HT for Women With Very Low Estradiol


MONTREAL — Postmenopausal women with extremely low levels of bioavailable estradiol may benefit most from the bone-building effects of ultralow-dose hormone therapy, according to a study presented here at the annual meeting of the International Bone and Mineral Society.

It remains unclear, however, whether these women are also more vulnerable to the negative effects of hormone therapy. Although estrogen therapy has been shown to suppress bone turnover in postmenopausal women, the Women's Health Study also revealed in 2002 that it may increase cardiovascular risk. Experts are therefore exploring the possibility that a dose of estrogen exists, at least for some women, that is high enough to improve bone parameters but too low to affect cardiovascular risk.

Dr. Alison Huang, of the University of California, San Francisco, and colleagues explored whether an ultralow dose of estradiol—only 0.014 mg/day delivered transdermally—could be of benefit to postmenopausal women with very low or even undetectable estradiol levels. This group of patients was considered to have a high likelihood of benefiting because, as a group, they have a lower bone mineral density (BMD), increased bone turnover, and are at an increased risk for hip and vertebral fractures.

For the trial, 417 postmenopausal women were randomized to a 0.014- mg/day transdermal estradiol patch or to placebo for 24 months. Bioavailable estradiol levels in these women were calculated as the ratio of total estradiol to sex hormone-binding globulin.

The investigators measured the women's levels of serum osteocalcin and bone-specific alkaline phosphatase (BSAP), both markers of bone turnover, at 12 months. They also measured total hip and lumbar spine BMD at 24 months in women who adhered at least 80% to the study protocol.

Women in the lowest quintile of bioavailable estradiol had significantly greater reductions in osteocalcin and BSAP than women in the highest quintile of bioavailable estrogen in response to therapy. In women in the lowest quintile, there was also a trend toward greater improvement in total hip BMD, compared with women in the highest quintile. There was no evident impact of treatment on spine BMD.

On the basis of these results, the authors concluded that “measurement of bioavailable estradiol levels identifies women for whom the ultralow-dose 0.014-mg/day transdermal estrogen therapy may have significant reductions in bone turnover.”

During a press conference, however, Dr. Huang warned that it is still not clear whether the very women who appear to have most to gain from estradiol therapy—those with very low baseline bioavailable estradiol levels—may also have most to lose. That is, these women may be most vulnerable to the effects of hormone therapy on cardiovascular health.

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