Percutaneous estrogen in prevention of early postmenopausal bone loss in Chinese women

OBJECTIVE: To identify the optimal dosage of 17beta-estradiol gel + oral progestin for preventing bone loss in postmenopausal Chinese women. METHODS: A 3-year open label, randomized, prospective clinical trial was conducted. Sixty healthy women who had been postmenopausal for 1 to 5 years were recruited and divided into following 4 groups: group 1, percutaneous gel 17beta-estradiol (E(2)) 1.5 mg/d plus micronized progesterone (MP) 100 mg/d; group 2, percutaneous gel 17beta-estradiol (E(2)) 1.5 mg/d plus medroxyprogesterone acetate (MPA) 2 mg/d; group 3, percutaneous gel 17beta-estradiol (E(2)) 0.75 mg/d plus micronized progesterone (MP) 100 mg/d; and group 4, percutaneous gel 17beta-estradiol (E(2)) 0.75 mg/d plus medroxyprogesterone acetate (MPA) 2 mg/d. Estrogen and progestin were given continuously for 25 days per month. Bone mineral density (BMD) was measured using quantitative computed tomography (QCT) for trabecular bone of L2-5 and dual energy X-ray absorptiometry (DEXA) for L2-4 and hip 5 times during the trial at baseline and at the 6-, 12-, 18-, 24- and 36-month visits. RESULTS: Fifty-nine patients (98.3%, 59/60) stayed in the study for 1 year, 56 patients (93.3%, 56/60) for 2 years, and 51 (85%, 51/50) for 3 years. On average, menopausal symptoms were relieved by 80% after 6 months of treatment. By the 24th month, the mean increase in BMD ranged from 4.3% to 7.5% in trabecular bone; and by the 36th month, it ranged from 4.2% to 6.2% in L2-4 and 1.61% to 3.77% in the neck. There were significant difference after treatment (P 0.05) was found in improvement of symptoms, levels of bone markers or BMD. CONCLUSION: A daily dose of estradiol gel, either 0.75 mg or 1.5 mg, is effective in preventing early postmenopausal bone loss and relieving menopausal symptoms. After 3-year treatment, spinal BMD could increase steadily, so does hip BMD, especially in the first 2 years.

Menopausal depression:comparison of hormone replacement therapy and hormone replacement therapy plus fluoxetine

BACKGROUND: To compare the efficacy and safety of hormone replacement therapy (HRT) combined with fluoxetine, with HRT alone, in post-menopausal women suffering from depression. METHODS: A randomized, open-label, parallel trial was applied. HRT was administered to all patients for 2 cycles, with 14 days of estrogen therapy and 14 days of estrogen plus progesterone. Patients who were randomly assigned to the HRT plus fluoxetine group were given fluoxetine in combination with HRT. Hamilton Depression Rating Scale (HAMD), Kupperman Menopausal Index (KMI), and Clinical Global Impressions scale were used to measure the efficacy. RESULTS: One hundred and twenty-three post-menopausal patients with depression were enrolled in the study. Among them, 120 had at least one post-treatment visit and entered into the statistical analysis. The mean total HAMD scores were significantly lower, and the percentages of HAMD score reductions were higher in the HRT plus fluoxetine Group compared with the HRT Group, after at least 3 weeks of treatment, with an average difference of 5 points at the endpoint. The Clinical Global Impression-Severity and Clinical Global Impression-Improvement scores were significantly different in the 2 groups, in favor of the combination therapy. The mean total KMI was significantly lower in the Combination Group compared with the HRT Group, after at least 6 weeks of treatment, with an average 4.5-point difference between the groups. No statistically significant differences were found in most of the adverse events reported in the Combination Group compared with the HRT group, with the exception of 3 symptoms, i.e., dry mouth, loss of appetite, and abdominal distention. They were mild to moderate in severity. Two patients in the HRT group, but none in the combination group, dropped out due to adverse events. CONCLUSION: HRT plus fluoxetine therapy was effective in the treatment of menopausal depression with a satisfactory safety profile.

