Decreased sensitivity in the brain to estrogen may help explain menopausal changes

December 21, 2004

A new study suggests that age-related changes in how the brain responds to the female sex hormone estrogen may be involved in a woman's transition through menopause. The study provides new clues about hormonal influences on hot flashes and night sweats experienced by some women in the menopause transition.

The findings are reported in the December 22/29, 2004, Journal of the American Medical Association* and are based on data from the Study of Women's Health Across the Nation (SWAN), a multi-site survey of women going through the menopause transition. This study is funded by the National Institutes of Health.

"Throughout a woman's reproductive life, there are not only age-related changes in estrogen levels, but also differences in how her body responds to given levels of estrogen. Researchers have been trying to understand how and why these changes take place," says Sherry Sherman, Ph.D., project director of the SWAN study, National Institute on Aging (NIA). "Hormone patterns found in this study could mean that, with age, a part of a woman's brain which regulates reproductive hormone levels may become less sensitive to estrogen. Other study findings suggest that the decreases in sensitivity can lead to significantly increased hot flashes and night sweats."

The analysis was led by Gerson Weiss, M.D., New Jersey Medical School at the University of Medicine and Dentistry of New Jersey (UMDNJ), who with his colleagues from the SWAN study reported the findings. UMDNJ is one of seven SWAN sites supported by the NIA, the National Institute of Nursing Research, and the Office of Research on Women's Health, all parts of the National Institutes of Health (NIH) at the Department of Health and Human Services.

SWAN follows more than 3,300 women, ages 42-52 at the beginning of the study in 1995, as they experience the changes associated with approaching menopause. The data for this report came from the Daily Hormone Study, a substudy that involves the daily collection of urine samples and completion of a questionnaire about symptoms, for a period of one menstrual cycle or a maximum of 50 days (if no menstruation occurs).

Through this sampling, the study characterized the fluctuations in hormones such as estrogen, which is produced by the ovary, and fluctuations in other hormones such as luteinizing hormone (LH), which is produced by the pituitary, a gland at the base of the brain. These reproductive hormones are needed for normal menstrual cycles and to prepare the body for pregnancy.

In this study, the hormone levels in some of these middle-aged women reflected a likely insensitivity to estrogen in the brain. The data showed three different patterns of hormone fluctuations in women who did not ovulate: the first group of women had a surge of LH--an "appropriate" response to increases in estrogen. In a second group, the same increases in estrogen were not associated with a surge in LH. In the third group, estrogen levels early in the cycle were similar to those of groups 1 and 2, but, unlike those two groups, did not show further increases. The LH levels in this group did not show a surge and were higher for most of the cycle than in the other groups. The hormonal patterns in groups 2 and 3 suggest different kinds of reduced sensitivity to estrogen (or abnormal estrogen "feedback") in the brain.

Interestingly, the women in the third group had significantly more hot flashes and night sweats than women in the other two groups. These findings suggest that the hormonal pattern associated with increases in symptoms reflects alterations in the sensitivity to estrogen in the brain. Additional follow-up of the women as they experience their final menstrual period and become postmenopausal is needed to further clarify the hormonal changes underlying the menopause transition as well as those causing hot flashes.

The findings in these women are the first to describe hormone patterns reflecting changes in responses to estrogen and are consistent with previous studies in other mammals that have described similar central nervous system insensitivity to estrogen with aging. A better understanding of the role of changing responses to reproductive hormones including estrogen in causing menopause-related symptoms is needed to develop new approaches for managing symptoms occurring at this time.

Because of the need to identify treatment options for women experiencing symptoms such as hot flashes during the menopause transition, the NIA and NIH's Office of Medical Applications of Research are sponsoring a State-of-the Science Conference on Management of Menopause-Related Symptoms, March 21-23, 2005, in Bethesda, MD. This meeting will bring together experts in the field who will present information on the biology of the menopause transition, common symptoms during this time, and possible treatments to an independent panel. This panel will prepare a state-of-the-science statement to provide guidance to women and their doctors, as well as to suggest future research directions.
-end-
Further information is available at www.consensus.nih.gov.

The NIA, www.nia.nih.gov, conducts and supports research on aging and age-related diseases. For more information on menopause, please visit the NIH's Menopausal Hormone Therapy page at http://www.nih.gov/PHTindex.htm. To request a free copy of the NIA brochure, Menopause: One Woman's Story, Every Woman's Story, visit www.niapublications.org, or call 1-800-222-2225. The National Institute of Nursing Research, http://ninr.nih.gov, supports clinical and basic research in order to provide a scientific basis for the care of individuals across the lifespan. The Office of Research on Women's Health, http://www4.od.nih.gov/orwh/, works to advance research activities on behalf of all women.

*Weiss, G, Skurnick, JH, Goldsmith, LT, Santoro, NF, and Park, SJ, Menopause and Hypothalamic-Pituitary Sensitivity to Estrogen. JAMA. 2004; 292: 2991-2996.

NIH/National Institute on Aging

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