estrone-sulfate and Osteoporosis--Postmenopausal

This study aims to assess the overall safety and potential endometrium-stimulating effects of soy isoflavone tablets consumed (3 y) by postmenopausal women and to determine endometrial thickness response to treatment among compliant women, taking into account hormone concentrations and other hypothesized modifying factors.. We randomized healthy postmenopausal women (aged 45.8-65.0 y) to placebo control or two doses (80 or 120 mg/d) of soy isoflavones at two sites. We used intent-to-treat analysis (N = 224) and compliant analysis (>95%; N = 208) to assess circulating hormone concentrations, adverse events, and endometrial thickness (via transvaginal ultrasound).. Median values for endometrial thickness (mm) declined from baseline through 36 months. Nonparametric analysis of variance for treatment differences among groups showed no differences in absolute (or percentage of change) endometrial thickness (χ(2) P ranged from 0.12 to 0.69) or in circulating hormones at any time point. A greater number of adverse events in the genitourinary system (P = 0.005) were noted in the 80 mg/day group compared with the 120 mg/day group, whereas other systems showed no treatment effects. The model predicting endometrial thickness response (using natural logarithm) to treatment among compliant women across time points was significant (P ≤ 0.0001), indicating that estrogen exposure (P = 0.0013), plasma 17β-estradiol (P = 0.0086), and alcohol intake (P = 0.023) contributed significantly to the response. Neither the 80 mg/day dose (P = 0.57) nor the 120 mg/day dose (P = 0.43) exerted an effect on endometrial thickness across time.. Our randomized controlled trial verifies the long-term overall safety of soy isoflavone tablet intake by postmenopausal women who display excellent compliance. We find no evidence of treatment effects on endometrial thickness, adverse events, or circulating hormone concentrations, most notably thyroid function, across a 3-year period.

Topics: Aged; Double-Blind Method; Endometrium; Estradiol; Estrogens; Estrone; Female; Humans; Intention to Treat Analysis; Isoflavones; Middle Aged; Osteoporosis, Postmenopausal; Sex Hormone-Binding Globulin; Soybean Proteins; Thyrotropin; Ultrasonography

Estrogen replacement therapy confers many beneficial effects to postmenopausal women, such as slowing the rate of bone loss and decreasing the risk of coronary artery disease. This multicenter, placebo-controlled study evaluated the lowest effective daily dose of estrone sulfate (0.3, 0.625, or 1.25 mg) combined with 1000 mg elemental calcium supplementation for preventing bone loss in the immediate supplementation for preventing bone loss in the immediate postmenopausal period. Spinal bone mineral density was measured using quantitative computed tomography. Compared with baseline, bone mineral density increased significantly (P less than .05) after 12 months of 0.625 mg daily (+ 1.9%) or 1.25 mg daily (+ 2.5%). The difference between the 0.625-mg and 1.25-mg doses was not statistically significant. Estrone sulfate administration (0.625 and 1.25 mg) produced significant changes in various lipid measurements at both the 6- and 12-month observation points. The prevalence rates for adverse events were comparable among the estrone sulfate groups and the placebo group. Estrone sulfate 0.625 mg daily, combined with 1000 mg elemental calcium supplementation, was the minimum effective dosage to prevent loss of spinal bone mineral density in postmenopausal women over a 12-month period.

Topics: Bone Density; Calcium Carbonate; Cholesterol; Dose-Response Relationship, Drug; Drug Therapy, Combination; Estrogen Replacement Therapy; Estrogens, Conjugated (USP); Estrone; Female; Humans; Middle Aged; Osteoporosis, Postmenopausal