Dr. Florence Haseltine of Bethesda, Md. turned 45 this summer, and she now defines herself, as perimenopausal. That's the new medical buzz word for women between the ages of 35 and 50 who have not yet gone through menopause but have started to experience subtle changes in their bodies that herald the end of their child-bearing years.
Haseltine, who is director of the Center for Population Research at the National Institute for Child Health and Human Development (NICHD), is one of an increasing number of physicians -- and women -- who are taking a more aggressive approach to this midlife period.
It used to be that little attention was given to menopause until after the cessation of menstruation had occurred -- usually around the age of 50. But now menopause is seen not as an event but as a long gradual process that begins in the thirties or forties.
Central to this new concept of menopause is the question of whether women should be treated with hormonal drugs in the hope of preventing some of the changes that can occur after the body essentially stops producing the female hormone estrogen.
"I've already started trying out estrogen replacement for myself," says Haseltine. In her view, the drug will help delay certain potentially serious problems that affect some women, such as bone thinning to the point of osteoporosis, vaginal thinning to the point of atrophy, breast reduction and clitoris shrinkage and, infrequently, even a loss of the skin's sensitivity to touch.
"I've also taken up heavy-duty exercising," she adds, her gym bag sitting prominently in her Bethesda office. "I have found it harder to keep my weight down in the past few years, and aerobics classes help."
Spurred in part by her personal stake in understanding the perimenopause, Haseltine now finds herself in the forefront of this emerging medical field, which is also called climacteric studies -- from the Greek for "rung of a ladder."
The new subspecialty gets an official nod from the federal government next April, when NICHD co-sponsors, with the American Fertility Society, a national conference on the perimenopause.
Yet this new attention to climacteric studies is fueling an old debate in women's health: Is perimenopause, like pregnancy, to be viewed as a disease to be treated? Or a natural process that rarely needs medical intervention?
What's more, not all physicians are enthusiastic about adding yet another subspecialty that reinforces menopause as a focal point in gynecology.
"I don't believe in defining a woman at 35 as premenopausal, or at 45 as perimenopausal," says Dr. Isaac Schiff, associate professor of obstetrics and gynecology at the Harvard Medical School and director of reproductive endocrinology services at the Brigham and Women's Hospital. "Those terms carry a certain stigma with them," he says, and falsely make menopause seem the single watershed event in a woman's life. Next for the Baby Boom
The Census Bureau reports that nearly 22 million women are between ages 35 and 50. But despite this large population bulge, soon to be even larger as the baby boom continues to age, physicians know surprisingly little about how perimenopausal women are different from -- and how they are the same as -- women of any other age.
One of the first studies to look at healthy midlife women, sponsored by the National Institute on Aging, is now in its final stages. The principal investigator, Dr. Sonja McKinlay of the American Institutes for Research, reports that, just as every woman responds differently to earlier hormonal upheavals -- puberty, menstruation, pregnancy -- so every woman responds differently to the hormonal changes of the perimenopause.
McKinlay's sample includes 2,500 Massachusetts women born between 1926 and 1936. Since 1982, when the youngest in the sample was 46, these women have been contacted for lengthy telephone interviews every nine months to assess their health status as they approach menopause.
The "vast majority" of these women, she says, "do not express regret at reaching menopause, do not report more symptoms or poorer health status and do not evidence any increased use of medical services."
Symptoms such as irritability, depression, weight gain, dizziness or tiredness were not associated with any of the life-style factors she studied, says McKinlay. These "vague" symptoms could not be tied to family situation, employment, socioeconomic status or the like. What she did find, says McKinlay, is that symptoms clustered in only a small proportion of the women. She says the women most likely to complain of any one symptom were those who had already complained of others.
McKinlay also found that most women in this age range do not seek a physician's advice about their health. In response to the question, "In the previous nine months, have you discussed any symptoms with a doctor or any other health professional?" only one third of the women surveyed said yes.
"This could have included only a phone call to the doctor or even a phone call to a nurse," says McKinlay. "We conclude from this that we tend to overestimate the women in this age range who go to the physician." Where the Action Is
The ovaries, obviously, are where the action is during the perimenopause. The medical definition of menopause is the complete cessation of menstrual periods for 12 consecutive months. When a woman's periods stop, it means her ovaries no longer produce estrogen, the female hormone needed to ripen an egg to maturity each menstrual cycle.
