Comparison between 1 year oral and transdermal oestradiol and sequential norethisterone acetate on circulating concentrations of leptin in postmenopausal women

BACKGROUND: Oral and transdermal postmenopausal hormone replacement therapy (HRT) affects lipid and glucose metabolism differently, which is of significance in the release of leptin by adipocytes. Moreover, oestrogen and progesterone can stimulate leptin secretion in women of reproductive age. Therefore, we compared the effects of oral and transdermal oestrogen plus progestin regimen on plasma leptin in 38 healthy postmenopausal women with normal body mass index (BMI), who wished to use HRT to control incapacitating climacteric symptoms. METHODS: The women were randomized to treatment with oral HRT (2 mg oestradiol on days 1--12, 2 mg oestradiol plus 1 mg norethisterone acetate (NETA) on days 13--22, and 1 mg oestradiol on days 23--28, n = 19), or with transdermal HRT (50 microg/day of oestradiol on days 1--13, and 50 microg oestradiol plus 250 microg/day NETA on days 14--28, n = 19) for 1 year. Plasma samples were collected before and at oestradiol + NETA phase after 2, 6 and 12 months treatment and were assayed for leptin. RESULTS: The baseline leptin, ranging from 3.3 to 34.9 microg/l, was significantly associated with BMI (r = 0.78, P < 0.0001 ), but showed no difference between women in oral HRT (geometric mean 13.9 microg/l, 95% confidence interval (CI) 10.1--17.6 microg/l) or transdermal HRT group (geometric mean 12.0 microg/l, 95% CI 9.7--14.3 microg/l). Neither oral nor transdermal oestradiol + NETA caused any significant changes in plasma leptin (or BMI) after 2, 6, or 12 months of treatment. CONCLUSION: Leptin is an unsuitable factor to detect oestradiol + NETA-induced metabolic changes in postmenopausal women.     

Effects of HRT on serum levels of IGF-I in postmenopausal women.

OBJECTIVES: It is thought that insulin-like growth factor-1 (IGF-I) stimulates bone formation. We aimed to determine the effects of oral and transdermal hormone replacement therapy (HRT) on serum IGF-I levels and to investigate the effects of basal IGF-I levels on the levels obtained at the end of the therapy. METHODS: Sixty-six postmenopausal women were administered either oral (n=44) or transdermal (n=22) HRT for 6 months. Serum levels of IGF-I were determined before and after HRT in all subjects. Groups were divided into two subgroups according to the median value of serum IGF-I levels (basal IGF-I levels above or below the median value). The increase of IGF-I levels after HRT were calculated (%) for all women. Mean increases of subgroups were compared. Furthermore, study groups were divided into three subgroups according to the changing of IGF-I (increase>25%, between 25% increase and 25% decrease and decrease>25%). Mean basal IGF-I levels of these three subgroups were compared. RESULTS: Mean serum levels of IGF-I before and after HRT were not significantly different in both oral and transdermal groups (P>0.05). Mean increases of IGF-I after HRT for the patients with low basal IGF-I levels, were 65% in oral and 77% in transdermal groups. However, mean increase of the patients with high basal IGF-I levels were -8 and -16% respectively. Moreover, mean level of basal IGF-I was significantly low in women who have more than a 25% increase after HRT (P<0.05). CONCLUSION: HRT seems to significantly increase serum levels of IGF-I in postmenopausal women with low basal levels of IGF-I.     

The values of urinary NTx in postmenopausal women undergoing HRT; the role of additional alendronate therapy

Objective: To determine the changes in levels of urinary NTx at the end of the 6th month of oral and transdermal hormone replacement therapy (HRT) and the effects of additional alendronate therapy for osteoporotic women. Method: Of 66 postmenopausal women 23 were treated with oral estradiol+norethisterone acetate (E+P), and 22 were treated with transdermal estradiol+norethisterone acetate. The third group consisted of 21 women with osteoporosis (bone mineral density<100 mg/cm³) and treated with oral E+P plus alendronate 10 mg/day. Result: Significant decreases of urinary NTx levels were seen after HRT in all study groups (P<0.05). But the decline of NTx levels was not different between the oral and transdermal HRT groups (P>0.05). There was no additional decrease in the levels of NTx with alendronate therapy (P>0.05) but NTx excretion diminished more in patients with high baseline levels. Conclusion: The decline of NTx at the end of the 6th month of HRT reflects the decrease of bone resorption and it is not related to the route of administration.     

