dose of testosterone reported a two- to threefold increase in sexual desire, masturbation, sexual intercourse, and sense of positive well-being as compared with placebo or conjugated estrogen alone.[4]

Besides helping women maintain lean muscle mass and an enjoyable sex life well into their forties, fifties, sixties and beyond, there is some evidence pointing to additional positive effects of testosterone on a woman’s health as she ages.  A report in the Journal of Women’s Health examined the hypothesis that testosterone deficiency is a key predictive factor for heart disease in aging women or women who have had hysterectomies.[5] Cardiovascular disease is the leading cause of death in postmenopausal women. Women who have hysterectomies are three times more likely to develop cardiovascular disease compared to women who have not had one. Women who have hysterectomies often receive estrogen replacement therapy but not testosterone replacement.  Although this seems to make sense in context of the numerous reports linking low testosterone to an increased risk of cardiovascular disease and premature death in men, a recent observational study may suggest the opposite.

In this study, researchers measured levels of testosterone in 344 women, aged 65-98 years. They found that women with the highest testosterone levels — in the top 25 percent of this study group— were three times as likely to have coronary heart disease compared to women with lower testosterone levels. These women were also three times as likely to have a group of metabolic risk factors called the metabolic syndrome compared to women with lower testosterone levels.   A greater degree of insulin resistance is the proposed mechanism.  Testosterone therapy reduces insulin resistance, metabolic syndrome and cardiovascular risk in men.  Curious.  This is a pre-publication report, so seeing the full study in next month’s Journal of Clinical Endocrinology and Metabolism should be interesting.

Breast cancer is the most common cancer in women.  Acting through androgen receptors, testosterone opposes estradiol induced proliferation of human breast cell lines[6]. Cases where endogenous testosterone levels are elevated, such as with polycystic ovary syndrome, are associated with breast tissue atrophy and a decreased risk of breast cancer.[7] There are, however, conflicting data on the potential role of supplemental testosterone in the development of breast cancer.

Though treatment with testosterone in the aging woman is gaining popularity, there is a definitive need for studies specific to this population to evaluate the safety and efficacy of testosterone as a therapeutic modality for postmenopausal women, as well as for younger women with loss of libido, to define its best use in prevention and wellness.   It is thought by some to be the missing link in hormone replacement therapy.  As more studies show the benefits of improved quality of life, preserved sexual function, restored libido, and healthy body composition from testosterone therapy, the more routine it will become for women seeking to optimize their health.

[1] Dolan S, Wilkie N. Arch effects of testosterone administration on human immunodeficiency virus-infected women with low weight. Arch Intern Med 2004;164:897–904.

[2] Davis S, Walker K. Effects of estradiol with and without testosterone on body composition and relationship with lipids in postmenopausal women. Menopause 2000;7:395–401.

[3] Miller K, Biller B, Beauregard C. Effects of testosterone replacement in androgen-deficient women with hypopituitarism; a randomized, double-blind, placebo-controlled study. J Clin Endocrinol Metab 2006;91:1683–90.

[4] Shifren J, Braunstein G, Simon J. Transdermal testosterone treatment in women with impaired sexual function after oophorectomy.        NEJM 2000;343:682–8.

[5] Rako S. Testosterone deficiency: a key factor in the increased cardiovascular risk to women following hysterectomy or with natural aging?    J Womens Health. 1998 Sep;7(7):825-9

[6] Ando S, De Amicis F. Breast cancer from estrogen to androgen receptor. V Mol Molecular and Cellular Endocrinology 2002;193:121–8.

[7] Gammon M, Thompson W. Polycystic ovaries and the risk of breast cancer.

Am J Epidemiol 1991;134:818–24.