Osteoporosis in male hypogonadism: responses to androgen substitution differ among men with primary and secondary hypogonadism.

BACKGROUND No randomized study exists comparing the effects of different modes of androgen substitution on bone mineral density (BMD). METHODS We performed a prospective, randomized, trial assigning 53 hypogonadal men to the following treatment groups: mesterolone 100 mg p.o. daily, testosterone undecanoate 160 mg p.o. daily, testosterone enanthate 250 mg i.m. every 21 days, or a single subcutaneous implantation of 1,200 mg crystalline testosterone. The BMD was determined by peripheral quantitative computed tomography. RESULTS At baseline, men with secondary hypogonadism (n = 33) had a lower BMD (-1.52 +/- 0.23 SDS; Z-scores) than men with primary hypogonadism (n = 20, -0.87 +/- 0.23 SDS, p < 0.01). In men with primary hypogonadism, the BMD increased dose dependently (crystalline testosterone +7.0 +/- 1.3%, testosterone enanthate +4.8 +/- 0.2%, testosterone undecanoate +3.4 +/- 2.5%, mesterolone +0.8 +/- 1.6%) after 6 months of therapy. Only secondary hypogonadal men treated with testosterone enanthate experienced an increase of the BMD. CONCLUSIONS In primary hypogonadal men the BMD responds dose dependently to testosterone substitution, whereas in secondary hypogonadism only testosterone enanthate treatment significantly increased the BMD.