A Tough Pill To Swallow Controversy Continues To Surround HRT

The controversy surrounding hormone replacement therapy (HRT) continues unabated, according to the recent release of new studies by HRT researchers.

A recent article included in the Oct. 6, 2004 Journal of the American Medical Association (JAMA) reported that HRT has been linked to higher occurrences of venous thrombosis, a dangerous type of blood clot, among women taking the HRT combination of estrogen and progestin.

HRT is used to treat symptoms associated with menopause, including hot flashes and night sweats, and to date is the most effective treatment on the market.
The recent findings regarding blood clots, though, emerged from a closer look by researchers at the Women’s Health Initiative, a government-funded study that examined the effects of HRT on a group of post-menopausal women. The study began in the late 1990s, but was halted in 2002 after significant findings suggesting increased risk of heart attacks, stroke, and breast cancer. Now, researchers quoted in the JAMA article, led by Mary Cushman, M.D., of the University of Vermont, Colchester, say that women taking estrogen-progestin HRT are as much as two-times more likely to suffer from venous thrombosis, or as much as four-times more likely if they are overweight.

Further, the U.S. Preventive Services Task Force (USPSTF), after examining the pros and cons of HRT, chose to recommend against the routine use of estrogen and progestin HRT for chronic conditions in post-menopausal women, based on the evidence of harmful side-effects weighed against possible benefits.

“The USPSTF concluded that the harmful effects of estrogen and progestin are likely to exceed the chronic disease prevention benefits in most women,” states a summary of the USPSTF recommendations regarding HRT.

Because of negative press, prescriptions and advertising of HRT have dropped and synthetic and natural alternatives to HRT are being both researched and promoted.

Dr. Ronald Burkman, chairman of Baystate Medical Center’s Department of Obstetrics and Gynecology, said other methods, such as the use of Selective Serotonin Reuptake Inhibitors (SSRIs) – anti-depressants like Prozac – and drugs for hypertension, such as Clonidine, have also proven effective in combating menopausal and post-menopausal conditions.

However, Burkman said alternatives have yet to match the effectiveness of HRT in relieving some symptoms of menopause, and many women are opting to remain on the therapy despite new evidence of risk factors.

“There has been a 40{06cf2b9696b159f874511d23dbc893eb1ac83014175ed30550cfff22781411e5} decline in HRT prescriptions since 2002,” Burkman said. “Far fewer patients want it, but for treating hot flashes and other symptoms, nothing works better. It is my responsibility to counsel women on both the benefits and the risks.”

Some potential benefits of HRT, in addition to increased bone mineral density in women with osteoporosis and preliminary findings of a reduction in instances of colorectal cancer, include a possible reduction of the risk of dementia in post-menopausal women, according to the USPSTF.

Some additional risks, though, could include increased risk for cholecystitis (inflammation of the bladder), endometrial and ovarian cancers, and a greater risk of abnormal mammograms, due to increased breast density.

Prescribing smaller doses of HRT, or prescribing estrogen alone rather than a combination, have shown to reduce some of the risks associated with estrogen-progestin HRT, Burkman said, but the potential for dangerous effects remains.

“Reducing dosage may reduce the risk of some of these effects,” he said. “We know it will reduce instances of blood clots; all hormones can cause blood clots, like birth control pills, and we know smaller doses take away some of that risk. But as far as strokes and heart attacks, the effects of reducing dosages of HRT are still unclear.”

The Oct. 6 JAMA article also reported that venous thrombosis may occur more frequently in women using a hormone therapy that includes conjugated equine estrogen (CEE), which is derived from horses, than in women using esterified (combined) estrogens.

Some hormone combination drugs, like Premarin, manufactured by Wyeth Pharmaceuticals, are created from the urine of pregnant horses; a practice that has created headlines of its own in recent years. Issues such as an overabundance of foals are created by using pregnant mare urine (PMU) as a primary HRT ingredient, which has attracted the attention of many, including animal rights groups such as People for the Ethical Treatment of Animals (PETA).

In order to match the effectiveness of HRT and eliminate both the risk of harmful side-effects and the controversial nature of some manufacturing processes, Burkman said drug companies internationally are currently engaged in a race to find an alternative drug or therapy.

“There are hundreds of these companies trying to develop new drugs,” he said. “Now we wait, to find out which one will be the winner.”