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Effects of Oral Androstenedione Administration on Serum Testosterone and Estradiol Levels in Postmenopausal Women

Endocrine Unit (B.Z.L., K.M.L., J.S.F.), Department of Medicine, and Biostatistics Center (H.L.), Massachusetts General Hospital, Boston, Massachusetts 02114; Departments of Medicine and Obstetrics and Gynecology (C.L.), University of Massachusetts Medical School, Worcester, Massachusetts 01655; and Departments of Medicine and Molecular and Medical Pharmacology (D.H.C.), Olympic Analytical Laboratory, University of California at Los Angeles, Los Angeles, California 90025

Address all correspondence and requests for reprints to: Benjamin Z. Leder, Endocrine Unit, Massachusetts General Hospital, Bulfinch 327, Fruit Street, Boston, Massachusetts 02114. E-mail: bzleder{at}partners.org.

Abstract

Androstenedione is a steroid hormone and an intermediate in the synthetic pathway of both testosterone and estradiol in men and women. It is available without prescription and taken with the expectation that it may have beneficial effects on strength, general well-being, libido, and quality of life. Although studies have shown that oral androstenedione increases serum testosterone and estradiol levels in men, the hormonal effects of androstenedione in postmenopausal women are unknown. We randomly assigned 30 healthy postmenopausal women to receive 0, 50, or 100 mg androstenedione as a single oral dose. After androstenedione administration, we made hourly measurements of serum androstenedione, estrone, estradiol, and testosterone concentrations during 12 h of frequent blood sampling. The mean change (±SD) in serum androstenedione area under the curve (AUC) was greater in both the 50-mg (79 ± 39%) and 100-mg dose groups (242 ± 184%) than in the control group (-29 ± 28%) (P < 0.0001 for controls vs. 50-mg group and controls vs. 100-mg group). The mean change in serum androstenedione AUC was also greater in the 100-mg than 50-mg dose group (P = 0.0026). The mean change in serum estrone AUC was greater in both the 50-mg (108 ± 72%) and 100-mg dose groups (116 ± 119%) than in the control group (-5 ± 19%), although the control vs. 100-mg group comparison did not quite meet statistical significance (P < 0.0001 for controls vs. 50-mg group, P = 0.0631 controls vs. 100-mg group). The mean change in serum estradiol AUC remained stable after supplementation in all groups without any between-group differences observed (-11 ± 17%, 2.8 ± 34%, -11 ± 27%, for the control, 50-mg, and 100-mg groups, respectively). The mean change in serum testosterone AUC was greater in both the 50-mg (185 ± 146%) and 100-mg dose groups (457 ± 601%) than in the control group (-27 ± 13%) (P < 0.0001 for controls vs. 50-mg group and for controls vs. 100-mg group). The mean change in testosterone AUC was also greater in the 100-mg dose group than 50-mg dose group (P = 0.0257). There was considerable individual variability in the changes of serum androstenedione, estrone, and testosterone levels in the treated groups with peak serum testosterone levels exceeding the upper limit of normal in 4 of 10 women in the 50-mg dose group and 6 of 10 in the 100-mg dose group. We concluded that the acute administration of both 50-mg and 100-mg of androstenedione increases serum testosterone and estrone levels, but not estradiol levels, in postmenopausal women. If these hormonal effects are sustained during long-term administration, regular use of this supplement by postmenopausal women could thus cause both beneficial and adverse effects.

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