Effects of Ultralow-Dose Transdermal Estradiol on Bone Mineral Density: A Randomized Clinical Trial
University of California, San Francisco, San Francisco, California, United States Obstetrics and Gynecology
(Impact Factor: 5.18).
10/2004; 104(3):443-51. DOI: 10.1097/01.AOG.0000137833.43248.79
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.
Available from: PubMed Central
- "Oral estrogen is known to decrease systemic insulin-like growth factor 1, while transdermal formulations maintain or increase concentrations of this growth factor.61,130 Transdermal estrogen replacement may be more effective than OCPs in maintaining or increasing BMD and preventing future fracture risk, as has been demonstrated in postmenopausal women.38,107,128 Because research on transdermal estrogen has been performed mainly in postmenopausal women and not in young amenorrheic athletes, further research is needed to determine its utility as a treatment option in the triad. "
[Show abstract] [Hide abstract]
ABSTRACT: The female athlete triad (the triad) is an interrelationship of menstrual dysfunction, low energy availability (with or without an eating disorder), and decreased bone mineral density; it is relatively common among young women participating in sports. Diagnosis and treatment of this potentially serious condition is complicated and often requires an interdisciplinary team.
Articles from 1981 to present found on PubMed were selected for review of major components of the female athlete triad as well as strategies for diagnosis and treatment of the conditions.
The main goal in treatment of young female athletes with the triad is a natural return of menses as well as enhancement of bone mineral density. While no specific drug intervention has been shown to consistently improve bone mineral density in this patient population, maximizing energy availability and optimizing vitamin D and calcium intake are recommended.
Treatment requires a multidisciplinary approach involving health care professionals as well as coaches and family members. Prevention of this condition is important to minimize complications of the female athlete triad.
07/2012; 4(4):302-11. DOI:10.1177/1941738112439685
Available from: Wendy E Ward
- "Results from a number of trials have shown that lower doses of HT are effective in improving BMD in the hip and lumbar spine (Table 2) [39–47]. In a substudy (n = 822) of the Women's Health, Osteoporosis, Progestin, Estrogen (HOPE) trial, standard and lower doses of orally administered CEE alone or in combination with MPA resulted in significant improvements from baseline (1.33–3.46%) in spine and hip BMD, as well as biochemical markers of bone turnover in healthy postmenopausal women within 4 years since the onset of menopause . "
[Show abstract] [Hide abstract]
ABSTRACT: The rapid decline in endogenous estrogen production that occurs during menopause is associated with significant bone loss and increased risk for fragility fracture. While hormone therapy (HT) is an effective means to re-establish endogenous estrogen levels and reduce the risk of future fracture, its use can be accompanied by undesirable side effects such as stroke and breast cancer. In this paper, we revisit the issue of whether HT can be both safe and effective for the prevention of postmenopausal bone loss by examining standard and alternative doses and formulations of HT. The aim of this paper is to continue the dialogue regarding the benefits and controversies of HT with the goal of encouraging the dissemination of-up-to date evidence that may influence how HT is viewed and prescribed.
Journal of Osteoporosis 06/2010; 2010:708931. DOI:10.4061/2010/708931
Available from: Lee P Shulman
- "Transdermal estrogen therapies have long been shown to be effective in maintaining or increasing bone mineral density among menopausal women (Samsioe 2004). However, the study by Ettinger and colleagues (2004) showing beneficial bone mineral density effects of an “ultralow-dose” transdermal estradiol patch provides important information to women and clinicians considering osteoporotic preventive and therapeutic options. Ettinger and colleagues were able to show in this randomized, placebo-controlled trial that a transdermal patch delivering 0.014 mg/d, did not impact vasomotor symptomatology but did increase lumbar spine bone mineral density by 2.6% versus 0.6 in the placebo group (p < 0.001) and did increase total hip bone mineral density by 0.4% compared to a 0.8% reduction among women in the placebo group (p < 0.001). "
[Show abstract] [Hide abstract]
ABSTRACT: The clinical aftermath of the reporting of the initial findings of the Women's Health Initiative (WHI) in 2002 was a profound reduction in the use of hormone therapies by menopausal women. This reduction led to a well documented increase in vasomotor symptoms and vaginal atrophy among those women who discontinued their hormone regimens. However, another adverse impact among these women, as well as many other menopausal women, is the well recognized increased likelihood of osteoporosis resulting from the decline in circulating estradiol levels associated with natural and surgical menopause. Although the use ofnon-hormonal drugs such as bisphosphonates has been shown to reduce the risk of fracture in women with osteoporosis, bisphosphonates have not been shown to reduce the risk of fracture in non-osteoporotic women. Indeed, only oral estrogen (as demonstrated in the WHI studies) has been shown to reduce the risk of fracture in osteoporotic and non-osteoporotic women. As non-oral hormone therapies have been shown to be as effective in treating vasomotor symptoms and vulvovaginal atrophy and to have a different (and perhaps more beneficial) physiological effect than oral regimens, it behooves us to assess the impact of non-oral hormone regimens on bone mineral density and fracture risk. Although there are no clinical trials that primarily assess the impact of non-oral regimens on fracture risk in menopausal women, numerous studies are consistent in demonstrating the positive impact of non-oral regimens in maintaining and increasing bone mineral density among users, even for those women using estrogen doses that are considered to be "too low" to have a beneficial impact on other menopausal symptoms.
Clinical Interventions in Aging 02/2008; 3(1):51-4. · 2.08 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.