This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Miller, K. K. Articles by Klibanski, A. Search for Related Content PubMed PubMed Citation Articles by Miller, K. K. Articles by Klibanski, A. Related Collections Neuroendocrinology and Pituitary Cardiovascular Endocrinology Female Endocrinology

Effects of Testosterone Therapy on Cardiovascular Risk Markers in Androgen-Deficient Women with Hypopituitarism

Neuroendocrine Unit (K.K.M., B.M.K.B., A.S., K.P.-L., A.K.), Massachusetts General Hospital, and Department of Laboratory Medicine, Children’s Hospital (G.B., N.R.), 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: Low-dose testosterone replacement therapy in women with relative androgen deficiency has been shown to have beneficial effects on body composition, bone mass, and psychosexual function. However, the safety of chronic testosterone administration on cardiovascular risk and insulin resistance is unknown.

Objective: The aim of the study was to determine the effects of physiological testosterone replacement on cardiovascular risk markers and insulin resistance in women.

Design: A 12-month, randomized, placebo-controlled study was conducted.

Setting: A General Clinical Research Center was the setting for the study.

Study Participants: A total of 51 women of reproductive age with androgen deficiency due to hypopituitarism participated.

Intervention: Study participants were randomized to physiological testosterone administration, 300 µg daily, or placebo, by patch.

Main Outcome Measures: We measured fasting glucose, fasting insulin, insulin-resistance homeostasis model of assessment (IRHOMA), quantitative insulin sensitivity check index (QUICKI), high-sensitivity C-reactive protein, vascular cell adhesion molecule (VCAM), leptin, lipoprotein (a), apolipoprotein A1, and homocysteine.

Results: At 12 months, fasting insulin and IRHOMA were significantly lower in the testosterone compared with the placebo group, and there was a trend toward a higher QUICKI level at 12 months in the testosterone compared with the placebo group. These differences were no longer significant after controlling for baseline levels. We observed no effect, either positive or negative, of testosterone administration on high-sensitivity C-reactive protein, VCAM leptin, lipoprotein (a), or apolipoprotein A1.

Conclusions: Our data suggest that physiological testosterone replacement in women with hypopituitarism for 12 months does not increase, and may improve, insulin resistance. Chronic low-dose testosterone administration does not increase markers of cardiovascular disease reflecting several different mechanistic pathways. Large, randomized, placebo-controlled, long-term prospective studies are needed to determine whether low-dose testosterone replacement affects cardiovascular risk and event rates in women.

This article has been cited by other articles:

				C. Baylis Sexual Dimorphism of the Aging Kidney: Role of Nitric Oxide Deficiency Physiology, June 1, 2008; 23(3): 142 - 150. [Abstract] [Full Text] [PDF]