Change in body weight after hormone replacement therapy in postmenopausal women is dependent on basal circulating leptin

Objective: To address the effect of leptin in the modulation of change in body weight after hormone replacement therapy (HRT), we prospectively examined the responses of body weight and serum leptin after estrogen–progestin replacement in postmenopausal women. Patients: Subjects consisted of 63 postmenopausal women aged 54–82 years on HRT for osteoporosis. Design: Thirty three of the subjects received 0.3 mg of conjugated equine estrogen (CEE) (group 1) while 30 were on 0.625 mg of CEE daily (group 2). All subjects also took 5 mg of medrogestone acetate and 750 mg elemental calcium supplement daily. Measurements: Fasting serum leptin was measured by RIA at baseline, 1 and 3 months after treatment. Data were expressed as mean±S.E.M. Results: Serum leptin was highly related to body weight both at baseline (r=0.40, P<0.001) and after 3 months of HRT (r=0.42, P<0.001). When divided the subjects into three equal groups according to baseline leptin levels, it was found that serum leptin significantly decreased in subjects with high baseline leptin at 3 months (−9.4±5.7%, P<0.05) while it increased in subjects whose baseline leptin levels were in the lowest tertile at 1 month (33.2±8.3%, P<0.001) and 3 month (27.8±8.3%, P<0.01). In regards to body weight, those with leptin in the highest tertile demonstrated a reduction of body weight at 3 (−1.9±0.6%, P<0.05) and 12 months (−3.2±0.5%, P<0.05) after HRT while those whose serum leptin levels were in the lowest and middle tertiles did not demonstrate change in body weight. By repeated measured analysis of variance, it was found that the decrease in body weight in subjects with high serum leptin was independent of the doses of estrogen. Conclusion: Postmenopausal hormone replacement does not cause weight gain. However, it results in a small reduction in body weight particularly in subjects with higher basal leptin concentrations.     

Bone density patterns after normal and premature menopause

Objectives: The investigation of the effect of time and type of menopause on bone mineral density (BMD) at different ages. Methods: Five hundred and fourteen women, who had never received any hormonal substitution were studied in a cross-sectional design: 177 with normal (NMP), 210 with surgical (SUMP) and 127 with premature natural (EMP) menopause. Age at menopause was 49.1±3.9, 38.3±4.7 and 38.1±4.2 years (mean±1 S.D.), respectively. BMD was measured at L2–L4 vertebrae and proximal femur by the DEXA method. Results: EMP women presented significantly lower vertebral BMD than NMP women in the 45–55-years segments (P<0.001), but did not differ from SUMP women. This group exhibited lower vertebral BMD than NMP between 45 and 50 years (P<0.001). Regarding femoral neck, EMP women exhibited lower values than SUMP in the 45–50 and 55–65 age segments (P<0.001) whereas SUMP women presented significantly higher BMD values than NMP women after 55 years of age (P<0.001). The percentages of women with vertebral BMD (T-score values) in the osteoporotic range were significantly greater in EMP compared with either NMP or SUMP groups (both P<0.001) whereas in femoral neck lower in SUMP than the other two categories. Conclusions: Women with either natural or surgical premature menopause exhibit lower BMD of trabecular bone compared with normal menopause women at the age segments 45–55 and 45–50, respectively. However, surgical menopause women exceed normal menopause women in their mixed bone BMD values after 60 years as well as premature natural menopause women at almost all age segments.     

Prophylaxis of osteoporosis with calcium, estrogens and/or eelcatonin: comparative longitudinal study of bone mass

