Efficacy and safety of standard versus low-dose Femarelle (DT56a) for the treatment of menopausal symptoms.

OBJECTIVE: In a previous study treatment with a daily standard dose of Femarelle (644 mg/day) resulted in a significant elevation in bone mineral density (BMD) while a reduced dose resulted in a decrease in BMD. The aim of the current study was to examine the efficacy and safety of the two doses of Femarelle in the treatment of menopausal symptoms. MATERIALS AND METHODS: Eighty healthy postmenopausal women were randomly allocated to receive either the standard dose (SD) or low dose (LD) of Femarelle (644 mg/day vs 344 mg/day). A detailed medical history was taken on enrollment, followed by a physical examination, pelvic ultrasound, and sex hormone and lipid profiles. A detailed Kupperman index for each patient was completed. These measures were repeated every three months for 12 months. RESULTS: In both groups there was a significant reduction in the Kupperman index following 12 weeks of treatment, which was sustained throughout the 12 months of treatment (p < 0.01). Seventy-six percent of the patients in the SD group reported a decrease in vasomotor symptoms and seventy eight % in the LD group (NS). This decrease was sustained following 12 months of treatment. There was no change in TSH and sex hormone levels or endometrial thickness during the study period. CONCLUSIONS: In the current study we found that menopausal symptoms were reduced similarly by LD and SD, however for the combined treatment of menopausal symptoms and osteoporosis the standard dosage of 644 mg/day of Femarelle is needed.

Renal reabsorption of inorganic phosphorus in pregnancy in relation to the calciotropic hormones.

OBJECTIVE: To measure renal reabsorption of inorganic phosphorus and the calciotropic hormones in early and late pregnancy. DESIGN: Prospective, cross-sectional study. SETTING: Endocrine Institute at Assaf Harofeh and E. Wolfson Medical Centers; the Department of Obstetrics and Gynaecology, Sheba Medical Centre and Tel Aviv University. POPULATION: Three groups of healthy women were studied: pregnant women at the end of the first trimester (n = 20), pregnant women at the end of the third, trimester (n = 22), and nonpregnant controls (n = 27). METHODS AND MAIN OUTCOME MEASURES: The renal tubular maximal phosphorus reabsorption per decilitre of glomerular filtrate (TmP/GFR) was measured in all women. Circulating levels of intact parathyroid hormone, calcitriol (1,25-dihydroxy vitamin D3) and insulin-like growth factor I were assayed in part of the women (8-11 of each group). RESULTS: TmP/GFR was elevated in the first trimester group (mean 0.263 mmol/L) compared with controls (95% CI 0.07-0.46, P = 0.003). Third trimester values did not differ from controls. Serum calcitriol in the first trimester group was higher (mean difference 17.68 pg/mL) compared with controls (95% CI 3.89-31.47, P = 0.006) and was higher still (mean difference 20.75 pg/mL) in the third trimester group (95% CI 1.01-40.49, P = 0.042). Serum parathyroid hormone in the first trimester group was lower than in controls or the third trimester group: mean differences were 4.40 pg/mL (95% CI-1.40 to 10.15, P = 0.078) and 8.18 pg/mL (95% CI 0.51-15.85, P = 0.019) respectively. Parathyroid hormone levels correlated negatively to calcitriol levels in the combined control and first trimester groups (r = -0.54, P = 0.022) and negatively to TmP/GFR values in the combined three groups (r = -0.68, P = 0.042). First trimester levels of insulin-like growth factor I were lower than those in controls or in the third trimester: mean differences were 10.24 nmol/L (95% CI 2.05-18.43, P = 0.007) and 13.57 nmol/L (95% CI 4.23-22.91, P = 0.003), respectively. CONCLUSIONS: The dominant change in mineral metabolism in pregnancy is a rise in calcitriol which most probably is responsible for the relative suppression of parathyroid hormone and thereby for the rise in TmP/GFR in early pregnancy. All the above support the transfer of minerals to the fetus without compromising maternal bone. The significance of circulating insulin-like growth factor I remains unclear.

The effect of estrogen replacement therapy on zinc in serum and urine.

OBJECTIVE: To ascertain the influence of estrogen replacement therapy (ERT) on blood and urinary zinc in postmenopausal women. METHODS: Thirty-seven postmenopausal women aged 53.2 +/- 3.7 years were examined. All were treated with conjugated estrogens 0.625 mg and medroxyprogesterone acetate 5 mg. Zinc, magnesium, calcium, phosphate, and alkaline phosphatase levels in blood were measured before and after 6 and 12 months of treatment. Urinary excretion of zinc, magnesium, calcium, phosphate, and hydroxyproline were evaluated before and after 3, 6, and 12 months of therapy. Bone mineral density was examined before treatment and after 1.7 +/- 0.3 years of ERT. Subjects were classified by 1) initial bone mineral density values (osteoporotics less than 0.850 g/cm2) and 2) zinc excretion as elevated (greater than 600 micrograms/g creatinine). RESULTS: At baseline, the values of most markers of bone turnover were higher in the osteoporotic women (Hotelling test, P = .06). After 1 year of treatment, a higher decrease of most indices was observed in the osteoporotic patients, and no statistical difference was found between the osteoporotic and the normal groups (Hotelling test, P = .31). A consistent negative association was observed between changes in bone mineral density and urinary zinc excretion in the osteoporosis group. Estrogen replacement therapy reduced excretion of zinc, magnesium, and hydroxyproline in the elevated zinc excretion group. Zinc excretion decreased 35% after 3 months and 26% after 1 year of treatment. The serum tests, with the exception of alkaline phosphatase, showed only negligible changes during ERT. CONCLUSION: A significant decrease in zinc excretion was observed after 3 months of ERT. This change was more pronounced in women with osteoporosis and elevated zinc excretion. Because zinc excretion is almost uninfluenced by variation in diet, it may be used as an additional marker of changes in bone metabolism.