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

Abstract

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. The aim of the study was to determine the effects of physiological testosterone replacement on cardiovascular risk markers and insulin resistance in women. A 12-month, randomized, placebo-controlled study was conducted. A General Clinical Research Center was the setting for the study. A total of 51 women of reproductive age with androgen deficiency due to hypopituitarism participated. Study participants were randomized to physiological testosterone administration, 300 mug daily, or placebo, by patch. 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. 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. 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.