Testosterone Replacement Safe, Effective in Premenopausal Women with Androgen Deficiency

BOSTON?Women of reproductive age with underactive pituitary glands who are treated with testosterone replacement therapy show clinically significant improvements in their mood and sexuality, according to new study data presented at the 88th Annual Meeting of the Endocrine Society.

The syndrome of androgen deficiency caused by hyposecretion of the adrenal or ovarian glands has been increasingly recognized by many sexual medicine experts and some primary care physicians, but no agreement exists about the risks and benefits of testosterone replacement therapy, in part because of the scarcity of randomized, placebo-controlled studies and safety data.

In a study using an investigational testosterone patch, use of testosterone replacement therapy resulted in improvements in overall well-being, levels of energy versus fatigue, general health, and even sleep quality. Contrary to previous suggestions, however, there were no improvements in most cognitive function test scores, other than a modest increase in spatial abilities.

"This is the first randomized, double-blind, placebo-controlled study to show that replacing testosterone levels to normal in women with hypopituitarism may improve mood, sexual function, and energy levels," said lead investigator Karen Miller, MD, of Harvard Medical School, Boston.

This 12-month study included 51 women (aged 19-50 years) who were randomly assigned to receive either the 300-?g testosterone patch Intrinsa (Procter & Gamble) or placebo. The testosterone dosage was adjusted to deliver a normal level of the hormone, and the patch was replaced twice weekly.

At baseline, mean free testosterone levels were below the lower limit of normal in all participants, and in 55% of the women testosterone levels were not detectable.

Mood was measured with the Beck Depression Inventory, and sexual function was assessed with the Derogatis Interview for Sexual Function. Quality-of-life measurements were assessed using the RAND 36-Item health survey, the Nottingham Health Profile, and the Psychologic General Well-Being index. Cognitive function was evaluated with the Wechsler Abbreviated Scale of Intelligence, the Vanderberg and Kuse Mental Rotations Test, the Hopkins Verbal Learning Test, the Woodcock Johnson Cross-out Test, and the Grooved Pegboard Test.

Compared with placebo, mood and sexual function improved in the women receiving testosterone. All patients treated with the patch attained physiologic testosterone levels. Treatment was well tolerated, with no increase in unwanted body hair or hair loss on the scalp. The only reported adverse effect was increased facial acne.

"For women with a severe deficiency of this important hormone, our study shows that treatment may make a difference in many important aspects of their lives," Dr Miller said.

IMWR

"This is a preliminary first study, but I think it is fairly promising," Dr Miller told .

"It may be useful to replace testosterone therapy in these women. This is proof of principle." She added, "Further studies are needed to determine which subsets of women benefit and to investigate the long-term safety of testosterone replacement in women."

KEY POINTS

The question of testosterone replacement therapy has been the topic of much debate in the past few years among sexual medicine experts.

A large percentage of women, old and young, are deficient in this important hormone, but safety and efficacy issues of such therapy have not been properly studied.

The results of this small but randomized, double-blind, placebo-controlled study suggest that addressing androgen-deficiency syndrome in women of reproductive age is appropriate and should be considered in the primary care setting.