Objective: To evaluate three different therapeutic regimens for the prevention of osteoporosis in natural and surgical postmenopausal women who had been found to have rapid bone loss in analytical studies. Methods: A total of 104 naturally or surgically postmenopausal women were studied, and subsequently followed-up during 1 year for avoidance of the influence of seasonal variation on bone mass, a factor overlooked in several studies. They were randomized into four groups of 26 patients each: the untreated control group (mean age 50 ± 5 years); the hormonal replacement treatment (HRT) group (mean age 48 ± 6 years), which was treated for 24 days each month with transdermal 17β-estradiol, 50 mg/day, together with medroxiprogesterone, 10 mg during 12 days; the calcium group (mean age 50 ± 4 years), which was treated with elemental calcium, 1 g/day; and the calcitonin group (mean age 50 ± 5 years), which was treated for 10 days each month with eel calcitonin, 40 IU/day and with elemental calcium, 500 mg/day. Full-body bone densitometry, for measuring total body bone mineral content (TBBMC), was carried out in all the women at baseline and 1 year. TBBMC was corrected for body weight by dividing its value by body weight (TBBMC/W). Results: After 1 year TBBMC/W was lower in every group: −2.14% (P < 0.001) in the control group; −0.14% (P = NS) in the HRT group (P < 0.05 vs. controls); −0.18% (P = NS) in the calcium group (P < 0.05 vs. controls); and −0.06% (P = NS) in the calcitonin group (P < 0.01 vs. controls; P < 0.05 vs. calcium and HRT). Conclusions: These findings show that all three treatments are effective in the prevention of postmenopausal loss of bone mass.     

Diurnal preference, sleep habits, circadian sleep propensity and melatonin rhythm in healthy human subjects

After 24-h sleep deprivation, 33 healthy young subjects entered the 10/20 min ultra-short sleep–wake schedule for 26 h. Melatonin rhythm was hourly assessed simultaneously. Results indicated that morning preference was significantly correlated with habitual sleep onset (r=−0.41, P=0.04), habitual sleep offset (r=−0.52, P=0.002), melatonin peak time (r=−0.36, P=0.04), and sleep propensity onset time (r=−0.36, P=0.04). The intervals between habitual sleep mid-point and melatonin peak time and between habitual sleep mid-point and sleep propensity onset time were significantly longer in morning-preference subjects than in evening-preference subjects (P<0.05). These findings suggest that the variance of diurnal preference may be related to differences in phase relations between habitual sleep timing and the circadian pacemaker.     

Decrease of bone mineral density during estrogen substitution therapy

A decrease in bone mineral density (BMD) in patients treated with hormone replacement therapy (HRT) is sometimes observed in clinical practice. In order to assess the frequency and the characteristics of these cases, we reviewed the data of 102 women treated with HRT for more than 2 years, and who had undergone at least 3 lumbar BMD measurements during that period. For each patient, a linear function was fitted to the BMD data in relation to time. The slope was calculated. There was an overall gain in BMD during treatment, mean (± S.E.M.) values of slope 0.007 g/cm²/year (± 0.002). Fifty-three patients had a slope higher than 0.005, 28 a slope close to 0 (between 0.005 and −0.005) and 21 a slope lower than −0.005. By dividing the patients in tertiles of slopes (tertile l: slope < 0; tertile II: 0 < slope < 0.011; tertile III: slope > 0.011), significant differences were observed between the three groups of slope for the initial BMD (P < 0.001), hydroxyproline/creatinine ratio (P < 0.01), weight, DHEAS and alkaline phosphatase (P < 0.05). Only 1 of the 15 patients with a low bone mass (lower than mean ± I S.D.) had a negative slope, while 9 of the 16 with a high-bone mass (higher than mean ± I S.D.), had a negative slope. Under HRT, about 21% of postmenopausal women have a slight decrease in BMD as assessed by DPA. Because of the DPA coefficient of variation, however, the exact number of bone losers cannot be determined. Nevertheless, the present study suggests that patients with low bone mass are likely to respond better than patients with high bone mass.     

