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Thursday, June 10, 2004
Hormone therapy for menopause?
By ROWAN HOOPER
The age of menopause doesn't seem to have changed much in the last few thousand years. Records from ancient Egypt and Greece indicate that menstruation ended when a woman was around 50 years old. Before that we don't really know, as a woman was unlikely to live much longer than 50.
We do know that a woman is born with all the eggs she's ever going to have, and that the menopause indicates the depletion of all those eggs. Or this was known until recently.
Research done in the 1950s showed that the number of eggs in the ovaries declines with age. Most are killed by their own body, in a natural cell-death process called apoptosis. At the fifth month of gestation the female fetus has around 6 million oocytes (egg cells), but at birth the ovaries contain only 1 to 2 million. In childhood, many more oocytes degenerate.
By the time a woman enters the menopause, around 400-500 oocytes will have been ovulated and expelled in menstruation. A few may have been fertilized and developed into fetuses themselves.
It was something like scientific dogma that female mammals were born with all their eggs and didn't produce new ones. Earlier this year, Harvard researchers challenged that dogma. They found that mouse ovaries contain stem cells that continue to produce eggs throughout life. This is radical enough news, but it is not yet known if human females have the same sort of stem cells in their ovaries.
If they do it could mean possible new treatments for menopause.
This milestone in women's lives would have different meanings in different cultures.
Only relatively recently (and mainly in Westernized cultures) has it been seen as a condition that requires treatment. Nineteenth-century doctors prescribed diets and purges, and recommended limited exercise. Later, clinicians fed women extracts of ovarian tissue, in the growing belief that the sex organs held the key to the physiology of fertility.
In other cultures, menopause is not seen in the same way. Hazda women in Tanzania celebrate the onset of menopause, and menopausal women are among the most valued members of their society (this example suggests that it isn't the increased emancipation of Western women that has led to the "something-to-be-treated" view of menopause).
In the West it is known for its symptoms, among them hot flushes, sleeplessness and vaginal dryness. Certainly menopause treatments could do with some good news at the moment. Hormone replacement therapy, the modern-day answer to feeding women tissue extracts, was abandoned by physicians in the United States in 2002.
The reason? The Women's Health Initiative clinical trials had found that women on combination estrogen and progestin therapy had a slightly higher risk of heart attacks, strokes and blood clots.
But despite this, last month researchers at University of California, Davis, said that hormone therapy still offers real potential. This is because new research into the biology of ovarian hormones indicates that not all estrogens and progestins are alike, nor do they behave identically in different tissues in the body.
Estrogens affect many tissues. During natural menopause, which occurs in women at an average age of 51, estrogen and progesterone secretion from the ovaries diminish. Afterward, the risk of coronary heart disease and osteoporosis increases. Strokes and dementia are also associated with aging.
"Estrogens and progestins provide women with important health advantages before menopause," said Judith Turgeon, professor of internal medicine at UC Davis and lead author of last month's paper in Science. "We need to remain open to the possibility that these same ovarian hormones can help women stay healthier after menopause as well."
There is much to learn about the physiology of menopause. "It's a complicated issue, and we don't have all the answers," Turgeon said in an e-mail interview.
"Diet may play a small role," she said. "Phytoestrogens [e.g. in soy] have the potential to activate estrogen receptors in some tissues. In Japan, where women eat a soy-based diet, hot flushes seem to be less common than in American women. This may be due in part to diet, but probably also to cultural differences in reporting symptoms."
In other words, Japanese women complain less than American ones.
And cultural pressure on women about body weight and dieting may influence symptoms too. This is because the level of estrogens remaining even after the ovaries have stopped making them depends on the amount of fat in the body.
"The adrenal glands -- and the ovaries to some extent -- continue to make androgens, and androgens are converted to estrogens by an enzyme present in several tissues, most notably the fat cells," Turgeon said. "Women with more fat cells generally have higher residual levels of estrogens."
"Men also experience a diminution in testicular function [andropause] as they age," Turgeon said, "but it is more gradual than the relatively abrupt diminution of ovarian function."
So what's the take-home message?
"Women should feel comfortable using hormone therapy and estrogen therapy right now for the symptoms of menopause," Turgeon concludes. "But the idea of continuing it long term to prevent chronic disease has fallen by the wayside for now."
A book of these columns translated into Japanese, "Nou to sekkusu no seibutsugaku," is published by Shinchosha. Rowan Hooper is a biologist at Trinity College Dublin. He welcomes comments at firstname.lastname@example.org