Estrogen is a major female sex hormone that is crucial to a woman’s development, ability to bear children and overall health. It is the hormone responsible for monthly menstruation and many changes throughout a woman’s life. Around the age of 50, the level of estrogen and other adrenal hormones such as progesterone begin to decline, and a woman stops menstruating. This time, known as menopause, is marked by a significant decrease in the amount of sex hormones produced by a woman’s body.
Estrogen appears to have a number of potent health benefits, including protection from heart disease and osteoporosis. Thus, when a woman enters menopause, her risk of heart disease begins to climb until it equals that of men. Similarly, she is at increased risk for bone diseases such as osteoporosis and cognitive diseases such as Alzheimer’s.
Hoping to recapture the benefits of estrogen for women in menopause, physicians began recommending hormone replacement therapy (HRT) with synthetic estrogen for post-menopausal women. Also, hormone replacement therapy was frequently prescribed to alleviate the symptoms of menopause, including hot flashes and other bothersome side effects, and for women who have had their ovaries removed after an illness.
Because estrogen-only therapy (e.g., unopposed estrogen) is associated with increased risk of certain cancers, progesterone was often paired with the estrogen, which reduced the risk of developing a hormone dependent cancer.
Recently, however, the clinical benefits of HRT have come under intense scrutiny. While HRT was effective for controlling the symptoms of menopause and reducing the risk of certain diseases, several major studies linked HRT to an increased risk of heart disease, blood clots, stroke and breast cancer. Current debate includes such considerations as:
Should HRT be used exclusively for menopausal symptoms, and not primarily for osteoporosis, risk of bone fractures, etc.?
Can menopausal symptoms be severe enough to warrant HRT, in light of its apparent risks?
Might there be an HRT dosage low enough to elude the risks, but otherwise have an effect on menopausal symptoms?
Regardless of whether or not women choose to take HRT, all women are encouraged to make healthy lifestyle changes such as quitting smoking, eating a heart-healthy diet and controlling conditions such as diabetes and high blood pressure.
About estrogen
Estrogen is the major female sex hormone. Hormones are chemical substances that carry important information and instructions from one group of cells to another.
Throughout a woman’s life, estrogen plays a crucial role in her development, ability to bear children and overall health. During puberty, it is mainly responsible for secondary sexual characteristics (e.g., breast development, pubic hair, broadening of hips). It is also chiefly involved in the internal physical changes that will allow a woman to carry a pregnancy.
There are three types of estrogen: estrone (E1), estradiol (E2) and estriol (E3). Normal concentrations of estrone are produced in body fat. Women who are exceptionally thin may not have monthly periods because there is not enough fat to produce estrone. Estradiol and estriol are the two types of estrogen produced in the two ovaries, which are connected to a woman’s uterus (womb) and contain ova (eggs). The ovaries begin producing estrogen around the age of eight or nine and gradually stop producing it around the time of menopause, which typically occurs around age 50. Not only is estrogen responsible for processes related to the female reproductive organs, but it is also present in hundreds of other tissues in the female body.
Estrogen protects premenopausal women in a variety of ways, including.
The blood vessels that supply the heart with blood have estrogen receptors that are sensitive to the effects of estrogen. Like a key fitting neatly into the ignition, the estrogen molecule can provoke reactions in the blood vessels. These reactions include controlling the growth of smooth muscle in the walls of the blood vessels, which helps them remain open and reduces the risk of atherosclerosis (“hardening” of the arteries). Although its other mechanisms for affecting the heart are still being investigated, estrogen also appears to increase the level of “good” (high-density lipoproteins or HDL) cholesterol and decrease the level of “bad” (low-density lipoproteins or LDL) cholesterol.
Estrogen may help to prevent the gradual decline of brain cells in four ways. First, it has an effect similar to antioxidants which block the harmful effects of oxygen free radicals. Second, it has effects similar to anti-inflammatories, which may help prevent the inflammation of the brain tissue that is often seen in Alzheimer’s patients. Third, it promotes the growth of both nerve pathways and nerve cells that release acetylcholine (ACh), which is an important chemical messenger (neurotransmitter). Fourth, estrogen appears to prevent one of the main causes of Alzheimer’s (beta-amyloid peptides) from being manufactured in the body.
