Associations of AMH in Midreproductive Years with Bone Mineral Density and Turnover Markers in Midlife

Abstract Context The concentration of circulating anti-Müllerian hormone (AMH) predicts short-term (3-5 years) bone loss around menopause. Whether AMH during midreproductive years predicts bone health over a decade later is unknown. Objective To study the association of AMH levels in midreproductive years with bone density and turnover biomarkers measured after ∼14 years of follow-up. Methods We assessed plasma AMH in 2003-2006 (mean 37.0 years, SD 5.1) among 450 parous women (71% White) in a US longitudinal cohort, and bone mineral density (BMD; spine, hip, and femoral neck, measured by dual-energy X-ray absorptiometry) in 2017-2021 (mean 51.0 years, SD 5.1). Secondary outcomes were plasma levels of procollagen type I N-propeptide (PINP) and type I collagen cross-linked C telopeptide (CTX-I). Results In linear regression models adjusted for demographics and lifestyle, compared with women with AMH >3.5 ng/mL, those with AMH <1.0 ng/mL had lower BMD (g/cm2) at follow-up (beta [95% CI] spine: −.06 [−0.10, −0.02]; hip: −.05 [−0.08, −0.02]; femoral neck: −.03 [−0.06, 0.00]) and higher bone turnover markers (beta [95% CI] PINP: .36 SD [0.10, 0.63]; CTX-I: .34 SD [0.07, 0.60]). The association of AMH with spine BMD was more pronounced among postmenopausal women in contrast to associations with bone turnover markers, which were more pronounced among women who had not yet reached menopause. The associations between AMH and BMD were primarily mediated by menopausal status at follow-up. Conclusion Lower AMH during midreproductive years is associated with lower BMD and higher bone turnover 14 years later. Ovarian reserve during midreproductive years may be a valuable predictor of long-term bone health.