The Ups and Downs of Hormone Replacement Therapy

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Before menopause, two hormones are produced in a woman's ovaries: (1) estrogen to regulate the monthly menstrual cycle and secondary sexual characteristics, and (2) progesterone to prepare the uterus for possible pregnancy. As a woman approaches menopause, usually around age 50, her body ceases to produce adequate levels of these hormones, and changes take place.

Many women have been treated with hormone replacement therapy (HRT). HRT is synthetic estrogen and progesterone (progestin) that is designed to replenish hormone levels and to reduce the symptoms of menopause. A lack of estrogen may cause hot flashes, vaginal dryness, sleep disturbances, and other bothersome quality-of-life disturbances.

Much controversy has occurred over the safety and effectiveness of these treatments. Early studies showed that HRT also prevented osteoporosis, heart disease, short-term memory loss, depression, and other postmenopausal conditions, but recent information has shed some doubt.

HRT has proved to be a highly effective treatment for menopausal symptoms and osteoporosis, but evidence exists that shows a link between HRT and an increased risk of breast cancer.

A treatment of estrogen alone has been shown to prevent heart disease in women, but without progestin to balance the hormonal levels, the tissue lining of the uterus becomes overstimulated (hyperplasia), and may lead to endometrial cancer. Progestin can counteract these risks, but it can also cause problems of its own.

Heart disease is the leading cause of death among postmenopausal women. A woman's risk of developing heart disease increases significantly during menopause. Past studies have shown hope that HRT can prevent heart disease, although conflicting results show no clear evidence either way. Some studies show that HRT may prevent spasm of the arteries that deliver blood and oxygen to the heart and that it can lower the amount of proteins that can cause harmful clots.

The National Institutes of Health (NIH) recently halted a large HRT study because the scheduled treatment of an estrogen/progestin dose was found to cause eight cases of invasive breast cancer for every 10,000 women receiving HRT, a 26 percent increased risk over women who did not take HRT. The NIH found that for every 10,000 women who took combined HRT, seven were more likely to have a heart attack, eight were more likely to have a stroke, and 18 were more likely to have blood clots, including eight women with pulmonary clots.

Osteoporosis is a common degenerative bone disease in women over 50 years of age. If HRT is taken during the first five years of menopause, it can be an effective treatment. HRT works as a preventative measure against osteoporosis only for as long as the woman receives treatment. Protection is lost once HRT is discontinued. The Women's Health Initiative (WHI) released a study that showed women had 34 percent fewer hip fractures and 24 percent fewer fractures overall while they took HRT, compared with those who did not take it. HRT, however, was shown to be ineffective for women above the age of 75 to 80. Supplemental calcium and vitamin D may be recommended for prevention and treatment of bone mass loss.

Alzheimer's disease is a degenerative condition characterized by confusion, memory loss, restlessness, perception difficulties, speech problems, and paranoia. There is currently no cure for this disease, but some researchers had thought that HRT might delay the development of the disease. No concrete evidence has been demonstrated.

Side effects of HRT vary among women, but the most common are boating, nausea, breast tenderness, vaginal bleeding, fluid retention, weight gain, depression, and migraine headaches.

There have been reports that HRT might increase the risk of a recurrence of endometrial cancer in women with a previous history of cancer, but there is no evidence to prove this.

There are also conflicting views on whether HRT increases the risk of blood clots in the veins. Women who have had phlebitis (vein inflammation) from either veins that are close to the skin or in the deep leg veins are not at an increased risk of blood clotting, but it is likely that HRT may cause increased clotting in previous clots associated with estrogen.

The most controversial potential side effect of HRT is the increased risk of breast cancer. Some studies have claimed that the increase in risk is minimal, whereas others claim that it is significant. There is an emerging consensus that short-term HRT (less than five years) does not significantly increase the breast cancer risk, but few long-term HRT studies have been completed.

A study in the Breast Cancer Detection Demonstration Project, a national breast cancer screening program, found that the risk of breast cancer increased by nearly 9 percent in women who received combined HRT, but those data have been repeated and misinterpreted in medical journals and in the media. Some people have claimed that the 9 percent increase was cumulative, meaning that in 10 years of HRT, a woman's risk of developing breast cancer would be 90 percent greater than someone who was not treated. This is an inaccurate understanding of the results, but no indisputable proof of HRT's safety has been shown.

An American Cancer Society study of more than 200,000 women suggests that use of HRT for more than 10 years might increase the risk of ovarian cancer. Researchers found that treatment with estrogen alone for more than 10 years might increases the risk of death from ovarian cancer. The study did not include any women who received combination HRT, so further research is needed before specific claims can be made.

Women are advised to seek advice from their physicians or healthcare professionals before beginning HRT.

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