Gene Variants Tied to Reproductive Aging Also Tied to Vasomotor Menopause Symptoms

(Reuters Health) – Certain genetic variants that are associated with reproductive aging also appear linked to vasomotor symptoms of menopause, a new study suggests.

Researchers examined data from the Study of Women’s Health Across the Nation (SWAN) genomic substudy for 702 white women, 306 Black women, 126 Chinese women, and 129 Japanese women. They created polygenic risk scores based on genome-wide studies of ages at menarche and menopause and vasomotor symptoms.

In particular, researchers focused on single nucleotide polymorphisms and polygenic risk scores for tachykinin receptor 3 (TACR3), previously identified as linked to vasomotor symptoms. Researchers examined the association between TACR3 and the timing and frequency of vasomotor symptoms as well as timing of final menstrual period for women in each of the different racial and ethnic groups in the study.

Black women with later menarche and a higher menarche polygenic risk score were significantly less likely to report frequent vasomotor symptoms (odds ratio 0.55), the study found. In addition, Black women with a higher polygenic risk score for age at menarche were less likely to have a trajectory of persistently high vasomotor symptoms (OR 0.55).

When white women had a higher menarche polygenic risk score, however, they were less likely to have a final menstrual period onset trajectory for vasomotor symptoms (OR 0.75). The study also found that in white women, the C-allele of rs74827081 in TACR3 was associated with a lower chance of frequent vasomotor symptoms (OR 0.49).

Chinese women were more likely to have frequent vasomotor symptoms when they had a higher menopause polygenic risk score (OR 2.29), the study also found.

“Multiple genes have been associated with age at menopause, suggesting that reproductive aging has a polygenic architecture,” said senior study author Sioban Harlow, director of the Center for Midlife Science in the School of Public Health at the University of Michigan in Ann Arbor.

“As the reproductive aging process is multifaceted, it is likely that some biological mechanisms contribute both to reproductive aging and to the symptoms that accompany major reproductive transitions like menarche and menopause,” Harlow said by email.

The study results are a first step in better characterizing the genetic complexity of the reproductive aging process and its related symptomatology, Harlow added.

“Further work to identify specific underlying biological pathways may help to identify targets for treatment and prevention and possibly to better identify people at greater risk for more intense vasomotor symptoms,” Harlow said.

One limitation of the study is that vasomotor symptoms, age at menarche and age at final menstrual period were all self-reported, and subject to recall bias, the study team notes in Menopause. The small sample is another limitation, particularly for the Japanese and Chinese women, researchers note.

It’s possible that the same genetic factors associated with reproductive aging also influence when the ovaries cease to work, resulting in vasomotor symptoms of menopause, said Dr. Stephanie Faubion, director of the Mayo Clinic Center for Women’s Health in Rochester, Minnesota, and medical director for the North American Menopause Society.

However, the findings are too preliminary to influence clinical practice, Dr. Faubion, who wasn’t involved in the study, said by email.

“These findings do not apply to clinical practice today — not yet anyway,” Dr. Faubion said. “Additional study in this area may allow for identification of novel therapeutic targets for drug development.”

SOURCE: Menopause, online April 28, 2021.

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