Plasma and urinary sex hormones are differently related to lipids in healthy postmenopausal women

OBJECTIVE: Endogenous sex hormones can be measured in plasma and urine. We determined the extent to which these two methods provide different information on hormonal status by relating them to lipid profile in postmenopausal women. METHODS: Thirty healthy postmenopausal women collected one 24-h urine sample and a blood sample was taken. Urinary estrone (UE), plasma estrone (PE) and serum lipids were measured. Sex hormone levels were measured with specific radioimmunoassays. Linear regression analysis was used to determine associations between estrone levels and lipids. Results are presented as beta-coefficients in mmol/l per standard deviation (SD) of endogenous estrone levels, adjusted for body mass index (BMI) and smoking (95% confidence interval). A stratified analysis for obese (BMI> or =27 kg/m(2)) versus lean women was performed. RESULTS: Mean levels of endogenous sex hormones were (SD): PE, 90.1 pmol/l (37.3); and UE, 7757 pmol/24 h (2659). PE showed significant associations with HDL-cholesterol (0.18 mmol/l, 95% CI: 0.06; 0.30), triglycerides (-0.25 mmol/l, 95% CI: -0.49; -0.009) and very-low-density-lipoprotein (VLDL-cholesterol) (-0.11 mmol/l, 95% CI: -0.22; -0.003), but not with total and low-density-lipoprotein (LDL-cholesterol). UE was inversely associated with total (-0.41 mmol/l, 95% CI: -0.85; 0.02) and LDL-cholesterols (-0.42 mmol/l, 95% CI: -0.83; -0.005), but not with HDL-cholesterol, triglycerides and VLDL-cholesterol. All associations appeared to be stronger in lean women. CONCLUSION: Both plasma and UE levels appear to be associated to serum lipids in healthy postmenopausal women. However, this relation appears to be different for estrone levels in plasma and urine. Depending on the research question, either blood samples or urine samples may be preferred.     

Hormone therapy and postural balance in elderly women

OBJECTIVE: Most fractures occur in elderly individuals without osteoporosis, and more than 90% of all hip fractures are associated with a fall. It is unclear whether hormone therapy (HT) can improve postural balance when initiated in elderly women and the effect of endogenous estradiol (E2) levels. DESIGN: Forty healthy women (33 assessable), age 60 years or older, were recruited through advertising in the local media. They were randomly and blindly assigned to receive either estradiol patches (50 microg/24 h) combined with oral medroxyprogesterone acetate (2.5 mg/d) or placebo for 6 months. Postural balance was assessed as sway velocity using a force platform. RESULTS: Low serum E2 levels were associated with greater impairment of sway velocity during the study in the placebo group. After 6 months sway velocity had improved (decreased) in the HT group by 4.3% from baseline and increased in the placebo group by 6.2%. The difference was not significant (1.30 cm/s, 95% CI: -3.0 to 0.4; P = 0.13). However, among women with low serum E2 levels at baseline (less than the median, 35 pmol/L), sway velocity improved in the HT group and deteriorated in the placebo group with a difference of 23% (2.9 cm/s, 95% CI: 0.6-5.1; P = 0.013). There were similar results after adjustment for baseline sway velocity (P = 0.003) and in the intention-to-treat analysis (P = 0.023). There was also a significant interaction between the study group and baseline serum E2 levels with regard to changes in sway velocity (P = 0.014). CONCLUSIONS: In elderly women low endogenous serum E2 levels were associated with greater impairment of postural balance function during the study, whereas HT, as compared with placebo, improved postural balance in women with low serum E2 levels.     

Evaluation of estrogen receptor-β expression in the epithelium of the oral mucosa in menopausal women under hormone replacement therapy

PurposeWe aimed to evaluate the ERβ expression in the epithelium of the oral mucosa in menopausal women treated with oral, transdermal or local (vaginal) menopausal hormone therapy.Material/methodsIn this study, we included 60 women treated with oral, transdermal or vaginal menopausal hormone therapy. The study material was obtained from swabs taken from the buccal mucosa before administering HRT, and after 6 weeks, 3 months, 6 months and 12 months of therapy. We assessed estrogen receptor-β (ERβ) expression levels in subsequent swabs by immunohistochemical analysis.ResultsThe highest increase in the ERβ expression was observed after 3 months of oral and transdermal hormone therapy.ConclusionsOral and transdermal HRT may be an effective method of treatment of oral discomfort in menopausal women.     

