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.
The authors said they expected further research to identify “a substantial number of additional common variants” that impact age of menopause, and that many of them will be located in genes identified in their study. The study examined more than 50,000 women of European descent who had experienced menopause between the ages of 40 and 60.
The research team noted that a large-scale study of menopause onset in African-American women is underway, which will help to determine whether the genetic variations that affect menopause onset in African-American women are similar or substantially different for women of primarily European descent.
Menopause and Breast Cancer
Breast cancer treatment often causes women to enter menopause prematurely. The change in hormone levels and estrogen depletion caused by stopping hormone replacement therapy or undergoing chemotherapy or hormonal therapy can trigger side effects commonly associated with menopause.
Although each woman reacts to therapy individually, certain side effects are common. We hope this information will provide you with useful tips to help you manage any side effects that you may be experiencing.
Before implementing these management strategies, please discuss your specific symptoms with your physician or nurse and ask any questions you may have. If you are seeing a complementary or alternative medicine practitioner, please let us know what you are using so we can incorporate the information into your care plan.
Besides Lunetta and Murabito, senior authors on the study include: Anna Murray, a senior lecturer in genetics at the Peninsula Medical School in Exeter (UK); and Jenny A. Visser, a scientist at Erasmus Medical Center in Rotterdam (Netherlands).
Menopause symptoms and breast cancer risk
“Menopausal women with hot flushes are half as likely as others to develop breast cancer,” reported the Daily Mirror. It said that the “sweating attacks are caused by a lack of the hormone oestrogen – but the shortfall may also cut the risks of getting tumours”.
This news story is based on a study that analysed information about women’s menopausal symptoms from about 1,000 postmenopausal women with breast cancer and 500 similarly aged controls without the disease. The main limitations are that women had to recall their past symptoms, and that some of the individual groups that were compared were relatively small.
Overall, a link between menopausal symptoms and the risk of breast cancer appears plausible, but larger prospective studies are needed to confirm whether this link exists and, if so, how strong it is. It is important to note the majority of women do experience some menopausal symptoms, even those who go on to develop breast cancer.
Boston University Medical Center