Estrogen may help to protect bones by maintaining a healthy balance between bone creation and bone resorption. After menopause, women tend to lose bone faster than they rebuild it, which can lead to decreased bone mineral density and osteoporosis. Estrogen has been shown to protect bone mineral density, thus reducing the risk of suffering from osteoporotic fractures, which are a major source of disability among post-menopausal women.
About hormone replacement therapy (HRT)
As its name suggests, hormone replacement therapy(HRT) involves the replacement of the sex hormones that are lost during menopause. HRT helps reduce symptoms (e.g., hot flashes, vaginal dryness, mood swings) experienced by women during and after menopause. It also helps prevent certain diseases (e.g., osteoporosis, colon cancer).
Originally, only estrogen was replaced (estrogen replacement therapy, ERT). When ERT is taken alone, however, it leads to abnormal thickening of the uterine lining (uterine hyperplasia), which significantly increases the risk of cancer in the uterus (uterine cancer) and cancer in the lining of the uterus (endometrial cancer).
The reason for this is that a postmenopausal woman’s ovaries not only stop producing estrogen, but they also stop producing another sex hormone called progesterone, which has anti-cancer effects by preventing the multiplication of uterine cells. Thus, traditional HRT has involved both estrogen and a synthetic progesterone called progestin.
Estrogen replacment therapy, however, is appropriate in some circumstances, including for women who have had their uterus removed. It is not recommended for women with an intact uterus.
Estrogen treatment is made synthetically from plants and other sources, or made from the urine of pregnant horses. The form of progesterone most often prescribed is chemically produced, a synthetic progesterone known as progestin.
HRT may be taken in various forms, including pills, skin patches, vaginal creams, vaginal rings, suppositories or injections. The method of delivery may depend on the nature of the patient’s symptoms.
Women should not take HRT drugs in either form if they have the following health conditions:
History of stroke or heart attack
History of blood clots
Pregnancy
Cancers of the breast or uterus
Liver disease
HRT and heart disease
Hormone replacement therapy (HRT) involves the replacement of hormones that are lost during menopause. For women who still have their uterus, estrogen is typically taken in combination with progestin for protection from uterine cancer. HRT can relieve some symptoms of menopause (e.g., hot flashes). It has also shown effectiveness in preventing osteoporosis by improving bone density and reducing the incidence of hip fractures. Finally, because natural estrogen protects younger women from heart disease, it was assumed that HRT could also help protect post-menopausal women from heart disease.
A pair of major studies was launched to study the effects of estrogen on heart disease in women. Known as the Women’s Health Initiative (WHI), these two studies did not measure the effect of estrogen on side effects of menopause. Instead, they considered only estrogen’s effect on the cardiovascular system. The first of the two studies looked at combination estrogen/progestin therapy in 16,000 postmenopausal women aged 50 to 70 who still had their uteruses. The second looked at estrogen-only therapy in 11,000 women who had no uteruses (and therefore did not need to take progestin).
Begun in 1997, the estrogen/progestin arm of the study was terminated on May 31, 2002, (three years before scheduled) when it was shown that the risks of estrogen/progestin outweighed its benefits. Researchers found that estrogen/progestin therapy increased the risks of heart attack, stroke, breast cancer, blood clots and overall cardiovascular disease. No protective effect was noticed when it came to Alzheimer’s disease and cognitive function. These findings overwhelmed the therapy’s protective effect against fractures and colon cancer. A separate study conducted by British researchers supported these results, adding that – for women in their 50s taking HRT for five years, breast cancer is the greater risk. Those in their 60s have a higher risk of stroke or pulmonary embolism.
The second part of the study, the estrogen-only portion, was discontinued in 2004 for similar reasons. Researchers found that the benefits of estrogen in women without uteruses were evenly balanced against its negative effects. While estrogen-only HRT did protect against fracture and colon cancer, there was a significant increase in the rate of stroke and blood clots. However, there was no statistically significant increase in breast cancer rates.
