Recently bio-identical hormones have received a lot of publicity through Oprah and Suzanne Summers. BHRT is the buzzword of today, and many women entering menopause want to know what they can do to escape the discomfort of night sweats, hot flashes, insomnia, irritability, body itching and short term memory loss that can result from their bodies decrease in the production of sex hormones.
Yet hormone therapy is quite controversial. Some books proclaim it to be “a miracle” while others decry it as a cause of cancer. This article will explore the differences between synthetic and bio-identical hormones, discuss the studies regarding their safety and identify why individualized bioidentical hormone therapy can be useful for many aspects of aging. It is also important to discuss these questions with your doctor before starting on hormone therapy. There are many who make the decision to go on hormones during a brief encounter with their doctor, and then stay on them for years without having any idea if they are using a synthetic or bio-identical formulation.
Why are synthetic hormones controversial?
This is an easy question. The Woman’s Health Initiative followed 16000 women on horse derived synthetic oral estrogen (Premarin,PemPro,) and progesterone (Provera) for 15 years. In 2002 the study was stopped because it was found that the FDA approved, synthetic non bioidentical hormones increased the risk of heart attack, stroke and breast cancer. Not surprisingly 50 percent of women on hormone replacement therapy decided to terminate their treatment, despite the misery of hot flashes and night sweats. This decline in hormone usage was followed by a 7% decline in breast cancer. (It should be pointed out that while both Premarin and PremPro are “natural”, being derived from horse urine, they are not at all identical to human estrogen. Furthermore the oral route of delivery, as opposed to transmucosal or transdermal, has been shown to contribute to blood clotting.)
So why would any thoughtful women, including Oprah, go on hormone replacement therapy?
Because not all hormones are the same. Bioidentical hormones are made from plants such as yam and have the exact same molecular structure as hormones found in the human body. And to date no studies have found a connection between bioidentical hormones and cancer. In fact quite the opposite is true – several of the hormones including estriol and progesterone, seem to have a protective effect. For instance, while many studies have shown that non bioidentical progesterone (Provera) clearly induces estrogen mediated breast cell proliferation and increases the risk of breast cancer, natural progesterone does neither. In fact a study of over 80000 women showed that using bioidentical estrogen and progesterone together significantly reduced the risk of breast cancer while using estrogen with non bioidentical progesterone increased the risk by 69% (Breast Cancer Res Treat. 2008 Jan:107 (1) 103-11).
There are three types of estrogen named estrone, estradiol and estriol. The percentage of these three estrogens in the body are generally 60-80% estriol, 10-20% estradiol, and 10-20% estrone. In menopause, this balance shifts. Estrone accumulates more than both estriol and estradiol did in the younger stages of a woman’s life. By using bio-identical hormone replacement, this naturally occurring balance may be restored. Estrone and estradiol are considered procarcinogenic, while estriol has been shown to be anticarcinogenic. Estrone and estradiol are approved by the FDA while estriol is not. Two very popular formulations of bioidentical estrogen are TriEst, which contains all three estrogens, and BiEst which contains just estradiol and estriol. BiEst is often used in menopause because the female body tends to produce more estrone as it ages.
Estradiol, actually 17 beta estradiol, is produced from testosterone. It is the most active form of endogenous estrogens and the one produced most predominantly by a woman’s ovaries before menopause. It is what “makes a woman a woman, being responsible for the development of hips and breasts at puberty. Estradiol levels fall after menopause and after hysterectomy when the ovaries are removed. It is the hormone that most effectively removes the vasomotor symptoms of menopause – that is hot flashes and night sweats. Estradiol has many functions and may protect againstosteoporosis, Alzheimer’s disease, colon cancer, elevated cholesterol levels, urinary incontinence, and tooth loss or decay. It may also enhance sleep, mood, memory, digestion, and sex drive.
Estriol (E3) is known as the “weak” estrogen. It is only produced in significant quantities during pregnancy as it is secreted by the placenta. Levels of estriol do not change significantly in non-pregnant women compared to after menopause. Estriol alone does not provide the cardiovascular benefits of estradiol, and very large doses are required to achieve increases in bone density. However estriol has shown some benefit in decreasing blood pressure.
Estriol does, when given with the more potent estradiol, have anti-carcinogenic effects on breast and endometrial tissues. It does this by sitting on the estrogen receptors and blocking the procarcinogenic estradiol from occupying all the receptor sites. In fact a prospective study of 15000 women who had high estriol during their first pregnancies showed that thirty years later their breast cancer risk was decreased by 58%. Estriol is not commercially available in the U.S., although it is available through compounding.
Both men and women have progesterone. This hormone is highest in a woman during the third trimester of pregnancy. A recent study at the Mayo clinic showed that women who had taken nonbioidentical progesterone (Provera) hadsubstantial improvement in their symptoms when switched to bioidentical progesterone including a reduction in sleep problems, depression, anxiety and cognitive difficulties. Bioidentical progesterone has also been shown to improve blood flow to the heart in postmenopausal women with a history of heart disease. Bioidentical progesterone also greatly decreases the risk of blood clots in women using oral estrogen, while nonbioidentical progesterone increases it by 290%. Bioidentical progesterone has even been shown to increase the good cholesterol (HDL levels). Exciting recent research shows that progesterone even exerts a neuroprotective effect after brain injury.
Testosterone is the sex hormone responsible for muscle mass development, sex drive, outlook (positive), drive, and aggression (positive and negative). It has the same effect in men and women. Bioidentical testosterone is made from soy and yam oils just like bioidentical estradiol and micronized progesterone. Testosterone levels decrease in both men and women as they age, and may contribute to low libido. It is often added to a woman’s bioidentical regimen especially if her blood tests show her to be deficient. Too much free testosterone in a woman may contribute to abdominal weight gain. (A short lesson about hormones – All sex hormones are made from cholesterol and they are present in women and men. The difference lies in the amounts of hormones made by the body. Women have more estrogen and progesterone, men have more testosterone.)
