Hormones in Women
Estrogen and progesterone are two hormones that play an important part in women’s menstrual cycle and pregnancy. Estrogen also helps maintain bone strength and may reduce the risk of heart disease and memory problems before menopause. Both estrogen and progesterone are produced naturally by the ovaries. However, after menopause, the ovaries make much less of these hormones. For more than 60 years, millions of women have used estrogen to relieve their menopausal symptoms, especially hot flashes and vaginal dryness. Some women may also be prescribed estrogen to prevent or treat osteoporosis—loss of bone strength—that often happens after menopause. The use of estrogen (by a woman whose uterus has been removed) or estrogen with progesterone or a progestin, a synthetic form of progesterone (by a woman with a uterus), to treat the symptoms of menopause is called menopausal hormone therapy (MHT), formerly known as hormone replacement therapy (HRT).
There is a rich research base investigating estrogen. Many large, reliable long-term studies of estrogen and its effects on the body have been conducted. Yet, much remains unknown. In fact, the history of estrogen research demonstrates why it is important to examine both the benefits and risks of any hormone therapy before it becomes widely used. Here’s what scientists know:
- Endometrial problems—While estrogen helps some women with symptom management during and after menopause, it can raise the risk of certain problems. Estrogen may cause a thickening of the lining of the uterus (endometrium) and increase the risk of endometrial cancer. To lessen these risks, doctors now prescribe progesterone or a progestin, in combination with estrogen, to women with a uterus to protect the lining.
- Heart disease—The role of estrogen in heart disease is complex. Early studies suggested MHT could lower postmenopausal women’s risk for heart disease—the number one killer of women in the United States. But results from the NIH Women’s Health Initiative (WHI) suggest that using estrogen with or without a progestin after menopause does not protect women from heart disease and may even increase their risk.
In 2002, WHI scientists reported that using estrogen plus progestin actually elevates some postmenopausal women’s chance of developing heart disease, stroke, blood clots, and breast cancer, but women also experienced fewer hip fractures and cases of colorectal cancer. In 2004, WHI scientists published another report, this time on postmenopausal women who used estrogen alone, which had some similar findings: women had an increased risk of stroke and blood clots, but fewer hip fractures. Then, in 2007, a closer analysis of the WHI results indicated that younger women, ages 50 to 59 at the start of the trial, who used estrogen alone, had significantly less calcified plaque in their coronary arteries than women not using estrogen. Increased plaque in coronary arteries is a risk factor for heart attacks. Scientists also noted that the risk of heart attack increased in women who started MHT more than 10 years after menopause (especially if these women had menopausal symptoms). There was no evidence of increased risk of heart attack in women who began MHT within 10 years of going through menopause.
- Dementia—Some observational studies have suggested that estrogen may protect against Alzheimer’s disease. However, testing in clinical trials in older, postmenopausal women has challenged that view. In 2003, researchers leading the WHI Memory Study (WHIMS), a substudy of the WHI, reported that women age 65 and older who took one kind of estrogen combined with progestin were at twice the risk for developing dementia compared to women who did not take any hormones. In 2004, WHIMS scientists reported that using the same kind of estrogen alone also increased the risk of developing dementia in women age 65 and older compared to women not taking any hormones. What possibly accounts for the different findings between the observational and clinical studies? One central issue may be timing. The women in the WHIMS trial started treatment a decade or more after menopause. In observational studies that reported estrogen’s positive effects on cognition, the majority of women began treatment soon after menopause. This has led researchers to wonder if it may be advantageous to begin treatment earlier, at a time closer to menopause. Additionally, it appears that progesterone and progestins (progesterone-like compounds) differ in their impact on brain health.
Despite research thus far, there are still many unknowns about the risks and benefits of MHT. For instance, because women in their early 50’s were only a small part of the WHI, scientists do not yet know if certain risks are applicable to younger women who use estrogen to relieve their symptoms during the menopausal transition.
You may also have heard about another approach to hormone therapy for women—“bioidentical hormones.” These are hormones derived from plants, such as soy or yams, that have identical chemical structures to hormones produced by the human body. The term “bioidentical hormones” is now also being applied to the use of compounded hormones. Large clinical trials of these compounded hormones have not been done, and many bioidentical hormones that are available without a prescription are not regulated or approved for safety and efficacy by the FDA. FDA-regulated bioidentical hormones, such as estradiol and progesterone, are available by prescription for women considering MHT.
For middle-age and older women, the decision to take hormones is far more complex and difficult than ever before. Questions about MHT remain. Would using a different estrogen and/or progestin or different dose change the risks? Would the results be different if the hormones were given as a patch or cream, rather than a pill? Would taking progestin less often be as effective and safe? Does starting MHT around the time of menopause, compared to years later, change the risks? Can we predict which women will benefit or be harmed by using MHT? As these and other questions are addressed by research, women should continue to review the pros and cons of MHT with their doctors. They should assess the benefits as well as personal risks to make an informed decision about whether or not this therapy is right for them