The reaction to this news was rapid and widespread. Between 1995 and 2001, the percentage of women aged 50 to 74 taking some form of HRT increased from 33 percent to 42 percent. By 2003, after the first of these results had been published, that number dropped to 28 percent. Overall, hormone therapy prescriptions dropped 38 percent in the first year after the study’s findings were published. Today, neither estrogen/progestin therapy nor estrogen-only therapy is recommended for the prevention of heart disease, osteoporosis or Alzheimer’s disease. However, HRT may still be recommended on short-term basis to control a variety of menopausal and post-menopausal symptoms.
It is important to note, however, that while these figures sound intimidating, they were derived from a large sample. In absolute terms, the level of increased risk to any individual woman on HRT is small. According to WHI researchers, the absolute risk of breast cancer or a cardiovascular complication from combination estrogen/progestin therapy is very low (about 19 events per 10,000 women). It is lower still for younger, postmenopausal women.
In addition, recent findings challenge some of the results of the WHI’s 2002 study. According to a new study conducted by researchers from Cornell and Stamford universities, the risk of heart disease may be lowered in women who begin taking HRT before the age of 60 or shortly after the onset of menopause. It should be noted, however, that for women who begin HRT after age 60 the same study had mixed results. For the older group of women participants, HRT increased the risk of heart attacks the first year of treatment, but after two years of treatment HRT began to reduce this risk.
The risk for heart disease and stroke varies with age and the overall health of a woman. Consultation with one’s physician is essential to weigh the family and person medical history, as well as potential risks and benefits with HRT over the short and long term.
Ongoing HRT research
Research continues into the effects of hormone replacement therapy (HRT). For example:
There has been considerable interest in "bioidentical hormone therapy" in the mainstream press, with companies and spokespeople advocating the benefits of "natural" HRT. According to the supporters of bioidentical hormone replacement therapy, it provides the same benefits as traditional HRT without the increased risk of vascular disease and cancer. Practitioners of bioidentical hormone replacement therapy rely on individualized blood tests to determine a woman's hormone levels, then compound custom hormone preparations to match her specific case. Unlike conventional hormone replacement therapy, bioidentical estrogens use all three of the estrogens naturally present in the human body. At this time, however, no controlled studies have shown a benefit to bioidentical hormone replacement therapy above and beyond standard HRT, nor a decreased risk profile. In general, this approach to HRT has not been subjected to rigorous human study. Also, because most insurers will not cover bioidentical HRT, it is much more expensive than traditional HRT. Any woman considering using bioidentical hormone therapy offered through compounding pharmacies should speak with her physician before launching a program.
A study found that the risk of heart disease, including ischemia, is higher among women with diabetes taking HRT versus diabetic women who did not take HRT.
A study sponsored by the National Heart, Lung and Blood Institute (of the U.S. National Institutes of Health) explored whether HRT and/or high-dose antioxidant vitamins could offer benefit. Known as the Women’s Angiographic Vitamin and Estrogen (WAVE) trial, 423 postmenopausal women were studied as they took various combinations of HRT, vitamin C and vitamin E supplements, or placebos. All participants were monitored over three years with coronary angiograms. The study found a greater progression of coronary artery disease in the women taking HRT, with no protection offered by the vitamins.
Low-dose HRT in postmenopausal women is being studied as a way to achieve increased bone density with minimal adverse effects. Although HRT is no longer recommended as first-line treatment for prevention of osteoporosis among post-menopausal women, the U.S. Food and Drug Administration has opposed two low-dose HRT program. The first uses 0.45 milligrams (mg) conjugated estrogen and 1.5 mg progestin. The second uses .3 mg conjugated estrogen and 1.5 mg progestin. In addition, low dose unopposed conjugated estrogen (0.45 mg) has been approved for the relief of menopausal symptoms. In general, studies have supported that lower doses still yield protective results against osteoporosis.
