Adequacy of androgen replacement influences bone density response to testosterone in androgen-deficient men

Abstract

Objective: Androgen deficiency (AD) leads to bone loss and contributes to osteoporotic fractures in men. Although low bone mineral density (BMD) in AD men is improved by testosterone replacement, the responses vary between individuals but the determinants of this variability are not well defined. Design and methods: Retrospective review of dual energy X-ray absorptiometry (DEXA) of the lumbar spine and proximal femur in men with established AD requiring regular androgen replacement therapy (ART). After a DEXA scan all men were treated with testosterone implants (800 mg, , 6 month intervals). Patients were classified as having a congenital, childhood, or post-pubertal onset, as well as according to the adequacy of treatment prior to their first DEXA scan as untreated, partially treated or well treated. Results: Men with AD requiring regular ART (n ¼ 169, aged 46.3^1.1 years, range 22 -84 years) underwent a DEXA scan prior to being treated with testosterone implants (800 mg, ,6 month intervals). In cross-sectional analysis at the time of the first DEXA scan untreated men (n ¼ 24) had significantly reduced age-adjusted BMD at all four sites (L1 -L4, femoral neck, Ward's triangle and trochanter). Well-treated men (n ¼ 77) had significantly better age-adjusted BMD at all four sites compared with those who were partially treated (n ¼ 66) or untreated (n ¼ 24) with their ageadjusted BMD being normalized. In a longitudinal assessment of men (n ¼ 60) who had two or more serial DEXA scans, at the second DEXA scan after a median of 3 years, men who were previously partially treated (n ¼ 19) or untreated (n ¼ 11) had proportionately greater improvements in BMD, significantly for Ward's triangle (P ¼ 0.025) and the trochanter (P ¼ 0.044) compared with men (n ¼ 30) previously well treated. Conclusions: The present study demonstrates a positive relationship between adequacy of testosterone replacement and BMD in men with overt organic AD. Additionally, the BMD of well-treated AD men approximates that of age-matched non-AD controls. The greatest BMD gains are made by those who have been either untreated or partially treated, and optimal treatment over time (median 3 years) normalizes BMD to the level expected for healthy men of the same age.European Journal of Endocrinology 152 881-886

Bone mineral density in Klinefelter syndrome is reduced and primarily determined by muscle strength and resorptive markers, but not directly by testosterone

“…Studies on hypogonadal men (other than KS) have shown a significant effect of testosterone treatment on BMD in both hip and spine during 36 months [33] and 42 months [34] of testosterone treatment, respectively. An Australian study showed that adequacy of testosterone supplementation determined BMD gain in hypogonadal men [35]. We found that KS were taller and more obese as seen from the higher BMI.…”

Factors influencing time course of pain after depot oil intramuscular injection of testosterone undecanoate

“…These features, together with the long interval between injections, contribute to the high patient acceptability and continuation rates compared with other shorteracting forms of T replacement therapy. Previous underreporting [8][9][10][12][13][14] or underestimation [11,14] of TU-related injection pain may be an unrecognized limitation for the most effective clinical uses of TU, which assume a high level of therapeutic compliance for optimal, life-long androgen replacement therapy [45], or for a well-accepted TU-based combination of hormonal male contraceptive regimens [46].…”

Testosterone for the aging male; current evidence and recommended practice

“…A large number of trials have demonstrated a positive effect of testosterone treatment on bone mineral density (Katznelson et al 1996;Behre et al 1997;Leifke et al 1998;Snyder et al 2000;Zacharin et al 2003;Wang, Cunningham et al 2004;Aminorroaya et al 2005;Benito et al 2005) and bone architecture (Benito et al 2005). These effects are often more impressive in longer trials, which have shown that adequate replacement will lead to near normal bone density but that the full effects may take two years or more (Snyder et al 2000;Wang, Cunningham et al 2004;Aminorroaya et al 2005).…”

“…These effects are often more impressive in longer trials, which have shown that adequate replacement will lead to near normal bone density but that the full effects may take two years or more (Snyder et al 2000;Wang, Cunningham et al 2004;Aminorroaya et al 2005). Three randomized placebo-controlled trials of testosterone treatment in aging males have been conducted (Snyder et al 1999;Kenny et al 2001;Amory et al 2004).…”