Estrogen Matters: Why Taking Hormones in Menopause Can Improve Women's Well-Being and Lengthen Their Lives -- Without Raising the Risk of Breast Cancer (2024 Revised and Updated Edition)

by Carol Tavris

By the early 1990s, researchers had fifty years of well-documented evidence showing estrogen’s benefits. Estrogen not only successfully controlled menopausal symptoms in most women but also significantly reduced the risks of heart disease, hip fractures, colon cancer, and Alzheimer’s. A 1991 New England Journal of Medicine editorial titled “Uncertainty about Postmenopausal Estrogen: Time for Action, Not Debate” reported a 40 to 50 percent reduction in atherosclerotic heart disease, which is responsible for the deaths of more than seven times as many American women as breast cancer.1 The long-running Framingham study reported a 50 percent drop in osteoporosis-associated hip fractures, which were linked to as many deaths every year as breast cancer. Two studies, one from the University of Wisconsin and one from the American Cancer Society, reported a 50 percent decrease in the risk of developing or dying of colon cancer. Among women with no history of breast cancer, estrogen did not increase the risk of developing it, even for women who took estrogen for 10 to 15 years. Most notably, women taking estrogen lived longer than women who did not take hormones. In 1997, three researchers reviewed the benefits of HRT for women after menopause and concluded that by reducing the risks of serious diseases, “HRT should increase life expectancy for nearly all postmenopausal women by up to 3 years.”2

WHI has walked back virtually all of its early alarmist findings.

The FDA continues to require an ominous black box on every estrogen product, warning of “cardiovascular disease, probable dementia, and breast cancer.” And yet the WHI investigators now say that estrogen does not increase deaths from heart disease and cancer. On the contrary, it increases longevity, most notably when begun within ten years of the last menstrual period. HRT is the best preventive for osteoporotic hip fractures. It is safe and effective when applied vaginally for local symptoms. And, in the most striking about-face from their 2003 headlines that HRT “did not have a clinically meaningful effect on health-related quality of life” for women in menopause, they stated in 2019 and again in 2021 that “hormone therapy is the most effective treatment for managing menopausal vasomotor symptoms” and thereby improving women’s quality of life.

In 2020, for example, the WHI investigators reported a decreased incidence of breast cancer among women randomized to estrogen after 19 years of follow-up.

It’s the combination of estrogen and progesterone (HRT), the WHI still maintains, that raises the risk.12 But as we will show in chapter 2, that finding was due to a statistical misinterpretation: The women on HRT did not have an increased risk; the control group had a reduced risk, because many of the women in that group had been on estrogen before the study. When they were removed from analysis, the supposed increased risk of HRT vanished.

in the Women’s Health Initiative (WHI), a higher proportion of those on HRT lost weight compared to the women on placebo.

At a conference devoted to the treatment of estrogen-deficiency symptoms, Nachtigall noted: “Among 2,000 postmenopausal women in a given year, 20 will develop heart disease, 11 bone loss, 6 breast cancer, and 3 endometrial cancer, but nearly 100 percent will develop urogenital atrophy.

According to the Study of Women’s Health Across the Nation (SWAN), a multiracial/multiethnic study that ran from 1996 to 2013 and followed more than 3,000 women as they entered menopause, about 80 percent of women experience some symptoms, and for half of them, those symptoms last for years. The median duration of hot flushes and other vasomotor symptoms among these women was 7.4 years; it was longer (10 years) for Black women and upwards of 12 years for women whose symptoms began during perimenopause.18 Black and Latina women also enter perimenopause much sooner on average, sometimes even in their thirties, so their symptoms start much earlier and can be more severe. Needless

