Ultra-Low-Dose Estradiol Patch Stops Bone Turnover, Increases Bone Density

Peggy Peck

May 04, 2004

May 4, 2004 (Philadelphia) — An ultra-low-dose transdermal estradiol patch appears to significantly reduce bone turnover and increase bone mineral density (BMD), according to results presented here at the 52nd annual clinical meeting of the American College of Obstetricians and Gynecologists.

Lead investigator Bruce Ettinger, MD, from Kaiser Permanente Medical Program in Oakland, California, told Medscape that the study results "indicate the efficacy of using estradiol to produce age-appropriate levels of estrogen rather than replacing to achieve estrogen levels similar to those in young women." He said a "normal" age-appropriate circulating estrogen level for postmenopausal women is "about 10 pg/mL." The patch dose is "roughly one fourth of the standard 0.625-mg dose usually prescribed for menopause symptoms."

Dr. Ettinger's study won the First Prize Paper award at the meeting.

The U.S. Food and Drug Administration is expected to approve the patch, which is made by Berlex, perhaps as soon as next month, said Dr. Ettinger, who is also a clinical professor at the University of California in San Francisco.

In the two-year study, women who were randomized to receive unopposed transdermal estradiol E2 (TE2) increased circulating estradiol levels by about "5 to 7 pg/mL, with a median estradiol of 8.9 pg/mL at 12 months and a median estradiol of 9.6 pg/mL at 24 months," Dr. Ettinger said.

That minimal increase translated into a "3% increase in BMD at the spine compared to placebo and a 1.5% increase at the hip compared to placebo." In general women with the lowest baseline estradiol "had the greatest benefit, so there does appear to be a dose effect." Overall bone turnover was reduced by 29%, he said.

Moreover, the positive effect on bone was achieved without causing endometrial proliferation in most cases. "Only about 2% of women had evidence of proliferation, thus it appears that this dose is safe to give unopposed," Dr. Ettinger said.

The study enrolled 417 postmenopausal women aged 60 to 80 years with an intact uterus and a BMD Z-score of -2.0 or better. The women were randomized to the TE2 patch (14 µg/day) or placebo. All women received 800 mg calcium and 400 IU vitamin D daily.

"This is a good study," Gerard Nahum, MD, FACOG, associate professor at Duke University College of Medicine, told Medscape. He said the paper "confirms what we thought all along — a little bit of estrogen goes a long way." Dr. Nahum was not involved in the study, but he is a member of ACOG's program committee.

He added that he was especially pleased that there was no evidence of endometrial "proliferation because we know from the evidence of the Women's Health Initiative that progestins themselves are not good, so if one can get by with delivering small amounts of unopposed estrogen it is preferable."

According to Dr. Ettinger, no adverse events were associated with the patch. Although he said the study did not evaluate deep vein thrombosis or other cardiovascular risks, he was cautiously optimistic about the cardiovascular profile of the patch. He noted, for example, that "there were about twice as many cardiovascular events in the placebo group as in the active treatment arm." But he pointed out that "the study population is too small — roughly 200 people for two years — to draw any conclusions."

Women receiving active treatment "were about three times as likely to have vaginal discharge, which suggests that the uterus was less atrophic," Dr. Ettinger said. He added that there are no data on the efficacy of the patch for relief of menopause symptoms.

ACOG 52nd Annual Clinical Meeting: Abstract 6S. Presented May 3, 2004.

Reviewed by Charlotte E. Grayson, MD


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