Regulation of hepatic blood flow in patients with liver cirrhosis and after liver transplantation

We studied liver blood flow at rest and its regulatory changes after exercise and food intake in ten patients with advanced liver cirrhosis and in 14 patients more than 10 months after orthotopic liver transplantation. The results were compared with those obtained in ten healthy volunteers. Sorbitol steady state infusion was employed to measure functional liver blood flow (FLBF). Thirty minutes of half-maximal muscular work, performed on a supine position ergometer and consumption of a standard meal were used as stimuli to study regulatory changes in hepatic perfusion. Results: FLBF at rest was reduced in end stage cirrhosis (mean 1257±105 ml/min in cirrhosis vs. 1707±76 ml/min in controls; P<0.01). After liver transplantation FLBF at rest was normalized (mean 1922±169 ml/min) in patients with stable graft function. Muscular exercise led to a reduction in FLBF, which in the transplanted patients was the same range as in normal controls (−26.7±3.7%; −24.7±0.7, respectively), but was reduced in cirrhosis (−19.1±2.1%; P<0.05). After ingestion of a standard meal FLBF increased substantially in normal controls (+40.2±2.3%), while in patients with cirrhosis this increase was rather small (+10.1±1.9%; P<0.001). After transplantation the food-induced increase in FLBF(+20.5±3.6%) was larger than in cirrhosis (P<0.05) but remained smaller than in the controls (P<0.01). We conclude that in cirrhosis FLBF is reduced and adaptive changes after exercise or food intake are impaired. After transplantation FLBF is normalized, but blood flow regulation, especially after food intake remains abnormal.     

Month 3 and month 6 measurements of bone mineral density predict the annual outcome in postmenopausal women with osteoporosis in whom alendronate was added to long-term HRT

Objective: To examine the predictive value of bone mineral density measurements done as early as months 3 and 6 after initiation of alendronate therapy (10 mg daily) in osteoporotic women already using long-term hormone replacement therapy. Method: Lumbar spine and femoral neck bone density (DPX by Lunar) were performed at baseline, 3, 6, 12 months of combined therapy. The study group included 45 women at baseline, but 2 dropped-out at day 67 and at month 6 because of gastric complaints, leaving 43 women for analyses. Results: Group characteristics at baseline were as follows: mean age 61±5 years, mean duration of HRT use 7±3 years, lumbar spine bone density 0.863±0.089 g/cm², with a t-score of −2.75±0.8 S.D., and femoral neck density 0.706±0.085 g/cm² with a t-score of −2.28±0.7 S.D. Bone density increased during 1 year of combined therapy, totaling a 3.2% gain for the spine and a 2.4% gain for the femur. Most of the annual change was already observed at month 3: 2.1% for the spine and 1.4% for the femur. Moreover, the baseline to month 6 percentage difference showed a very good correlation with the yearly outcome (r=0.74, P<0.001 for both spine and femur). When different arbitrary cut-off definitions for a successful treatment (1%, 1.5% or 2% gain in density) were used in analyses, in the majority of cases the bone density at 1 year, whether elevated or not, could be predicted by months 3 and 6 results. Although urine deoxypyridinoline decreased throughout the study period, demonstrating a significant time trend (P=0.001), the baseline to month 3 changes did not correlate with baseline to annual bone density results. Conclusions: In specific clinical settings when patients or physicians are looking for a good way to anticipate whether additional alendronate in hormone users would turn out to be beneficial, bone density measurements performed as early as 3–6 months after initiation of therapy might give the answer.     

Effects of postmenopausal hypoestrogenism on skin collagen

Objective: The aim of our study was to evaluate the effect of aging and postmenopausal hypoestrogenism on skin collagen content. Methods: Thirty-two women (mean age 48.78±9.86; year±S.D., range 28–68), 14 in premenopause and 18 in postmenopause, underwent skin biopsies performed during laparotomic operation. The amount of collagen type I, III and type III/type I ratio was evaluated by immunohistochemistry and computerised image analysis, and was related to age and years of postmenopause. Results: In the postmenopausal patients, a significant (P<0.01) decrease of percentage of skin collagen type I, type III and type III/type I ratio was observed in comparison to premenopausal women. The percentages of collagen type I, type III and type III/I ratio of all patients studied was significantly (P<0.01) correlated with chronological age (r=0.88, 0.89 and 0.61, respectively). Considering only postmenopausal subjects, the correlation with chronological age was significant (P<0.01) for collagen type I and type III of postmenopausal women (r=0.59, r=0.64, respectively), but not for the type III/I ratio (r=0.37, P=0.131). The percentages of collagen type I, type III and type III/I ratio of postmenopausal women showed a significant (P<0.01) inverse correlation with years of postmenopause (r=0.76, 0.73 and 0.73, respectively). Conclusions: Our data suggest that the decrease of skin collagen is an estrogen-related phenomenon.     

