In July 2002, everything many doctors thought they knew about menopausal hormone therapy (called hormone replacement therapy (HRT) at the time) was called into question when researchers announced that they were stopping the Women's Health Initiative (WHI), a large randomized placebo-controlled study designed to measure the benefits and risks of menopausal hormone therapy. The study was stopped because an interim data analysis indicated that the risks of this therapy outweighed any benefits the drugs had to offer.
Estrogen was first approved by the FDA to treat menopausal symptoms in 1942. In the mid-1970s, progestin was added to estrogen after studies found that giving women estrogen alone increased the risk of uterine cancer. By the 1990s, the combination of estrogen and progestin, which had become known as hormone replacement therapy, had become the second most frequently prescribed medication in the US. It was widely marketed as a drug that would not only prevent hot flashes but also keep postmenopausal women healthier as they aged.
Now, due to the WHI, we are aware that taking estrogen does not keep women healthy. More than 16,000 women between the ages of 50–79 were enrolled in the WHI trial. Half of the women were given menopausal hormone therapy; half of women were given a placebo. To ensure women's safety during the trial, the researchers had established an independent data and safety monitoring board (DSMB) to review interim results semiannually. During the tenth analysis, on May 31, 2002, the DSMB found an increased risk for breast cancer, coronary heart disease, stroke, and blood clots that outweighed the benefit of reduced fractures or colon cancer risk. This finding led the DSMB to recommend that the trial be stopped. Today, it is not recommended that women who have or have had breast cancer take menopausal hormone therapy.
How big of a risk did the study find? If 10,000 women were taking menopausal hormone therapy for a year and 10,000 women were not, there would be eight more women in the menopausal hormone therapy group who would develop invasive breast cancer, seven more who would develop heart disease, eight more who would have a stroke, and eight more who would develop blood clots. There would also be six fewer colorectal cancers and five fewer hip fractures.
The WHI trial began around the same time that Wyeth, the drug company that makes the leading HRT drug Prempro, began a randomized, controlled trial called the Heart and Estrogen/Progestin Replacement Study (HERS). This trial included about 2,700 women; half were given Prempro while the other half received a placebo. Findings from the HERS trial, published on July 3, 2002, in the Journal of the American Medical Association, indicated that menopausal hormone therapy did not prevent heart attacks in older women with heart disease and that it increased blood clots and gallbladder disease. This confirmed previous findings from the HERS trial that had been published in 1998.
It is now clear that menopausal hormone therapy is not the women's wonder drug that many thought it would be. We now know that menopausal hormones:
- If used for more than five years, increase the risk for invasive breast cancer.
- Increase the risk for heart attacks, strokes, and blood clots.
- Increase the rate of incontinence and uterine prolapse.
- Don't appear to prevent heart disease.
- Have not been proven to prevent Alzheimer's disease.
- Does not improve quality of life in women who do not have menopausal symptoms.
As a result, it is now recommended that only a low dose of menopausal hormone therapy be used. Several studies have shown that low-dose hormone therapy (.3mg or .15mg of Premarin, Menest, Estratab, Ogen, Ortho-Est, or Cenestin) combined with a daily supplement of 1,000mg of calcium maintains bone density as well as high-dose HRT.
Women should stay on hormones for as short a time as is possible—at most three to five years—to help with menopausal symptoms, like severe hot flashes, night sweats, or vaginal dryness, and then begin tapering off. Women who begin taking hormones in their 30s and 40s following an oophorectomy should begin tapering off in their early 50s.
We currently don't know if one form of estrogen is better than any other. If one type of hormone therapy is not working for you, you may want to try another. The steadfast rule is that any woman who has a uterus must take an estrogen and a progesterone. (Progesterone was added to decrease the risk of uterine cancer.) Women who do not have a uterus can take only estrogen. In addition to pills, several patches are now available that deliver micronized estradiol. The estrogen passes through the skin into the blood without being broken down in the digestive system (as a pill would be).
Bioidentical Hormones: Are They Better?
After concerns began to be raised about the dangers of menopausal hormone therapy, some women and their doctors began to tout the benefits of bioidentical hormones. Practitioners who use these drugs and the compounding pharmacies that make them claim that bioidentical hormones are better because they are made with natural, rather than synthetic, hormones that are better absorbed by the body. They also claim that because these hormones are similar to those a woman produces, side effects are less likely to occur. Is this true?
Bioidentical hormones are plant-derived; they are made from concentrated soy and yam. So, yes, they are natural in that they are produced by nature. But that doesn't necessarily mean they are better than the drugs made by pharmaceutical companies. In fact, Premarin (estrogen alone) and Prempro (a combination of estrogen and progestin) contain estrogen that comes from pregnant mares' urine. That is certainly natural. (Whether it is right is another question. PETA and other animal rights activists are opposed to the practice.)
