Osteoporosis affects over 20 million Americans and leads to considerable morbidity and mortality. Although osteoporosis is more common in women, largely due to postmenopausal estrogen deficiency, it also develops in men. Hypogonadism is a leading risk factor for osteoporosis in men. Still, it is unknown if androgen deficiency, estrogen deficiency, or both lead to hypogonadal bone loss in men. In the proposed study, 75 normal men (ages 20-45) will be randomly assigned to one of three groups (n=25 per group). Group 1 will receive a GnRH agonist (Zoladex, 3.6 mg q 4 wks) for 12 weeks, thereby suppressing endogenous gonadal steroids to pre-pubertal levels. Group 2 will receive the GnRH agonist plus testosterone replacement (Androderm, 5 mg/day), thereby normalizing circulating testosterone and estradiol levels. Group 3 will receive the GnRH agonist plus Androderm plus an aromatase inhibitor (Femara, 2.5 mg/day), thereby normalizing testosterone but causing a selective estrogen deficiency. Bone turnover markers (bone specific alkaline phosphatase, osteocalcin, urinary N-telopeptide, and urinary deoxypyridinoline) and calcium regulatory hormones will be measured every 4 weeks. Bone turnover will increase in Group 1 and should remain unchanged in Group 2. If androgens alone are sufficient to maintain normal bone turnover in adult males, bone turnover should not increase in Group 3. If, however, estrogens are also required to maintain normal bone turnover in men, bone turnover should increase in Group 3.
| Leder, Benjamin Z; LeBlanc, Karen M; Schoenfeld, David A et al. (2003) Differential effects of androgens and estrogens on bone turnover in normal men. J Clin Endocrinol Metab 88:204-10 |
