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BRCA1/2 mutation associated with early menopause
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Carriers of the BRCA1/2 mutation entered menopause 3 years earlier than noncarriers, according to results of a cross-sectional study.
The finding could have implications on fertility of women who carry this mutation, according to researchers.
The investigators aimed to determine whether BRCA1/2 mutation carriers are more likely to enter menopause earlier than noncarriers. They also sought to more clearly describe loss of fertility among mutation carriers who receive risk-reducing salpingo-oophorectomy.
The study included 382 white women who carried the BRCA1/2 gene and 765 nonclinic-based white women in northern California.
The median age at time of natural menopause was reported for each group. Adjustments were made for known risk factors, and the role of smoking within each group also underwent analysis.
Carriers entered natural menopause at age 50 years vs. 53 years among noncarriers (P<.001).
BRCA1/2 mutation was associated with an unadjusted HR of 4.06 (95% CI, 3.03-5.45) for natural menopause. After adjusting for smoking, parity and oral contraceptive use, the HR was 3.98 (95% CI, 2.87-5.53).
Current heavy smokers — defined as at least 20 cigarettes/day — who carried the mutation entered menopause at 46 years compared with 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,” the researchers concluded.
The findings suggest BRCA1/2 carriers may have a narrower reproductive window than noncarriers, the researchers said.
“In addition to discussing risk-reducing salpingo-oophorectomy, we would encourage the early initiation of fertility counseling for BRCA1/2 carriers and the consideration of earlier childbearing,” they wrote.
Perspective
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Harry S. Jacob, MD, FRCPath(Hon)
Interesting association suggesting balanced polymorphism — that is, early menopause/decreased estrogen mutations evolving to ameliorate another deleterious mutation causing estrogen-driven gynecologic cancers.
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