Effects of transdermal testosterone gel on bone turnover markers and bone mineral density in hypogonadal men

OBJECTIVE Androgen replacement has been reported to increase bone mineral d ensity (BMD) in hypogonadal men. We studied the effects of 6 months of trea tment with a new transdermal testosterone (T) gel preparation on bone turno ver markers and BMD. DESIGN This was a prospective, randomized, multicentre, parallel clinical t rial where 227 hypogonadal men, mean age 51 years (range: 19-68 years) were studied in 16 academic and research institutions in the USA. Subjects were randomized to apply 1% T gel containing 50 or 100 mg T (delivering approxi mately 5-10 mg T/day) or two T patches (delivering 5 mg T/day) transdermall y for 90 days. At day 91, depending on the serum T concentration, the T gel dose was adjusted upward or downward to 75 mg T/day until day 180. No dose adjustment occurred in the T patch group. MEASUREMENTS Serum T, free T and oestradiol, bone turnover markers and BMD were measured on days 0, 30, 90 and 180 before and after treatment. RESULTS Application of T gel 100 mg/day resulted in serum T concentrations 1.4 and 1.9-fold higher than in the T gel 50 mg/day and the T patch groups, respectively, Proportional increases occurred in serum oestradiol. Urine N -telopeptide/creatinine ratio, a marker for bone resorption, decreased sign ificantly (P = 0.0019) only in the T gel 100 mg/day group, Serum bone osteo blastic activity markers (osteocalcin, procollagen and skeletal alkaline ph osphatase) increased significantly during the first 90 days of treatment wi thout intergroup differences but declined to baseline thereafter. BMD incre ased significantly both in the hip (+1.1 +/- 0.3%) and spine (+2.2 +/- 0.5% ) only in the T gel 100 mg/day group (P = 0.0001). CONCLUSIONS Transdermal testosterone gel application for 6 months decreased bone resorption markers and increased osteoblastic activity markers for a short period, which resulted in a small but significant increase in BMD. On going long-term studies should answer whether the observed increases in BMD are sustained or continue to be dependent on the dose of testosterone admi nistered.