Gene variants linked to reproductive aging also linked to symptoms of vasomotor menopause


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

The researchers examined data from the Nationwide Women’s Health Study (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, the researchers focused on single nucleotide polymorphisms and polygenic risk scores for tachykinin receptor 3 (TACR3), previously identified as related to vasomotor symptoms. The researchers examined the association between TACR3 and the timing and frequency of vasomotor symptoms, as well as the timing of the final menstrual period for women in each of the different racial and ethnic groups in the study.

The study found that black women with posterior menarche and a higher meningeal polygenic risk score were significantly less likely to report frequent vasomotor symptoms (probability of 0.55). In addition, black women with a higher polygenic risk score by age in menarche were less likely to have a trajectory of persistently elevated vasomotor symptoms (OR 0.55).

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

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

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

“Because the reproductive aging process is multifaceted, it is likely that some biological mechanisms contribute to both reproductive aging and the symptoms that accompany major reproductive transitions, such as menarche and menopause,” Harlow said in an email.

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

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

One of the limitations of the study is that vasomotor symptoms, age at menarche, and age during the final menstrual period were reported on their own and bias could be recalled, the study team notes. at menopause. The small sample is another limitation, especially for Japanese and Chinese women, the researchers note.

It is possible that the same genetic factors associated with reproductive aging also influence when the ovaries stop working, causing 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 American Menopausal Society.

However, the findings are too preliminary to influence clinical practice, Dr. emailed. Faubion, who did not participate in the study.

“These findings do not apply to current clinical practice, although not anyway,” Drs. Faubion. “An additional study in this area may allow the identification of new therapeutic targets for drug development.”

SOURCE: Menopause, online April 28, 2021.

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