Context: Data regarding gender-specific efficacy of growth hormone (GH) on critical endpoints are lacking. There are no randomized, placebo-controlled studies of physiologic GH therapy solely in women.

Objective: To determine the effects of physiologic GH replacement on cardiovascular risk markers and body composition in women with GHD.

Design: 6-month, randomized, placebo-controlled, double-blind study

Setting: GCRC

Study Participants: 43 women with GHD due to hypopituitarism

Intervention: Study participants were randomized to receive GH (goal mid-normal serum IGF-I) or placebo.

Main Outcome Measures: Cardiovascular risk markers, including high sensitivity C-reactive protein, tissue plasminogen activator, and body composition, including visceral adipose tissue by cross-sectional computed tomography.

Results: Mean daily GH dose was 0.67 mg. The mean IGF-I SD score increased from -2.5 ± 0.3 to -1.4 ± 0.9 (GH) (p<0.0001 vs. placebo). High sensitivity C-reactive protein decreased by 38.2 ± 9.6% (GH) vs. 18.2 ± 6.0% (placebo) (p=0.03). Tissue plasminogen activator and total cholesterol decreased and high-density lipoprotein increased. Homeostasis model assessment: insulin resistance and other markers were unchanged. Body fat decreased [-5.1 ± 2.0 (GH) vs. 1.9 ± 1.0% (placebo), p=0.002], as did visceral adipose tissue [-9.0 ± 5.9 (GH) vs. 4.3 ± 2.7% (placebo), p=0.03]. Change in IGF-I level was inversely associated with % change in visceral adipose tissue (r= -0.61, p=0.002), total body fat (r= -0.69, p<0.0001), and high sensitivity C-reactive protein (r= -0.51, p=0.003).

Conclusions: Low-dose GH replacement in women with GHD decreased total and visceral adipose tissue, and improved cardiovascular markers with a relatively modest increase in IGF-I levels without worsening insulin resistance.