The age-dependent decline of the gonadal and somatotopic axis has been causally linked to frailty in the elderly by their effects on muscle mass and bone mineral density. However, for healthy men data on serum oestrogens and androgens, as well as IGF-1, as a common outcome measure covering the whole adult age range are scarce. We therefore studied healthy, nonobese male subjects between 20 and 80 years of age to asses their morning concentrations of total (T), free (FT), bioavailable testosterone (bT), oestradiol (E2), bioavailable oestradiol (bE2), oestrone (E1), sex-hormone binding globulin (SHBG), and insulin-like growth factor 1 (IGF-1). Five hundred and seventy-two male healthy volunteers with a BMI < 30 kg/m2 recruited from regular blood donors and senior sports clubs participated in the study. Serum samples were obtained during morning hours and T, FT, E2, E1, SHBG, albumin and IGF-1 were measured by radio-immunoassay systems. In addition, bT and bE2 were calculated. A potential relationship between sex hormones and IGF-1 was tested by multiple regression analysis including age and BMI. Ageing was negatively related to serum levels of sex steroids and IGF-1 (both P < 0.0001) with a mean decrease (youngest vs. oldest) of 51% for T, 64% for FT, 78% for bT, 32% for E2, 62% for bE2, 29% for E1 and 51% for IGF-1 starting in early adulthood whereas SHBG increased after the 5th decade of life (ANOVA P < 0.001). The decline of sex hormones and IGF-1 remained relatively unchanged after adjustment for BMI. Multiple regression analysis revealed an age-and BMI- independent association between oestradiol and IGF-1. In contrast to the female situation sex hormones in healthy, nonobese men decline continuously with age. This process has already started in the third decade, and is paralleled by a decline of IGF-1 serum levels leading to a substantial proportion of elderly men with markedly lowered serum levels of bioavailable sex hormones and IGF-1 compared to the young adult male range. With the recent demonstration of beneficial effects of androgen replacement therapy in healthy males on general well being, muscle mass and bone mineral density the present data may underline the importance of more detailed studies on the biological significance of hormonal changes in men with age.

Sex steroids are essential for accretion and maintenance of bone mass. Their importance for osteoporotic fractures in men, however, are undefined. We determined circulating levels of testosterone (T), non-SHBG-bound T (bT), free testosterone (FT), oestradiol (E2), intact parathormone (iPTH), 25-OH-vitamin D (25(OH)D), and trabecular bone mineral density at spinal level (tBMD) by single quantitative computed tomography (QCT), respectively, in elderly men 1-3.5 months after minimal traumatic hip fractures (MTHF, age=75+/-10 ys, n=27). A group of patients with non-immobilising stroke (S; age=73+/-8 ys, n=12) served as controls. Men with known secondary osteoporosis were excluded from the study. Furthermore, serum levels of T and E2 were compared to healthy controls aged 20-30 years (n=138) and 60-80 years (n=110). In addition a literature-based analysis of studies on testosterone in men hip fractures were conducted. Mean tBMD of men with MTFH (52.7+/-17.6 mg/cm3, T-score=- 4.5+/-0.6) was significantly lower than in men with S (78+/-16.3 mg/cm3, T-score=- 3.5+/-0.8). Significant differences of the means between both groups were observed for T, bT, and FT but not for E2, 25(OH)D, and iPTH, respectively. About 90 % of men with MTHF had T serum levels 2 SD below the mean of young controls. This proportion reduced to 30 % if compared with serum levels of 60-80-year-old healthy men whereas men after S remained well within the normal range adjusted for age. Mean serum levels of iPTH were within the normal range (1-6.8 pmol/l); 25(OH)D serum levels were at the lower end of the normal control levels (30-190 nmol/l). There was an inverse relationship between iPTH and 25(OH)D (r=- 0,4; p<0,03). In conclusion, low serum T is common in men with MTHF and only partly due to age. It appears to be a primary factor in fragility fractures in men and not simply secondary to morbidity following the fracture. In view of the scarce and inconsistent data published on this issue (1 longitudinal and 6 cross-sectional studies) the present study supports the patho-physiological relevance of low serum testosterone for the occurrence of MTHF in men.

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