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Comparison of age at natural menopause in BRCA1/2 mutation carriers with a non–clinic-based sample of women in northern California
Article first published online: 29 JAN 2013
Copyright © 2013 American Cancer Society
Volume 119, Issue 9, pages 1652–1659, 1 May 2013
How to Cite
Lin, W. T., Beattie, M., Chen, L.-m., Oktay, K., Crawford, S. L., Gold, E. B., Cedars, M. and Rosen, M. (2013), Comparison of age at natural menopause in BRCA1/2 mutation carriers with a non–clinic-based sample of women in northern California. Cancer, 119: 1652–1659. doi: 10.1002/cncr.27952
- Issue published online: 22 APR 2013
- Article first published online: 29 JAN 2013
- Manuscript Accepted: 19 NOV 2012
- Manuscript Revised: 5 NOV 2012
- Manuscript Received: 24 AUG 2012
- BRCA1 gene;
- BRCA2 gene;
- primary ovarian insufficiency;
Germline mutations in BRCA1 and BRCA2 (BRCA1/2) are related to an increased lifetime risk of developing breast and ovarian cancer. Although risk-reducing salpingo-oophorectomy reduces the risk of both cancers, loss of fertility is a major concern. A recent study suggested an association between BRCA1 mutation and occult primary ovarian insufficiency. The objective of the current study was to determine whether BRCA1/2 mutation carriers have an earlier onset of natural menopause compared with unaffected women.
White carriers of the BRCA1/2 gene (n = 382) were identified within the Breast Cancer Risk Program Registry at the University of California at San Francisco and compared with non–clinic-based white women in northern California (n = 765). The 2 groups were compared with regard to median age at the time of natural menopause before and after adjustment for known risk factors, and the role of smoking within each group was examined using the Kaplan-Meier approach for unadjusted analyses and Cox proportional hazards regression analyses for adjusted analyses.
The median age at the time of natural menopause in the BRCA1/2 carriers was significantly younger than among the unaffected sample (50 years vs 53 years; P < .001). The unadjusted hazard ratio for natural menopause when comparing BRCA1/2 carriers with unaffected women was 4.06 (95% confidence interval, 3.03-5.45) and was 3.98 (95% confidence interval, 2.87-5.53) after adjusting for smoking, parity, and oral contraceptive use. For BRCA1/2 carriers who were current heavy smokers (smoking ≥ 20 cigarettes/day), the median age at natural menopause was 46 years versus 49 years for nonsmokers (P = .027).
The BRCA1/2 mutation was associated with a significantly earlier age at natural menopause, and heavy smoking compounded this risk. Because the relationship between menopause and the end of natural fertility is considered to be fixed, these findings suggest the risk of earlier infertility among BRCA1/2 carriers. Cancer 2013. © 2012 American Cancer Society.