Endogenous Estrogen Levels and the Effects of Ultra-Low-Dose Transdermal Estradiol Therapy on Bone Turnover and BMD in Postmenopausal Women

Veterans Affairs Medical Center, San Francisco, California, USA.
Journal of Bone and Mineral Research (Impact Factor: 6.83). 11/2007; 22(11):1791-7. DOI: 10.1359/jbmr.070707
Source: PubMed


In a randomized controlled trial of a 0.014 mg/d transdermal estradiol patch, serum bone turnover markers decreased to a greater degree in postmenopausal women with lower versus higher endogenous estradiol levels. This suggests that the protective effects of ultra-low-dose estrogen therapy on the postmenopausal skeletal health may depend critically on women's endogenous estrogen levels before treatment.
Postmenopausal women with very low or undetectable estradiol levels have lower BMD, increased bone turnover, and increased risk of hip and vertebral fracture. We assessed whether the effects of ultra-low-dose 0.014 mg/d transdermal estradiol (Menostar; Berlex, Montvale, NJ, USA) on bone turnover and BMD are influenced by endogenous estradiol levels.
We analyzed data from postmenopausal women (mean age, 66 yr) randomized to an 0.014-mg/d transdermal estradiol patch or placebo in the ultra-low-dose transdermal estrogen (ULTRA) trial. The free estradiol index (FEI), calculated as the ratio of total estradiol (by mass spectometry) to sex hormone-binding globulin (SHBG; by immunoradiometric assay) x 100, was used to estimate bioavailable estradiol at baseline. Among the 382 women who adhered to >or=80% of study medication, we examined change in serum osteocalcin and bone-specific alkaline phosphatase levels at 12 mo and total hip and lumbar spine BMD at 24 mo in each quintile of FEI.
Compared with women in the highest quintile of FEI, those in the lowest quintile of FEI had a 26% greater reduction in bone-specific alkaline phosphatase and 15% greater reduction in osteocalcin in response to ultra-low estradiol treatment (p for trend across quintiles < 0.05). There was a trend toward greater improvement in total hip BMD (p = 0.06) but not spine BMD (p = 0.90) in those with lower versus higher FEI levels.
The beneficial effects of ultra-low-dose 0.014-mg/d transdermal estrogen therapy on skeletal health may depend critically on women's endogenous estrogen levels before treatment.

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    • "The decline in endogenous estrogen production that occurs during menopause has important implications for skeletal health because estrogen plays a major role in the development and maintenance of the human skeleton throughout the lifespan. In postmenopausal women, reduced levels of endogenous bioavailable estrogen are associated with lower bone mineral density (BMD) and higher risk for fragility fractures [4] [5] [6] [7]. The repletion of endogenous estrogen through the use of hormone therapy (HT) effectively prevents postmenopausal bone loss and reduces the risk of fragility fractures [8] [9] [10] [11] [12]. "
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    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.
    Full-text · Article · Jun 2010 · Journal of Osteoporosis
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    • "Subsequently, Jurkat cells were incubated in either 4 pg/ml or 40 pg/ml estradiol (E2) for 48 hours. Based on recent studies, the 4 pg/ml estradiol level was used to correspond to the postmenopausal levels (midpoint within the observed postmenopausal range, [44]), while 40 pg/ml estradiol represents a level associated with the mean of follicular and luteal phases of premenopausal women [45]. Cell viability was evaluated by trypan blue exclusion and all cultures utilized for this study were > 95% viable. "
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