Comparison of age at natural menopause in BRCA1/2 mutation carriers with a non–clinic-based sample of women in northern California

Authors

  • Wayne T. Lin MD, MPH,

    1. Department of Obstetrics, Gynecology and Reproductive Sciences, University of California at San Francisco, San Francisco, California
    2. Center for Infertility and Reproductive Surgery, Brigham and Women's Hospital, Harvard Medical School
    Search for more papers by this author
  • Mary Beattie MD,

    1. Department of Medicine, University of California at San Francisco Helen Diller Family Comprehensive Cancer Center, University of California at San Francisco, San Francisco, California
    Search for more papers by this author
  • Lee-may Chen MD,

    1. Department of Obstetrics, Gynecology and Reproductive Sciences, University of California at San Francisco, San Francisco, California
    Search for more papers by this author
  • Kutluk Oktay MD,

    1. Department of Obstetrics and Gynecology, New York Medical College, Valhalla, New York
    Search for more papers by this author
  • Sybil L. Crawford PhD,

    1. Biostatistics Research Group, Division of Preventive Medicine, Department of Preventive and Behavioral Medicine, University of Massachusetts Medical School, North Worcester, Massachusetts
    Search for more papers by this author
  • Ellen B. Gold PhD,

    1. Division of Epidemiology, Department of Public Health Sciences, University of California at Davis, Davis, California
    Search for more papers by this author
  • Marcelle Cedars MD,

    1. Department of Obstetrics, Gynecology and Reproductive Sciences, University of California at San Francisco, San Francisco, California
    Search for more papers by this author
  • Mitchell Rosen MD

    Corresponding author
    1. Department of Obstetrics, Gynecology and Reproductive Sciences, University of California at San Francisco, San Francisco, California
    • Division of Reproductive Endocrinology and Infertility, Department of Obstetrics, Gynecology and Reproductive Sciences, UCSF Center for Reproductive Health, UCSF Medical Center, San Francisco, CA 94122

    Search for more papers by this author
    • Fax: (415) 353-7744


Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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).

CONCLUSIONS:

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.

Ancillary