were reached after 24 months of transdermal testosterone therapy and then decreased or leveled off (testosterone levels reached the normal range within 3 months and then leveled off). Two studies found that osteopenia persisted in hypogonadal men undergoing long-term testosterone supplementation (Medras et al., 2001; Ishizaka et al., 2002).
Studies of biochemical markers of bone turnover have widely variable results. Wang and colleagues (2001) found that osteoblastic activity markers increased significantly during 90-day treatment of hypogonadal men with either a 50 or 100 mg dose of testosterone gel daily; the study also found an increase in BMD of the hip and spine in those receiving the 100 mg/day dose. Serum osteocalcin, a bone formation marker, increased in studies of elderly men undergoing testosterone therapy (Morley et al., 1993; Brill et al., 2002), and levels were maintained in a study of elderly men that suppressed endogenous testosterone production and then examined testosterone and estrogen replacement (Falahati-Nini et al., 2000). Anderson and colleagues (1997) found decreases in bone markers with testosterone therapy in eugonadal men with osteoporotic vertebral crush fractures, indicating to the investigators that testosterone suppressed bone resorption.
Positive effects on body composition and muscle strength were reported in testosterone therapy studies of males diagnosed or identified as hypogonadal, including increases in lean body mass (also termed fat-free mass in the journal articles), muscle volume and area, and muscle strength (Brodsky et al., 1996; Katznelson et al., 1996; Wang et al., 1996b; Bhasin et al., 1997; Leifke et al., 1998; Snyder et al., 2000). Many of the studies included older hypogonadal males but were not placebo-controlled studies. A study of strength measures by Wang and colleagues (2000) of 227 hypogonadal men receiving 180 days of transdermal treatment found increases in several measures of strength compared to baseline. Improvements were seen in the leg press exercise during the first 90 days, but further improvement after this period was not significant.
Studies in eugonadal male populations with normal levels of testosterone also generally found increases in lean body mass, muscle volume, and/or muscle strength with testosterone administration (Friedl et al., 1991; Forbes et al., 1992; Young et al., 1993; Urban et al., 1995; Bhasin et al., 1996, 2001b; Giorgi et al., 1999; Sinha-Hikim et al., 2002; Woodhouse et al., 2003). Most of these studies were in populations of young adults who received supraphysiologic doses for 3 to 6 months. Bhasin and colleagues (1996) assessed the effect of testosterone and exercise and found that the group undergoing testosterone therapy with exercise had greater in-