A comparison of effects of sequential transdermal administration versus oral administration of estradiol plus norethisterone acetate on serum NO levels in postmenopausal women

AIM: To compare the effects of sequential transdermal administration versus oral administration of estradiol plus NETA on serum nitric oxide (NO) levels in postmenopausal women (PMW). MATERIALS AND METHODS: Eighty postmenopausal subjects without any prior hormone replacement therapy (HRT) usage were enrolled in this study. All participants were healthy, ambulatory, non-smoker and had similar life styles with dietary habits. HRT was given to participants according to desired HRT administration, in group A (n=50); oral estradiol hemi-hydrate (2 mg)/norethisterone acetate (1 mg), and in group B (n=30); transdermal combined patch comprising estradiol (0.05 mg) alone and estradiol (0.05 mg)/norethisterone acetate (0.25 mg), were given sequential for 12 months. Serum NO levels were studied using Total Oxide Assay Kit (Assay Designs, Inc.) according to manufacturer's instructions prior to and after 12 months from the HRT treatment. RESULTS: The mean serum NO levels prior to the HRT in groups A and B was 0.48+/-0.46 (range, 0.27-0.76 nmol/mL) nmol/mL and 0.47+/-0.48 nmol/mL (range, 0.29-0.693 nmol/mL) (p>0.05). The mean serum NO levels after the HRT in groups A and B was 0.53+/-0.33 nmol/mL (range, 0.29-2.10 nmol/mL) and 2.91+/-0.50 nmol/mL (range, 2.10-3.67 nmol/mL) (p<0.05). A significant difference was found between mean serum NO levels prior to and after the treatment in group B (p<0.05). CONCLUSIONS: Transdermal sequential combined HRT with estradiol hemi-hydrate/NETA was found to be superior to sequential combined oral HRT in increasing serum NO levels.     

The detrimental influence of functional ovarian cysts during in-vitro fertilization cycles.

Reviewing 780 in-vitro fertilization (IVF) cycles, where buserelin was commenced in the preceding luteal phase and human menopausal gonadotrophin on day 4 of the ensuing menses, 53 cycles were identified with sonolucent cysts (30-50 mm diameter). Of the latter 53 cycles, the serum oestradiol was significantly greater on day 4 in 22 cycles abandoned for poor follicular development than in 31 cycles which proceeded to oocyte retrieval (P less than 0.05). Of the 31 cycles proceeding to oocyte retrieval, nine had a day 4 serum oestradiol greater than 200 pmol/l (95th centile for day 4 oestradiol in patients without apparent cysts), and these cycles produced significantly fewer grade 1 embryos than the cycles with day 4 oestradiol levels less than or equal to 200 pmol/l (P less than 0.05). Six of the 53 cycles with cysts resulted in conception, and all of these cycles had a day 4 serum oestradiol less than 200 pmol/l. Among the 53 cycles with ovarian cysts, the serum progesterone on the day of abandonment in four cycles and on the day of human chorionic gonadotrophin administration in one non-abandoned cycle, was above the range established for 104 cycles without cysts. No significant difference was seen in day 4 serum androstenedione levels, and the day 4 serum progesterone was less than 5 nmol/l in all but one patient. Functional activity of ovarian cysts is associated with an adverse influence on IVF cycles.     

The efficacy of two dosages of a continuous combined hormone replacement regimen

OBJECTIVES: To evaluate the efficacy of a low-dose combination of estradiol (E2) and norethisterone acetate (NETA) on bone markers, lipid and bleeding profiles and menopausal symptoms. METHOD: Ninety-six healthy Chinese postmenopausal women were allocated randomly to receive 1 mg E2/0.5 mg NETA (low-dose hormone replacement therapy (HRT)) or 2 mg E2/1 mg NETA (high-dose HRT) for 6 months. RESULTS: Bone resorption markers (collagen I N-terminal telopeptides (NTX) and deoxypyridinoline (dPyr)) were significantly reduced; -66 and -32%, respectively, in high-dose HRT versus -55 and -24%, respectively, in low-dose HRT. Bone-specific alkaline phosphatase remained unchanged with either combination of hormones. Total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) levels were decreased significantly (-12 and -13%, respectively, in high-dose HRT vs. -7 and -8% in low-dose HRT). High density lipoprotein cholesterol (HDL-C) was decreased to a lesser extent in low-dose HRT and triglycerides (TG) levels remained unchanged. Both the low and high-dose HRT were effective in alleviating menopausal symptoms. After 6 months of treatment, 2% of women in the low-dose HRT were bleeding compared with 23% in the high-dose HRT. Breast pain occurred in 2% of women in low-dose HRT compared with 15% in high-dose HRT. The endometrium in the majority of the women remained normal. CONCLUSION: Menopausal symptoms were reduced effectively in postmenopausal women on either low-dose or high-dose HRT. TC, LDL-C levels and bone resorption markers were reduced in a dose-dependent manner. Low-dose HRT provided a better bleeding profile and the incidence of breast pain was low.     