Effects of percutaneous oestradiol versus oral oestrogens on bone density

In order to compare the effects on bone density of 1.5 mg/day percutaneous 17β-estradiol (E₂) and of 0.625 mg/day oral conjugated oestrogens (CEE), 68 women who had undergone hysterectomy were studied. The subjects were randomly allocated to one of three study groups. A total of 15 women dropped out from these groups during the study. The percutaneous group (n = 20) received treatment for 36 months and the oral group (n = 17) for 24 months, while the untreated group (n = 16) served as controls over a period of 24 months. Bone mineral density (BMD) was measured by dual gammagraphic densitometry (Novo 22A densitometer) in the lumbar spine (L2-L4). The percentage gain in the percutaneous group was 1.7% ± 3.9% after 12 months, 5.6% ± 2.9% (P < 0.001) after 24 months and 4.7% ± 3.2% (P < 0.001) after 36 months. In the oral group the gain was 3.5% ± 13.0% after 12 months and 4.3% ± 9.2% (P < 0.001) after 24 months. In the untreated group the bone density loss was 6.6% ± 3.5% (P < 0.001) after 12 months and 9.1% ± 3.4% (P < 0.001) after 24 months. On the basis of our results we concluded that both 1.5 mg/day percutaneous E₂ and 0.625 mg/day oral CEE not only prevented bone loss but also increased BMD, as was confirmed by our findings after 36 and 24 months of treatment, respectively.     

The influence of physical activity on the response of bone mineral density to 5 years tibolone

Objectives: Menopausal hormone replacement therapy (HRT) maintains bone mineral density (BMD) and reduces risk of fracture in postmenopausal women. It has been suggested that sex steroids and loading may have synergistic effects on bone. We therefore investigated whether habitual physical activity influences the response of BMD to tibolone in postmenopausal women. Methods: The subjects were 42 postmenopausal women aged mean (SE) 65.8±6.2 year who had taken tibolone for prevention/ treatment of osteoporosis over 5 years. Bone mineral density was measured annually by dual X-ray absorptiometry and physical activity was assessed using accelerometers after 5 years therapy. Results: Twenty-six women were classified as having low physical activity (LPA; <15 min day⁻¹) and sixteen as high physical activity (HPA; >15 min day⁻¹). Spine BMD did not differ significantly between groups at baseline and increased significantly by 2 years of treatment with further increase to 5 years. The magnitude of increase did not differ between groups. Hip BMD at baseline was 7.3% higher in HPA women (P=0.07). Hip BMD increased over 2 years tibolone treatment in LPA women (+5.6%, P<0.01) whilst no significant change occurred in the HPA group (−0.5%). This difference in response between groups was statistically significant (P=0.002) and persisted after adjustment for age and body mass (P=0.002). Hip BMD was maintained in both groups over the subsequent 3 years of treatment. Conclusions: Spine BMD increased significantly in response to tibolone irrespective of physical activity participation. The more physically active women had higher hip BMD at baseline but the response to tibolone was greater in the less physically active women. The difference in response between groups may be due to physically active women having lower resorption at the hip and hence reduced response to anti-resorptive effects of HRT.     

