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BRCA gene mutations linked to earlier menopause

Tuesday January 29, 2013
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Women with mutations in the BRCA gene, which put them at higher risk of developing breast and ovarian cancer, tend to undergo menopause significantly sooner than other women, according to a study.

This early onset of menopause means a briefer reproductive window and possibly a higher risk of infertility. The researchers also found that carriers of the mutation who are heavy smokers enter menopause at an even earlier age than non-smoking women with the mutation.

Although further research is needed, women with the abnormal gene mutation should consider earlier childbearing, and their physicians should encourage them to initiate fertility counseling along with other medical treatments, said researchers with the University of California, San Francisco.

Scheduled for publication in the journal Cancer, the study is said to be the first controlled trial to explore the association between BRCA1 and BRCA2 and the age at onset of menopause, the authors said.

"Our findings show that mutation of these genes has been linked to early menopause, which may lead to a higher incidence of infertility," Mitchell Rosen, MD, the study’s senior author and associate professor in the UCSF Department of Obstetrics, Gynecology and Reproductive Sciences, said in a news release.

"This can add to the significant psychological implications of being a BRCA1/2 carrier, and will likely have an impact on reproductive decision-making."

Mutations in either the BRCA1 or BRCA2 gene can produce a hereditary, lifetime risk of developing breast cancer and ovarian cancer. Some women decide to reduce their risk by undergoing prophylactic surgery to remove at-risk tissue, including their breasts and ovaries, the researchers noted. The abnormal genes are the most identified inherited cause of breast cancer, with carriers five times more likely to develop breast cancer than those without the mutations, according to the National Cancer Institute.

The new study was designed to determine whether women with the BRCA1 or BRCA2 mutation have an earlier onset of menopause compared with unaffected women. The researchers looked at nearly 400 female carriers of mutations in the BRCA gene in Northern California and compared their onset of menopause to that of 765 women in the same geographic area without the mutation. Most of the women in the study were white, as are almost all the BRCA1/2 carriers in the UCSF cancer risk registry.

The researchers found that women with the harmful mutation experienced menopause at age 50, compared with age 53 for the other midlife women.

For heavy smokers (20 or more cigarettes a day) with the abnormal gene, menopause onset happened at an average age of 46. For context, only 7% of white women in northern California had undergone menopause by that age, the authors said. Smoking has been shown to alter menstrual cycles and estrogen status, among other effects.

The authors pointed out that while their study shows a possible increased risk of infertility for BRCA mutation carriers, further study of that finding is needed. They also said data regarding the age of natural menopause is limited because most women with the mutation are recommended to undergo risk-reducing surgery after they complete childbearing.

"Women with the mutation are faced with challenges in reproductive choices," Lee-may Chen, MD, a study co-author and professor in the UCSF Department of Obstetrics, Gynecology and Reproductive Services, said in the news release. "These data may help women understand that their childbearing years may be even more limited by earlier menopause, so that they can make decisions about their reproductive choices and cancer risk-reducing surgery."

The study abstract is available at http://onlinelibrary.wiley.com/doi/10.1002/cncr.27952/abstract.


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