MON-094 Aromatase Inhibitors and Weight Loss in Severely Obese Male Veterans with Hypogonadism: A Randomized Clinical Trial

Introduction: The prevalence of hypogonadism among males is influenced by aging and obesity. The increased expression of the aromatase enzyme in the adipose tissue of obese men leads to a high conversion of androgens to estrogen, exerting a negative feedback on the hypothalamus-pituitary-gonadal axis contributing to hypogonadotropic hypogonadism. Our objective is to determine if anastrozole, an aromatase inhibitor (AI), in combination with weight loss could have a positive effect on symptoms of hypogonadism and muscle strength, and to evaluate the impact on bone mineral density (BMD) and bone quality. Methods: Twenty-three obese men (BMI≥35kg/m2) aged 35-65 years old with hypogonadotropic hypogonadism were randomized in a 6-month double-blind placebo-controlled trial of weight loss (with diet and exercise) plus either anastrozole (n=12) or placebo (PBO) (n=11). The inclusion criteria were morning testosterone 10.9 pg/mL, and LH <9 IU/L. The hypogonadal symptoms were evaluated by 4 questionnaires: IPSS, qADAM, IWQOL, and IIEF-5, and the muscle strength was measured by Biodex machine. The body composition and BMD were determined by DXA, and the bone microarchitecture by HR-pQCT. The hormonal levels, hypogonadal symptoms, muscle strength, and body composition were assessed at baseline, 3 months, and 6 months; whereas the BMD and bone microarchitecture were evaluated at baseline and 6 months. Results: Average weight loss at 6 months was -7.0±6.9% in the AI group vs -2.4±2.9% in the PBO group (p=0.12). At 6 months, testosterone levels increased by +95.2±66.3% in the AI group vs +0.8±29.4% in the PBO group (p<0.01), and estradiol levels decreased by -60.9±21.8% in the AI group vs +5.2±18.6% in the PBO group (p<0.01). LH levels increased by +66.6±89.3% in patients treated with AI and decreased by -4.8±24.2% in those who received PBO (p=0.06). There was no improvement of symptoms in the AI group (+18.9±48.7%) vs placebo (+7.8±34.1%) based on IIEF-5 questionnaire (p=NS) and no significant difference in muscle strength between groups. Lean mass was better preserved in the AI compared to the PBO group (-0.73±2.5% vs -3.60±2.70%, respectively; p=0.05). There was no change in spine BMD in the AI compared to the PBO group (-0.71±3.32% vs +3.22±4.90%, respectively; p=0.08), and no change in tibial trabecular bone area in the AI compared to the decrease in the PBO group (+0.12±0.68% vs -2.09±2.20%, respectively; p<0.05). Conclusion: AI plus weight loss improves the hormonal profile of severely obese men with hypogonadism and prevents weight loss-induced loss of lean mass without causing major side effect on BMD within 6 months of therapy. However, in this short-term study with limited sample size, we found no significant improvement in symptoms of hypogonadism. Further large and long-term trials are needed to confirm these results.