Effects of menopause and hormone replacement therapy on plasma lipids, lipoproteins and LDL-receptor activity

A cross-sectional study of ninety six women was conducted to examine the effect of menopause and hormone replacement therapy (HRT) on plasma lipids, lipoproteins and oxidation of low density lipoproteins. The sample consisted of 26 premenopausal women, 26 postmenopausal women taking no replacement hormones and 43 postmenopausal women on hormone replacement therapy. Postmenopausal women not taking replacement hormones had significantly higher plasma cholesterol, low density lipoprotein (LDL) cholesterol and lipoprotein[a] (Lp[a]) levels compared to premenopausal women or postmenopausal women on HRT [6.00±0.15, 5.36±0.17 (P<0.01), 5.63±0.13 (P<0.05) mmol/l, respectively for total cholesterol; 4.13±0.15, 3.64±0.15 (P<0.05), 3.82±0.12 (P<0.05) mmol/l, respectively for LDL-cholesterol; 48.19±9.90, 26.59±5.53 (P<0.03), 25.12±4.62 (P<0.03) mg/dl, respectively for Lp[a]]. The differences in LDL cholesterol concentrations were inversely related to changes in LDL receptor activity (r=−0.27, P<0.01). HRT use was found to be associated with a significantly smaller LDL particle size. Plasma triglyceride was significantly higher in women on HRT (1.16±0.07 mmol/l) than in the premenopausal group (0.96±0.07) or postmenopausal group not using HRT (0.87±0.06). There were no differences in LDL oxidation between the groups when LDL was oxidised in the presence of copper. Nor was there any difference in the uptake of copper-oxidised or macrophage-modified LDL into J774 macrophages. These results confirm the effect of menopause and exogenous hormones on plasma lipids and lipoproteins, and suggest that HRT modifies the activity of the LDL receptor. Hormone replacement did not appear to protect LDL from oxidation.     

Effect of estrogen replacement therapy on speed of sound at multiple skeletal sites

Objectives: To evaluate the effect of estrogen replacement therapy (ERT) on postmenopausal bone loss by multi-site ultrasound measurement. Methods: A cross-sectional comparison of postmenopausal women, ERT users and non-users. The two study groups were enrolled for the reference database collection for the Sunlight Omnisense™ (Omnisense) and were matched by years since menopause. Speed of sound (SOS) was measured at the distal radius (RAD), mid-shaft tibia (TIB), fifth metatarsus (MTR) and proximal phalanx (PLX). Results: 143 ERT users for 5.2±3.6 years were compared with 139 ERT non-users (age: 57.0±5.3 and 57.5±5.5, respectively). Both groups were 7.1±5.0 years since menopause. SOS, expressed in T-score units, was higher at the RAD in ERT users as compared to ERT non-users (−0.55±1.30 and −1.36±1.60, respectively, P<0.0001), and at the TIB (−0.73±1.34 and −1.28±1.45, respectively, P=0.003). Same trend was observed at the MTR and PLX, but not statistically significant because of fewer observations. In early post menopause period, the ERT-non users RAD data shows an annual SOS decrease of 0.17 versus annual increase of 0.12 T-score units (P=0.037). Similar effect is observed at the TIB, though not statistically significant (non-users decrease of 0.20 vs. users increase of 0.08 T-score units/year, P=0.086). Conclusions: SOS measurements by Omnisense at multiple skeletal sites support the ERT protective effect on bone.     

Morphometric study of the brachiobicarotid trunk in human fetuses

The study was conducted to define a normal range for the length, external diameter and volume of the brachiobicarotid trunk during gestation. The material examined consisted of 128 human fetuses of both sexes (63 male, 65 female) aged from 15 to 34 weeks, from spontaneous abortions or stillbirths. The arterial bed was filled with white latex LBS 3060, specimens were fixed in a 10% formalin, and then branches of the aortic arch were dissected, recorded using a camera, and digitalized to JPEG images. Afterwards, the brachiobicarotid trunks underwent morphometric analysis with the digital image analysis system of Leica QWin Pro16. Regression analysis was used to investigate the growth of the brachiobicarotid trunk during gestation. The brachiobicarotid trunk was observed in 27 of the 128 fetuses studied (21.09%). The results showed the brachiobicarotid trunk length as a function of fetal age, which could be expressed by y=−1.250+0.1433x±0.7682, and the brachiobicarotid trunk diameter by y=−3.034+0.2845±0.4253. The volumetric growth of the brachiobicarotid trunk followed the quadratic function y=178.5−19.69x+0.545x²±20.112. The correlation coefficients between arterial length or external diameter and fetal age, and the coefficient of determination between arterial volume and fetal age were as follows: r=0.76 for length, r=0.97 for external diameter, and R²=0.84 for volume (P<0.001). The relative diameter of the brachiobicarotid trunk increased from 0.738±0.089 to 0.916±0.088 during the study period.     

