Abstract

Background: Common changes with menopause and aging include an increase in visceral adiposity and loss of lean body mass. Declines in sex steroid hormones contribute to these body composition changes, but emerging evidence also implicates increased pituitary production of follicle stimulating hormone (FSH). Blocking FSH action with an FSH-β subunit antibody reduced adiposity and increased lean body mass in ovariectomized female mice, and both male and female intact mice (Liu Nature 2017). Some, but not all, clinical observational studies have demonstrated positive associations between FSH and measures of adiposity (Zaidi Endocrinology 2018). Objective: To investigate the associations between endogenous FSH levels and measures of body composition in older adults from the AGES-Reykjavik cohort, independent of sex steroid hormones. Methods/Results: Participants were recruited from the AGES-R study, excluding those using sex steroid hormone agonists or antagonists. FSH (ELISA), total estradiol and total testosterone (GC/MS) were measured from fasting serum. Total body fat (kg), total body lean mass (kg), and appendicular lean mass (kg) were measured with total body DXA. Appendicular lean mass index (ALMI) was calculated as appendicular lean mass/height2 (kg/m2). Visceral adipose tissue (VAT) area (cm2) and subcutaneous adipose tissue (SAT) area (cm2) were measured with abdominal CT. Linear regression analyses of FSH in association with body composition parameters were performed, stratified by gender, both unadjusted and adjusted for age, visit window, BMI, total estradiol and total testosterone levels. Among the 245 men, the mean age was 82.4 (SD 4.0) years, mean BMI was 26.7 (SD 3.6) kg/m2 and mean FSH 19.0 (SD 16.9) IU/L . Among the 238 women, the mean age was 80.6 (SD 4.0) years, mean BMI 27.4 (SD 4.1) kg/m2 and mean FSH 71.6 (SD 23.2) IU/L. In models adjusted for age, visit window, BMI, estradiol and testosterone, there were no significant associations between FSH and any measure of body composition in men. In adjusted models in women, each SD increase in FSH was associated with a 2.67% greater SAT area (p=0.03) but no significant difference in VAT area or total body fat. Conversely, each SD increase in FSH was associated with a1.62% lower total body lean mass (p=0.005) in women, but no significant difference in ALMI. Conclusion: Consistent with preclinical models, we found higher FSH to be associated with greater subcutaneous adiposity and lower lean body mass in older women. We found no associations between FSH and measures of body composition in older men. Further research is needed to determine whether FSH-directed therapy may be an effective means of combatting the body composition changes associated with menopause.

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