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.     

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.     

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.     

Effect of hormone replacement therapy on serum levels of tumor markers in healthy postmenopausal women

Objective: The effect of hormone replacement therapy (HRT) on serum levels of tumor markers is barely defined. The aim of this study was to evaluate the effect of HRT on levels of tumor markers CA 125, CA 15-3, CA 19-9, CEA and -FP. Methods: Retrospective analysis of prospectively collected data in healthy postmenopausal women under oral estrogen replacement therapy (ERT, conjugated equine estrogen (CEE) 0.625 mg (n=21) or estradiol 2 mg (n=31)), and continuous combined estrogen and progesterone regimen (HRT, CEE 0.625 mg plus medroxyprogesterone acetate 2.5 mg (n=34) or estradiol 2 mg plus norethisterone acetate 1 mg (n=37)). One hundred and twenty-three healthy women among a sampled population of 654 postmenopausal patients with complete records, initial normal tumor marker levels, and at least 1 year of follow-up were included into the study. Tumor markers were measured with 1-year interval. Results: Fifty-two (41.5%) patients were under ERT and 71 (58.5%) were under combined HRT. The number of months since menopause, age and age at menopause did not influence tumor marker levels at first admission. All of the tumor marker levels were in normal range after 1 year. Pretreatment CA 125 II, CA 15-3 and CEA levels were significantly low (median and range) 5.0 (1.0–11.8) versus 7.45 (1.0–18.1) U/ml for CA 125, 27.05 (7.3–37.5) versus 32.6 (12.5–37.9) U/ml for CA 15-3, 0.88 (0.58–2.8) versus 1.34 (0.53–2.41) ng/ml for CEA in women with hysterectomy when compared to women without hysterectomy. There was no effect of ERT on CA 125 II, CA 19-9, CEA and -FP levels. E2 led to a significant decrease in post-treatment CA 15-3 levels [32.9 (8.1–34.9) vs. 18.1 (6.7–31.4); P<0.001]. CA 125 levels were only significantly reduced in hysterectomised women using continuously combined HRT [7.9 (2.6–17.7) vs. 5.6 (1.3–19.2) for CEE+MPA, and 7 (1–18.1) vs. 5.8 (1.8–17.4) for E2+NETA; P<0.05]. There was a small, but not significant, increase in CA 125 levels in women under ERT. Conclusion: Although there was a statistically significant decrease in CA 15-3 levels in current E2 and E2+NETA users, and a decrease in CA 125 levels in combined regimens, this change is clinically not relevant in healthy postmenopausal women. This data will be useful for the caregivers in the management and follow-up of cancer survivors who preferred replacement therapy as the only treatment of their postmenopausal symptoms.     

Anticardiolipin antibodies during hormone replacement therapy in healthy postmenopausal women

Objective: The aim of the study was to investigate IgG and IgM anticardiolipin (aCL) antibodies in the course of hormone replacement therapy (HRT).

Subjects and methods: Thirty clinically healthy postmenopausal women with no history of previous thrombotic events or autoimmune disease were divided in two groups: control group (n=12, mean age 52.9±4.5 years, and 6.2±3.6 years duration of amenorrhea) and a second group (n=18, mean age 53.6±3.5 years, and 5.7±4.5 years of amenorrhea) who were allocated to HRT, containing 2 mg 17-beta estradiol plus 1 mg norethisterone acetate daily for 6 months. ACL antibodies of IgG and IgM isotype were assessed using ELISA and the Kupperman menopausal index (KI) was calculated at baseline and after 3 and 6 months of treatment. Results: HRT had a beneficial effect on climacteric symptoms, evaluated by KI (baseline versus 3rd month and 3rd month versus 6th month, P<0.001). The KI did not change in the control group. The values of IgG at the three studied periods did not change significantly and were 14.1±4.2, 13.1±4.9 and 13.4±3.7 in the HRT group and 12.7±3.1, 13.7±1.8 and 13.1±3.8 GPL, respectively, in the control group. IgM aCL antibodies increased during HRT and were as follows: 7.7±4.8 at baseline, 12.9±5.6 at 3rd month and 9.3±3.2 MPL at 6th month. In the control group, IgM were 8.0±2.8; 7.9±2.3 and 7.1±2.3 MPL, respectively. The differences between the two groups were significant at the third and the 6th month (P<0.01 and P<0.05). Conclusion: These data suggest that HRT is associated with elevation of IgM ACA in healthy postmenopausal women. As IgG aACA are considered more pathogenic, it seems unlikely that the early prothrombogenic effects of HRT can be assigned to ACA.     

