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WOMENS MEDICO-LEGAL ISSUES (PART I): Hormone Replacement TherapyMay 1, 2004 Hormone Replacement Therapy (“HRT”) has been a long-standing and widely accepted treatment for women experiencing some of the more uncomfortable effects of menopause. In the past few years, however, this popular therapy has come under fire as a result of evidence linking HRT to many serious health risks. In fact, a number of studies suggest that women undergoing HRT are exposing themselves to long-term harm that far outweighs the severity of the symptoms being treated.
For some women, HRT might consist of an estrogen-only treatment while others are given a combination of estrogen and progestin. This latter option is slightly less common but is still a popular solution to menopausal discomfort. Both types of HRT are used by an estimated 13.5 million women in the United States alone.
HRT has been around since the early 1940s when women began taking high doses of estrogen to counteract many of the temporary, but recurring, discomforts of menopause. In the 1970s, however, it was discovered that this particular form of estrogen therapy created an unacceptably high risk of uterine cancer. This prompted the trend by doctors to prescribe progestin along with significantly lower doses of estrogen.
Recent studies now show that there are too many health risks associated with HRT to justify its being used automatically as a “cookie cutter” treatment of choice or as if it were a woman’s only available option. Women should consult their physicians to discover whether HRT would be a benefit or a detriment given their own particular circumstances. While HRT undoubtedly alleviates a number of menopausal symptoms in many women, for some, the cost of that immediate relief may include unwanted long-term effects.
Prempro and Premarin:
Prempro and Premarin are the two major HRT drugs. Both are manufactured by Wyeth Pharmaceuticals. Prempro is a combination estrogen-progestin treatment and Premarin is an estrogen-only treatment. There are approximately 6 million women taking Prempro and 11 million women taking Premarin. Last year, the two drugs had combined sales of $2.1 billion dollars.
Although Premarin, the first HRT drug, was introduced in 1942 for the purpose of alleviating symptoms of menopause such as hot flashes and vaginal dryness, a recent study in the Journal of American Medical Association (“JAMA”) has linked it to ovarian cancer.
Prempro, on the other hand, has been linked to various serious side effects including dementia, Alzheimer’s disease, stroke, blood clots, pulmonary embolisms, lupus, hearty attack and breast cancer. Women taking Prempro have a 29% higher risk of heart attack, a 41% higher risk of stroke, and a 26% higher risk of breast cancer. Those figures alone should prompt women to consult their physicians regarding alternative treatments or methods of treatment. This is especially so for women who experience only minor symptoms of menopause such as vaginal dryness for which respond to alternative treatments such as creams and vitamin E.
The most important thing stressed by researchers and medical professionals alike is that Prempro, Premarin and other HRT drugs should be taken in the smallest dosages (that produce effective results) for the shortest duration as possible. In addition, women who are only experiencing minor symptoms of menopause might want to forego HRT therapy altogether. Finally, even women seeking relief from more severe symptoms should do their own benefit/risk analysis by asking questions, reading available reports, and keeping in mind the potential risks associated with HRT.
Harmful Effects of HRT:
As Prempro and Premarin are the two major existing HRT drugs, the following information is primarily related to the usage of one or the other. However, other drugs and treatments may have the same harmful effects and you should consult a physician if you believe the treatment you are on may be harmful to your health.
HRT medications can double the risk of vascular dementia and Alzheimer’s disease, especially in women over 65. Short rather than long-term use is recommended in order to avoid this unwanted side-effect. This information was first made public in an issue of the Journal of American Medicine released in May of 2003. The Women’s Health Initiative Memory Study, which was funded by Wyeth, analyzed data from about 4,500 women, aged 65, who had not been diagnosed with dementia before the study. During the five-year study, each woman took Prempro daily. The results found that of the 61 women who developed dementia, 40 (66%) had been given the hormones while only 21 (34%) had taken the placebo.
Another study published at the same time revealed that, in addition to the increased risk of dementia, HRT may have harmful effects on the general cognitive function of older women leading to mild memory loss amongst other things. While these increased risks are numerically small, they do represent a significant increase in the percentage involved. (Obviously, 19 additional cases of dementia in 4,500 participants [40 to 19] is a small “number” but it does represent almost a 50% differential [66% to 34%]). Thus, this particular increased risk should be taken seriously and a physician should be consulted if you plan to begin HRT or are already undergoing HRT and are experiencing any symptom of this side-effect.
