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Effects of Testosterone Replacement in Androgen-Deficient Women with Hypopituitarism: A Randomized, Double-Blind, Placebo-Controlled Study

Neuroendocrine Unit (K.K.M., B.M.K.B., C.B., J.G.L., J.J., A.K.) and Departments of Neurosurgery (B.S.) and Radiation Oncology (J.L.), Massachusetts General Hospital Biostatistics Center (D.S.), and Psychology Assessment Center (J.C.S.), Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114

Address all correspondence and requests for reprints to: Karen K. Miller, Neuroendocrine Unit, Bulfinch 457B, Massachusetts General Hospital, Boston, Massachusetts 02114. E-mail: kkmiller{at}partners.org.

Context: Hypopituitarism in women is characterized by profound androgen deficiency due to a loss of adrenal and/or ovarian function. The effects of testosterone replacement in this population have not been reported.

Objective: The objective of the study was to determine whether physiologic testosterone replacement improves bone density, body composition, and/or neurobehavioral function in women with severe androgen deficiency secondary to hypopituitarism.

Design: This was a 12-month randomized, placebo-controlled study.

Setting: The study was conducted at a general clinical research center.

Study Participants: Fifty-one women of reproductive age with androgen deficiency due to hypopituitarism participated.

Intervention: Physiologic testosterone administration using a patch that delivers 300 µg daily or placebo was administered.

Main Outcome Measures: Bone density, fat-free mass, and fat mass were measured by dual x-ray absorptiometry. Thigh muscle and abdominal cross-sectional area were measured by computed tomography scan. Mood, sexual function, quality of life, and cognitive function were assessed using self-administered questionnaires.

Results: Mean free testosterone increased into the normal range during testosterone administration. Mean hip (P = 0.023) and radius (P = 0.007), but not posteroanterior spine, bone mineral density increased in the group receiving testosterone, compared with placebo, as did mean fat-free mass (P = 0.040) and thigh muscle area (P = 0.038), but there was no change in fat mass. Mood (P = 0.029) and sexual function (P = 0.044) improved, as did some aspects of quality of life, but not cognitive function. Testosterone at physiologic replacement levels was well tolerated, with few side effects.

Conclusions: This is the first randomized, double-blind, placebo-controlled study to show a positive effect of testosterone on bone density, body composition, and neurobehavioral function in women with severe androgen deficiency due to hypopituitarism.

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