"Efectos de dosis ultrabajas de estradiol transdermal en la densidad mineral del hueso: Un ensayo clínico seleccionado al azar."
Bruce Ettinger, MD*, Kristine E. Ensrud, MD, MPH, Robert Wallace, MD, Karen C. Johnson, MD, MPH, Steven R. Cummings, MD¶, Vladimir Yankov, MD||, Eric Vittinghoff, PhD, MPH* and Deborah Grady, MD, MPH*¶||*
From the *Division of Research, Kaiser Permanente Medical Care Program, Oakland, California; Epidemiology Clinical Research Center, University of Minnesota, and Veteran's Administration Medical Center, Minneapolis, Minnesota; Department of Epidemiology, University of Iowa, Iowa City, Iowa; Department of Preventive Medicine, University of Tennessee Health Sciences Center, Memphis, Tennessee; ¶Department of Epidemiology and Biostatistics, University of California, and Clinical Research Division, California Pacific Medical Center Research Institute, San Francisco, California; ||Ferring Pharmaceuticals, Inc, Suffern, New York; and **Department of Epidemiology and Biostatistics and Women's Health Clinical Research Center, Mount Zion Medical Center, University of California, San Francisco, California. <p OBJECTIVE:
Because small increments in levels of endogenous plasma estradiol are associated with higher postmenopausal bone mineral density, we investigated the safety and effectiveness in preventing bone loss of unopposed, very-low-dose transdermal estradiol for postmenopausal women.
METHODS:
This was a randomized, placebo-controlled, double-blind trial with 2-year follow-up at 9 United States clinical centers. The study population comprised 417 postmenopausal women, aged 6080 years, with intact uterus and bone mineral density z scores of 2.0 or higher, who were randomly assigned to receive either unopposed transdermal estradiol at 0.014 mg/d (n = 208) or placebo (n = 209). All participants received calcium and vitamin D supplementation. Lumbar spine and total hip bone mineral density change was measured by dual-energy X-ray absorptiometry; endometrial hyperplasia incidence was assessed by endometrial biopsy.
RESULTS:
Median plasma estradiol level in the estradiol group increased from 4.8 pg/mL at baseline to 8.5 pg/mL at 1 year (P < .001 versus baseline) and to 8.6 pg/mL at 2 years (P < .001 versus baseline) and was unchanged in the placebo group. Lumbar spine bone mineral density increased 2.6% in the estradiol group and 0.6% in the placebo group (between-group difference 2.0%, P < .001). Mean total hip bone mineral density increased 0.4% in the estradiol group and decreased 0.8% in the placebo group (between-group difference 1.2%, P < .001). Osteocalcin levels and bone-specific alkaline phosphatase were lower in the estradiol group than the placebo group (P < .001 each). Endometrial hyperplasia developed in 1 woman in the estradiol group but in none of the placebo group (difference in 2-year rates 0.5%, 95% confidence interval 07.3%).
CONCLUSION:
Postmenopausal treatment with low-dose, unopposed estradiol increased bone mineral density and decreased markers of bone turnover without causing endometrial hyperplasia.
Obstetrics & Gynecology 2004;104:443-451
