| Decreased Sensitivity in the Brain to Estrogen
May Help Explain Menopausal Changes
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
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
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, 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. 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.