The Wisdom of Menopause
Page 20
BIOIDENTICAL HORMONES:
NATURE’S IDEAL DESIGN
In contrast to Premarin, Provera, and Prempro, the hormones that I recommend are exactly the same as those found in the female body. Though they are synthesized in the lab from hormone precursors found in soybeans or yams, their molecular structure is designed to be an exact match of the hormones found in the human body. Hence we call them bioidentical, a term that is far more precise than natural, which can be used in confusing and ambiguous ways—for example, Premarin is said by some people to be a “natural” product because it is made from horse urine. As Joel Hargrove, M.D., a pioneer in the use of bioidentical hormones and the former medical director of the Menopause Center at Vanderbilt University Medical Center in Tennessee, has said, “Premarin is a natural hormone if your native food is hay.”
Because bioidentical hormones are just like the hormones that our bodies were designed to recognize and utilize, their effects are more physiologic—consistent with our normal biochemistry—with less chance for unpredictable side effects at low replacement doses than with synthetic, non-bioidentical hormones.
Finally, large-scale clinical trials are beginning to study bioidentical hormones. The Early Versus Late Intervention Trial with Estradiol (ELITE) study, sponsored by the National Institute on Aging and conducted by researchers at the Keck School of Medicine at the University of Southern California, started in 2004 and is slated to end in 2012. This study is looking at whether natural estrogen therapy will reduce the progression of early atherosclerosis if it is started soon after menopause. Similarly, the Kronos Early Estrogen Prevention Study (KEEPS; www.keepstudy.com), conducted by the Phoenixbased nonprofit Kronos Longevity Research Institute, is a multicenter prospective trial comparing the use of bioidentical hormone therapy with conjugated estrogen therapy (Premarin) in newly menopausal women. This placebo-controlled study, which began in 2006 and will be completed in 2012, is designed to find a more definitive answer to the question of whether either Premarin or bioidentical estrogen therapy, if begun within a couple of years of menopause, decreases the risk of heart disease in women.
To take advantage of the benefits of bioidentical hormone therapy, you first have to give up the notion that there is an easy, one-size-fits-all answer. There isn’t. Some women need or want hormone therapy; some don’t. Some will need to use it for only a year or two; some will want to stay on it longer. (For additional information and guidance about bioidentical hormones, I recommend you visit the website of the Bioidentical Hormone Initiative, www.bioidenticalhormoneinitiative.org.)
When it comes to hormone therapy, the science we look to for answers is inconsistent, influenced by market forces, and confusing to researchers, doctors, and patients alike. The blessing is that this dilemma forces us to tune in more fully to our inner wisdom, and to make our choices in partnership with our intuition and intellect. This approach is the essence of feminine wisdom.
Moving Beyond Premarin
When Premarin was introduced, the technology to produce other types of estrogen was not yet available, so it became the gold standard. However, these equine estrogens aren’t normally found in the human female body, and they are often associated with side effects such as headaches, bloating, and sore breasts. In addition, the metabolic breakdown products of Premarin in the human female are biologically stronger and more active than the original equine estrogens. A host of studies have shown that these breakdown products can produce DNA damage that is carcinogenic in tissue. Given this, it’s no wonder that the incidence of breast cancer statistically increases when women are on this drug.6 In contrast, the metabolic breakdown products of bioidentical estrogens are biologically weaker, so their effects on tissue do not last as long.
There’s reason to believe that bioidentical estrogen at individualized low doses doesn’t have the same carcinogenic effect on breast tissue as Premarin or Prempro. But until we have long-term studies of bioidentical estrogen to compare with the vast amount of data on Premarin, we won’t have the scientific verification we need. Unfortunately, long-term studies are enormously expensive. The Women’s Health Initiative study cost the American public well over $628 million.7 It was also funded in part by Wyeth-Ayerst, the manufacturer of Premarin and Prempro, because the company hoped to be able to advertise its drugs as both preventives and treatments for heart disease, which is the leading cause of premature death among women.8 Given the untoward results from the initial WHI study, what are the odds that a hormone manufacturer will take such a financial risk again? That remains to be seen. Nonetheless, many clinicians find that prescribing bioidentical hormone therapy for short-term relief of symptoms, such as vaginal dryness, hot flashes, and even mood swings, can work wonders for some women. The shifting news about Premarin and Prempro has actually opened the minds of many women and their doctors to these more physiologic and welltolerated alternatives. Remember, this is all an ongoing process. So now, more than ever, you need to make the hormone choice in concert with your inner guidance.
HORMONE THERAPY: RESEARCH SUMMARY
Benefits of Estrogen
~ Hot flashes: Estrogen gives better hot flash relief than just about any other treatment. It can take up to four weeks to notice the effect.
~ Skin: Estrogen, either systemic or applied to the skin, can increase skin thickness and enhance the collagen layer in women whose estrogen is low. It can also help reduce wrinkling.
