Estradiol by Ray Sahelian, M.D.

Estradiol is the most potent estrogen of a group of endogenous estrogen steroids which includes estrone and estriol. In women estradiol is responsible for growth of the breast and reproductive epithelia, maturation of long bones and development of the secondary sexual characteristics. Estradiol is produced mainly by the ovaries with secondary production by the adrenal glands and conversion of steroid precursors into estrogens in fat tissue.

Estradiol Vaginal Ring

Comparison of a contraceptive vaginal ring with an oral contraceptive suggests that the ethinyl estradiol delivery from either device is comparable. The apparent exposure of the liver to 15 mcg of ethinyl estradiol given via the vagina is similar to 30 mcg given orally. A single vaginal ring can provide contraception for about one year. The ethynil estradiol ring was designed for use in developing countries by the Population Council

The Estradiol Patch

Estradiol delivered via skin patch over two years has no harmful effect on cognitive abilities or health-related quality of life. However, longer term side effects of an estradiol patch is not known. Sometimes it takes 5, 10, or more years to discover side effects of hormones.
     A study led by researchers at the San Francisco VA Medical Center has shown that extremely low doses of estradiol had no ill effects on the cognitive abilities or general health of older women over the course of 2 years. The lead author was Kristine Yaffe, MD, chief of geriatric psychiatry at SFVAMC and associate professor of psychiatry, neurology, and epidemiology at the University of California, San Francisco. In 2004, study results from the Women's Health Initiative (WHI), a nationwide longitudinal study sponsored by the National Institutes of Health, indicated that estrogen was associated with an increased risk of dementia among women 65 and older, as well as with an increased risk of heart attack and stroke. The current study, published in the July 2006 issue of Archives of Neurology, looked specifically at the potential effects of estradiol on cognitive abilities and quality of life. A group of 417 post-menopausal women aged 60 to 80 were randomly assigned to receive a daily.014 milligram dose of either estradiol, a form of estrogen, or a placebo through a skin patch for two years. At the end of the study, there was no difference between the two groups in either cognitive abilities or health-related quality of life.
     A related study of the same group of women showed a significant increase in bone density in the women who took estradiol compared to the women who took placebo. Yaffe speculates that the differences in health and cognition outcomes between these two studies and the WHI studies could be related to three factors: dose, type of estrogen, and means of delivery. The women in the WHI studies received.625 milligrams per day of conjugated estrogen – a mixture of estrogen from several different sources – in pill form. In contrast, the women studied by Yaffe and her associates received a daily dose of estradiol – pure human estrogen – that was over 44 times smaller and delivered through a skin patch. "The different between a patch and a pill is significant because medications taken in pill form are processed through the liver before they reach the bloodstream," explains Yaffe. "It's thought that estrogen in pill form might stimulate the liver to produce substances that can lead to clotting or other adverse side effects. With a patch, you bypass the liver and go straight to the blood." Coauthors of the study are Eric Vittinghoff, PhD, of UCSF; Kristine E. Ensrud, MD, MPH, of the University of Minnesota and the Minneapolis VA Medical Center; Karen C. Johnson, MD, MPH, of the University of Tennessee Health Sciences Center; Susan Diem, MD, MPH, of UM; Vladmir Hanes, MD, of Berlex, Inc.; and Deborah Grady, MD, MPH, of SFVAMC and UCSF.
     "The results are very reassuring, because it suggests that women can use this patch without harm for two years," says Yaffe. "It would benefit their bones and might have a beneficial effect in terms of hot flashes."
     Dr. Sahelian comments: I don't understand how Dr. Yaffe can make such a claim of estradiol causing "no harm." Everybody knows it takes years to find out the side effects of hormones, particularly as estrogen or estradiol relate to breast and other cancers. In my opinion, there is some bias here. The research was funded by Berlex, Inc., with partial support from the National Institute of Aging.