Effects of Transdermal Estrogen Therapy on Expressions of Estrogen Receptors and T-lymphocyte Apoptosis in Surgically Menopausal Women

Studies have demonstrated estrogen replacement therapy can improve the life quality of surgically menopausal women. However, the mechanisms in this process remain poorly defined. Here we show the effect of transdermal estrogen therapy on expressions of estrogen receptors and T-lymphocyte apoptosis in surgically postmenopausal women. Fifteen surgically menopausal women, 15 naturally menopausal women and 15 young women were chosen in our studies. Peripheral vein blood was collected and serum E2 and FSH levels were assessed using ACCESS. T-lymphocyte apoptosis and the expressions of Fas, FasL and ER subtypes α and β were determined. The serum E2 levels of surgically menopausal woman were significantly higher, and the ＂Improved Kupperman Index＂ and the scores of ＂Menopause Specific Quality of Life Questionnaire＂ in surgically menopausal women were significantly low after ERT. The rates of T-lymphocyte apoptosis and FasL expression in surgically menopausal women were decreased after ERT, but the difference was not significant. The expressions of ERa and ERβ in two menopausal groups were significantly lower than those of the young group. They were both significantly up-regulated after 3 months of ERT. Transdermal ERT could significantly upregulate the serum E2 level, could improve menopausal symptoms and life quality of surgically menopausal women and upregulate ERa and ERβ expressions on T lymphocytes, especially ERp. Thus, the low dose of transdermal ERT may have a protective effect on menopausal women＇s immune function and aging.

Impact of ovariectomy and estradiol-17β(E_(2))replacement on the brain steroid levels of the Indian stinging catfish Heteropneustes fossilis

In the present study,effects of ovariectomy(Ovx)and estradiol-17β(E2)replacement on the brain steroid levels were investigated in the resting and prespawning phases of the female catfish Heteropneustes fossilis.The study showed that Ovx resulted in significant decreases in plasma levels of estradiol-17β(E2)and its precursors,and the effect varied with the reproductive stage and duration.Our study showed that E2 supplementation reversed the effect of Ovx in 3-week Ovx fish group,either restored or increased according to the dose.In contrast,E2 levels increased in the brain after Ovx in the resting stage and produced a biphasic effect of significant decreases on week 1 and 2,and significant increases on week 3,4 and 5 in the pre-spawning stage.The brain E2 levels significantly inhibited in E2 supplementation groups.The testosterone(T)levels showed biphasic effects,an initial decrease(up to 3 weeks Ovx)and an increase later(week 4,5)in the resting stage.In the pre-spawning stage,the T levels increased significantly after Ovx.The E2 supplementation significantly inhibited the T levels,more severely in the low dose group in the resting and pre-spawning stages.Brain 17-hydroxyprogesterone(17-OHP4)levels increased(week 1,2,3)but decreased on week 4 and 5 of Ovx in the resting stage and increased throughout Ovx in the pre-spawning stage except in the 5th week(though compared to other steroids,level was very low;almost negligible).The E2 replacement significantly decreased the steroid levels further down compared to the Ovx control group.Brain progesterone(P4)and pregnenolone(P5)levels decreased initially(week 1 and 2 Ovx)and recovered later.The E2 replacement significantly decreased P4 levels in the Ovx fish in the pre-spawning stage and in the lower dose group in the resting stage.The P5 levels remained inhibited after the E2 supplementation in the resting stage but unchanged or increased it in the pre-spawning stage.Brain cortisol(F)levels were inhibited initially(1 and 2 weeks and later increased after OVX in the resting stage.In the pre-spawning stage,the F levels increased in the week 1,2 and 3 of Ovx and decreased in the 4th and 5th weeks.The E2 supplementation inhibited the cortisol(F)levels in both phases.The results show that ovarian steroids influence neurosteroidogenesis in a reproductive stage-dependent manner.