Interest of biochemical markers of bone turnover for long-term prediction of new vertebral fracture in postmenopausal osteoporotic women

Objective: To analyse the interest of baseline levels and short-term (3-months) changes in serum osteocalcin (BGP), serum bone-specific alkaline phosphatase (BALP) and urinary C-telopeptide of type I collagen/creatinine ratio (U-CTX) to predict 3-years changes in bone mineral density (BMD) and spinal deformity index (SDI) in postmenopausal osteoporotic women. Methods: Data were derived from a cohort of 603 osteoporotic women corresponding to the placebo arm of a 3-years prospective, double-blind study. Results: Baseline values of BALP, BGP and U-CTX were negatively and significantly correlated with baseline spinal BMD. Significant correlations were also observed between the changes in BMD observed after 36 months at the spine and baseline BALP (r=0.20, P=0.0001), BGP (r=0.09, P=0.05) and U-CTX (r=−0.11, P=0.02). At 3 years, 71 women (15.9%) showed an increase in their SDI, corresponding to the occurrence of at least one new vertebral deformity. Baseline values of the four bone turnover markers (BTM) were not significantly related to the occurrence of new vertebral deformities. However, when considering the changes in the BTM observed after 3-months of follow-up, BGP (P=0.003) and U-CTX (P=0.047) were identified as significant predictors of an increase of SDI. The associated odds ratios (95% confidence interval (CI)) were 10.922 (2.218–53.78) for unit changes of log BGP and 1.369 (1.003–1.867) for unit changes of log U-CTX. The relative risk (RR) (IC 95%) of having a new vertebral fracture over 36 months was 0.31 (0.15–0.65) when being in the lowest quartile of 3-months changes in BGP as compared with the highest. Conclusion: We conclude that two sequential measurements of BGP and U-CTX performed at 3-months intervals could be of interest to identify postmenopausal osteoporotic women with the highest risk to present new vertebral deformities.     

Plasma leptin levels in obese and non-obese postmenopausal women before and after hormone replacement therapy

Objective: the aim of this study was to investigate the effect of hormone replacement therapy (HRT) on plasma leptin levels in postmenopausal women, and the relationship between the plasma leptin levels and obesity. Methods: premenopausal women with normal cycles (n=30; mean ages, 35.4±8.3 years) and postmenopausal women (n=45; mean ages, 49.5±4.7 years) were randomly selected. Women were classified as obese (BMI>27 kg/m²) and as non-obese (BMI<27 kg/m²). Blood samples were obtained from the premenopausal women at the beginning of cycle, and from the postmenopausal women before and 6 months after HRT. Plasma leptin levels were measured by radioimmunassay. Results: plasma leptin levels were significantly higher in premenopausal women than in postmenopausal women (18.60±5.0; 3.67±2.44 ng/ml, respectively, P<0.001). Obese premenopausal women (n=15) had significantly higher plasma leptin levels (24. 60±7.81 ng/ml) in comparison with the levels of the non-obese premenopausal women (n=15; 12.50±4. 63 ng/ml) (P<0.001). Although there was no significant difference in the plasma leptin levels between obese (n=25) and non-obese (n=20) postmenopausal women before HRT, plasma leptin levels were significantly elevated in both obese and non-obese postmenopausal women after HRT (P<0.001), and the obese women had significantly higher plasma leptin levels than the non-obese (29.05±10.53; 14.78±6.76 ng/ml, respectively, P<0.001). Conclusion: HRT is effective in the elevation of the plasma leptin levels in postmenopausal women, and in obese women the increase of the plasma leptin levels are more marked than the non-obese women after HRT.     