Beneficial effects of hormonal replacement therapy on chromium status and glucose and lipid metabolism in postmenopausal women

OBJECTIVES: Postmenopausal women exhibit an increased incidence of cardiovascular diseases, and type 2 diabetes mellitus compared with younger women. However, women receiving hormonal replacement therapy (HRT) seem to be protected. Since chromium (Cr) functions in glucose, lipid and corticosteroid metabolism and these variables, as well as Cr status, decline with age, Cr status may be a contributing factor in the effects of hormone replacement therapy. Therefore, the objective of this study was to determine the effects of hormonal replacement therapy (HRT) on serum and urinary Cr, plasma lipids, glucose, fructosamine and the related hormonal variables, estradiol, insulin, leptin, cortisol, and DHEA-sulfate. METHODS: Forty-four healthy postmenopausal women 50-60 years old participated in the study. Eighteen were treated by combined oral hormonal replacement therapy (estradiol 2 mg per day during days 1-25 and 10 mg of dydrogesterone on days 10-25) for at least 2 years, and 26 were untreated. RESULTS: Serum Cr concentrations were significantly lower in untreated postmenopausal women than in women receiving HRT (0.070+/-0.008 vs. 0.100+/-0.008 ng/ml) whereas urinary Cr excretion was increased (0.14+/-0.02 vs. 0.07+/-0.01 ng of Cr/mg creatinine). The urinary losses of Cr were inversely correlated with plasma estradiol. Median value of urinary Cr was higher in postmenopausal women exhibiting endogenous estradiol levels below 250 pmol/l, whereas women with estradiol levels >250 pmol/l, exhibited lower Cr values. Plasma fructosamine, total and LDL cholesterol and TC/HDL ratio, which are all decreased by improved Cr nutrition, were also improved in the women receiving HRT. There were also nonsignificant decreasing trends in DHEA-sulfate (P<0.06) and cortisol (0.07). CONCLUSIONS: Chromium status, based upon blood and urinary analyses, and glucose, insulin and lipid variables were improved in postmenopausal women receiving HRT. Additional studies are needed to determine if improved Cr status due to supplemental Cr can elicit effects consistent with those of hormone replacement therapy.     

Plasma osteoprotegerin as a biochemical marker for vascular dementia and Alzheimer's disease

Elevated level of osteoprotegerin (OPG), a pleiotropic cytokine involved in bone metabolism, has been associated with coronary heart disease and higher cardiovascular mortality. Because cardiovascular disorders are recognized risk factors for dementia, the study of OPG as a disease marker in vascular dementia (VaD) and Alzheimer's disease (AD) seemed worthy of investigation. OPG concentration was determined by ELISA in an Italian cohort consisting of 39 VaD patients, 36 AD patients, and 39 non-demented controls strictly matched for age and gender. Plasma OPG levels were positively related to age in both demented and non-demented persons. OPG concentrations were significantly higher in both VaD (median: 4.75 pmol/l; interquartile range: 3.42-6.85 pmol/l; P<0.0001) and AD (median: 4.02 pmol/l; interquartile range: 3.07-4.77 pmol/l; P=0.0278) compared to non-demented controls (median: 3.24 pmol/l, interquartile range: 2.70-3.98 pmol/l). After allowance for confounding factors (age, gender and APOE epsilon4 allele), plasma OPG levels remained independently associated with the presence of VaD (OR = 2.51; 95% CI 1.46-4.32; P=0.0009) and AD (OR = 2.17; 95% CI 1.18-3.99; P=0.0126). Our study demonstrates that OPG may be regarded as a novel biomarker of dementia in the Italian population. These results further support the hypothesis that vascular factors may not only play a role in the pathogenesis of VaD but also in the pathogenesis of AD.     