"The ovary is the most precisely doomed structure in the human body: It carries in its makeup the destruction of its own seeds," wrote Dr. Daniel D. Federman, dean of the Harvard Medical School, in the New England Journal of Medicine in July. Oocytes (cells that eventually mature into egg cells) disappear with dizzying -- and, to date, unexplained -- rapidity.
There are 7 million egg cells in a fetus's ovaries, Federman wrote, but only 3 million at birth, 400,000 at puberty and 100,000 at menopause. A woman releases on average just one mature egg each month during the 35 to 40 years of her menstrual life; the fate of the other 250,000 oocytes lost during those years remains a mystery.
But ovarian activity doesn't come to a screeching halt at the age of 50. Instead it tapers off slowly, with women in their 40s and even late 30s manufacturing progressively lower amounts of estrogen. This gradual loss of estrogen translates into a gradual loss of fertility as well. "The likelihood of a 40-year-old woman conceiving is about one third to one half of what it would have been in her mid-20s," says Dr. S. Mitchell Harman, an endocrinologist at the Gerontology Research Center of the National Institute on Aging (NIA).
Fertility drops by 40, he says, because a perimenopausal woman cannot always make enough estrogen to stimulate ovulation, even though she continues to menstruate regularly.
In addition, says Harman, the slow decline in estrogen production also can lead to menstrual irregularities -- longer cycles, shorter cycles, less bleeding, more bleeding or any combination of these changes from one month to the next.
Nor does estrogen production stop altogether when a woman's periods stop. Even women of 60 or 70 continue producing estrogen, although postmenopausal estrogen, called estrone, is one 1/100th as potent as is estradiol, the estrogen produced during the reproductive years. (Estriol, a third form of estrogen, is manufactured by the placenta during pregnancy.) Estrone is made after menopause in the fat cells, where a weak male hormone -- called androstenedione, produced by the ovaries and adrenal glands in women of all ages -- is converted into a weak female hormone.
But as gradual and open-ended as this estrogen loss may be, there's no getting around the fact that a woman past 45 has less estrogen than she had at 25, and a woman past 55 has even less.
Traditionally, this estrogen loss has been central to the definition of menopause. And menopause, in turn, has long been known in medical texts and doctors' offices as a hormone deficiency disease.
The women's self-help health movement has, since the 1971 publication of "Our Bodies, Ourselves," shunned such a designation. "Many doctors still think of menopause as a disease and offer medical solutions far more often than necessary," wrote members of the Boston Woman's Health Book Collective in their most recent edition of that landmark self-help book. In the book's resource section, the authors recommend a pamphlet available from the San Francisco Women's Health Center called "Menopause: A Natural Process."
"Natural?" says Harman of NIA. "So is Hashimoto's thyroiditis natural, but we give a hormone for that."
The comparison is meant to be more than catchy. Harman says treatment of thyroid hormone deficiency -- of which Hashimoto's thyroiditis is the most common -- is a model for the way he'd like to see perimenopause treated. For both conditions, Harman's creed is this: "If someone is deficient in a hormone he has had for most of his life, a hormone that does many of his organs considerable good, the thing to do -- in the absence of problems that could cause complications -- is to replace it." Not Just the Ovaries
Perimenopause is not something that happens just to the ovaries -- or, notwithstanding the publicity given recently to osteoporosis, just to the bones. "Everyone concentrates on the ovaries because they are a point of demarcation," says Haseltine. "And everyone concentrates on the skeleton because it can be measured, talked about, analyzed and you can show pictures of it." But many other organs, she says, undergo significant age-related changes that women may begin to recognize as soon as their early 40s or even their late 30s.
Most prominent among these changing organs are the skin and the brain.
Touch aversion is one little understood, but distressing, side effect of perimenopause. The skin of some women in these years "bruises more easily, feels dry and may develop itching, burning and tingling sensations, sometimes described as 'ants crawling under the skin,' " notes Dr. Herant Katchadourian, professor of psychiatry and behavioral science at Stanford University, in his new book "Fifty: Midlife in Perspective."
Partly because of these sensations, he continues, "women become more sensitive to being touched. They may find that even the sensation of tight clothing on their skin is unpleasant, and they feel most comfortable in a loose nightgown or robe. Severe cases extend to downright aversion to being touched by others, including husbands."
A woman in midlife who begins pulling away from her husband, adds Haseltine, might not make the connection at all to changes in nerve conduction. Nor might her husband, who himself is probably experiencing some of the physical and sexual changes of middle age (see box).
