Effects of ultralow-dose transdermal estradiol on bone mineral density: A randomized clinical trial
ABSTRACT 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 60-80 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 0-7.3%).
Postmenopausal treatment with low-dose, unopposed estradiol increased bone mineral density and decreased markers of bone turnover without causing endometrial hyperplasia.
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ABSTRACT: To investigate the effect of transvaginal estradiol on bone mineral density and bone metabolism. One hundred and fifteen women (mean age 73.8+/-3.2 years) were randomly assigned to a 2-year open-label parallel group clinical trial and were treated with either transvaginal estradiol (7.5 microg/24h), or no estradiol. Both groups received 400 IU vitamin D and 500 mg calcium/day. The bone mineral density (BMD) was assessed in the hip and spine using DXA technique and in the heel using DXL technique. The intention to treat analysis showed that the increase in BMD in the estradiol group was significant at total hip by 0.6% (P=0.04) while the control group decreased in their BMD by 0.7%. At lumbar spine the estradiol group increased in BMD by 2.6% (P=0.011) while the control group increased by 2.2%. Bone turnover markers and PTH-levels decreased while 25-OH vitamin D levels increased in both groups, a probable effect of the calcium and vitamin D supplementation. The bone resorption marker CTx decreased more significantly in the treatment group (P=0.016). The transvaginal estradiol treatment of 7.5 microg/24h had a small but significant effect on the BMD of total hip and lumbar spine after a follow-up of 2 years.Maturitas 09/2007; 57(4):370-81. DOI:10.1016/j.maturitas.2007.03.005 · 2.86 Impact Factor
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ABSTRACT: HRT has been widely used for the relief of menopausal symptoms and the prevention and treatment of post-menopausal osteoporosis. However, following the publication of the Women's Health Initiative (WHI) and the Million Women Study (MWS), regulatory authorities issued an urgent safety restriction on HRT use in preventing post-menopausal osteoporosis, recommending that it now be considered a second-line treatment. Are such recommendations justified? Treatments for osteoporosis, in women with increased future risk for fractures but who have not yet developed the disease, should prevent all types of osteoporotic fractures. Of the available therapies, none other than HRT has been clearly demonstrated to prevent hip fractures in such women. Thus, HRT should be recommended as first-line treatment for osteoporosis prevention. Potential risks of HRT, such as increased development of breast cancer and increased thromboembolism, have long been known. The WHI showed risks in less than 0.3% of women studied, and the MWS appears to have overestimated the risk of breast cancer. Thus, no new safety issues have been identified, and the regulatory authorities may have misinterpreted the data from these recent studies. When given for the correct indications, HRT is of major benefit to many women.Human Reproduction 08/2006; 21(7):1668-71. DOI:10.1093/humrep/del043 · 4.59 Impact Factor
- Journal of Endocrinology, Metabolism and Diabetes of South Africa 08/2014; 15(1). DOI:10.1080/22201009.2010.10872224