Biology 103

2005 Final Paper

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In the early 1990's, however, a group of scientists started the Women's Health Initiative (WHI) to conduct more extensive research on the long-term effects of HRT. The WHI study was the first long-term, randomized, clinical trial of HRT; approximately 67,000 women nationwide participated in the study (5). Both estrogen alone as well as estrogen-progesterone combination treatments were studied. In July of 2002, the combination treatment studies were halted because it was decided that the health dangers outweighed the research benefits. In March of 2004, the estrogen treatments were stopped for the same reason (4). It had become clear that there were far more risks involved in HRT than earlier studies had shown.

The WHI found that there was indeed a significant decrease in the occurrence of osteoporosis-induced hip fractures (34% fewer) and other fractures (24% fewer). This was caused by the estrogen boost provided by HRT, because the results were the same in women who took the estrogen-only treatments and women who took the combined treatments. However, there were also significant increases in the occurrence of heart attacks (29% more among women taking the combined treatments) and strokes (42% more among women taking both types of treatments). Thus, HRT was shown to be successful in decreasing women's risk of osteoporosis but unsuccessful (even harmful) in affecting their risk of heart disease (4).

Not only did researchers see a notable increase in heart disease, but HRT also had a significant effect on several different types of cancer. WHI results showed a 26% increase in the development of breast cancer among women taking both types of HRT treatments. Estrogen promotes the proliferation of breast cells, which produces the genetic mutations that cause breast cancer; it also stimulates the growth of breast cells, including those which are cancerous. The link between high estrogen levels and breast cancer is also supported by the positive correlation between the occurrence of breast cancer and the length of a woman's exposure to estrogen due to natural causes (such as an early menstruation onset or late menopause). In addition, researchers have found a strong positive correlation between high bone density and increased occurrence of breast cancer; the high bone density would partially be a result of estrogen (2). Thus, estrogen seems to be the hormone at fault, and a boost in estrogen levels would logically lead to an increased risk for developing breast cancer. Another research group called HABITS studied women who had been treated for breast cancer prior to their exposure to HRT; there was also a significant increase in the reoccurrence of breast cancer in these women (2).

Estrogen and combined treatments also affect two other types of cancer: endometrial and ovarian. Endometrial cancer, the most common type of uterine cancer, occurs in the lining of the uterus. Estrogen causes this lining to grow during menstruation, which increases the likelihood that it will develop cancerous cells. The rate of endometrial cancer among women in the WHI study who were taking the estrogen-only treatment was 6-8 times higher than women who were not taking HRT. Progesterone, on the other hand, causes the uterine lining to decrease in size at the end of each menstrual cycle, which in a HRT treatment counteracts the effect of estrogen on the lining. Thus, women taking the combined estrogen and progesterone treatments did not have a heightened risk of developing endometrial cancer (4). A different study, conducted by the National Cancer Institute in 2002, showed an increase in the risk of developing ovarian cancer among women taking estrogen-only treatments. There was also a positive correlation between the length of the women's exposure to the estrogen and the number of occurrences of ovarian cancer; for example, women who had been exposed to estrogen supplements for 20 years were at about three times the risk as women who had been taking it for fewer than 5 years (4).

In summary, both types of treatments showed the expected decrease in osteoporosis-induced bone fractures. However, a number of highly dangerous side effects were noticed among the women in the study. Women taking the estrogen and progesterone combined treatments experienced significantly increased risks of invasive breast cancer, heart disease, strokes, and blood clots in the legs and lungs. Women taking the estrogen-only treatments showed increased rates of breast cancer and strokes and did not exhibit the expected decrease in the likelihood of heart disease (3).

Overall, researchers concluded that the risks of taking HRT treatments far outweighed the benefits. In accordance with new American Heart Association guidelines, most experts have stopped recommending combined-hormone treatments to women approaching menopause. Some doctors still recommend estrogen-only treatments (because this type of treatment seems to result in only a few of the long-term risks caused by combined treatments), but even estrogen-only treatments are prescribed in very conservative doses and for the shortest possible duration (3). Even for women who have already been taking HRT treatments for a considerable length of time, it's not too late; when the women in the WHI study stopped taking HRT, their risk of developing breast cancer and other cancers decreased. Alternatives to HRT have been developed in order to help women at risk for osteoporosis, such as Vitamin D and calcium supplements as well as medications (calcitonin, risedronate, etc.). However, women who are already at high risk to develop osteoporosis for other reasons, and who take HRT to decrease this risk, are warned that the benefits of HRT in maintaining their bone density and strength do disappear when the estrogen boost is removed from their system. Thus, some doctors may still recommend that these women keep taking HRT treatments (4). Most other women have either already opted to stop their HRT or are currently easing off the treatments due to these new research findings.

Web Sources:

1)Patient information: Alternatives to posmenopausal hormone therapy

2)Patient information: Postmenopausal hormone therapy and breast cancer

3)Postmenopausal Hormone Therapy and Cardiovascular Disease in Women

4)Medical Encyclopedia: Hormone replacement therapy (HRT)

5)Bad News About Hormone Replacement Therapy


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