"Frequently, partners misunderstand which sexual changes are a natural part of this stage of life," says Haseltine. But communication -- with each other and with a knowledgeable physician -- is especially important in midlife, she says. Without it, couples can feel threatened by those changes.
If a woman doesn't want to be touched, Haseltine says, it's not because she no longer loves her husband; if a man takes more time to become aroused, it's not because he no longer finds his wife desirable. Both can be explained, says Haseltine, by the physiology of midlife. "And the dissolution of relationships because people don't understand sexual function and dysfunction seems pretty silly."
Other changes that occur in a woman's 40s, and might indirectly lead to problems with touching, are neurological. Haseltine says physicians have recently noted a decline among perimenopausal women in "two-point sensitivity" -- the distance required for a woman to detect, with her eyes closed, that her hand is being pinched by two separate probes rather than one. As a woman ages, this distance increases, which might mean that the nerve endings in her hand, and possibly other regions, are becoming progressively less refined.
A recent autopsy study at the New York State Psychiatric Institute found that in their 40s, both women and men begin to accumulate cellular wastes in one region of the brain, the locus ceruleus. Because the locus ceruleus is one of the main receptor sites for norepinephrine -- the neurotransmitter that accounts for anxiety, fear and attentiveness -- scientists now suspect that this accumulation of wastes and its resulting functional losses can account for the often observed "mellowing out" of the middle-aged personality. Hot Flashes: The Hallmark
Hot flashes are common for women after menopause, affecting an estimated 75 to 80 percent of women who have had their last menstrual period. But flashes also can be a problem for younger women whose last period is years away.
"Maybe the woman started out just waking up warm in the middle of the night, and only later did she realize she had been having hot flashes," says Dr. Fredi Kronenberg, associate research scientist at the Center for Geriatrics, Gerontology and Long-Term Care of Columbia University. "Certainly at the age of 40 you don't think, 'These are hot flashes.' "
Neither does the woman's physician. A 40-year-old who complains to her doctor of sleeplessness, feverishness, chills, anxiety and heart palpitations, says Kronenberg, might be put through a wide range of diagnostic tests, at significant expense and with considerable worry, only to discover that she's just having perimenopausal hot flashes.
"Medical textbooks say hot flashes begin at menopause and last for five years after," says Kronenberg, who also is research director of the Women's Association for Research in Menopause (WARM). But in her experience -- which includes leading a weekly support group in Manhattan for hot flash sufferers -- flashes "generally start five to 10 years earlier than menopause."
And they don't always stop, either. Kronenberg knows of one woman who says she started having hot flashes at 37, had a natural menopause at age 50, and today, at 79, is still flashing.
While estrogen replacement therapy is the primary treatment, Kronenberg is now doing studies of the effect on hot flashes of alternative therapies, such as acupuncture, hypnosis, biofeedback and vitamin E. Sex After 40
Vaginal atrophy to some degree is inevitable with the loss of estrogen. The walls of the vagina become much thinner. At the height of a woman's reproductive years, the vagina has developed a lining of mucous membranes 20 layers thick. Within two years of menopause, that lining has shrunk to just two layers. The clitoris and vulva also shrink as estrogen declines.
While much has been made of the fact that women, unlike men, can have orgasms in late life that look and feel just as they always did, the anatomical changes of the genitals can indeed have an effect on sexuality in some women.
"Atrophic tissue is not unhealthy," says Haseltine, "but it is dysfunctional." Vaginal atrophy, especially when combined with a decrease in vaginal lubrication common in the perimenopause, can cause pain or even bleeding with intercourse.
A thinner vagina also is a poor barrier to bacteria and other pathogens, so that urinary tract infections become more common with age. Cystocele (protrusion of the bladder through the vaginal wall) and rectocele (a similar protrusion of the rectum) also can occur if the vagina has atrophied. Both can be corrected surgically. Replacing What Was Lost
"Estrogen replacement therapy may get the vagina and clitoris to look normal," says Haseltine, "but we need to figure out just how it's done. When do you start treatment? At 45? Later? How do you know in any individual woman when to consider medication? And what are the roles of other sex hormones, like the androgens?"
There are still many questions about estrogen replacement therapy during perimenopause, especially in women who have not developed problems. At the same time, the treatment is known to relieve certain conditions. Hot flashes and vaginal atrophy improve with ERT, and usually do not return after one or two years on the drug if the medication is withdrawn slowly. In addition, estrogen for bone loss is the treatment of choice, rather than calcium supplements alone, according to a recent consensus conference on osteoporosis.