Stiffness index identifies patients with osteoporotic fractures better than ultrasound velocity or attenuation alone

Objectives: To compare a composite ultrasonometry variable, the stiffness index (SI), with its two component variables of speed of sound (SOS) and broadband ultrasound attenuation (BUA), in identifying post-menopausal women with low bone mineral density (BMD) and/or osteoporotic fracture. Methods: A cross sectional sample of 1217 women (mean (S.D.) age 53.9 (9.7) years) was studied. Risk factors for osteoporosis were assessed by detailed questionnaire and women with diseases, or those taking treatments known to affect bone metabolism were excluded. Women were allocated to one of four groups: pre-menopausal women (n=476), healthy post-menopausal women (n=583), post-menopausal women with low BMD (n=101), and post-menopausal women with osteoporotic fracture (n=57). An Achilles ultrasonometer was used to perform quantitative ultrasonometry (QUS) at the os calcis. The SI, calculated mathematically from SOS and BUA, was computed. Results: Analysis of receiver operating curves (ROC) between healthy post-menopausal women and post-menopausal women with low BMD but no fracture, showed that the area under the curve (AUC) for SI was significantly greater than that for BUA (P<0.001) or SOS (P<0.05). For healthy post-menopausal women compared to women with fracture, the area AUC for SI was significantly greater than that for BUA (P<0.05) or SOS (P<0.001). No significant difference was found for AUC between BUA and SOS. Conclusion: QUS variables discriminated women with low density or fracture from healthy postmenopausal controls. The SI was a significantly better indicator than BUA or SOS in this retrospective study.     

Difference in the effects of body composition on bone mineral density between pre- and postmenopausal women

Objective: This study was to investigate whether the effect of lean and fat mass component on bone mineral density (BMD) differs between pre- and postmenopausal women. Materials and methods: Subjects were 360 pre- and 193 postmenopausal Japanese women with right side dominance. Age, height, and years since menopause (YSM, in postmenopausal women) were recorded. Body fat and lean body mass were measured by whole body scanning with dual-energy X-ray absorptiometry (DEXA). BMD of the vertical axis (L2-4 of the lumbar spine, pelvis, bilateral legs, and total body) and horizontal axis (arms) were also measured by DEXA. Results: In premenopausal women, lean body mass was independently correlated with BMD of the left arm (partial correlation COEFFICIENT=0.417), right arm (0.430), L2-4 (0.285), pelvis (0.276), left leg (0.403), right leg (0.412), and total body (0.377) (P<0.001). However, body fat mass was not correlated with several BMD sites except for pelvis BMD (0.187, P<0.01). In postmenopausal women, body fat mass was independently correlated with BMD of the left arm (0.248, P<0.01), L2-4 (0.188, P<0.05), pelvis (0.263, P<0.01), left leg (0.228, P<0.01), right leg (0.319, P<0.001), and total body (0.188, P<0.01)). However, lean body mass was correlated with BMD in only three segmental regions including left arm (0.175), right arm (0.217), and left leg (0.210; P<0.05). Conclusion: Lean body mass is a significant determinant of BMD in premenopausal women, while body fat mass is a significant determinant in postmenopausal women.     

QT dispersion in the surface electrocardiogram in elderly patients with major depression

Background: QT dispersion (QTd) is a measure of interlead variations of QT interval of the surface 12-lead electrocardiogram (ECG). Increased QTd, found in various cardiac diseases, reflects cardiac instability and is associated with increased cardiac death. Major depressive disorder (MDD) was found to be associated with high cardiovascular mortality rates. This study compares QTd in elderly patients with MDD to normal controls. Methods: QTd and rate-corrected QTd of 18 physically healthy elderly patients (69.9±7.6 years) with MDD was compared to nine physically and mentally healthy age- and gender-matched controls (64.1±12.2 years). Results: QTd and rate-corrected QTd were significantly higher in MDD compared to controls (68±30 vs. 40±13 ms, P=0.002 and 81±39 vs. 43±13 ms, P=0.001, respectively). Intra- and inter- observer reproducibilities were highly correlated (r=0.96, P <0.0001; r=0.88, P <0.001, respectively). Limitations and Conclusions: The major limitations of this study are the small number of subjects and the fact that all the patients were maintained on antidepressant medication. However, it seems that QTd analysis might shed light on possible autonomic imbalance and also provide a novel cardiovascular risk factor for increased cardiac death in MDD.     

