«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.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.
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.
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%).
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