Effects of long-term long-acting testosterone undecanoate on bone mineral density in men with late-onset hypogonadism and metabolic syndrome
Effects of long-acting testosterone undecanoate on bone mineral density in middle-aged men with late-onset hypogonadism and metabolic syndrome: results from a 36 months controlled study. Aversa A, Bruzziches R, Francomano D, et al. Aging Male 2011;15(2):96-102.
This Research News article reviews an open-access article available in full from informa healthcare.
This study evaluated the long-term effects of testosterone therapy on the bone mineral density (BMD) of obese patients with metabolic syndrome (MetS) and/or type 2 diabetes mellitus (T2DM) and late-onset hypogonadism. Sixty Caucasian men aged 45–65 (mean 57) years with low serum testosterone (>11 nmol/L [320 ng/dL]) or calculated free testosterone >74 pg/mL (255 pmol/L) were enrolled. Treatment consisted of intramuscular testosterone undecanoate 4 times/year for 36 months (20 men). Twenty age-matched hypogonadal men with MetS in whom testosterone therapy was contraindicated were used as controls.
The remaining 20 men in the testosterone therapy group did not complete the study (and were not included in the analysis) because of mild and transient erythrocytosis (4 patients), increased prostate-specific antigen levels (1), personal reasons (6) or dropped out before completing the 36 months of observation (9).1At baseline, mean lumbar BMD was 0.891±0.097 g/cm2, femoral BMD was 0.847±0.117 g/cm2, lumbar T-score was –1.6±0.9 and femoral neck T-score was 0.9±0.8, indicating that patients had mild osteopenia.
What is known
Osteoporosis, characterized by increased risk of spontaneous and traumatic fractures due to reduced bone strength, is an underestimated, underdiagnosed and undertreated condition in men.2,3 Men with late-onset hypogonadism or those receiving androgen deprivation therapy for prostate cancer are at particular increased risk of osteoporosis.1,4 Studies have shown a positive association between BMD and endogenous androgen levels in the aging male population.5 It has been postulated that testosterone plays an important role in the maintenance of male bone health, in large part through the aromatization of testosterone to estradiol.6
The MetS, a cluster of risk factors for cardiovascular disease, characterized by abdominal obesity, insulin resistance, impaired glucose tolerance, dyslipidaemia and hypertension,7,8 is associated with low testosterone levels.9,10 Furthermore, an association between severe obesity and decreased BMD has also been demonstrated.11 However, data from interventional studies to investigate the effects of testosterone therapy on BMD in men with MetS and late-onset hypogonadism are limited and contradictory. Therefore this study aimed to determine whether testosterone therapy with a long-acting formulation of testosterone undecanoate could induce modifications in BMD in men affected by MetS and/or T2DM and late-onset hypogonadism.
What this study adds
This study shows for the first time the long-term effects of testosterone therapy with testosterone undecanoate on BMD in a small patient population of middle-aged men with MetS and/or T2DM and late-onset hypogonadism. Testosterone undecanoate was associated with a significant increase in vertebral and femoral BMD. While there was correlation between vertebral and femoral BMD and serum testosterone levels achieved, circulating estradiol levels did not appear to play a crucial role in improving BMD.1 Improvements in bone architecture were apparent after 12 months of testosterone undecanoate treatment, and progressively increased throughout the 36-month trial.
The authors speculated that the data support the hypothesis that testosterone may exert a specific action on the osteoblast through direct activation of the androgen receptor. Furthermore, the observed reduction in the inflammatory marker, hs-CRP, suggests that testosterone-mediated reduction in inflammation may be an additional mechanism for a beneficial effect on bone, in parallel with the suggested effect of estrogen in women.12 Additional and larger studies are warranted to further clarify the specific mechanisms underlying the actions of testosterone on BMD.