Hormone Replacement Therapy: Patch or Pill?

Hormone replacement therapy (HRT) is regularly prescribed to women for the relief of hot flashes, night sweats, and other symptoms of menopause. Currently, around 1 million women are taking HRT, with an estimated three out of four using the pill form. Previous studies have shown HRT to be associated with an increased risk of coronary heart disease, breast cancer, and venous thromboembolism (VTE), a potentially fatal blood clot in the vein. While these studies spurred millions of women to abandon HRT drugs, they did not access the risk-benefit ratio for women or whether the risk varies with the type of therapy.

However, French researchers recently completed an investigation into the risk of blood clots from two different forms of HRT; the pill and the patch. Dr. Pierre-Yves Scarabin, director of research at the National Institute of Health and Medical Research, and colleagues reviewed data from eight observational studies and nine randomized controlled trials on HRT and VTE and found that women who take oral HRT have double the risk of blood clots compared to women who use skin patches, and 2.5 times the risk of women taking no estrogen. They also found the risk to be significantly higher during the first year of treatment and in women who were overweight or predisposed toward developing blood clots. The increased risk translates into an additional 11 cases per 10,000 women per year based on combination HRT, or two extra cases per 10,000 for estrogen-only HRT, according to the study authors. Women who stopped taking HRT saw their risk return to normal.

The researchers said the reason for the risk difference between oral therapy and the patch might be due to the way estrogen is absorbed into the blood stream. When taken orally, estrogen enters through the digestive system and is processed by the liver. This process might impair the balance between clotting and anti-clotting factors in the blood. The authors added that since most of the data came from existing observational trials, the findings should be interpreted with caution.

Other experts, such as Dr. Suzanne Steinbaum, director of women and heart disease at Lenox Hill Hospital in New York City, agree. "It's observational and very interesting, but clearly more studies need to be done. Maybe this opens the door for a way to give hormones more safely to those who need it," she said.

Dr. John Stevenson, chairman of Women's Health Concern, which provides advice to women on menopause, said the increased risk of VTE for HRT users is well recognized. "It is linked to the estrogen and is dose-dependent, so the risk can be reduced by using lower doses or non-oral therapy such as patches."

Still others see the study as flawed. The International Menopause Society (IMS) released a statement just days before the French study was published in the online issue of the British Medical Journal stating that for women in their 50's, HRT was safe and effective and did not raise the risk of heart disease. The panel also concluded that HRT had a ‘minimal' impact on the risk of breast cancer. "The IMS expert group concluded that the only remaining risk of HRT in the age group 50-59 years was that of a thromboembolic event-a blood clot," said Dr. David Sturdee, British gynecologist and president of the IMS. "This very slightly increased risk of a blood clot should not discourage healthy women from using HRT if it is needed."