RETHINKING HRT FOR OSTEOPOROSIS
David Hurst, MD asks: "Is Premarin (conjugated equine estrogens; CEE), at a dose of 0.3 mg daily, sufficient to benefit patients with osteoporosis?"
The latest study looking at whether low-dose oral estrogen (CEE 0.3 mg daily), alone or in combination with progestin, is as effective as standard dosing (e.g. CEE 0.625 mg or equivalent) was conducted by Heaney and colleagues (Ann Intern Med 1999 Jun 1;130(11):897-904). Using serial bone mineral density (BMD) testing, they found that low-dose estrogen in combination with continuous progestin did indeed boost or preserve bone mass in older women who also received calcium and vitamin D, compared to a placebo group taking only those supplements. Because of the study size, they couldn't comment reliably on fracture prevention, but there wasn't any difference in the incidence of vertebral fractures between the two groups during the study period. The researchers caution that their study population represented a healthy self-selected group, and that these results may not necessarily apply to a younger or early postmenopausal cohort. They also stressed that hormones need to be combined with appropriate calcium and vitamin D for optimal results. The recent data that have been in the news, however, bring into question the role of HRT in preserving bone density, treating osteoporosis and preventing fractures. The Women's Health Initiative (WHI) study on hormone replacement therapy (HRT) was stopped early due to a higher incidence of adverse events -- more strokes, heart attacks, blood clots and a higher risk of invasive breast cancer-- compared to placebo. The current message is that, in the absence of significant postmenopausal symptoms, the choice of HRT may now be less appropriate than using bone-specific agents. This is similar to the earlier recognition that treating cardiovascular risk factors and disease is best done with proven and specific agents. Taking all these issues into consideration, choosing even low-dose estrogen as an initial therapy in the older woman for bone density concerns is unlikely. But for women already on long-term HRT for appropriate reasons, consider moving to the lowest effective dose (if menopausal symptom relief is a concern), either alone or, if indicated, in combination with a bone-specific agent. The question of response can only be reliably determined on an individual basis by serial dual-energy x-ray absorptiometry (DEXA). Although bone biomarkers may hold promise for the future. LR