A Double-Blind, Placebo-Controlled, Randomized Clinical Trial of Recombinant Human Chorionic Gonadotropin on Muscle Strength and Physical Function and Activity in Older Men with Partial Age-Related Androgen Deficiency

Abstract

Despite partial androgen deficiency, the safety and efficacy of androgen therapy in older men remains controversial because controlled studies of testosterone have given equivocal results. Human chorionic gonadotropin (hCG) can be conveniently and infrequently self-administered, and it increases not only circulating testosterone but also estradiol and other testicular steroids. We evaluated the efficacy and safety of 3 months of treatment with sc recombinant hCG (r-hCG, Ovidrel) on muscle mass, strength, mobility, and physical activity in ambulant, community-dwelling men more than 60 yr old having partial androgen deficiency (testosterone ≤ 15 nmol/liter, twice). Forty eligible men (mean age, 67 yr; range, 60–85 yr) were randomized to receive r-hCG (5000 IU, 250 μg) or placebo by twice weekly sc self-injection and were studied before treatment, monthly during treatment, and 1 month after treatment. All completed the study, and treatment groups were well matched. r-hCG significantly increased body weight (∼1 kg; P < 0.05) and lean body mass (∼2 kg; P < 0.001) and reduced fat mass (∼1 kg, P < 0.05). However, anthropometric measures of skinfold thickness (biceps, triceps, subscapular, suprailiac) and circumferences (midarm, waist, hip, and midthigh), including the waist-hip ratio, did not change significantly. Shoulder and knee strength (peak torque), as measured by isokinetic and isometric dynamometry, was not significantly increased, nor was physical activity (accelerometry and Physical Activity Scale for Elderly self-report) or gait and balance (modified Guralnik and Frailty and Injuries: Cooperative Studies of Intervention Techniques performance batteries) altered. Total and free testosterone and estradiol were markedly (150%; P < 0.001) and stably increased, whereas LH, FSH, and urea were significantly decreased. Testis volume was significantly decreased (∼5 ml; P < 0.05). There were no significant changes in hemoglobin, osteocalcin, or prostate-specific antigen, and the International Prostate Symptom Score did not change. Three men developed nipple tenderness that did not progress to gynecomastia. We conclude that 3 months of treatment with twice weekly r-hCG demonstrates sustained androgenic effects on hormones and muscle mass but has no effect on muscle strength or physical functioning.