SUBLINGUAL TESTOSTERONE REPLACEMENT IMPROVES MUSCLE MASS AND STRENGTH, DECREASES BONE-RESORPTION, AND INCREASES BONE-FORMATION MARKERS IN HYPOGONADAL MEN - A CLINICAL RESEARCH-CENTER STUDY

To study the effects of androgen replacement therapy on muscle mass an d strength and bone turnover markers in hypogonadal men, we administer ed sublingual testosterone (T) cyclodextrin (SLT; 5 mg, three times da ily) to 67 hypogonadal men (baseline serum T, <8.4 nmol/L) recruited f rom 4 centers in the U.S.: Torrance (n = 34), Durham (n = 12), New Yor k (n = 9), and Salem (n = 12). Subjects who had received prior T thera py were withdrawn from injections for at least 6 weeks and from oral t herapy for 4 weeks. Body composition, muscle strength, and serum and u rinary bone turnover markers were measured before and after 6 months o f SLT. We have shown previously that this regimen for 60 days will mai ntain adequate serum T levels and restore sexual function. Total body (P = 0.0104) and lean body mass (P = 0.007) increased with SLT treatme nt in the 34 subjects in whom body composition was assessed. There was no significant change in total body fat or percent fat. The increase in lean body mass was mainly in the legs; the right leg lean mass incr eased from 8.9 +/- 0.3 kg at 0 months to 9.2 +/- 0.3 kg at 6 months (P = 0.0008). This increase in leg lean mass was associated with increas ed leg muscle strength, assessed by leg press (0 months, 139.0 +/- 4.0 kg; 6 months, 147.7 +/- 4.2 kg; P = 0.0038).SLT replacement in hypogo nadal men led to small, but significant, decreases in serum Ca (P = 0. 0029) and the urinary calcium/creatinine ratio (P = 0.0066), which wer e associated with increases in serum PTH (P = 0.0001). At baseline, th e urinary type I collagen-cross linked N-telopeptides/creatinine ratio [75.6 +/- 7.9 nmol bone collagen equivalents (BCE)/mmol] was twice th e normal adult male mean (41.0 +/- 3.6 nmol BCE/mmol) and was signific antly decreased in response to SLT treatment at 6 months(68.2 +/- 7.7 nmol BCE/mmol; P = 0.0304) without significant changes in urinary crea tinine. Serum skeletal alkaline phosphatase did not change. In additio n, SLT replacement caused significant increases in serum osteocalcin ( P = 0.0001) and type I procollagen (P = 0.0012). Bone mineral density did not change during the 6 months of SLT treatment. We conclude that SLT replacement therapy resulted in increases in lean muscle mass and muscle strength. Like estrogen replacement in hypogonadal postmenopaus al females, androgen replacement therapy fed to decreased bone resorpt ion and urinary calcium excretion. Moreover, androgen replacement ther apy may have the additional benefit of increasing bone formation. A lo nger term study for several years duration would be necessary to demon strate whether these changes in bone turnover marker levels will resul t in increased bone mineral density, decreased fracture risks, and red uced frailty in hypogonadal men.