Mid-cycle serum levels of endogenous LH are not associated with the likelihood of pregnancy in artificial frozen-thawed embryo transfer cycles without pituitary suppression

BACKGROUND: The aim of the present study was to evaluate the association between clinical pregnancy and serum luteinizing hormone (LH) levels, assessed after 14 days of endometrial preparation with estradiol (E(2)) in the absence of pituitary suppression during a frozen-thawed embryo transfer (FRET) cycle. METHODS: A total of 513 patients undergoing their first FRET cycle (01/99 to 11/05) participated in this prospective study. Endometrium preparation for FRET was started on cycle day 1 and continued for a fixed period of 14 days with trans-dermal E(2) patches. On day 14, serum LH, progesterone and E(2) levels were assessed. On day 15, progesterone supplementation was initiated and patients underwent embryo transfer on day 17 or day 18. The association between clinical pregnancy and LH levels was evaluated in groups of patients defined according to Tukey's Hinges percentile analysis of LH levels on day 14. In addition, robust logistic regression was performed with the dependent variable clinical pregnancy and independent variables LH, progesterone, embryos score, cycle rank and gravidity. RESULTS: Age, BMI, parity, cycle rank, embryo number, embryo score, endometrial diameter, E(2) and progesterone were not significantly different in cycles with low (0.1-8.1 IU/l; n = 132), intermediate (8.2-19.4 IU/l; n = 238) and high (20.0-78.0 IU/l; n = 143) levels of LH, respectively. Clinical pregnancy rates were not significantly different in cycles with low [12.1%, 95% confidence intervel (CI) 7.6-18.8], intermediate (13.4%, 9.7-18.4) and high levels of LH (16.1%, 11.0-23.0). Robust logistic regression analysis indicated that embryo score [Odds ratios (OR) 1.04, 95% CI 1.02-1.06, P < 0.01] was statistically significantly associated with the likelihood of clinical pregnancy achievement, but not day 14 levels of LH or progesterone, gravidity or cycle rank. CONCLUSIONS: The likelihood of clinical pregnancy is not associated with serum LH levels on day 14 of an artificial FRET cycle. Hormonal monitoring of LH levels does not yield useful information with regard to cycle management and patient prognosis, and should therefore not be conducted.     

Effects of short-term transdermal hormone replacement therapy on glycaemic control,lipid metabolism,C-reactive protein and proteinuria in postmenopausal women with type 2 diabetes or hypertension

BACKGROUND: The study was carried out to evaluate the effects of short-term transdermal hormone replacement therapy (HRT) on glycaemic control, lipid metabolism, C-reactive protein (CRP) and proteinuria in high-risk postmenopausal women. METHODS: A total of 20 well-controlled type 2 diabetic, hypertensive and 21 well-controlled glucose-tolerant, hypertensive postmenopausal women were prospectively enrolled. After 12 weeks of transdermal HRT, the changes in serum lipid sub-fractions, fasting glucose, fructosamine, glycated haemoglobin (HbA(1c)), CRP, creatinine, 24 h urine protein levels, creatinine clearance and blood pressure were evaluated. RESULTS: After 12 weeks of treatment, serum total-cholesterol and low-density cholesterols (LDL-cholesterol) appeared slightly reduced and serum triglyceride slightly elevated, although non-significantly so in both groups. The increase in HDL-cholesterol (P < 0.05) and reduction in very low density (VLDL)-cholesterol (P < 0.05) levels were significant in hypertensive patients. Elevation in the Apolipoprotein A1 (P < 0.05) and reduction in the Apolipoprotein B (P < 0.05) levels were statistically significant in all patients. HRT was associated with significant decreases in serum fasting glucose (P < 0.05) and fructosamine (P < 0.05) levels in diabetic patients. Serum HbA(1c), CRP, creatinine, 24 h urine protein levels, creatinine clearance and systolic and diastolic blood pressure did not change significantly in either group. CONCLUSIONS: There were no detrimental effects of transdermal HRT on lipid profile, glucose metabolism, CRP and urine protein levels in our well-controlled diabetic or hypertensive patients. A decision regarding HRT use should be taken on a case-by-case basis.     

