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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

Sullivan, Shannon D. MD, PhD1; Lehman, Amy MAS2; Thomas, Fridtjof PhD3; Johnson, Karen C. MD, MPH3; Jackson, Rebecca MD4; Wactawski-Wende, Jean PhD5; Ko, Marcia MD6; Chen, Zhao PhD, MPH7; Curb, J. David MD, MPH8; Howard, Barbara V. PhD9

doi: 10.1097/GME.0000000000000451
Original Articles
Editorial

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 hip 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, −0.05 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 decreased BMD 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.

1Division of Endocrinology and Metabolism, Department of Medicine, Medstar Washington Hospital Center, Washington, DC

2Center for Biostatistics, The Ohio State University, Columbus, OH

3Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis, TN

4Department of Medicine, The Ohio State University, Columbus, OH

5Department of Social and Preventive Medicine, State University of New York, University at Buffalo, Buffalo, NY

6Department of Women's Health Internal Medicine, Mayo Clinic, Phoenix, AZ

7Department of Epidemiology and Biostatistics, Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, AZ

8Department of Geriatric Medicine, University of Hawaii, Honolulu, HI

9Department of Medicine, Biostatistics, and Epidemiology, Medstar Health Research Institute, Hyattesville, MD.

Address correspondence to: Shannon D. Sullivan, MD, PhD, Division of Endocrinology and Metabolism, Department of Medicine, Medstar Washington Hospital Center, Suite 2A-72, 110 Irving St, NW, Washington, DC 20010. E-mail: Shannon.d.sullivan@medstar.net

Received 16 October, 2014

Revised 22 January, 2015

Accepted 22 January, 2015

J. David Curb, deceased.

Funding/support: The Women's Health Initiative program was funded by the National Heart, Lung, and Blood Institute and the US Department of Health and Human Services. No additional financial support was obtained for the preparation of this manuscript.

Financial disclosure/conflicts of interest: None reported.

© 2015 by The North American Menopause Society.