The FDA has approved bioidentical hormones of estradiol (E2). It has not approved estriol (E3). If you remember estriol is the most anticarcinogenic of the three estrogens, as well as helping urinary tract symptoms and rebuilding bone mass. Estriol has been used in Europe for the last sixty years without a problem.
However Wyeth, the maker of horse urine hormones Premarin and Pempro, asked the FDA to prohibit compounding pharmacies from providing bio-identical hormones. After the Woman’s Health initiative demonstrated that their products, Premarin and Prempo, caused a significant increase in breast cancer, blood clots to the lungs, heart attacks and stroke, Wyeth experienced a 70 percent decline in its sales of these products. Perhaps by seeking to eliminate its competition, compounding pharmacies, it hopes to regain market share. Wyeth has two estriol formulations it markets in Germany so it would seem that safety is not the issue. The other part of the complaint, that compounding pharmacies are not standarized, is untrue. They have their own regulatory agency, called the Professional Compounding Accreditation Board, which sets standards for the production of compounded products. The Tucson compounding pharmacies which have met these standards can be found at www.pcab.org.
FDA approved bioidentical hormones do exist. However they all supply only 17 beta estradiol, or E2. They are available as a gel (Divigel, Elestrin, EstroGel), spray (Evamist), patch (Climara, Vivelle, Alora, Menostar, cream (Estrace), vaginal ring (Estring, Femring) and suppository (Vagifem). Progesterone comes as a capsule in peanut oil called Prometrium or vaginal cream (Prochieve, Crinone).
Breast cancer protective nutrients
It is wise to remember that the absolute safety of bioidenticals has not been demonstrated. The somewhat sobering statistics are that over the course of a woman’s lifetime she has a one in eight chance of having breast cancer. So incorporating some cancer prevention strategies seems prudent.
Iodine stimulates the conversion of estradiol into estriol, the carcinogenic protective estrogen. It also is extremely helpful in reducing fibrocystic breast disease as well as ovarian cysts. It stimulates the formation of iodolipids (iodine + fat) Iodolipids kill many types of breast cancer cells. However many patients with autoimmune disease may do worse on iodine, and too high a level of iodine can have some harmful effects. Therefore iodine supplementation is best done with a doctor skilled in that area.
Vitamin D. Women with Vitamin D levels above 50 have been shown to have half the rate of breast cancer as those with lower levels. A prospective study of women taking 1100 IU of Vitamin D a day had a 77 percent reduction in developingany cancer. These studies would seem to indicate ensuring a vitamin D level over 50ng/ml is a vital step in reducing cancer.
Cruciferous vegetables. Broccoli, cabbage, kale, Brussels sprouts and cauliflower all contain compounds that neutralize some of the dangerous breakdown products of estrogens. Indole 3 carbinol is the best studied of these compounds. It has been shown to increase the breakdown of estrogen into 2 hydroxyestrone which is associated with protection against breast cancer. This can be obtained through diet alone or by supplementation.
Other useful foods for decreasing breast cancer are soy (although many authors believe that on the whole soy is more harmful than helpful for the human body), fish oil and flax lignans.
The effects of declining hormones such as poor memory, decreased sleep, pain and increased anxiety can start five years before the menses actually cease. This is called perimenopause. Women have several alternatives before jumping to bioidentical hormone replacement therapy. Improving diet by increasing protein and saturated fats and decreasing carbohydrates, especially grains and sweets, can help. Food should be organic, local grass fed and hormone and antibiotic free. Removing wheat and dairy from the diet have also been helpful for many. Increasing exercise, especially aerobic, is often helpful. Phytoestrogens such as licorice, alfafa and black cohosh are sufficient for some women to decrease hot flashes and night sweats. Fish oil and green tea, with its polyphenols, can also be useful. Acupuncture and homeopathy have also been helpful for some. However when diet and lifestyle changes are not enough bio-identicals may be able to help.
In conclusion, the decision to go on bio-identical hormones is a personal one. Women who are suffering from the usual menopausal symptoms of hot flashes, night sweats, irritability, anxiety, mood swings and cognitive decline have a good chance of finding relief with bio-identicals. Women with a family history of osteoporosis, or those who have already been diagnosed with osteopenia should also expect to benefit from bioidentical hormone therapy. The positive aspects of bio-identicals include relief from the vasomotor symptoms as well as improvement in depression and anxiety. Many women also enjoy the positive benefits of improved libido, youthful skin and a generally better sense of wellbeing. Dr. Wright, a well recognized pioneer in bioidentical therapy has stated the best reason to stay on hormonal therapy is “to keep your marbles”, ie as a preventive against Alzheimer’s Disease. In fact a very common response in perimenopausal women who have been started on estrogen is “it’s like someone turned on a light bulb in my brain”. However women with a family history of breast cancer may wish to avoid them.
A recent study of over 80,000 nurses which included more than 8 years of followup, showed that there is no increased incidence of cancer in women on bioidentical hormones. In contrast, however, the Women’s Health Initiative study clearly showed a 30 percent increase in cancer for women on synthetic hormones. It is difficult to understand, after these findings, anyone being on the synthetic hormones Premarin and Provera, or that they are even allowed to be sold. HRT is, for the most part, contraindicated in women with estrogen receptor positive breast cancer. If you decide to pursue using bioidentical hormone therapy it is best to find a doctor who has experience with them and also has the time to answer all your questions, individualize your treatment and provide follow up assessments.