BU study finds new genetic loci associated with menopause onset

An international team of researchers from the Boston University Schools of Public Health and Medicine and other institutions has uncovered 13 genetic loci, linked to immune function and DNA repair, that are factors in the age of onset of menopause.

Menopause - the cessation of reproductive function of the ovaries - is a major hormonal change that affects most women when they are in their early 50s. Most prior studies of the age of onset of menopause have focused on genes from the estrogen-production pathway or vascular components.

In the new study, published online Jan. 22 in Nature Genetics, a research team led by Kathryn Lunetta, professor of biostatistics at the BU School of Public Health, and Joanne Murabito, associate professor of medicine at the BU School of Medicine, identified 13 novel loci associated with menopause onset, while confirming four previously established loci. Most of the 17 loci are associated with genes related to DNA damage repair or auto-immune disease; others are linked to hormonal regulation.

"Our findings demonstrate the role of genes which regulate DNA repair and immune function, as well as genes affecting neuroendocrine pathways of ovarian function in regulating age at menopause, indicating the process of aging is involved in both somatic and germ line aging" the authors said.

Lunetta said the new findings "bring us closer to understanding the genetic basis for the timing of menopause. They may also provide clues to the genetic basis of early onset or premature menopause and reduced fertility.

"We hope that as a better understanding of the biologic effects of these menopause-related variants are uncovered, we will gain new insights into the connections between menopause and cardiovascular disease, breast cancer, osteoporosis, and other traits related to aging, and that this will provide avenues for prevention and treatment of these conditions," she said.

According to Murabito, director of the research clinic at the Framingham Heart Study, "It will be important to determine if a genetic variant that directly influences age at menopause also increases risk for later life health conditions, such as breast cancer."

Age at the Onset of Menopause

Since early menopause is often linked with an increased risk of many diseases, the age at the onset of menopause becomes a key factor. Every woman produces approximately 400 fertilizable eggs in one lifetime, and they typically ovulate once per month every month between their first period and the onset of menopause.

As you age, the quality and the amount of follicles in your ovaries decrease. Longer or shorter, lighter or heavier menses are a sign that you are irregular and not ovulating. As a result, progesterone ceases production. This stage is called perimenopause. During this time, estrogen levels also lessen dramatically and cause menopausal symptoms - such as hot flashes, insomnia, anxiety, depression and bone loss. While the average age at the onset of puberty has steadily declined, the typical age at the onset of menopause has remained constant at 52-years-old.