The hormonal pattern associated with increases in menopausal symptoms may reflects alterations in the sensitivity to estrogen in the brain.

Response to Estrogen Changes a Mystery

"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," Sherman notes.

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.

Brain May Develop Estrogen Insensitivity

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 study characterized the fluctuations in estrogen, which is produced by the ovary, as well as 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.

The hormone levels in some of the middle-aged women reflected a likely insensitivity to estrogen in the brain.

Three Patterns

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.

Age-Related CNS Insensitivity to Estrogen

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 such symptoms 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, Maryland. 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.