PREgnant MARes urINeDecember 2002
Confusion about estrogen
Premarin has created a big problem. Because of its huge sales, the drug has become synonymous with "estrogen". Even researchers have confused this estrogen-like product with estrogen.** Others have mistakenly referred to Premarin as "hormone replacement therapy" (HRT) as if this one drug is all there is to HRT. There are many hormones that decline with age (horse estrogen in humans not being one of them). HRT can be achieved with any number of hormones-growth hormone, testosterone, progesterone, etc. To limit hormone replacement therapy to Premarin is like limiting a fireplace to one brick.
Premarin has created another problem. According to its manufacturer, Premarin is a very unique estrogen-like product, unlike any other estrogen on the market. This argument, repeated for decades to the FDA, has kept a cheaper generic off the market. Because Premarin is in a class by itself, so unique that a generic cannot even be made without that manufacturer also keeping thousands of pregnant horses in stalls and collecting their urine, then it's important to realize that any effects or benefits Premarin has cannot be extrapolated to any other estrogen product. This means that all so-called HRT studies on Premarin products are nothing more than drug trials for Wyeth-Ayerst. The results cannot be applied to other estrogens, which leaves Americans, for the most part, without any meaningful studies on estrogen or hormone replacement. And there are dozens of possibilities-everything from natural progesterone to supplements, to herbs and other drugs.
Since the bubble has burst, some women have argued that they take Premarin, and feel fine. They also say that if they try to stop taking it, they get severe hot flashes or other negative symptoms. In response, it should be pointed out that if a woman taking Premarin or related drugs is diagnosed with breast cancer, the first thing her physician will do is take her off of it. One day it's safe, the next day, it's not. That's something to consider. In addition, "feeling fine" is no indication of health. Many women diagnosed with breast cancer or a stroke, felt fine the day before. Women should take the new warnings for Premarin, Prempro and Premphase to heart. Those warnings make it clear that women should take the drugs the shortest amount of time possible, and that in many cases, the risks outweigh the benefits.
A couple of other things are worth noting. A recent study in Archives of Internal Medicine reports that if a woman is taking hormone replacement therapy, and she finds a lump in her breast, she is more likely to be reassured by her doctor that it is a fibroid, not cancer. Researchers don't know why yet.
On a similar note, synthetic estrogen and progestin drugs make breast tissue dense, and harder to read on mammograms. Harder-to-detect cancer coupled with false assurances about lumps add up to the fact that a woman taking hormone drugs is less likely to get diagnosed with a disease she's more likely to get. That doesn't mean that every woman taking the drugs is going to get serious side effects. Most do not. The problem is that nobody knows which women will and which women won't.
Switching from Premarin
Some women have reported difficulties in stopping Premarin and related drugs. They report getting severe hot flashes and other side effects if they try to stop. This has never been scientifically investigated, but there is some evidence that the body adjusts to Premarin, and that sudden withdrawal may cause a reaction. Premarin increases the number of estrogen receptors-meaning that it makes physical changes on cells. It's also been reported that the drug activates or deactivates at least 32 genes in the rat uterus. What this means for women is not known. But if it does something similar in humans, the sudden withdrawal of the drug could produce side effects.
"Feeling fine" is no indication of health. Many women diagnosed with breast cancer, or a stroke, felt fine the day before. Women should take the new warnings for Premarin, Prempro and Premphase to heart.
There isn't any official documentation of women having problems switching from Premarin drugs to something else, so the extent of the problem, if any, is unknown. The best advice to a woman who wants to replace Premarin with something else is to reduce the amount of drug slowly while at the same time increasing the amount of the replacement, allowing the body to adjust and detoxify. This can take months for some women. Women need to realize that there's no one hormone-replacement strategy that works for everybody. Women who successfully move from Premarin to something else keep trying various combinations until they find something that works.
Do you need it at all?
Finally, women should be aware of something that's very important to the entire discussion of hormone replacement therapy. It may surprise many to learn this, but millions of women all over the world don't get menopausal symptoms. Menopausal symptoms are not "a natural part of aging" in other cultures. Hot flashes, osteoporosis and the like occur rarely if at all. Surprised? To find out more about this, read our companion report on natural hormone replacement.
*Some of the FDA enforcement letters to Wyeth-Ayerst are available on its website at www.fda.gov. See enforcement letter. We define "estrogen" here as that made by the human body.*
Grodstein F, et al. 1996. Postmenopausal estrogen and progestin use and the risk of cardiovascular disease. NEJM 335:453-61.
Hemminki E, et al. 1997. Impact of postmenopausal hormone therapy on cardiovascular events and cancer: pooled data from clinical trials. BMJ 315:149-53.
Hulley S, et al. 1998. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. JAMA 280:605-13.
Stampfer MJ, et al. 1991. Postmenopausal estrogen therapy and cardiovascular disease: ten-year follow-up from the Nurses' Health Study. NEJM 325:756-62.
Writing Group. 2002. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the women's health initiative randomized controlled trial. JAMA 288:321-333.