In the years leading up to menopause, usually from the ages of 45 to 54, a woman’s ovaries start to shrink, and the levels of the female hormones they produce, estrogen and progesterone, become irregular.

This can cause problems for some women, such as hot flashes, sweats and sleep disorders, and doctors often prescribe hormone replacement therapy to alleviate them.

Leaving aside for the moment the question of what, in an evolutionary sense, menopause is for (that is, what is its function?), when it happens the risk of a number of diseases increases. The rate of bone loss speeds up, leading to a greater risk of osteoporosis, and the risk of heart disease also rises.

In the past heart disease has been considered a male problem, but it is the leading killer of women in the United States, striking 10 years later than in men.

Early results suggested that HRT reduced the risk of the disease. But assessing disease risk is a hugely complex problem. Lifestyle, diet, environment and genetics all play a part, and several studies have given conflicting answers.

Now a new study sponsored by the National Heart, Lung and Blood Institute in Bethesda, Md., has found that postmenopausal women with heart disease who took hormone therapy and high-dose antioxidant vitamins — either alone or in combination with hormones — did not have fewer heart attacks, deaths or progression of coronary disease. In fact, both treatments showed a potential for harm.

Although the actual numbers of deaths in the study were small, participants taking both active hormones and vitamins had the highest death rate while participants on placebo versions of both treatments had the lowest death rate. Moreover, participants taking hormones and vitamins had either greater or equal progression of their coronary disease compared to participants taking placebo versions of these treatments.

The results of this Women’s Angiographic Vitamin and Estrogen trial were published in the Nov. 20 issue of the Journal of the American Medical Association and presented, on the same day, at the American Heart Association’s annual meeting in Chicago.

“This study adds to the growing body of evidence that hormone therapy is not helpful in the treatment, or in the prevention, of heart disease, and it provides new information on the absence of benefit from high-dose antioxidant vitamins,” said NHLBI Director Claude Lenfant.

The WAVE trial, which studied 423 postmenopausal women at seven clinical centers in the U.S. and Canada, is the largest trial to use angiography (an X-ray technique that shows blockages in the blood vessels of the heart) to assess the effects of HRT. It is also the first angiographic trial to look at antioxidants — high-dose vitamins E and C — in conjunction with hormone therapy.

The vitamin doses in the WAVE study were much higher than what is used in standard, over-the-counter multi-vitamin preparations.

“Although some other studies with lower doses of vitamins have suggested that antioxidant vitamin supplements might not be helpful, the trend toward more deaths found in WAVE was unexpected,” said David Waters, WAVE’s principal investigator, chief of cardiology at San Francisco General Hospital and professor of medicine at the University of California, San Francisco.

“The good news is that there are proven therapies to treat and prevent coronary heart disease, including weight control and controlling high blood cholesterol and high blood pressure,” added Waters.

Despite the existence of such therapies, with all the problems menopause brings, wouldn’t it be “better” for women to continue menstruating, just as men continue to produce sperm in old age? Menopause was shaped by natural selection, like all other aspects of human biology. But why?

In a paper published in Nature in 1998, University of Minnesota ecology professor Craig Packer said that evidence from lions and baboons points to menopause as a simple result of aging. The metabolic costs of menstruation, it would seem, are too high to continue after a certain age. (Sperm, on the other hand, are cheap to make.) If this is correct, then we can say what menopause is “for” — it is for avoiding the costs of continuing to menstruate.

And the timing of menopause is fine-tuned by natural selection. The time of onset, Packer found, is determined by how long a species needs to raise last-born infants to the age of independence. As an individual female ages, the reproductive system is the first to go, but that’s no problem at the point when the female won’t live long enough to be able to fully raise an additional child, he said.

“Since humans have a more prolonged period of infant dependency than other species, we’d expect menopause to occur earlier in life,” said Packer.

The theory predicts that reproductive decline will begin once the mother’s life expectancy drops below the time required to raise additional offspring. For example, if women in pretechnological societies could expect to live 50 years, and if a child, in order to survive, needed its mother until the age of 10, then reproductive decline could begin at age 40. Packer’s research illustrates this concept in baboons and lions.

Female baboons don’t live past age 26 or 27, and their infants require at least two years of maternal care. Baboon reproductive rates decline around age 21, which allows enough time for the youngest infant to reach independence.

It had been suggested that menopause evolved in humans to avoid the increased dangers of childbirth in middle age. But Packer found no evidence for this in elderly baboons and lions. Menopause occurs in nonhuman primates, rodents, whales, dogs, rabbits, elephants and domestic livestock. It appears to be a universal feature of mammalian females.

“Since female mammals are the primary caretakers of infants, we would expect menopause to evolve whenever child-rearing is extensive and prolonged,” Packer said.

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