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

Abstract

Although testosterone (T) replacement has salutary effects in androgen-deficient men, its efficacy in women with anterior pituitary dysfunction is not clear. Hypopituitarism in women is characterized by marked androgen deficiency secondary to loss of adrenal and/or ovarian function. The investigators carried out a 12-month randomized, placebo-controlled study evaluating T replacement in 51 women of reproductive age who were androgen-deficient because of hypopituitarism leading to adrenal insufficiency, hypogonadism, or both. Twenty-four of them were randomized to receive transdermal testosterone and 27 others received placebo. Two 150-μg patches (Intrinsa) were placed on the abdomen and changed twice a week. The mean time-averaged increase in serum free T was 2.7 pg/mL, and serum levels remained relatively constant for 96 hours after applying the patch. Baseline demographic and clinical features were comparable in the T-treated and control groups. No T was detected in more than half the women but levels became normal during active treatment. In more than one third of cases, the dose of T was halved to maintain levels within the normal range. Bone density increased significantly at both the hip and radius but not in the spine. Fat-free mass also rose significantly in T-treated women; the mean increase was 3.4% and 0.6%, respectively, in the actively treated and placebo groups. Mood, measured using the Beck Depression Inventory, improved with T treatment, as did sexual function, but there was no change in cognition. Several quality-of-life scales pointed to significant improvement in T-treated women compared with placebo recipients. One third of T-treated patients described increased acne. Three patients withdrew from the study because of severe irritation at patch sites. Less severe patch reactions occurred in both groups. Total cholesterol increased by 6% on average in women given T, but there were no significant changes in other lipid or lipoprotein levels. Alanine aminotransferase levels tended to decline in actively treated women. This trial, the first randomized, double-blind, placebo-controlled trial of testosterone therapy, demonstrated positive effects on bone density, body composition, and some aspects of neurobehavioral function in women with severe androgen deficiency secondary to hypopituitarism. Treatment at physiological replacement levels was well tolerated.