New information on hormone replacement therapy (HRT)

The menopause is the transition between a woman's childbearing years and her non-childbearing years. It is the last stage of a biological process during which the ovaries gradually produce lower levels of sex hormones - oestrogen, progesterone, and testosterone. By the time natural menopause is complete (usually between 45 and 55 years of age), hormone output decreases significantly. Women who have surgery to remove both of their ovaries (an operation called bilateral oophorectomy) experience "surgical menopause," the immediate cessation of ovarian hormone production and menstruation.

In postmenopausal women, oestrogen levels are about one-tenth the level in  premenopausal women and progesterone is nearly absent. The low levels of oestrogen after menopause are produced by the adrenal glands and fat cells. Oestrogen usage, with or without progestogen, approximately doubles the oestrogen level of a postmenopausal woman. Therefore, even with hormone treatment, oestrogen and progesterone levels of a postmenopausal woman do not reach the natural levels of a premenopausal woman.

Hormone replacement therapy

Postmenopausal hormone replacement therapy usually involves treatment with either oestrogen alone or more commonly in combination with progestogen to compensate for the decrease in natural hormones that occurs at the menopause. Oestrogen is a natural hormone manufactured primarily by the ovaries. It is involved in the development and maintenance of secondary sex characteristics such as breasts in females and affects many aspects of women's physical and emotional health. Progestogens are preparations that have effects similar to those of the natural hormone progesterone, which is primarily responsible for regulating the reproductive cycle. Among women who use postmenopausal hormones, women who have had their uterus removed use oestrogen alone, whereas women with a uterus take a combination of oestrogen plus progestogen.

New information from the Women's Health Initiative

Choosing whether or not to use hormone replacement therapy (commonly known as HRT) is one of the most important decisions that women face as they become older. In July 2002, new findings were released about the risks and benefits of a type of hormone therapy that uses oestrogen in combination with progestogen. The findings offer women important new information when they are considering the long-term use of this type of hormone replacement therapy.

The findings come from the Women's Health Initiative (WHI), a 15-year study of ways to prevent heart disease, breast and colorectal cancer, and osteoporosis (a condition that results in weak bones and an increased risk of fractures). The Women’s Health Initiative, which consists of a set of clinical studies and an observational study, began in 1991 and involves more than 161,000 healthy post-menopausal women. The Women’s Health Initiative is funded by the American National Heart, Lung, and Blood Institute (NHLBI) in collaboration with other units of the American National Institutes of Health.

One of the clinical studies involved 16,608 women with a uterus who took either oestrogen plus progestogen therapy or a placebo (a substance that looks like the real drug but has no biological effect). The main goal was to see if the therapy would help prevent heart disease and hip fractures. Another goal was to see if the possible benefits were greater than the possible risks for breast cancer, endometrial cancer, and blood clots in the legs and lungs.

The study was stopped early because after just over 5 years the treatment's risks outweighed and outnumbered its benefits. Another Women’s Health Initiative study seeks to answer the same questions for oestrogen-only therapy and continues, with results expected in 2005.

Understanding The Results

Results from the oestrogen plus progestogen study are given below and in the boxes. They show that the therapy did not protect against heart disease but actually increased the risk of heart attacks, stroke, and blood clots. It also increased the risk of breast cancer. The therapy also produced some benefits too: It reduced the risk of colorectal cancer and bone fractures.

It's important to understand that these increased risks apply to an entire population and women should not be unduly alarmed by the results. Furthermore, although the size of the increase in risks looks dramatic, the increased risk for an individual woman would be small. For instance, each woman in the study who took the oestrogen plus progestogen therapy had an increased risk of breast cancer of less than a tenth of 1 percent per year.

Study Results

Hormone replacement therapy resulted in a 26% increase in breast cancer, which caused the study to be stopped. No increase in deaths from breast cancer occurred from the combined therapy or in deaths from other causes.

• 26% increase in breast cancer

• 41% increase in strokes

• 29% increase in heart attacks

• Doubled rates of blood clots in legs and lungs

• 37% less colorectal cancer

• 34% fewer hip fractures and 24% less total fractures

Another way of looking at the results is to consider the actual risks of the treatment, rather than the relative increase. For every 10,000 women taking oestrogen plus progestogen pills:

• 38 developed breast cancer each year compared to 30 breast cancers for every 10,000 women taking placebo pills each year.

• 37 had a heart attack compared to 30 out of every 10,000 women taking placebo pills.

• 29 had a stroke each year, compared to 21 out of every 10,000 women taking placebo pills.

• 34 had blood clots in the lungs or legs, compared to 16 women out of every 10,000 women taking placebo pills.

For every 10,000 women taking oestrogen plus progestogen pills:

• 10 had a hip fracture each year, compared to 15 out of every 10,000 women taking placebo pills each year.

• 10 developed colon cancer each year, compared to 16 out of every 10,000 women taking placebo pills.

Recommendations

The new findings allow the following recommendations for combined hormone replacement therapy to be made:

Firstly, the therapy should not be continued or started to prevent heart disease. Women should consult their doctor about other methods of prevention, such as lifestyle changes, and cholesterol-lowering and blood pressure-lowering drugs.

Secondly, for osteoporosis prevention, women should consult their doctor and weigh the benefits against their personal risks for heart attack, stroke, blood clots, and breast cancer. Alternate treatments are also available to prevent osteoporosis and fractures.

Thirdly, women should keep up with their regular schedule of mammograms and breast self-examinations, along with their cervical screening tests.

Fourthly, while short-term use was not studied, women taking the therapy for relief of menopausal symptoms may reap more benefits than risks. Women should talk with their doctor about their personal risks and benefits.

Finally, women considering taking HRT for longer than five years need to discuss the risks and benefits of doing this with their doctor. Some women may feel that for them the improvements in their psychological and sexual health, and the reduction in their risk of breaking a bone, outweigh the small (in absolute terms) increase in risk of breast cancer, heart disease, and embolism. However, they should only decide this after are have been fully informed about the risks and benefits of long-term hormone replacement therapy treatment.

This article was adapted from: http://www.nhlbi.nih.gov/whi/hrtupd/index.htm