The WISDOM study, an acronym for the Women’s International Study of Long-Duration Oestrogen After the Menopause, was a randomized, placebo-controlled trial of 3,721 postmenopausal women in Australia, New Zealand, and the United Kingdom. The women ranged in age from 50 to 69 and were randomly assigned to take HRT or placebo. Compared to the women given the placebo, women on HRT experienced improved sleep, reduced hot flushes and night sweats, fewer aching joints and muscles, less vaginal dryness, and improved sexual functioning.24 The researchers particularly emphasized the benefits of HRT on improving sleep and reducing insomnia, given that inadequate sleep is “associated with an increased risk of illnesses such as obesity, diabetes, hypertension, and cardiovascular disease. Reducing sleep deprivation might therefore have considerable health benefits.” Further, because many menopausal women report joint and muscle pain and increased arthritic symptoms—as we said, that’s another set of symptoms not popularly associated with menopause—the WISDOM researchers highlighted their finding that women reported lower levels of bodily pain after a year on HRT. Indeed, they cited the WHI, which had (quietly) gotten the same result: “A follow-up study with participants in the Women’s Health Initiative that looked at joint symptoms showed a higher prevalence of pain or stiffness in those women who stopped taking combined HRT compared with placebo.”

Although the WISDOM study found no alleviation of symptoms of depression among the participants, two randomized trials of estrogen therapy reported remarkable success. Women suffering from depressive episodes received four to twelve weeks of estrogen or placebo. Those in the estrogen group had a 60 to 75 percent improvement versus a 20 to 30 percent improvement for women given placebo.27 That estrogen was so much better than antidepressants, and without the side effects antidepressants often have,28 should have been big news.

There is no scientific basis for the admonition to take as low a dose of postmenopausal hormones for as short a period as possible.

In that 2021 paper, they reported that after 13 years of follow-up, HRT did not increase the risk of venous thromboembolism or stroke. But in 2023, they said that it did increase the risk of thromboembolism and stroke and so, they concluded, “vasomotor symptoms should only be treated if they are bothersome.”

Over and over, studies find that about 20 percent of women who take herbs—red clover, soy, flaxseed, dong quai, evening primrose oil, ginseng, wild yam, chaste tree, hops, and sage—report improvement of symptoms, which is precisely the percentage reported by women given the placebo.

the American College of Obstetrics and Gynecology’s practice guidelines explicitly note that complementary botanicals and natural products, including over-the-counter isoflavones, Chinese herbs, black cohosh, ginseng, St. John’s wort, and ginkgo biloba, have not been shown to be effective.

In 2020, the National Academies of Science confirmed the unreliability of compounded bioidentical hormones (cBHT). After 21 months of data collection and analysis, the investigating committee concluded: “Given the paucity of data on the safety and effectiveness of cBHT… there is insufficient evidence to support the overall clinical utility of cBHT as treatment for menopause.”

The WHI investigators reported that women who were randomly assigned to take estrogen on its own had had no increased risk of breast cancer. Those who still had a uterus and were assigned to take the combination of estrogen and progestin (HRT) had a small increased risk of breast cancer (of 1.26) when compared with women who were randomly assigned to a placebo.33 That number, 1.26, means a 26 percent increase in risk. Few noticed this sentence: “The 26 percent increase in breast cancer incidence among the HRT group compared with the placebo group almost reached nominal statistical significance.” Almost means it did not reach statistical significance, and that means it could have been a spurious association.

Fully 35 percent of the women were considerably overweight, and another 34 percent were obese; nearly 36 percent were being treated for high blood pressure; nearly half were either current or past cigarette smokers.38 Moreover, the median age of participants was 63, considerably past menopause. Therefore, there is no credible reason for generalizing from the results of this study to the entire population of menopausal women.

breast cancer incidence rates in the United States have increased by roughly 0.5 percent annually since the premature termination of the WHI’s trial in 2002, even though hormone use has remained low;46 according to the FDA, in 2023, 82 percent of American women over 45 reported at least one menopausal symptom, but only 10.5 percent had used any form of menopausal hormone therapy.47 And third, breast cancer usually takes from 9 to 16 years to become clinically identifiable.

the strongest disconfirming evidence for the claim that estrogen causes breast cancer is this: the administration of estrogen has been shown to have beneficial effects even in women with advanced breast cancer.

in 2019, one-third of women who died of a sudden cardiac arrest had had normal ECGs.

