Longterm effects of androgen replacement therapy on bone mineral density (BMD) in hypogonad men

Androgen deficiency leads to bone loss and contributes to osteoporotic fractures in men. Yet, the long-term effects of androgen replacement therapy on bone mineral density (BMD) are not well defined. We therefore reviewed the effect of testosterone treatment on BMD and its effect modifiers from prospectively collected dual energy xـray absorptiometry (DXA) of the lumbar spine and proximal femur. Men (n=137, aged 39±1 years, range 17 to 79 years) with established androgen deficiency (58% with primary hypergonadotropic hypogonadism) requiring regular androgen replacement therapy (ART) were treated with testosterone implants (800 mg, 4-6 month intervals) and had DXA scan at 2 to 3-year intervals. Patients were classified into four subgroups according to adequacy of prior treatment at the time of first DXA study comprising those (a) never treated, (b) well treated, (c) poorly treated (<1 year of inadequate treatment) and (d) off treatment (off all treatment >1 year). In the cross sectional analysis, none had fractures but WHO-defined osteoporosis and osteopenia were present in 8% and 29% in the lumbar spine and 5% and 31%, in the femoral neck, respectively. Testosterone treatment was associated with higher BMD but there was no significant difference between those well treated and recently off treatment. Adjustment for age, physique or type of hypogonadism did not modify the findings. In a longitudinal analysis of 48 men who had two BMD measurements at a median of 3 years (range 1-7 years) apart, BMD was significantly increased in lumbar spine (2. 0±0. 5% per year) and trochanter (1. 1±0. 5% per year) but did not change in femoral neck or Ward’s triangle. 22 of these patients had osteopenia and osteoporosis at their 1st BMD measurement. With a follow up period of 1ـ-5 (median 2) years, increases in their bone mineral density was observed at all bone sites. The present study confirms that androgen deficiency reduces, and ART improves BMD in men at lumbar spine and trochanter but not at femoral neck or Ward’s triangle. It increases BMD at all bone sites in those patients with osteopenia or osteoporosis at 1st DXA scan. These observations suggest that reversing the effects of androgen deficiency requires adequate testosterone treatment and that beneficial effects of testosterone are durable despite even short-term interruption of treatment. The consequences of these findings for he potential androgen treatment to prevent bone loss and fractures related to male ageing and chronic diseases associated with mild androgen deficiency remain to be determined. Keywords: BMD, Bone, Osteoporosis, Men, Testosterone, Androgen, Hypogonadism, Osteopeina