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Am Fam Physician. 2000;61(3):838

It is estimated that postmenopausal women lose up to 5 percent of bone mass per year. Oral estrogen therapy equivalent to 1 mg of estradiol or 0.625 mg of equine estrogens has been demonstrated to prevent bone loss, and it has been suggested that lower dosages may also be effective. Less information is available concerning estrogen delivered by transdermal formulations. Weiss and colleagues studied the effect of four dosages of estradiol delivered transdermally on bone loss in post-menopausal women.

The multicenter study enrolled women more than 40 years of age who had undergone hysterectomy or oophorectomy. All women gave a history consistent with menopausal vasomotor symptoms one to five years before the study. Menopausal status was confirmed by serum estradiol and follicle-stimulating hormone concentrations. Initial assessment also included bone mineral density and serum lipid profiles. Women with bone disease or a recent history of fractures or immobilization, and those taking hormones or drugs that affect bone metabolism were ineligible for the study. Participants were randomly assigned to receive placebo or one of four dosages (0.025, 0.05, 0.06 and 0.1 mg per day) of transdermal estradiol therapy.

All participants received daily supplementation of 1,500 mg of calcium. Initial assessment included complete medical history, physical and pelvic examination, and laboratory profile, including markers of bone metabolism. Bone mineral density was measured at the lumbar spine, radius, hip and femoral neck.

Of the 175 women enrolled, 97 (55 percent) completed the two-year study. Only 20 women withdrew because of adverse effects, mostly local skin reactions. Other women withdrew consent, were lost to follow-up or had protocol violations.

In all groups receiving active treatment, the bone mineral density of the lumbar spine increased. The increase was related to estrogen dosage. Mean increases for the 0.025-, 0.05-, 0.06- and 0.1-mg estradiol groups were 2.37, 4.09, 3.28 and 4.70 percent, respectively, at month 24. In contrast, the placebo group showed a 2.49 percent decrease. Similar results were found for bone mineral density of the total hip. The mean increases for the four treatment groups were 0.26, 2.85, 3.05 and 2.03 percent, respectively, compared with a 2.04 percent loss in the placebo group. Of women taking the 0.1-mg dosage, more than 90 percent did not lose bone at the lumbar spine, and 76 percent did not lose bone at the hip. Comparable figures for the placebo group were 29 and 38 percent.

The authors conclude that transdermal estrogen effectively prevented postmenopausal bone loss even at low dosages. They advocate use of transdermal systems to overcome some of the barriers to compliance in hormone replacement therapy.

editor's note: Until recently, only oral conjugated equine estrogens had been extensively studied in hormone replacement therapy. This and other studies provide evidence for benefit from a greater range of treatment strategies. Family physicians can now individualize therapy in dosage, type of hormone and delivery system to optimize benefit for each woman. Although the “one-size-fits-all” treatments of the old days were simple for physicians, the unacceptable rates of compliance have necessitated a change to a more individualized approach.—a.d.w.

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