Medical consensus about estrogen replacement therapy has gone from love to hate and back to love again in two short decades.
During the 1960s, estrogen was hailed as a miracle youth pill, a way to keep a woman "feminine forever" and to help her avoid the discomforts of menopause, especially hot flashes, genital changes, depression, even breast sag and wrinkles.
By the 1970s, medical reports began to focus on the risks of estrogen replacement therapy (ERT), especially its association with endometrial (uterine) cancer.
In 1985, doctors are back to talking about estrogen's benefits, including its ability to prevent bone thinning, and possibly even heart disease and breast cancer.
Why the recent change? Partly because estrogen tends to be administrered differently now than it was 10 years ago -- in smaller doses and often in combination with another female hormone, progesterone, that seems to eliminate the risk of endometrial cancer.
Most experts now agree that estrogen probably does not significantly increase a woman's cancer risk. Indeed, some go so far as to say it decreases the risk. One 1983 study, for example, found that women on ERT had a reduced rate of death from all causes, including death from cancer.
Based on such findings, the federal government has been moving toward a more enthusiastic endorsement of ERT. "Estrogen is terrific -- for certain symptoms," said Dr. Jacob Brody, associate director of the National Institutue on Aging. "If a woman is sufficiently uncomfortable, we can recommend that she not hesitate taking estrogen. You have to weigh the small possibility of a bad outcome against the virtual certainty of getting rid of vaginal atrophy, hot flashes and possibly depression."
According to the Food and Drug Administration, estrogen use, which declined sharply during the cancer scare of the late 1970s, has been on the rise since 1980. In 1983, the latest year for which information is available, 17 million prescriptions were written for estrogen, 7 million of them to treat menopausal symptoms. (Other common uses of estrogen include treatment of ovarian dysfunction in younger women.)
In the same year, 3.1 million prescriptions were written for progestin, the artificial form of the hormone progesterone, 700,000 of them for postmenopausal women.
Despite its growing popularity (and despite some women's secret hopes when they begin therapy), estrogen is not a fountain of youth. But it does have a well-documented effect on certain symptoms -- hot flashes and genital changes -- that affect about 25 to 30 percent of menopausal women.
Many women on ERT report that they sleep better, have more energy and feel less depressed than they did before.
Women receiving ERT to relieve menopausal symptoms usually are weaned off estrogen after a year or two, after which the symptoms usually do not return.
But ERT is being advocated for a new purpose that probably requires that a woman stay on estrogen indefinitely -- the prevention of osteoporosis, the rapid loss of bone mass that results in spontaneous fractures of the wrist, hip and spine in about 25 percent of white women over 60.
Last April, the National Institutes of Health recommended that all white women past menopause "consider" ERT to prevent osteoporosis. (Black women were excluded because they seem to be at lower risk of osteoporosis, beginning life with denser bones.) But to prevent osteoporosis, a woman must take estrogen for many years.
"You can block the acceleration of bone loss that usually occurs right after menopause by beginning ERT early," said Dr. Diane Meier, director of the Coffey Geriatrics Clinic at The Mount Sinai Medical Center in New York. "But once youstop the estrogen, a woman experiences that same acceleration of bone loss."
Long-term use of ERT concerns Meier. Although ERT is getting a good reputation when it is used for a few years, she says, "We have no sufficient data to show what happens after several decades of estrogen use."
Consumer activists also worry about prolonged use of ERT. "Osteoporosis is a serious and scary problem, but I'm afraid it's being used to seduce women back to estrogen," says Davi Birnbaum, cofounder of the Menopause Collective of Boston and a board member of the National Women's Health Network. Other techniques to prevent osteoporosis may reduce the risk of that disease without the hazards of ERT.
And just what are those hazards? In about 10 percent of women on ERT, side effects are so disruptive -- including cramps, fluid retention, headache, nausea, swollen breasts, vaginal discharge and weight gain -- that the dosage must be reduced or discontinued.
In addition, a woman on estrogen runs more than twice the normal risk of developing gallbladder disease and four to eight times the risk of developing endometrial cancer.
The risk of endometrial cancer from ERT falls to near zero when estrogen is taken in combination with progestin.
Progestin is found in the birth control pill, where it also exerts a protective effect on the uterine lining -- a protection that seems to last for many years. Researchers at the Centers for Disease Control recently found that ERT users who had been on the pill for at least one year were less likely to develop endometrial cancer than ERT users who had never taken birth control pills.
No link has been shown between breast cancer, a leading cancer killer in women, and ERT. But breast cancer takes many years to develop; it took 30 years to establish a link between breast cancer and DES, the artificial estrogen once prescribed to prevent miscarriage.
Many physicians are cautious about prescribing estrogen for women with a strong family history of breast cancer, and will not prescribe it for women who have had the disease themselves.
But a few doctors, led by Dr. R. Don Gambrell Jr., professor of endocrinology at the Medical College of Georgia, do just the opposite. Gambrell says that estrogen plus progestin might help prevent breast cancer in women at highest risk.
"In our studies of 5,500 menopausal women," he said, "the incidence of breast cancer for women on estrogen and progestin was reduced to almost one tenth the usual incidence."
The evidence about ERT and cardiovascular disease is incomplete and sometimes contradictory. Estrogen increaes the blood level of HDL, the form of cholesterol that protects against coronary artery disease; in this respect, ERT could help prevent heart attacks after menopause.
But progestin interferes with this beneficial action on HDL and creates some hazards of its own, increasing the risk of blood clots, heart attack and stroke.
On balance, estrogen replacement therapy is probably less dangerous than it seemed to be 10 years ago. But a woman who decides to take estrogen, with or without progestin, must understand that she probably is increasing certain risks for the sake of minimizing others.
In the years ahead some of the big questions about estrogen replacement therapy may be answered. In the meantime, a woman's personal history, family history and desire for treatment are the most important factors in reaching a decision about whether estrogen replacement therapy is for her.