Before July 2002, more than 14 million American women were taking Menopausal Hormone Therapy, or MHT-- previously known as Hormone Replacement Therapy, or HRT. Generally, American doctors agreed that the risk/benefit balance for long-term treatment with a combination of estrogen and progestin to allay hot flashes, dry eyes, vaginal dryness, and other discomforts associated with menopause was favorable for most women. Moreover, studies had shown that MHT offered protection against heart attack and post-menopausal bone loss that led to osteoporosis.
But confidence in the benefits of MHT began to erode in 1998, when a published study showed that MHT did nothing to prevent new heart attacks in women who already had heart disease. When another major study published in July 2002 -- as part of the national Women's Health Initiative (WHI) -- raised further doubts about its ability to prevent coronary problems and the specter of a possible link to breast cancer, MHT became an even greater source of consternation and controversy within the medical and scientific community.
Today, there are still deep divisions within that community about whether the benefits of MHT really outweigh its risks. To help you understand the controversy and make informed decisions, let's take a brief look at what female hormones actually do, summarize what the studies found, and see what questions remain.
Understanding estrogens and progesterone
The female sex hormones, estrogens and progesterone, are steroids: fat
soluble molecules related to cholesterol. They are responsible for the changes in appearance (e.g., breast development) that occur during puberty. They also stimulate the lining of the uterus, creating conditions required for fertility and normal menstrual cycles.
Progesterone is the hormone responsible for regulating the uterine lining. MHT includes progesterone-like drugs, or progestins, that protect the uterine lining from overgrowing and bleeding or forming cancers, which may happen when estrogen is given alone.
Natural estrogen comes in two forms:
- Estradiol is the main form, produced by the ovaries.
- Estrone is a secondary form, produced by substances in adrenal, fat, liver, and other tissues.
These naturally occurring estrogens help maintain bone mass by preventing loss of calcium, and they protect women against coronary heart disease. After menopause, when estradiol levels drop, women may experience hot flashes, accelerated loss of bone calcium, and perhaps accelerated development of coronary disease. New studies suggest that estrogen deficiency also makes women more vulnerable to Alzheimer's disease and loss of mental capacity.
In the decades preceding 2002, the benefits of taking drugs to compensate for estrogen loss were confirmed through many scientific studies comparing large populations of menopausal women who decided to take MHT with women of the same age who did not. Several studies found that women taking estrogen had lower death rates from all causes. Others showed 40-to-60 percent reductions in coronary heart disease and bone fractures. Heart disease is approximately five times more likely to kill women over age 60 than breast cancer, and estrogens reduce risk of heart disease by lowering "bad" cholesterol (LDL) and raising "good" cholesterol (HDL). In women over 70, hip fractures contribute almost as much to disability and death as does breast cancer -- and estrogen replacement prevents the formation of cells that break down bones (osteoclasts).
The controversy
For the medical community, the major source of controversy regarding the benefits that pre-2002 studies claimed for estrogen was the lack of controlled trials with enough women to confirm or deny those claims. Skeptics pointed out that often the users and non-users of MHT came from different backgrounds already associated with different incidences of heart problems. Perhaps lifestyle differences, not the MHT, accounted for lower rates of heart disease among MHT users. Recent studies have not resolved this issue, and results of the WHI study actually suggested that MHT may fail to protect against cardiovascular disease.
Why were the results of this study so different from those of studies conducted during the previous 30 years? We are not certain. One explanation may be that the oral estrogens used in the 2002 study increase the tendency for blood clots to form on the plaque lining of the heart's arterial walls, and this is what causes most heart attacks. If significant numbers of women in the study had pre-existing coronary plaque, then they were more susceptible to clot formation -- and therefore to heart attacks. A related study of more than 4,000 women with no previous symptoms of heart disease showed that buildup of coronary plaque increases rapidly after menopause, and most women in the WHI study fell into that category.
MHT or not?
The results of the WHI study have left many post-menopausal women asking, "Should we start, continue or discontinue MHT?" There are many questions left to answer:
- Does initiating MHT at menopause provide significant protection against coronary disease?
- If you take estrogen using a patch, gel, or cream rather than a pill, does that make it less likely to cause blood clots?
- Would an alternative progestin, such as natural progesterone, produce less risk of breast cancer?
Until these issues are addressed by new trials or further data analysis, it is probably not a good idea to start a continuous course of oral MHT after menopause. Some physicians suggest that you can protect your heart by using drugs that improve cholesterol, such as statins or niacin, and reduce bone loss with drugs such as bis-phosphonates. However, these agents are really for treating severely elevated cholesterol and remediating existing osteoporosis - not preventing it. They have adverse effects of their own and do not deal with other post-menopausal symptoms such as hot flashes, vaginal dryness, and so forth.
If you feel confused, understand that your physician is grappling with the same questions. Doctors and scientists everywhere are hoping that appropriately focused clinical trials will clarify these issues in the near future. In the meantime, the best advice we can offer is to talk with specialists about lower-risk remedies for relieving specific post-menopausal symptoms, get plenty of rest and exercise, and eat a healthy diet. These keys to longevity are also good strategies for reducing the severity of hot flashes as well as maintaining a healthy heart and strong bones.
