The Genetics of Menopause

BRCA gene mutation carriers did not have earlier natural menopause than noncarriers

/ Author:  / Reviewed by: Joseph V. Madia, MD Beth Bolt, RPh

(RxWiki News) Women who have mutations in the BRCA genes are at higher risk of breast and ovarian cancer. Research has suggested that women with these altered genes may also have problems conceiving children and that they go through menopause earlier than women without the defective genes.

Researchers conducted a study to determine if women who have mutations in the BRCA genes would experience menopause at a younger age than women without the altered genes.

The study found no difference in early natural menopause between BRCA carriers and noncarriers.

"If you have a family history of breast cancer, find out about BRCA testing."

Ian M. Collins, MD, of the Peter MacCallum Cancer Centre at the University of Melbourne in Melbourne, Australia, and colleagues conducted this research to find out how mutations in the BRCA1 and BRCA2 genes impacted the timing of menopause onset.

Natural menopause is defined as the end of menstruation for 12 months without a medical cause, the researchers explained.

For this study, a total of 1,810 women with and without mutations in the BRCA1 and BRCA2 genes were identified in families with histories of breast cancer enrolled in the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer (kConFab) between 1997 and 2011.

These women were surveyed at the time of enrollment and every three years thereafter.

The questionnaires asked a number of questions relating to health, childbirth history, lifestyle history (smoking and alcohol consumption), use of oral contraceptives, fertility medications and hormone therapies.

A woman would be eliminated from the study at the time she was diagnosed with cancer or if she underwent surgery involving ovary removal. Some women choose to have both ovaries removed to prevent ovarian cancer.

During the study period, 19 percent of all the women reached natural menopause.

The researchers discovered that a lower proportion of BRCA carriers reached natural menopause compared to noncarriers — 11 percent of BRCA1 carriers versus 25 percent of their relatives without BRCA1 mutations and 13 percent of BRCA2 carriers versus 24 percent of their relatives without BRCA2 mutations.

However, more BRCA carriers were eliminated from the study at the time of a cancer diagnosis — 40 percent of BRCA1 and 29 percent of BRCA2 carriers versus 7 percent for both groups of noncarrier family members.

The researchers found that women who smoked had a 30 percent higher risk of natural menopause than nonsmokers.

Other factors such as body mass index (BMI), childbirth history and alcohol use did not impact risk of natural menopause, the study found.

“We found no evidence that BRCA1 and BRCA2 mutation carriers are at higher risk of NM at a given age than their noncarrier relatives,” the researchers concluded.

Adam M. Brufsky, MD, PhD, professor of medicine at the University of Pittsburgh School of Medicine, told dailyRx News, "It is encouraging that ovarian reserve [number of eggs capable of being fertilized] appears to be the same in BRCA carriers and noncarriers.”

The researchers added, "In view of the recently published data from California, with conflicting results to ours, we believe that whether BRCA1 and/or BRCA2 mutation carriers are at risk of early menopause and subsequent fertility problems remains an open question."

Findings from this study were published in the Journal of Clinical Oncology.

The research was supported by the National Health and Medical Research Foundation, the Queensland Cancer Fund; the Cancer Councils of New South Wales, Victoria, Tasmania, and South Australia; and the Cancer Foundation of Western Australia.

No conflicts of interest were disclosed.

Review Date: 
October 31, 2013
Last Updated:
December 31, 2013