Effects of clomiphene citrate on male obesity-associated hypogonadism: a randomized, double-blind, placebo-controlled study

Background Obesity causes secondary hypogonadism (HG) in men. Standard testosterone (T) replacement therapy improves metabolic parameters but leads to infertility. Objective To evaluate clomiphene citrate (CC) treatment of adult men with male obesity-associated secondary hypogonadism (MOSH). Design Single-center, randomized, double-blind, placebo-controlled trial. Participants Seventy-eight men aged 36.5 +/- 7.8 years with a body mass index (BMI) > 30 kg/m(2), total testosterone (TT) <= 300 ng/dL, and symptoms in the ADAM questionnaire. Intervention Random allocation to receive 50 mg CC or placebo (PLB) for 12 weeks. Outcomes (1) Clinical features: ADAM and sexual behavior questionnaires; (2) hormonal profile: serum TT, free T, estradiol (E2), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and sex hormone-binding globulin (SHBG); (3) body composition: BMI, waist circumference, and bioelectric impedance analysis; (4) metabolic profile: blood pressure, fasting blood glucose, HbA lc, insulin, HOMA-IR, and lipid profile; (5) endothelial function: flow-mediated dilation of the brachial artery, quantitative assessment of endothelial progenitor cells and serum sICAM-1, sVCAM-1, and selectin-sE levels; (6) safety aspects: hematocrit, serum prostate-specific antigen, International Prostate Symptom Score, and self-reported adverse effects. Results There was an improvement in one sexual complaint (weaker erections; P < 0.001); increases (P < 0.001) in TT, free T, E2, LH, FSH, and SHBG; and improvements in lean mass (P < 0.001), fat-free mass (P = 0.004), and muscle mass (P < 0.001) in the CC group. CC reduced HDL (P < 0.001). No statistically significant differences were seen in endothelial function. Conclusions CC appeared to effectively improve the hormonal profile and body composition. CC may be an alternative treatment for MOSH in adult men.