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/m2 , 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, HbA1c, 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.