Overview

Estrogen therapy is still widely recommended for short-term treatment of troublesome menopausal symptoms such as hot flashes and vaginal atrophy, although non-estrogenic vaginal lubricants can also be effective for vaginal symptoms.

Estrogen therapy is no longer advised for long-term protection against cardiovascular disease because of the negative outcome of the Women’s Health Initiative study.   However, some researchers suggest that much lower doses of estrogen given to women very soon after the onset of menopause could help protect against later cardiovascular disease, and this is being tested in clinical trials such as the Kronos Early Estrogen Prevention Study (KEEPS).  This trial is currently enrolling 720 women early in menopause for the evaluation of lower estrogen doses (0.45 mg/day oral conjugated equine estrogens or 0.05 mg/day transdermal estradiol) in combination with cyclic oral micronized progesterone (Prometrium®, 200 mg/day for 12 days per month) compared with placebo.  The researchers are looking at measures of cardiovascular health.  Completion of the study is expected in 2010. Also, the Early Versus Late Intervention Trial With Estradiol (ELITE) is enrolling 504 women either less than 6 years or 10 years or more after menopause.  They will be randomized to receive either 1 mg/day oral estradiol or placebo (with 4% vaginal progesterone gel or placebo respectively for 10 days each month in women with a uterus) and cardiovascular outcomes measured.   

Estrogens have also been prescribed for the prevention of bone loss because of the known effect of estrogen in inhibiting bone resorption.   Again, the long-term adverse effects with estrogen therapy seen in clinical trials have led to recommendations for a lower estrogen dosage.

Bioidentical estrogens given transdermally (patches or creams) can be used in much lower doses than oral estrogens. This is because they avoid the “first-pass metabolism” by the liver when drugs are given orally.  The recent study by Ho and colleagues below also demonstrates a cardiovascular protective effect of transdermal bioidentical estradiol without the damaging inflammatory effects of oral conjugated estrogens.  Atherosclerotic vascular disease is now widely thought to be a result of inflammation.

Synopsis of Bioidentical Estrogen Studies >>

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