Alternatives to HRT
A number of alternatives to traditional hormone replacement therapy (HRT) are available to patients, including:
A fairly new class of estrogen-like drugs is being designed to offer postmenopausal women the benefits of HRT without any harmful effects on the reproductive organs. These compounds are called selective estrogen receptor modulators (SERMs). They are designed to specifically target the areas of the body that require protection and to avoid the areas of the body that would be harmed by estrogen. For women with a personal or family history of breast cancer, SERMs might be an attractive alternative to HRT. Some SERMs are already available to postmenopausal women, such as raloxifene. This drug, normally prescribed to postmenopausal women to treat osteoporosis, has also shown to significantly reduce fatal and non-fatal strokes, as well as total and low-density lipoprotein (so-called “bad”) cholesterol.
Low-dose estrogen and HRT is available through patches that are changed approximately weekly. Estrogen doses as low as 0.014 milligrams (mg) have been approved for the prevention of osteoporosis. Transdermal patches can also deliver low-dose progestins for the relief of hot flashes.
There are some herbal and other nonprescription strategies for dealing with both perimenopausal changes and the higher risks associated with postmenopause. Among the most common of these is the use of soy supplements, which contain chemicals that are chemically similar to estrogen (e.g., phytoestrogens). However, unlike prescription drugs, the health claims made by manufacturers of these preparations do not undergo scrutiny by the U.S. Food and Drug Administration. Therefore, women are encouraged to speak with their physician before taking any over-the-counter products.
There are also nonprescription strategies for dealing with the greater postmenopausal risks of heart disease, osteoporosis and Alzheimer’s. These include:
Achieve and maintain a healthy weight. Women should maintain a weight deemed healthy by their physician.
Quit smoking. Smoking increases bone loss, probably because it decreases a woman’s production of estrogen and reduces the body’s ability to absorb calcium.
Eat a healthy diet. Women should eat plenty of whole-grain products, vegetables and fruits. They should choose foods that are low in fat and cholesterol and get enough of the vitamins and minerals that are good for their heart and bones. Menopausal and postmenopausal women need about 1,500 milligrams of calcium a day to keep strong bones.
Exercise regularly. A substudy of the Women’s Health Initiative found a protective effect against breast cancer in postmenopausal women who engage in regular physical activity. Women should try to get at least 30 minutes of exercise on most days of the week. Weight-bearing exercises such as walking, running or dancing can help strengthen bones and reduce the risk of osteoporosis. In addition, exercise may help control weight and it has benefits for the heart.
Limit alcohol use. Women should not have more than one alcoholic drink a day.
Stay mentally active (e.g., by attending community lectures, doing crossword puzzles, reading the newspaper, spending time with friends/family, volunteering in the community and watching the news).
Talk with a physician about taking vitamin/mineral supplements for optimum health of the heart and bones, including calcium and vitamin D supplements to help prevent osteoporosis.
Although good health and sound lifestyle choices can reduce the likelihood of symptoms, most women will experience at least some ill effects associated with menopause. If and when these symptoms occur, steps can be taken to reduce their severity. These include:
Hot flashes. Women should avoid triggers such as warm environments, eating or drinking hot or spicy foods, drinking alcohol and caffeine and stress. Dressing in layers, exercising regularly and using a fan in the home or workplace can also help women prevent or reduce hot flashes. Some alternative remedies, such as herbs or acupuncture, may reduce hot flashes as well. Women may also benefit from breathing slowly and deeply when feeling a hot flash coming on.
Mood swings. Sufficient sleep and regular physical activity can often help women combat mood swings during menopause. Women should also keep the lines of communication open and learn strategies for stress management. In addition, physicians can recommend relaxation exercises and prescribe antidepressants, if necessary. Women should see a counselor if feeling either depressed, or uninterested in activities usually enjoyed, more days than not, for two full weeks. Support groups also prove beneficial for many menopausal women.
Sleeping problems. Regular exercise may help women achieve a better night’s sleep, but strenuous exercise should be avoided right before going bed. Avoiding alcohol, caffeine, sugar, large meals and work right before bedtime can also help prevent sleep problems. Some women find they are better able to sleep after drinking a warm, non-caffeinated beverage before bedtime. Women who are having trouble sleeping should avoid napping. In addition, they should try to go to bed and get up at the same time every day, and should keep their bedroom at a comfortable temperature. Women should discuss the use of over-the-counter and prescription medicine for sleep with their physician if they continue to experience difficulties.