But just because something is "natural" does not mean it's safe. Currently, only a handful of small studies have been conducted on compounded bioidentical hormones. They indicate that these drugs are effective. But that does not mean they are safe, or safer than other types of HRT. Not one large randomized trial—the gold standard of medical research—has been conducted with bioidentical hormones. And there have been no randomized trials comparing bioidentical hormones to a drug like Prempro.
Practitioners who recommend bioidentical hormones give women prescriptions to be filled by pharmacies that have the ability to "compound," or make, individualized doses. Typically, the practitioner determines which hormone to use and at what strength by conducting hormone tests on a woman's blood or saliva. There is currently no evidence to support these methods as a means of determining what levels of hormones a woman's individualized menopausal hormones cocktail should be comprised of.
The real benefit of the bio-identical movement is that it has spearheaded a move away from the one-size-fits-all approach of recommending menopausal hormones to all women as they enter menopause. If you prefer using a product that is plant-derived rather than animal-derived, then they might be a good option for you. But there is no indication that these drugs are safer than other forms of menopausal hormones, and you should not stay on them for more than three to five years.
Going Off Menopausal Hormone Therapy
As women who have been diagnosed with breast cancer know firsthand, it is possible—and from a medical perspective, perfectly okay—to stop hormones cold turkey. In fact, about half of all women who stop taking hormones cold turkey will do just fine. The other half will find that the menopausal symptoms that led them to take hormones in the first place come back with a vengeance. This is because stopping hormones turns on the menopausal switch, and that is likely to result in the side effects that women typically go on menopausal hormones to avoid—hot flashes, vaginal dryness, and sleep problems.
Since there is no way to predict which women will experience symptoms and which women won't when they go off menopausal hormones, every woman must determine which method of going off menopausal hormones is right for her. One option is to taper off menopausal hormones gradually, which allows the body to adjust to decreasing doses of hormones and helps to reduce side effects. The second option is to quit cold turkey and then see if you are one of the lucky ones who don't have symptoms. If you are in the lucky 50%, you can throw your menopausal hormones away. If you're not, you can go back on and then begin tapering off gradually.
If you take combination menopausal hormones, which has estrogen and progesterone in the same pill, to begin tapering off you should ask your doctor for two separate prescriptions. This will allow you to better control the dose of each aspect of your menopausal hormones as you taper off. As you taper off, you should also begin taking a daily supplement of 1,000mg of calcium. Once you have tapered off completely, you should take a daily supplement of 1,200mg of calcium along with 400¬–800 IU of vitamin D.
If you are taking standard menopausal hormones, the best way to begin tapering off is to start taking low-dose menopausal hormones—0.3mg (.5mg of Estrace). If you have symptoms on the lower dose, you will need to raise your dose and decrease it more gradually. You can do this by alternating low- and high-dose pills (Monday = high dose, Tuesday = low dose, Wednesday = high dose, Thursday = low dose, etc.) for three to six months before trying to take only the low-dose pills.
A second option is to take the high-dose pills Monday through Friday and not take any pills on the weekends. After you have done this for three to six months, you can then try the low-dose pills again. The only way to know when you can fully drop down to the low dose is by trying it and then seeing if symptoms develop. If they do, and are unbearable, you will need to go back to the routine you were on and taper more gradually. If you are alternating a high-dose pill with a low-dose pill, you can do this by replacing one of the days you are taking a high-dose pill with a low-dose pill (Monday = high dose, Tuesday = low dose, Wednesday = low dose instead of high dose, Thursday = low dose, etc.). Once you have done this for a few months, then try adding in another low-dose day.
If you are taking menopausal hormones Monday through Friday and skipping weekends, try skipping another day, like Wednesday. Then, after a few months, you can try skipping another day. In general, the rule to follow is to go as slowly as you need to and to not go to the next reduction until symptoms that may have developed are easy to handle.
After a few months on the lower dose, you have two options: You can discontinue estrogen altogether or you can continue to take a smaller amount by cutting your pills first in half and taking a half dosage for a few weeks, and then cutting the pills in quarters and taking a quarter dose for a few weeks. Another option is to take a low-dose pill every other day.
If you are currently taking a higher dose of menopausal hormones—1.25mg (2mg Estrace)—you should begin tapering by dropping down to the standard dose—.635mg (1mg Estrace). You should continue to take the progesterone until you taper down to the low-dose level—0.3mg (0.5mg of Estrace). Once you are at the lower dose, you can discuss with your clinician whether to remain on the progesterone while you finish tapering off.
Money tip: menopausal hormones costs the same regardless of the dosage you are prescribed. To help reduce your costs you may want to keep your prescription dosage the same, but cut your pills in half.