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.     

The effects of hormone replacement therapy on plasma lipids in type II diabetes

Objectives: The effects of hormone replacement therapy on cardiovascular risk factors in postmenopausal women with non-insulin dependent diabetes mellitus (type II diabetes) is uncertain. Methods: The effects of estrogen replacement therapy (ERT, conjugated equine estrogen 0.625 mg orally daily), combined estrogen and continuous progestogen therapy (HRT, 0.625 mg of conjugated equine estrogens plus medroxyprogesterone acetate 5 mg daily) or placebo was compared in 20 postmenopausal type II diabetic women and 20 normal postmenopausal women in a double blind, randomised, crossover study. Patients receiving insulin were excluded from the study and all lipid modifying drugs were ceased at least 4 weeks prior to randomisation. Other medication including oral hypoglycaemics was kept constant for the duration of the study. Results: Women with type II diabetes were a similar age (58.7±1.3 years) to the non-diabetic women (59.6±1.6 years) but they had a significantly greater body mass index, a higher incidence of treated hypertension, higher fasting plasma glucose levels, higher triglycerides and lower HDL cholesterol levels than non-diabetic women. ERT reduced total cholesterol and LDL cholesterol by a similar extent (8.9–12.3%) in normal and type II diabetic women and increased HDL cholesterol to a similar extent in both groups (11.0 and 8.9% respectively). ERT did not significantly alter fasting triglyceride levels in either group. The addition of medroxyprogesterone acetate 5 mg daily abolished the increase in HDL cholesterol associated with ERT in both groups but did not significantly affect any of the other lipid measurements. ERT and HRT did not significantly alter fasting insulin levels nor alter fasting glucose levels in either non-diabetic women or women with type II diabetes. Conclusions: ERT and HRT have similar effects on lipids in women with type II diabetes and non-diabetic women after 1 month of therapy.     

Bone turnover and its relationship with bone mineral density in pre- and postmenopausal women with or without fractures

Objective: This work was carried out in order to investigate possible relationships between bone turnover rate, as evaluated by bone biomarkers and skeletal mass, as evaluated by bone mineral density (BMD). Method: Fifty-eight normal women and 30 female patients with osteoporotic fractures were enrolled. Three groups were defined: (1) fertile subjects (n=24), mean age 33.7±8.1 years; (2) postmenopausal women (n=32, including 11 patients with fractures) whose BMD values, in terms of T score, were less than −2.5 S.D. below the young adult mean obtained in our laboratory (mean age 61.7±7.9 years; and years since menopause (ysm), 12.6±8.3); (3) postmenopausal women (n=32, including 19 patients with fractures) whose BMD values in terms of T score, were below −2.5 S.D. (mean age 62.9±8.6 years; and ysm 15.9±9.0). Groups II and III characterised, by inclusion criteria, by significant different mean BMD values, were similar as far as chronological and menopausal age were considered. Metabolic tests included a short urine collection to determine calcium, hydroxyproline, cross-linked N-telopeptides of type I collagen (NTx) and creatinine (Cr); half-way through this collection, a blood sample was taken for the measurement of total alkaline phosphatase activity (ALP) and tartrate-resistant acid phosphatase activity (TRAP). BMD at lumbar spine was evaluated. Results: There were significant differences amongst the three groups in mean ALP (P<0.001, by analysis of variance) TRAP (P<0.006) and NTx/Cr (P<0.001) values, but not as far as mean values of calcium/Cr or hydroxyproline/Cr ratios were concerned. Considering the group as a whole, there were significant inverse correlations between NTx/Cr, ALP, TRAP and BMD controlling for both age (r=−0.392, P<0.001; r=−0.447, P<0.001 and r=−0.327, P<0.002, respectively) and ysm (r=−0.374, P<0.001; r=−0.474, P<0.001 and r=−0.333, P<0.002). Conclusions: Our results indicate, that, even after controlling for both ageing and oestrogen status, there is an inverse relationship between bone mass (that at a given time represents the balance of all previous metabolic events) and a biochemical marker (which reflects bone turnover at the time of examination). These findings are in line with the belief that increased bone turnover should be regarded as a risk factor for osteoporosis. Furthermore, our results indicate that, unless there is no increase of hepatic isozyme, total ALP still maintains a possible role as a first analysis to evaluate bone turnover before requesting markers with greater specificity, sensitivity but also more expensive and whose analysis is sometimes time-consuming.     

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.     