A comparison of the central effects of different progestins used in hormone replacement therapy

Objective: To evaluate the central effect exerted by different progestins used for hormone replacement therapy. Methods: Randomised, placebo-controlled study. One hundred-twenty postmenopausal women on continuous hormonal replacement therapy with transdermal estradiol (50 μg per day) associated, for 10 days every 28 days, with four different progestins: dydrogesterone (DYD; 10 mg per day; n=20), medroxyprogesterone acetete (MPA; 10 mg per day; n=20), nomegestrol acetate (NMG; 5 mg per day; n=20) or norethisterone acetate (NETA; 10 mg per day; n=20). Other 40 women, 10 for each treatment group, were used as controls and were monitored for a single cycle of 28 days during the administration of transdermal estradiol plus placebo. Morning basal body temperature (BBT) was monitored for 28 days. Anxiety, by the state-trait anxiety inventory, and depression, by the self-evaluation depression scale of Zung, were evaluated just prior to and in the last 2 days of the 10-day progestins adjunct. Results: All progestins except DYD increased (P<0.0001) BBT by 0.3–0.5 °C. Anxiety was decreased by DYD (−2.3+1.1; P<0.01) and MPA (−1.5+0.5; P<0.01), but not by NMG or NETA. Depression did not significantly increase during progestins and actually decreased during MPA (−3.0+0.7; P<0.01). Only the effect of DYD on anxiety and that of MPA on depression were significant versus the control group (P<0.05). Conclusions: Different progestins exert different central effects. DYD has the peculiarity of not increasing BBT and of decreasing anxiety, which is also decreased by MPA. Depression is not negatively affected by the tested progestins and it may be ameliorated by MPA. The present data may help to individualise the progestin choice of hormone replacement therapy.     

Testosterone enhances estradiol''s effects on postmenopausal bone density and sexuality

To investigate the role of androgens in increasing bone density and improving low libido in postmenopausal women, we have studied the long-term effects of estradiol and testosterone implants on bone mineral density and sexuality in a prospective, 2 year, single-blind randomised trial. Thirty-four postmenopausal volunteers were randomised to treatment with either estradiol implants 50 mg alone (E) or estradiol 50 mg plus testosterone 50 mg (E&T), administered 3-monthly for 2 years. Cyclical oral progestins were taken by those women with an intact uterus. Thirty-two women completed the study. BMD (DEXA) of total body, lumbar vertebrae (L1–L4) and hip area increased significantly in both treatment groups. BMD increased more rapidly in the testosterone treated group at all sites. A substantially greater increase in BMD occurred in the E&T group for total body (P < 0.008), vertebral L1–L4 (P < 0.001) and trochanteric (P < 0.005) measurements. All sexual parameters (Sabbatsberg sexual self-rating scale) improved significantly in both groups. Addition of testosterone resulted in a significantly greater improvement compared to E for sexual activity (P < 0.03), satisfaction (P < 0.03), pleasure (P<0.01), orgasm (P < 0.035) and relevancy (P < 0.05). Total cholesterol and LDL-cholesterol fell in both groups as did total body fat. Total body fat-free mass (DEXA, anthropometry, impedance) increased in the E&T group only. We concluded that in postmenopausal women, treatment with combined estradiol and testosterone implants was more effective in increasing bone mineral density in the hip and lumbar spine than estradiol implants alone. Significantly greater improvement in sexuality was observed with combined therapy, verifying the therapeutic value of testosterone implants for diminished libido in postmenopausal women. The favourable estrogenic effects on lipids were preserved in women treated with T, in association with beneficial changes in body composition.