Combination therapy consisting of estrogen and progestin, such as Prempro, has now been linked to an increased heart attack risk of up to 81% in the first year of treatment. One possibility for this newly discovered heart attack risk is that HRT might cause more rapid clotting and therefore, a woman with one or more narrowed blood vessels would be at risk if there was a sudden clotting of the blood in those constricted areas. While it was previously believed that combination estrogen-progestin drugs could actually prevent heart attack, a recent study found that hormones do not slow the clogging of arteries. In fact, all women who take hormones appear to be at a higher risk for heart attack.
The Women’s Health Initiative (“WHI”), a federally sponsored organization, conducted a study to determine the risks associated with HRT. (The study was actually abruptly aborted in 2002 as too many women were being put in harm’s way and experiencing a variety of severe side-effects such as heart disease, stroke, blood clots, and breast cancer.) Of the 16,608 women who participated in the study, there were 190 incidents of heart attack and 39 fatalities among the group given Prempro. The placebo group had 148 heart attacks and 34 fatalities. Again, the numerical increase in the risk does not seem so great. However, the overall percentage increase in the heart attack risk is about 30% which is significant enough to be taken into account when making the decision about HRT.
The discovery of this increased heart attack risk should prompt doctors to be more careful about whom they are placing on HRT therapy. Healthy, middle-aged women are the ideal candidates for drugs like Prempro as they are not usually at an increased risk for heart attack before beginning treatment. Women who are already at greater risk, including those with high cholesterol or those with a personal or family history of cardiac problems are not good candidates for HRT. It should be remembered, however, that the increased risk applies to all women.
Estrogen-progestin pills such as Prempro are now being linked to an aggressive form of breast cancer. The WHI study was responsible for discovering crucial information regarding this dangerous risk. Of the 16,608 women in the study ranging from ages 50-79, breast cancer developed in 245 women who used estrogen-progestin pills and 185 women in the placebo group. Collectively, the women on hormones had larger tumors which began to spread to nearby tissue and distant parts of the body in about 25% of hormone users with cancer as opposed to only 16% of the women with cancer in the placebo group. Tumors may also grow at a faster rate in women taking hormones.
A similar longitudinal study conducted in Britain concluded that women who were receiving HRT had a greater risk of developing breast cancer in comparison to women not receiving therapy. The study involved 1 million women between the ages of 50 and 64. Those who took the hormones demonstrated a 66% greater risk of developing breast cancer and a 22% greater risk of dying from it within 6 years. Women who took estrogen alone had only a 30% increased risk of developing breast cancer leading some experts to conclude that the original (estrogen only) option is a safer one despite the fact that it, too, has been shown to increase the risk of breast cancer. The researchers determined that, over a decade, HRT would be responsible for 10,000 extra cases of breast cancer in England and an extra 100,000 cases in the United States among menopausal women ages 50-64.
Yet another study conducted in Sweden concluded that women who were receiving HRT were more prone to new and recurring cancer. This study was also stopped due to the unacceptably dangerous risks posed to the 345 women participating in the study.
Perhaps the most dangerous risk regarding HRT and breast cancer is the newfound risk of inaccurate and abnormal mammograms. Out of the estimated 3 million women on HRT in the United States, about 120,000, or 4%, could experience abnormal mammograms related to the HRT. Combined HRT, such as Prempro, causes the breast tissue to increase in density thereby making it more difficult to obtain a clear and accurate mammogram. In cases where there is a delay in detecting the cancer treatment, options are more limited and the prognosis is less favorable. In an editorial from the Feinberg School of Medicine at Northwestern University, Peter H. Gann and Monica Morrow accurately sum up this disturbing finding by stating: “The ability of combined hormone therapy to decrease mammographic sensitivity creates an almost unique situation in which an agent increases the risk of developing a disease while simultaneously delaying its detection.”
Note: Ovarian and uterine cancers have also been linked to HRT even though it was previously thought that hormones would help to prevent the onset of such cancers.
Some women who are skeptical of the pharmaceutical solutions to menopausal symptoms have sought alternate treatments such as herbal remedies. But some herbal hormonal treatments may also increase the risk of breast and uterine cancer for women, especially those with a history or a family history of these cancers. Herbs such as clover, motherwort, palmetto, and rhodiola can actually have such a powerful estrogenic effect that, just like other HRT treatments, they can cause estrogen-related cancers. Extracts of maca root, cramp bark, and tumeric root can also be harmful if taken in large amounts.
