Whether or not to take hormone replacement therapy (HRT) is a complex decision. Previous research had suggested it protects against osteoporosis and colon cancer, and possibly heart disease and stroke. Then there was the article published in the July 17, 2002 issue of the Journal of the American Medical Association, reporting that a large study of HRT in postmenopausal women was stopped three years early due to evidence that HRT may increase the risk of breast cancer, heart disease, stroke, and blood clots. See: "HRT study stopped early because risks seem to outweigh benefits"

There’s even more to the story, though, because various forms of HRT contain different types and combinations of the hormones estrogen and progesterone. Some therapies contain only estrogen (ERT) while others contain estrogen and progesterone in various formulations (HRT). To date, research has consistently shown that ERT increases the risk of endometrial cancer (cancer of the lining of the uterus) in women with an intact uterus. For this reason, women who haven’t had a hysterectomy routinely take HRT. But should they take sequential estrogen and progesterone cycled every month or continuous combined estrogen and progesterone? Some research suggests that the sequential regimen may modestly increase the risk of endometrial cancer. But a study published in the August 3, 2002 issue of BMJ suggests that continuous combined estrogen-progestogen may actually protect against endometrial cancer.

About the study

British and Dutch researchers studied 534 postmenopausal women at 31 clinics in the United Kingdom. Prior to the study, 360 women had taken sequential estrogen-progestogen, 164 had taken no HRT, and 10 had taken estrogen-only (ERT). In addition, 22 women had complex hyperplasia of the endometrial tissue (a risk factor for endometrial cancer), 21 of whom had taken sequential estrogen-progestogen.

At the start of the study, a sample of endometrial tissue (uterine lining) was taken from each woman’s uterus. Then the women began taking continuous combined estrogen-progestogen (2 mg 17beta-estradiol and 1 mg norethisterone acetate) daily for 9 months. Another endometrial biopsy was taken at 9 months. For women who chose to continue the medication after 9 months, another biopsy was taken between 24 and 36 months, as well as at 5 years.

A pathologist examined the endometrial biopsies to see if any women developed hyperplasia while taking HRT and if hyperplasia had worsened or improved in women who had hyperplasia at the start of the study.

This study was sponsored by Novo Nordisk, a company that manufactures several HRT products, including a continuous combined estrogen-progestogen product.

The findings

According to the biopsies at 9 months, 24 to 36 months, and 5 years, none of the women had endometrial hyperplasia. What is particularly remarkable is that endometrial tissues in the 22 women who had hyperplasia before the study had reverted to normal. This suggests that continuous combined estrogen-progestogen does not increase risk of endometrial cancer, and that it may even prevent it by reversing hyperplasia.

Remember, 21 of the 22 women who had hyperplasia at the beginning of the study had taken sequential estrogen-progestogen. This implies that sequential, but continuous, combined HRT may be associated with increased risk of endometrial cancer.

Although these finding suggest that continuous combined HRT may help prevent endometrial cancer, this study has its limitations. First, this study did not include a comparison group of women who took no HRT. Without a comparison group, the evidence for a protective effect of HRT is not very compelling. Second, this study did not assess the effects of HRT on risk of heart disease, stroke, and breast cancer—all of which have been identified in other studies as risks associated with taking HRT. Third, longer-term research is needed to determine the effects of HRT beyond 5 years. Finally, only one formulation of estrogen-progestogen was used in this study. Other formulations may produce different results.

How does this affect you?

Should you take HRT solely to protect yourself from endometrial cancer? Probably not. Although this study suggests that continuous combined HRT does not increase the risk of endometrial cancer, and may in fact prevent it, other research has identified risks associated with combined HRT—heart disease, stroke, and breast cancer. However, because there are several formulations of estrogen and progesterone on the market, more research is needed to determine the beneficial and negative effects of each one.

If you suffer from uncomfortable symptoms of menopause, such as hot flashes, insomnia, and vaginal dryness, it may make sense to take HRT to relieve these symptoms in the short term. Again, the decision to take HRT is a complex one involving your personal risk factors for various conditions and the different formulations of HRT hormones. Whether you decide to use HRT or not, you can still take steps, such as exercise and dietary measures, to minimize your risk of developing osteoporosis, breast cancer, heart disease, and other conditions associated with menopause.