Abstract

Therapeutic strategies using progestins, androgens, and synthetic steroids such as tibolone are based on the understanding that estrogen, progesterone, and androgen receptors are localized to reproductive target tissues, brain, and bone. Unfortunately, these sex steroid receptors are widely distributed and localized to other tissues, often resulting in unintended effects. Progestins at high doses have been shown to be effective at reducing hot flashes by approximately 80% to 90%. Side effects include weight gain, mastalgia, fluid retention, vaginal discharge, and dry mouth. Dehydroepiandrosterone (DHEA), an adrenal-derived androgen, can be considered a prohormone that is peripherally converted to more potent androgens and estrogens. In studies with small numbers of subjects, DHEA has been reported to reduce vasomotor symptoms, increase sexual arousal, and improve cognitive performance. With regard to use of other androgens, there are no current testosterone preparations approved by the US Food and Drug Administration (FDA) for use in menopausal women. In phase 3 trials, a testosterone transdermal matrix patch has been shown to be effective in treatment of hypoactive sexual desire disorder in menopausal women on estrogen therapy. Tibolone, a synthetic steroid with estrogenic, androgenic, and progestational properties has been shown to be effective in the treatment of vasomotor symptoms and in preserving bone density, and it may provide positive effects on sexual function. The beneficial effects of these compounds in the menopausal woman for treatment of vasomotor symptoms, general well-being, cognitive deficits, bone loss, mood disorders, and sexual function are discussed. The overall clinical trial evidence for benefits and side effects also is presented.

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