Warnings and Labels:
Due to the mounting evidence suggesting that HRT is not the best option for menopausal women, the FDA and other health advisory groups have issued several warnings and label requirements in order to keep the public informed about the recent developments relating to Prempro, Premarin, and any other estrogen or estrogen-progestin drugs. In response to the results of various studies, there has been a significant decrease in the number of women taking and asking for conventional HRT treatments.
• 1/09/03: The FDA approved new labels for Wyeth which included an updated warning that explains the increased risk of heart disease, heart attacks, and breast cancer. The new label emphasizes that the drugs do not prevent heart disease. In addition, doctors were advised to prescribe the lowest dose possible for the shortest amount of time. The FDA’s actions also apply to any product containing estrogen alone or a combination of estrogen-progestin.
• 2/03/03: The head of the American Cancer Society released a statement to the effect that it is “unwise” for women with a history of breast cancer to undergo HRT.
• 1/09/04: The Canadian Cancer Society urged women to avoid estrogen-progestin therapy since it causes an increased risk of breast cancer, especially when used over an extended period of time. They advised women not to take the drug(s) unless they are suffering severe menopausal symptoms and have not responded to any other form of treatment.
• 2/10/04: The FDA proposed that manufacturers of hormone replacement drugs change their warning labels once again to include warnings for dementia and abnormal mammograms. The new labels should also list the approved usages of the drugs and instruct doctors to pursue alternatives with their patients.
• The number of Australian women using HRT declined rapidly after new information regarding health risks was made public.
• A 71 year-old woman, along with 15 other women, from Houston, Texas is suing Wyeth claiming that Premarin caused her to develop breast cancer. The suit alleges that, despite the fact that Wyeth knew, or should have known, that Premarin was responsible for the development of estrogen-related cancers; it continues to market the product as a “fountain-of-youth” drug.
In the past few years there has been extensive evidence to suggest that HRT is not the safest option for women over 50 experiencing unpleasant menopausal symptoms. Studies have shown that there are undeniable health risks for women who take estrogen or a combination estrogen-progestin drug on either a short or long-term basis. Some doctors, however, argue that there is still not enough persuasive evidence from which to conclude what negative effects are linked to short-term use. Nonetheless, there is ample proof to strongly suggest that HRT is a risky treatment for the woes of menopause and that its use should be carefully considered on a case by case basis. Those women already on HRT should carefully monitor their health and be on the lookout for any possible condition which may be associated with the drugs they are taking. In either situation, women should discuss the pros and cons of HRT with a qualified doctor especially in light of complicating health factors, personal and family medical history, and dosage size and treatment duration.
Presently, there are not many alternatives to HRT with respect to the more severe symptoms of menopause. In February, 2004, the FDA approved a product manufactured by Solvay Pharmaceuticals called EstroGel. EstroGel is an estrogen gel which is absorbed through the skin of the arm. There are now a few other similar alternatives such as hormones in the form of lotions and skin patches. Although the FDA has approved these products, it is not certain if these alternatives are any safer than pills.
Perhaps the revelation which most convincingly demonstrates the serious nature of the risks associated with HRT is the early termination of the studies discussed above. It is a sobering thought indeed that studies to determine the dangers associated with a drug were stopped in mid-course because of the extreme risks posed to the participants in the study itself. In addition to the combination estrogen-progestin studies mentioned above, a clinical trial involving estrogen-only HRT is currently underway and is expected to be completed in 2005.
Despite controversial evidence and mounting concerns, HRT is still being used by millions of menopausal women worldwide. The drugs have not been taken off the market and may still be legally prescribed to any woman seeking relief from problems associated with menopause. If you are currently taking hormones for menopause-related symptoms and are concerned about any health risks associated with the medication, consult your primary care physician or gynecologist immediately. If you suspect that you suffer from or have developed any medical condition associated with HRT or any of the drugs discussed herein, contact Parker and Waichman for a free case assessment.
In our continuing exploration of medico-legal issues affecting women, we will be discussing numerous matters relating to breast cancer (Part II – June) as well as specific subjects which pertain to women only (Part III – July).