~ Sexual function: Estrogen can enhance sexual function by eliminating vaginal dryness and thinning, which in many women cause sexual intercourse to be painful. It works equally well either systemically or topically. Some studies suggest that estrogen enhances sexual desire. High-dose transdermal testosterone has been shown to increase desire in some women who’ve undergone surgical menopause.
~ Urinary tract: Locally applied estrogen may decrease the incidence of urinary tract infection. Note: Systemic estrogen has been shown to increase the risk of stress urinary incontinence.
~ Cognition: Estrogen and other steroid hormones have well-documented effects on nerve cells. Although estrogen does not improve already established dementia, research suggests that estrogen—particularly the estradiol patch—may give moderate protection against cognitive decline if the HT is begun soon after menopause.9
~ Depression: Estrogen may have an antidepressive effect in some women but shouldn’t be used as primary treatment. Synthetic progestins may have a depressive effect in some women. Menopause itself is not associated with an increase in depression.
~ Osteoporosis: Estrogen has a well-documented beneficial effect on bone density that is equivalent to the bisphosphonates (e.g., Fosamax). It definitely reduces fracture risk and probably does so in a different way than the SERMs (see A Note About “Designer Estrogens”: SERMs) or bisphosphonates.
~ Heart and blood vessels: Many studies have documented the positive effect of estrogen on the cardiovascular system. However, this has been a controversial subject since the WHI study released in 2002 showed that Prempro increased the risk of heart attack and stroke. This study followed mostly older women who started hormone therapy (in this case estrogen plus synthetic progesterone) ten years or more after menopause. The 2006 and 2010 reanalyses of the data on the WHI and Nurses’ Health studies showed confusing data about the effect of estrogen on the risk of heart attack. Two large studies (the ELITE and KEEPS studies) are currently looking into this question further, hoping to provide more definitive data on the relationship between HT and heart health. But for now, most authorities (and the latest evidence-based position statement from the North American Menopause Society) don’t recommend estrogen for the prevention of chronic diseases.
Risks of Estrogen
~ Breast cancer: Several randomized clinical trials and observational studies have shown that estrogen increases the risk of breast cancer. Once estrogen is discontinued, the risk quickly dissipates. The absolute risk of breast cancer with conventional HT (estrogen plus synthetic progesterone) is very lo
w (twenty additional cases over what would be expected per 10,000 women over five years). Note: Many well-designed studies do not show an increased risk of breast cancer with hormone therapy, including one of the largest studies to date comparing breast cancer risk with the use of natural bioidentical hormones and synthetic hormone therapy. The results of this study, which followed more than 80,000 postmenopausal women for more than eight years, showed that the natural hormones have significantly less associated risk of breast cancer.10
~ Ovarian cancer: Risk of ovarian cancer for women who use estrogen-only hormone therapy increases 63 percent compared with nonusers, according to findings from the European Prospective Investigation into Cancer and Nutrition, presented at the 2010 conference of the American Association for Cancer Research.11 Risk for ovarian cancer increased 29 percent for women on any form of HT compared to those not taking any hormones, although risk wasn’t statistically significant for women taking a combination of estrogen and progestin.
~ Pancreatitis and gallstones: Women with high triglyceride levels are at increased risk for pancreatitis, which is sometimes fatal, when they take oral estrogen with or without progesterone. There is an increased risk of gallstones and problems requiring biliary tract surgery with the use of estrogen in all women.
~ Blood clots and stroke: Estrogen appears to double the risk of blood clots. It also increases the risk of pulmonary embolism. Embolism is most likely to occur in the first year of therapy and especially in those with a history of blood clots. Randomized trials also show an increased risk for stroke with unopposed estrogen. This risk is greater in smokers and older women.
Neutral Effects of Estrogen
~ Weight changes and insulin resistance: Estrogen doesn’t cause weight gain nor does it appear to affect blood sugar in those with diabetes.
~ Osteoarthritis: Estrogen doesn’t help or hurt those with osteoarthritis.
~ Ovarian, endometrial, and bowel cancer: Some studies show an increased risk of ovarian cancer when estrogen is used for ten years or more. Estrogen therapy without the addition of progesterone increases the risk of endometrial cancer, but adding progesterone eliminates this risk. Estrogen definitely decreases the risk of colorectal cancer, but experts agree that it shouldn’t be prescribed solely for this purpose.
Source: American College of Obstetrics and Gynecology Hormone Therapy Task Force, Obstetrics and Gynecology 104, suppl. 4 (October 2004): 35–45.
The Balanced Approach:
Individualized Bioidentical Hormone Therapy
A full range of bioidentical hormones—either singly or in combination—is available by prescription from formulary pharmacies (pharmacies that make up preparations to order). The dosages can be individually adjusted. Hormones can be prescribed based on a woman’s test results and symptoms, so she is taking only what she needs to maintain the optimal levels of hormones in her body. This approach is standard with thyroid hormone, but it wasn’t applied to sex hormones until recently. (See Resources for how to locate a formulary pharmacy in your area.) It is also possible to create a bioidentical hormone therapy regimen using hormone preparations available in all conventional pharmacies. You just have to know which brands are bioidentical and which are not. (See the chart on page 181.)
