Study challenges old notion that menopause starts in the ovaries.

Some of the most unpleasant symptoms of menopause, such as hot flashes and night sweats, have long been believed to originate in the ovaries.

But new research challenges that assumption, and instead suggests that menopausal symptoms, at least in part, may begin in the brain.

That’s because the hypothalamus and the pituitary gland stop reacting normally to estrogen in some women, suggesting they may have developed a reduced sensitivity to estrogen, researchers at the New Jersey Medical School report in the Dec. 22/29 issue of the Journal of the American Medical Association.

“This is an important new concept: Menopause doesn’t just originate in the ovary, but also in the brain,” said Laura Goldsmith, a professor of obstetrics and gynecology and women’s health at the New Jersey Medical School of the University of Medicine and Dentistry of New Jersey.

These findings may lead the way to further research that will ultimately help doctors predict the type of menopausal transition a woman might have, and help to design non-estrogen medications that could help reduce symptoms that women experience as they enter this phase of life, said Dr. Gerson Weiss, chairman of obstetrics and gynecology and women’s health at the New Jersey Medical School.

Menopause refers to the time when menstruation stops. A woman is not considered menopausal until she has not had a period for 12 consecutive months, according to the North American Menopausal Society. The time before menopause, which is often rife with symptoms due to hormonal fluctuations, is called perimenopause. During perimenopause, common symptoms include hot flashes, trouble sleeping, vaginal dryness, mood swings and irregular periods.

This study stemmed from research done for the Study of Women’s Health Across the Nation (SWAN), which was funded by the National Institutes of Health, that examined women’s’ health as they approached menopause.

The SWAN study included more than 3,300 women between the ages of 42 and 52 at the start of the study. A subset group of 840 women provided daily urine samples, which were tested for hormone levels. The samples were collected daily for one full menstrual cycle or 50 days, whichever came first.

From that group, the researchers learned that 160 did not ovulate. After further analyzing the hormone levels from the non-ovulating women, the researchers discovered that these women fell into three distinct groups.

The first group had an increase in their levels of estrogen, and then had an appropriate surge of luteinizing hormone (LH) that should have triggered ovulation, but didn’t. According to Weiss, this lack of response indicated a problem originating in the ovary.

In the second group, estrogen levels peaked, but there was no correlating surge in LH, which Weiss said should be triggered by the hypothalamus and pituitary gland responding to higher estrogen levels.

The third group had similar estrogen levels early in their cycles, but didn’t have an increase in estrogen later as the first and second groups did. LH levels didn’t surge, but were higher for most of the cycle than they were in the other groups.

According to Weiss, this is “clear evidence that the brain is not responding to hormones,” suggesting the second and third groups showed different kinds of decreased sensitivity to estrogen in the brain.

The women in the third group were also the ones most likely to report symptoms, such as hot flashes and night sweats.

Goldsmith said the researchers hope to continue studying these women. She said they’d especially like to learn how the timing of menopause correlates with their findings. For example, the researchers would like to see if the women in the third group were, perhaps, further along in the menopausal process.

“It appears that what’s going on in menopause isn’t only ovarian,” said Dr. Steven Goldstein, a professor of obstetrics and gynecology at New York University School of Medicine. “We thought the pituitary responded to lower levels of estrogen, but there may be a lack of sensitivity to estrogen in the hypothalamus and pituitary.”

What’s important for women to know, said Goldsmith, is that there are “real biochemical changes occurring during menopause.” Researchers are beginning to understand how those changes start to occur, which is the first step in trying to come up with more effective treatments.