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Bioequivalent estradiol may be safer than conjugated equine estrogens

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Friday, October 4, 2013. The journal JAMA Internal Medicine published an article on October 30, 2013 which reported a lower risk of venous blood clots in association with the use of orally administered bioequivalent estradiol in comparison with conjugated equine estrogens (CEEs, marketed under the name of Premarin®) for the treatment of menopausal symptoms.

"Pharmaceutical estrogens are molecularly distinct," write authors Nicholas L. Smith, PhD and his colleagues. "Conjugated equine estrogens are manufactured from the urine of pregnant mares and contain 10 known biologically active estrogen compounds, as well as others that have yet to be described. The primary compounds are estrone and equilin sulfate. Estradiol is a 'natural' or 'bioequivalent' estrogen."

The investigation included 384 postmenopausal women who were enrolled in the Heart and Vascular Health Study, a case-control study of cardiovascular events involving subjects between the ages of 30 to 79 years. Subjects in the current study used oral CEEs or estradiol from 2003 to 2009. Sixty-eight women who had experienced venous thrombosis (deep vein thrombosis or pulmonary embolism), 67 women who had undergone a heart attack and 48 subjects who had an ischemic stroke were matched for age and other factors with 201 control subjects.

Among women who used CEEs, the risk of experiencing venous thrombosis was more than double that of subjects who used estradiol. Conjugated equine estrogen users also experienced a greater risk of heart attack which did not reach statistical significance. Analysis of plasma samples from 140 control subjects also indicated stronger propensity for blood clotting among those who used CEEs.

"Although oral estrogens are effective for managing menopause symptoms, not enough is known about the cardiovascular safety of different oral hormone therapy products relative to each other," noted Dr Smith, who is a professor of epidemiology at the University of Washington School of Public Health in Seattle. "If our results are confirmed, women seeking menopausal treatment and their providers would find this information helpful when selecting a drug."

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Avoidance of estrogen replacement by hysterectomized women estimated to result in lost lives

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In an article published on July 18, 2013 in the American Journal of Public Health Yale researchers calculate that nearly 50,000 unnecessary deaths have occurred among women between the ages of 50 and 69 years who had a hysterectomy yet had not availed themselves of estrogen replacement therapy due to fear of its adverse risks.

Findings from the Women's Health Initiative (WHI) study published in 2002 indicated a greater risk of breast cancer and coronary heart disease among women who used a combination of estrogen and progestin as menopausal hormone replacement therapy. Progestin is routinely combined with estrogen to protect against increased proliferation of the uterine lining that can result from the administration of unopposed estrogen. However, in the WHI study arm that investigated the use of estrogen alone (which is prescribed without progestin to women who have had hysterectomies) there was a decrease in the risk of breast cancer and heart disease, and a lower rate of mortality in comparison with women who received a placebo. Nevertheless, the backlash from the widely publicized findings of the first arm of the study frightened many women away from any kind of hormone replacement therapy, including estrogen alone or bioidentical hormones that have been associated with fewer risks. "Sadly, the media, women, and health care providers did not appreciate the difference between the two kinds of hormone therapy," commented lead researcher Philip Sarrel, MD. "As a result, the use of all forms of FDA-approved menopausal hormone therapy declined precipitously."

"Estrogen avoidance has resulted in a real cost in women's lives every year for the last 10 years—and the deaths continue," he added. "We hope this article will stir an overdue debate and raise consciousness about the health benefits of estrogen-only therapy for women in their 50s with no uterus."

Life Extension Magazine® October 2013 Issue Now Online!

Life Extension Magazine October, 2013 

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