Vaginal dryness. Various over-the-counter vaginal lubricant products are available for women experiencing vaginal dryness. Prescription estrogen replacement creams might also offer relief for some women.
Memory problems. A physician can recommend mental exercises to improve memory during menopause. Adequate sleep and regular physical activity may also help prevent memory problems in menopausal women.
Regardless of which strategies are chosen, it is important for all women to get regular screening tests including a blood pressure check, bone density test, cholesterol screening/lipid profile, height measurement, Pap smear, and vision test.
FDA guidelines for HRT
Based on the findings of the Women’s Health Initiative, on January 8, 2003, the U.S. Food and Drug Administration (FDA) announced that it was revising the information found on the labels of hormone replacement therapy (HRT).
Consistent with previous labeling, HRT is indicated for the treatment of “moderate to severe” symptoms associated with menopause (e.g., hot flashes).
HRT is indicated to treat “moderate to severe” vulvar and vaginal dryness and irritation. However, if this is the sole reason for HRT, “topical vaginal products should be considered.”
HRT is indicated for the “prevention of postmenopausal osteoporosis (weak bones).” If this is the sole reason for HRT, then “approved non-estrogen treatments should be carefully considered.” Most experts no longer recommend HRT as a first-line treatment for osteoporosis, however.
The FDA recognizes that women may still want to use HRT for a variety of menopausal and postmenopausal symptoms. Consultation with a physician is essential to weigh family and person medical history, as well as potential risks and benefits with HRT over the short and long term.
Testosterone and the female sex drive
Hormone replacement therapy (HRT) may also include the male hormone, testosterone. Although women normally have a much lower level of testosterone than men, they have twice as much of it during their reproductive years as they do postmenopause. Testosterone has been linked to a women’s healthy sex drive, and it may be offered to postmenopausal women who continue to feel a loss of their sex drive even after taking the following suggestions:
Breaking up any sexual routine that may have developed (e.g., not doing it the same way every time).
Communicating with one’s partner if there is anger or any other uncomfortable feeling that may be interfering with mutually satisfying sex.
Learning to relax with one’s partner, letting go of worries and stress.
Spending more time kissing, touching and other types of foreplay before having sex.
Talking with one’s partner about any changes in lovemaking that may make it more comfortable or enjoyable, remembering that your partner is not a mind–reader.
Using water-based gel lubricants instead of the heavier oil-based lubricants which may irritate vaginal tissues.
If women have tried these suggestions but continue to feel a loss of their sex drive, some experts recommend very small amounts of testosterone. Others say that testosterone is probably unnecessary. Still others insist that replacing testosterone levels is essential for healthy vitality and sexual functioning, regardless of whether the above suggestions have been tried or not. Testosterone has been shown to decrease the level of both “good” high-density lipoproteins (HDL) and “bad” low-density lipoproteins (LDL) cholesteroland build bone mass. Women are encouraged to speak with their physician about this choice.
Questions for your doctor
Preparing questions in advance can help patients to have more meaningful discussions with their physicians regarding their conditions. Patients may wish to ask their doctor the following questions about estrogen and HRT:
Do I need to have my estrogen levels and progesterone levels measured before beginning HRT?
Are there any other ways to achieve the same benefit without increased risk?
What do you think my personal risk profile is with HRT, considering my other risk factors for heart disease?
How long will symptoms of menopause typically last? Can I wait this out instead of using HRT?
Do you feel that conventional HRT is safe?
I've heard that soy-based foods can help prevent symptoms of menopause and protect against osteoporosis. Is this true?
What other strategies are available to reduce my symptoms?
Can I consider low-dose estrogen therapy?
I've read about natural progesterone creams, derived from yams and other natural sources. Are these better than synthetic progestins?
What do you think about bioidentical hormone replacement therapy?
