Twenty postmenopausal women (aged 50-65 years) received 25 mg/day of dehydroepiandrosterone (DHEA) orally for 12 months. The mean serum concentrations of testosterone, estrone, and estradiol increased significantly and progressively, each reaching a 3- to 4-fold increase after 12 months. The mean serum concentration of progesterone increased significantly after 6 months, reaching a maximum increase of approximately 2.5-fold after 12 months. The mean concentration of growth hormone also increased significantly and progressively, reaching a maximum increase of more than 2-fold after 12 months. Plasma levels of luteinizing hormone and follicle-stimulating hormone decreased progressively, with the decrease becoming significant after 3 months for FSH and 6 months for LH. The mean Kupperman score (a measure of the severity of climacteric symptoms) showed progressive improvement, with the improvement becoming statistically significant after 3 months; after 12 months the degree of improvement was 76% in women who were 2 to 3 years postmenopausal and 67% in women who were 5 or more years postmenopausal. No side effects or uterine bleeding occurred. Ultrasound evaluation showed no significant increase in endometrial thickness in any of the patients after 6 and 12 months of therapy.

Comment: The results of this study demonstrate that administration of 25 mg/day of DHEA to postmenopausal women modulated a wide range of endocrine parameters and relieved climacteric symptoms, without causing uterine bleeding or endometrial hyperplasia. Although the clinical significance of raising the serum levels of estrogen, progesterone, testosterone, and growth hormone is not entirely clear, the levels of these hormones tend to decline with advancing age, and each of these hormones has been used to prevent or treat menopausal symptoms or various manifestations of aging.

Considering the multitude of adverse effects that are now known to occur with conventional hormone-replacement therapy, DHEA may turn out to be a safe and effective alternative to such therapy. Additional studies are needed to determine the long-term safety of DHEA, which some scientists believe might increase the risk of certain cancers. The safest and most effective hormone-replacement therapy for postmenopausal women will probably turn out to be small doses of various combinations of the four hormones produced by the human ovary (e.g., estrogen, progesterone, DHEA, and testosterone), with the doses individualized according to the needs of each particular patient.

Genazzani AD, et al. Long-term low-dose dehydroepiandrosterone oral supplementation in early and late postmenopausal women modulates endocrine parameters and synthesis of neuroactive steroids. Fertil Steril 2003;80:1495-1501.