Differential effects of oral conjugated equine estrogen and transdermal estrogen on atherosclerotic vascular disease risk markers and endothelial function in healthy postmenopausal women

BACKGROUND: Recent studies have revealed that HRT may increase the risk for atherosclerotic vascular disease (ASVD). METHODS: We investigated the effects of HRT via different administration routes on the markers for ASVD and endothelial function in healthy postmenopausal women. The oral HRT group (n=18) received conjugated equine estrogen 0.625 mg/day; the transdermal HRT group (n=18) received 17beta-estradiol (E2) gel 0.6 mg/day for 6 months. The control group (n=30) had no treatment for 6 months. RESULTS: The C-reactive protein (CRP) rose from 0.129+/-0.116 to 0.752+/-0.794 mg/dl (P<0.01) in the oral HRT group but remained unchanged in the transdermal HRT and control groups. The flow-mediated vasodilation (FMD) in the brachial artery was increased significantly by HRT from 6.0% before oral HRT to 14.7% after oral HRT (P<0.001) and from 5.9% before transdermal HRT to 13.9% after transdermal HRT (P=0.001). CONCLUSIONS: These data suggest that oral estrogen induces ASVD risk by increasing acute inflammation; however, transdermal estrogen avoids this untoward effect. Additionally, transdermal estrogen exerts a positive effect on endothelial function similar to that of oral estrogen. Therefore, the transdermal route might be favourable in terms of ASVD risks.     

更年期女性激素补充治疗对T细胞及白细胞介素-2水平的影响

目的 探究更年期女性内分泌和免疫功能的变化以及激素治疗后的改善情况.方法 随机选取2012年3月至2014年3月当阳市妇幼保健院收治的更年期综合征女性患者70例,给予两个月的雌激素补充治疗,观察并比较患者治疗前后血清中雌二醇(E2)、卵泡刺激素(FSH)、黄体生成素(LH)的水平以及外周血中白细胞介素-2(IL-2)水平,T淋巴细胞中CD3+、CD4+、CD8+构成比和CD4+与CD8+的比值.结果 治疗前患者血清E2、FSH、LH和IL-2水平分别为(445.21±78.62) pmol/L、(41.09±6.13) IU/L、(38.84±7.27) IU/L和(3.14±1.28) kU/L,治疗后分别为(708.65±82.76)pmol/L、(32.54±5.69) IU/L、(29.52±4.83) IU/L和(12.09±5.92) kU/L,差异均有统计学意义(P＜0.05).治疗前患者外周血中T淋巴细胞亚群中,CD3+、CD4+所占比例及CD4+与CD8+的比值分别为(41.76±7.29)％、(27.88±7.91)％和(0.91±0.27)％,治疗后分别为(60.52±9.17)％、(39.16±8.28)％和1.87±0.31,差异均有统计学意义(P＜0.05).结论 对于更年期导致的生殖内分泌功能紊乱以及免疫功能低下的女性患者,给予雌激素补充治疗可明显提高体内E2和IL-2的水平以及T淋巴细胞亚群中CD3+、CD4+所占的比例,降低FSH和LH的水平.有助于患者调节内分泌失衡状态,提高免疫力,从而避免出现由更年期引起的并发症.     

Effects of alendronate and hormone replacement therapy, alone or in combination, on bone mass in postmenopausal women with osteoporosis: a prospective, randomized study

The effectiveness of hormone replacement therapy (HRT) and alendronate, alone and in combination, was evaluated in 120 postmenopausal patients with osteoporosis with bone mineral density (BMD) measurements at least 2 SD below the mean value for young premenopausal subjects. They had no contra-indications to HRT or alendronate use and were randomized to three different treatment groups. Group I was treated with micronized 17 beta-oestradiol 2 mg and norethisterone acetate 1 mg/day per os, group II received alendronate 10 mg/day per os and group III received micronized 17 beta-oestradiol 2 mg, norethisterone acetate 1 mg/day per os and alendronate 10 mg/day per os for 1 year. Elementary calcium 1500 mg/day was supplied to patients in all three groups. Spinal and femoral neck BMD and markers of bone mineral metabolism were measured on each patient before treatment and 6 and 12 months after treatment in 95 patients. At the end of the 12th month, significant increases in spinal and femoral neck BMD were found in all groups. Increases in spinal BMD were significantly higher in patients treated with alendronate and alendronate with HRT when compared with patients treated with HRT only. No significant difference was found in femoral neck BMD changes between the groups. Significant decreases in bone resorption and markers of bone formation were observed in all groups. Alendronate was found to be more effective than HRT and could have a very beneficial effect when added to the HRT regimen in patients with postmenopausal osteoporosis. Alendronate might also be used in postmenopausal patients with osteoporosis when HRT is contra-indicated or when there is reluctance to use hormonal treatment.     

