Effects of self-reported age at nonsurgical menopause on time to first fracture and bone mineral density in the Women's Health Initiative Observational Study

Objective: Menopause is a risk factor for fracture; thus, menopause age may affect bone mass and fracture rates. We compared bone mineral density (BMD) and fracture rates among healthy postmenopausal women with varying ages at self-reported nonsurgical menopause. Methods: We compared hazard ratios for fractures and differences in BMD among 21,711 postmenopausal women from the Women's Health Initiative Observational Study cohort who had no prior hysterectomy, oophorectomy, or hormone therapy and had varying self-reported ages at menopause (<40, 40-49, or ≥50 y). Results: Before multivariable adjustments, we found no differences in absolute fracture risk among menopause age groups. After multivariable adjustments for known risk factors for fracture, women who underwent menopause before age 40 years had a higher fracture risk at any site compared with women who underwent menopause at age 50 years or older (hazard ratio, 1.21; 95% CI, 1.02 to 1.44; P=0.03). In a subset with BMD measurements (n=1,351), whole-body BMD was lower in women who reported menopause before age 40 years than in women who reported menopause at ages 40 to 49 years (estimated difference, -0.034 g/cm²; 95% CI, -0.07 to -0.004; P=0.03) and women who reported menopause at age 50 years or older (estimated difference, -0.05 g/cm²; 95% CI, -0.08 to -0.02; P<0.01). Left hipBMD was lower in women who underwent menopause before age 40 years than in women who underwent menopause at age 50 years or older (estimated difference, -0.05 g/cm²; 95% CI, -0.08 to -0.01; P=0.01), and total spine BMD was lower in women who underwent menopause before age 40 years than in women who underwent menopause at age 50 years or older (estimated difference, -0.11 g/cm²; 95% CI, -0.16 to -0.06; P<0.01) and women who underwent menopause at ages 40 to 49 years (estimated difference, -0.09 g/cm²; 95% CI, -0.15 to -0.04; P<0.01). Conclusions: In the absence of hormone therapy, younger age at menopause may be a risk factor contributing to decreasedBMD and increased fracture risk in healthy postmenopausal women. Our data suggest that menopause age should be taken into consideration, along with other osteoporotic risk factors, when estimating fracture risk in postmenopausal women.