The women whose symptoms are most dramatically eased with hormones are those whose symptoms are most severe in the first place. These are women who have undergone a surgical menopause, whose ovaries have been removed (usually in conjunction with a hysterectomy, removal of the uterus). Their symptoms are severe because their menopause was sudden. Also, they lack one important source of estrone -- the ovaries themselves -- so their estrogen withdrawal is not only sudden, but virtually complete.
When a perimenopausal woman's ovaries are removed, she is almost always given estrogen replacement therapy -- at least until the age of natural menopause.
But what about a perimenopausal woman whose ovaries are intact, but diminishing? "There is increasingly a consensus among gynecological endocrinologists," says Harman of NIA, "that most women shouldn't ever experience menopause, because as soon as a woman starts to she should begin estrogen replacement therapy."
There are even physicians, such as Dr. John Berryman of the George Washington University Medical School, who suggest that women should stay on birth control pills until the mid-40s, at which time they should begin estrogen replacement therapy, which contains about one fifth the estrogen of the pill. These women, according to Berryman, never experience any of the hormonal fluctuations -- and, in theory, none of the bone loss and other health problems, of the perimenopause.
In 1985 the American College of Obstetricians and Gynecologists issued its first policy statement on the use of contraceptive pills for perimenopausal women. Past the age of 35, said the gynecologists, "healthy, nonsmoking women" can safely take the birth control pill; even after age 40, they said, these low-risk women can probably continue to take new low-dose pills (lower than 50 micrograms of ethanol estradiol) at a risk so low it "may be even less than that associated with a normal pregnancy."
This new view of the pill reflects the turnabout in population studies of women taking estrogen.
Ten years ago, ERT was associated with an increased risk of cancer of the uterine lining. But today, estrogen is given in much lower doses, and in combination with another female hormone, progesterone, to more closely mimic the premenopausal hormone cycle.
One study of more than 2,000 women, coordinated by the National Heart, Lung, and Blood Institute, found in 1983 that women ages 40 to 69 who were taking estrogen not only had no increased risk of uterine cancer but actually had a lower overall death rate from all causes, including heart disease and cancer.
"The risk-benefit ratio of estrogen replacement therapy is so much in favor of taking it," concludes Harman, "that any woman who isn't is doing herself a disservice."
Still, uses of ERT are controversial, and other scientists are a bit less sanguine about who should get estrogen. "I don't have any blanket rule that all women should get estrogen -- or that all women should not," says Harvard's Schiff. Echoing the caution of many mainstream gynecologists, Schiff says, "I make my decision on a case-by-case basis."
Staving Off the Changes
Not many gynecologists go so far as to say that no woman need experience the perimenopause. But most would agree that no woman need suffer through it.
Estrogen replacement therapy is now considered safe enough that most women can take it for hot flashes, vaginal atrophy and possibly some of the mood swings that can go along with the hormonal changes of this stage of life.
Very long-term use of estrogen is still an open question, though, since no good studies have been done on women taking ERT for more than 10 years. "Taking estrogen for more than 20 or 30 years, as you might have to for the prevention of osteoporosis, is a great unknown," Harman says. "When people ask my opinion about that, all I can say is we need more data."
In the meantime, changes in life style can make a big difference in how a woman gets through the perimenopause. Vigorous exercise has been shown to reduce the rate of bone loss that can lead to osteoporosis, to raise the level of lipoproteins in the blood that protect against heart disease (which becomes more common in women after menopause) and even to relieve hot flashes.
Sexual changes can be avoided by staying sexually active. One study found, for example, that women who reached orgasm at least once a week were significantly less likely to suffer vaginal atrophy than were women who had sex less than once a month. Exercises of the vaginal muscles by deliberate rhythmic contractions of the sphincter that holds in urine flow, called Kegel exercises, also can help prevent cystocele and rectocele despite the thinning of the vaginal walls.
Still, the use of birth control pills and estrogen replacement therapy remains a central issue in research on the perimenopausal period.
One goal of next year's national conference on perimenopause, says Haseltine, who is coordinating it, is to establish the conditions in which a woman in this phase of life should start considering estrogen replacement therapy.
Now that medical scientists are approaching the perimenopause as a distinct and scientifically interesting stage of life, new information will be uncovered about what makes a 40-year-old woman different from a 20-year-old or a 60-year-old. For women of the baby boom who are entering the perimenopausal stage of life, that will be good news. Because when menopause finally arrives, they will have one third or more of their lives still to live.