Influence of transdermal estradiol in the regulation of leptin levels of postmenopausal women: a double-blind, placebo-controlled study.

OBJECTIVE: To investigate whether the administration of transdermal estradiol is capable of modifying circulating levels of leptin. DESIGN: Forty postmenopausal women randomly received in a double-blind fashion, a transdermal patch containing either placebo or estradiol (50 microg/day). After 2 months of treatment, they were switched to the alternate treatment for another 2 months. Leptin levels were measured at the end of the placebo and estradiol administration. In a subset of 28 women an evaluation of body composition via bioelectrical impedance and an oral glucose tolerance test (OGTT; 75 g) were also performed at the end of the placebo and estradiol administration. Glucose, insulin, and leptin levels were measured in all OGTT samples. RESULTS: Leptin levels were related directly to body mass index (BMI), fat mass, and insulin, and inversely related to lean mass. In comparison to placebo, transdermal estradiol increased estradiol (from 77.8 +/- 8.4 pmol/l to 183.1 +/- 20.9 pmol/l; p < 0.0001) but did not significantly modify leptin (19.1 +/- 2.4 microg/l vs. 18.6 +/- 2 microg/l) or BMI. Estradiol did not modify fat mass or lean mass, significantly increased intracellular water (31.1 +/- 0.7% vs. 37.2 +/- 2.3%, p < 0.05), and decreased extracellular water (40.5 +/- 0.7% vs. 36.3 +/- 1.7%; p < 0.04). Leptin did not increase during OGTT, but a significant decrease, linearly related to BMI ( r = 0.519; p = 0.0189), was observed at the end of the test. CONCLUSIONS: Low doses of transdermal estradiol exert no influence on fasting leptin levels or BMI. The possibility that different doses of estradiol exert a more pronounced effect on circulating leptin needs to be addressed in comparative studies.     

Prevention of postmenopausal bone loss with exchange for short-term HRT for 1alpha-hydroxycholecalciferol

OBJECTIVE: The present study investigated bone turnover with exchange of hormone replacement therapy (HRT) by treatment with 1alpha-hydroxycholecalciferol in early postmenopausal women. METHODS: Subjects included a total of 75 postmenopausal women between 49 and 59 years of age who visited the Department of Obstetrics and Gynecology at Osaka Medical College Hospital for regular gynecological checkups and menopausal disorder, postmenopausal osteoporosis or hyperlipidemia, and were diagnosed with menopausal disorder or osteopenia. Changes in bone turnover and vertebral bone mineral density (BMD) in 28 patients who had undergone HRT; conjugated equine estrogen 0.625 mg daily and medroxyprogesterone acetate 2.5 mg daily) for at least 2 years and then switched to 1alpha-hydroxycholecalciferol (0.5 microg orally twice daily) and in 26 patients who were observed without drug administration after discontinuation of HRT were compared with those in 37 patients who continued HRT. BMD of the lumbar spine (L2-4) was determined using Dual Energy X-ray Absorptiometry. RESULTS: While we observed a significant decrease in vertebral bone mass in the HRT-no medication group at 12 months (P=0.049) and 18 months (P=0.013), there was no significant decrease in vertebral bone mass in either the continuous HRT group or the group with change of HRT to 1alpha-hydroxycholecalciferol. In the group with change of HRT to 1alpha-hydroxycholecalciferol, although urinary pyridinoline level increased significantly from the baseline level throughout the study period (P<0.05), serum propeptide of type-1 procollagen (P1CP) level also increased significantly from the baseline level throughout this period (P<0.001). Furthermore, significant increase from the baseline value (P<0.01) was observed in serum osteocalcin level at 6, 12 and 18 months. CONCLUSIONS: These results indicate that switching to 1alpha-hydroxycholecalciferol therapy after short-term HRT increased both bone resorption and bone formation, and permitted maintenance of increase in bone mass due to HRT for at least 18 months, though this switching accelerated bone turnover. This may have occurred because stimulation of bone formation induced by HRT was maintained by 1alpha-hydroxycholecalciferol, though bone turnover was slightly promoted because of withdrawal of HRT. This method was thus found to be very effective in preventing bone loss in patients who have discontinued HRT and are considered relatively contraindicated for use of estrogen.     