“most, but not all, studies of hormone replacement therapy in postmenopausal women show around a 50% reduction in the risk of a coronary event in women using unopposed oral estrogen.”

women who started HRT within ten years of the onset of menopause actually reduced their risk of coronary artery disease, while those who started after that slightly increased their risk.22 The Nurses’ Health Study came to the same conclusion.

in women who do have underlying heart disease, estrogen can potentially be harmful—it can induce inflammation in existing arterial plaques, causing a stable plaque to rupture, and it can also promote bleeding into the plaque, both of which can block critical coronary arteries. Estrogen, with or without progesterone, may also cause platelet clumping, which can further obstruct coronary arteries. After the first year of hormone therapy, women no longer have an increased risk of cardiovascular events—even women with preexisting coronary artery disease.

Women over the age of 50 have four times the rate of osteoporosis than men do, and their fractures occur five to ten years earlier than men’s.

Women fear dying of breast cancer, but that risk and the lifetime risk of dying of complications of a hip fracture—primarily circulatory diseases and dementia—are about the same.

Although calcium is crucial for the development of strong bones in children and adolescents, once bones are formed, additional calcium neither prevents nor treats bone loss.

Orthopedic surgeons in China performed a meta-analysis of 33 randomized trials involving 51,145 people. They evaluated the incidence of fractures in people taking supplements compared to those taking a placebo or getting no treatment. Taking calcium on its own, vitamin D on its own, or calcium plus vitamin D were not associated with a lower risk of fractures. The WHI confirmed these results in 2013 and again in 2024.11

A 2022 study of supplemental vitamin D given to 13,085 women ages 55 and older reported no reduced risk of fractures compared to placebo.

Both estrogen and progesterone stimulate bone formation and inhibit bone loss, and no therapy studied has proven to be better than estrogen in preventing osteoporosis and fractures in the spine and hips.

for estrogen to reduce the risk of fractures that occur ten to thirty years after menopause, postmenopausal women must be on HRT for at least ten years—and possibly for the rest of their lives.

There is no question that estrogen is an effective and metabolically appropriate preventive strategy for osteoporotic fractures, and that osteoporosis is a chronic disease with tremendous impact in postmenopausal women.”

Almost two-thirds of all people with Alzheimer’s are women, and a woman in her sixties is twice as likely to develop Alzheimer’s as she is to develop breast cancer.

estrogen, administered when menopause begins, may prevent, or at least delay, the onset of dementia, including dementia resulting from Alzheimer’s disease.

“the use of HRT for 5 years should not be considered deleterious for the appearance of breast cancer, cardiovascular diseases, strokes, and pulmonary embolisms.”

In a database of RCTs of women given hormone therapy or placebo and followed for at least six months—a total of 19 trials with more than 40,000 women—women who started hormone therapy less than ten years after menopause had fewer deaths from cardiovascular causes and lower rates of coronary heart disease than women on placebo or no treatment.

women on HRT live longer and have a lower death rate from breast cancer than those who are not on HRT.

one other important consideration to keep in mind about the benefits of HRT: It appreciably reduces the risk of colon cancer, the third most common cancer in the United States.

After menopause, women who take HRT have a lower risk of getting colon cancer and a lower mortality rate if they do get it compared with women not on hormones.

In the early years, when the pill contained relatively high doses of estrogen (Enovid had as much as 10 milligrams of ethinyl estradiol), a small but worrying number of women developed blood clots in their veins, usually in the legs. Sometimes, fragments of those clots broke off and traveled to the lungs, leading to pulmonary emboli and, in some cases, death.

the dose of hormones in these pills was cut way down, and emboli are now extremely rare.

available evidence suggests that oral contraceptives decrease the risk of ovarian cancer by 40 to 80 percent.

women taking the pill for more than ten years reduced their overall risk of ovarian cancer by as much as 80 percent, and this benefit persisted for nearly twenty years after they stopped oral contraception.

women who started HRT in the first 10 years following their last menstrual period in fact reduced their risk of coronary artery disease.

In 2021, the WHI reported finding no difference between women on hormones (estrogen alone or HRT) and those on placebo in their risk of venous clots or pulmonary embolism.26