These individualized hormones can be taken orally, transdermally, or vaginally, whichever route works best for the patient. Though most women are accustomed to taking pills, the transdermal route is the more physiologically appropriate way to take hormones because they go directly into the bloodstream from the skin. You can also keep the dose much lower with this route because absorption is more direct than through the GI tract. (The body’s own hormones are secreted directly into the bloodstream by the endocrine organs.)
Oral preparations, on the other hand, have to be first absorbed from the gut and then transported to the liver, where they must undergo further metabolic breakdown before finally getting to the bloodstream. This process causes the liver to manufacture more clotting factors, which is one of the reasons that oral estrogen, especially at high doses, is associated with an increased risk of stroke, heart attack, and thrombophlebitis.
One popular form of hormone therapy is to have a prescription created especially for you using one or more of the bioidentical estrogens (estradiol, estrone, estriol) combined with bioidentical progesterone and an androgen in the form of DHEA or testosterone, if needed. These hormones are mixed into a lotion, cream, or other base and applied to the skin.
Research has clearly shown that these bioidentical transdermal hormone therapy regimens provide adequate blood levels of hormone, protect the uterine lining from overstimulation, prevent breakthrough bleeding, and give very effective relief for perimenopausal symptoms.12 I prefer the transdermal method of hormone therapy because a woman can very easily adjust her dose as needed without danger of side effects. For example, if she is having PMS symptoms, such as water retention, headaches, and bloating, she’s getting too much estrogen and needs to decrease her dose. The same is true if she develops vaginal bleeding. If she’s getting hot flashes without PMS, she needs more estrogen and should increase her dose. The usual starting dose is 0.3 mg 17-beta estradiol and 100 mg bioidentical progesterone, applied as a cream to the inside of the wrists or elsewhere on the body. A woman can gradually increase the dosage to 0.6 mg estradiol and 200 mg progesterone daily.
Why So Many Hormones Are Synthetic
Though it should be intuitively and scientifically obvious that bioidentical hormones in individualized doses would give the best results, many scientists and physicians have turned a blind eye to this concept. The answer is simple: economics.
Bioidentical hormones cannot be patented, so there are no financial incentives for a pharmaceutical company to do the expensive research and development necessary to develop new products containing them. (Unique delivery systems can be patented, however, which is why patches such as Climara, Estraderm, and Vivelle, and the vaginal ring Estring, all of which contain bioidentical estradiol, can be profitable.)
Synthetic hormones, on the other hand, are made by altering the molecular structure of a hormone enough so that it can be patented. These maintain some of the activity of the natural hormone, but any change in the three-dimensional structure of a hormone, no matter how small, changes its biological effects on the cell in ways that are not completely understood. (Note: Premarin is bioidentical for a horse, not a human.)
Frankly, I trust the wisdom coming from Mother Nature’s millions of years of experimentation much more than I trust fifty years of biochemical wizardry from Father Pharmaceutical. But not all women feel this way. Some feel far safer going with what their doctor prescribes. And since beliefs affect biology, what you believe can shape your experience. It’s your decision, and my approach is not meant to undermine any individual’s positive experience.
What About Birth Control Pills?
Birth control pills are widely prescribed as a convenient way to put the perimenopausal body and its symptoms on autopilot until it’s time to move to conventional hormone therapy. There’s a currently popular trend to convince women that our menstrual periods themselves are dangerous and that going on the pill as early as our teenage years, and staying on it except to have children, will prevent long-term health problems. Please note, however, that all birth control pills consist of synthetics that mask our natural hormonal rhythms and the messages about our health that they convey. Birth control pills are also associated with a wide variety of side effects, including blood clots, headaches, and PMS. Although they are appropriate in some cases, I’d rather keep my hormones tuned in to the cycle of the moon and the planets—as opposed to the energy of a pharmaceutical company. You may not be prepared to use other birth control methods right now, or you may be using the pill to quell symptoms such as heavy or irregular periods, but just be aware that other options are available. Some women love how they feel on the pill. Others hate it. Make your choice based on how you feel!
A HORMONE PR
IMER: ESSENTIAL INFORMATION
EVERY WOMAN SHOULD KNOW
It’s important to keep in mind that hormone therapy involves more than just estrogen. It also includes the other hormones produced by the ovaries: progesterone and androgens such as testosterone. Some women might be perfectly comfortable with no supplemental hormones; some might need progesterone only; some might need all three. Understanding their original roles in a woman’s body, and the kinds of responses some women see when levels drop, can help you make your own very personal HT decision.
Estrogen
For generations, estrogen has been the first (and often the only) hormone to be prescribed for women suffering from symptoms such as hot flashes, vaginal dryness, and mood swings. However, as I noted in chapter 4, estrogen levels don’t fall until late in the menopausal transition, and the majority of perimenopausal symptoms in women with intact ovaries are related more to a lack of progesterone than to a lack of estrogen.