维生素缺乏对老年人髋部骨折的影响

目的 对比老年髋部骨折患者与老年非骨折的骨病患者维生素水平及缺乏情况,分析维生素缺乏对老年髋部骨折的影响。方法 回顾性病例对照研究。纳入2020年11月—2022年2月深圳市第二人民医院均行血清维生素水平检测的老年髋部骨折患者172例（骨折组）及老年非骨折的髋膝关节骨病患者345（非骨折组）例。骨折组患者中男50例、女122例,年龄65~97（81.0±8.2）岁;非骨折组中男89例、女256例,年龄65~90（72.1±5.9）岁。采用液相色谱串联质谱法检测血清维生素A、B1、B2、B3、B5、B6、B9、E、K1,以及25-羟基维生素D（D2和D3）的含量,将维生素水平低于正常值下限定义为相应维生素缺乏。观察指标：（1）观察骨折组与非骨折组是否缺乏维生素,并比较2组患者维生素水平的差异。（2）将标准化后的维生素水平作为自变量,骨折与否作为因变量,年龄和性别作为协变量,采用多因素logistic回归分析标准化后维生素水平对老年髋部骨折的影响。结果 （1）骨折组患者维生素A、B1、B3、B9、E缺乏情况更为严重,骨折组占比分别为62.8% （59/94）、62.4% （58/93）、19.4% （18/93）、50.0% （52/104）、14.9% （14/94）,非骨折组为20.2% （49/243）、41.2% （100/243）、5.0% （12/241）、16.3% （41/251）、4.5% （11/243）,差异均有统计学意义（χ²=56.49、12.15、15.82、43.10、10.61,P值均<0.05）。骨折组患者的血清25-羟维生素D、D3,以及维生素A、B1、B3、B5、B6、B9、E、K1水平较非骨折组明显降低,差异均有统计学意义（Z=-4.41、-2.53、-7.08、-3.43、-5.25、-2.08、-2.46、-6.80、-3.26、-7.93,P值均<0.05）;25-羟维生素D2和维生素B2水平2组差异均无统计学意义（P值均>0.05）。（2）多因素回归分析显示,维生素A[比值比（OR）=0.30,95%可信区间（CI）0.20~0.45]、维生素K1（OR=0.31,95% CI 0.21~0.46）、维生素B9（OR=0.33,95% CI 0.23~0.47）、维生素B3（OR=0.50,95% CI 0.36~0.70）、维生素B5（OR=0.50,95% CI 0.37~0.69）、维生素B1（OR=0.52,95% CI 0.38~0.72）、维生素E（OR=0.61,95% CI 0.45~0.83）、25-羟基维生素D（OR=0.70,95% CI 0.55~0.89）和维生素B6（OR=0.71,95% CI 0.54~0.95）水平的降低均会导致老年髋部骨折的风险增加（P值均<0.05）。结论 老年髋部骨折患者和老年非骨折的髋膝关节退行性骨病患者都普遍存在各种维生素缺乏,而且以25-羟基维生素D的缺乏最为严重。髋部骨折患者相对于非骨折患者的多种维生素水平更低,血清维生素A、B1、B3、B5、B6、B9、E、K1、25-羟基维生素D水平的降低会增加髋部骨折的风险。     

The influence of apo E phenotypes on the plasma triglycerides response to hormonal replacement therapy during the menopause.

OBJECTIVE: To study the influence of apo E phenotype in plasma lipids, especially in triglycerides levels, in menopausal women receiving hormonal replacement therapy (HRT). METHODS: One hundred and ten postmenopausal women were studied. Plasma total cholesterol (TC), HDL-C and triglycerides (TG) were measured before and after 3 months of HRT and the apo E phenotype was determined. According to the apo E phenotype the sample was divided into three groups: E2/E3 (n=28), E3/E3 (n=96) and E4/E3 (n=25). RESULTS: In the pre-treatment state, higher plasma levels of TC and TC/HDL-C ratio were observed in women with phenotype E3/E4 (P<0.0001 and P<0.02, respectively), while higher plasma TG levels were found in the apo E2/E3 group (P<0.0001). After HRT, women with phenotype E3/E4 showed higher levels of TC and TC/HDL-C ratio (P<0.0001 and P<0.006, respectively). The apo E2/E3 phenotype group showed increased levels of TG (P<0.0001). In the multivariant analysis the changes of TG after HRT were related to the type of treatment used (P<0.001), age (P=0.05) and the apo E phenotype (E2/E3). CONCLUSION: Women with phenotype E2/E3 have higher plasma TG levels and show a significant post HRT increase compared with the other phenotypes. Other factors with a lower impact on TG levels are age and progestagen association.