Abstract
Disclosure: S.T. Hills: None. T.A. Mansfield: None. E.S. Orwoll: None. Background. Sex hormones (SH) play key regulator role in a variety of homeostatic functions, with declines in SH levels potentially leading to adverse effects. Based on cross-sectional and short longitudinal studies, levels SH change with age in men. However, there are limited data about SH and SH changes in men over 80 years old, and few longitudinal studies >10 years characterizing SH change in men. Methods. Cross-sectionally, we studied 477 community dwelling men, ages 78-97 years old years, who participated in the Osteoporotic Fractures in Men (MrOS) study. In addition, in 215 of those men SH levels were compared to baseline levels obtained 14.0±0.7 years earlier. Medical history was obtained via clinical visits and questionnaires. Serum sex steroid levels (total testosterone, estradiol, estrogen, dihydrotestosterone (DHT)) were assayed using mass spectrometric (MS), free testosterone by equilibrium dialysis, and sex hormone binding globulin (SHBG) by chemiluminescent immunoassay. Baseline SH concentrations measured with different MS or immunoassay methods were harmonized to current measures. Results. In cross-sectional analyses, mean total testosterone levels were 414±180 ng/dL, with considerable variation among participants. In 21.4% of men, total T levels were <275 ng/dL. Similarly, directly measured free T levels were low in 37.6% (<6.6 ng/dL). Total testosterone levels were modestly correlated with directly measured free T, estradiol, estrone, DHT and SHBG, and weakly negatively associated with BMI and smoking. In longitudinal analyses over 14 years of follow-up, average total testosterone, estradiol and estrone levels decreased, while SHBG increased (for all SH changes, p<0.0001), but interindividual changes were highly variable. In longitudinal analyses, median (IQR) annualized percent change in total testosterone was -1.01%/year (-2.59, 0.28), in estradiol -0.93%/year (-2.15, 0.15), in estrone -1.06%/year (-2.49, 0.7) and in SHBG 1.79%/year (0.06, 3.54). Of the men with total T levels >275 ng/dL at baseline, total T levels decreased below that threshold on follow up in 20.5%. Conclusion. In these men, ages 78-97 years, there was a broad range of total testosterone levels, and about 1/5 of them could be considered hypogonadal. In longitudinal analyses, although there was considerable interindividual variation, there were gradual declines in median total testosterone, estradiol and estrone with gradual increases in SHBG. These age-related endocrine changes require further investigation to understand their effects on the health of older men. Presentation: Saturday, July 12, 2025