Hormone replacement in postmenopausal women: impact of progestogens on autonomic tone and blood pressure regulation

OBJECTIVE: Depressed heart rate variability (HRV) reflects an imbalance of autonomic tone and independently predicts increased cardiovascular risk in patients with congestive heart failure or after acute myocardial infarction. While hormone replacement therapy (HRT) with estrogens beneficially modulates autonomic tone and blood pressure (BP) regulation in postmenopausal women, the impact of concomitant treatment with progestogens remains unclear. DESIGN: In this cross-sectional study, HRV and BP were examined in 62 healthy women (ages 48-71 years) using digital beat-to-beat interval recordings of heart rate and 24-hour ambulatory BP measurements. RESULTS: Demographic parameters did not differ among women without HRT (n = 23), on estrogen (n = 17; ERT), or on progestogen-estrogen containing HRT (n = 22; PERT). Total power of HRV was significantly lower, whereas mean heart rate (HR) was significantly higher among women on PERT group versus controls and ERT (total power: 1611 +/- 146 vs. 2497 +/- 308 and 2472 +/- 348 ms(2); heart rate: 80.7 +/- 1.2 vs. 75.0 +/- 1.4 and 74.0 +/- 2.2 bpm; p < 0.05). In addition, low-frequency power and time-dependent parameters of HRV were lower among women on PERT group versus controls and ERT (p < 0.05). ERT use was associated with reduced systolic and diastolic daytime BP, whereas no significant differences were evident PERT users compared with controls. CONCLUSIONS: Progestogen-containing replacement therapy was associated with increased HR and an attenuation of HRV in postmenopausal women. BP was lower in women on ERT, whereas this effect was offset in the PERT group. These observations could at least partially explain the ambiguous results of progestogen-containing HRT on cardiovascular risk in the Heart and Estrogen/Progestin Replacement Study (HERS).     

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 bezafibrate and simvastatin on plasma lipoproteins in hypercholesterolemia resistant to hormone replacement therapy

Objectives: Estrogen replacement therapy has favorable effects on serum lipoprotein levels in postmenopausal women with hypercholesterolemia. However, there are some patients who fail to respond to hormone replacement therapy (HRT) to lower the serum cholesterol level. In these cases, a conventional lipid-lowering therapy will be applied in addition to HRT, while the effects of these drugs are not well understood. In this study, we studied the effects of simvastatin and bezafibrate administered in addition to HRT. Methods: Patients who were hypercholesterolemic even after HRT were randomly assigned to three treatment groups: HRT only (control group, n=10), HRT+simvastatin (10 mg/day, n=10), or HRT+bezafibrate (400 mg/day, n=10). Serum lipids and lipoprotein levels were measured throughout 12 weeks. Results: The serum triglyceride levels were decreased by 24±28 and 38±13% in the HRT+simvastatin and HRT+bezafibrate groups, respectively. HRT+simvastatin decreased the total cholesterol (21±10%) and low-density lipoprotein cholesterol (28±12%) levels without affecting the high-density lipoprotein cholesterol (HDL-C) level, while HRT+bezafibrate increased the HDL-C level (12±11%). Conclusions: Treatment with simvastatin or bezafibrate in addition to HRT should be considered in cases of postmenopausal hypercholesterolemia in which HRT alone fails to lower the serum lipoprotein levels.     

Influence of hormonal replacement therapy on the regional cerebral blood flow in postmenopausal women

Objectives: The aim of this study was evaluation of the influence of hormonal replacement therapy (HRT) on the regional cerebral blood flow in postmenopausal women. Methods: The study group were 20 postmenopausal women, mean age 48.7 years (S.D. ±4.9 years). The control group were ten regularly menstruating women, mean age 32.6 years (S.D. ±13.2 years). In the studied group we measured the severity of climacteric syndrome with the use of Kupperman index and serum FSH and 17β-estradiol level with the use of radioimmunological method. Cerebral blood flow was measured at rest using Single Photon Emission Computed Tomography (SPECT). Tracer accumulation evaluation was performed in three slices defined as: cerebellar slice, thalamic slice and ventricular slice, the reference region was delineated in the cerebellum. In ten women with an impairment in the cerebral blood flow at the beginning of the study all the tests were repeated after 12 months of HRT. Results: Before HRT mean value of the Kupperman index in the study group was 29.8 points (S.D. ±7.1 points); 17β-estradiol 27 pg/ml (S.D. ±2 pg/ml); FSH 56 IU/l (S.D. ±49.5 IU/l); SPECT study revealed cerebral blood flow impairment in ten women. In all the studied slices cerebral blood flow was lower in the study group than in the controls. After 12 months of HRT the mean value of the Kupperman index in the study group was 13.2 points (S.D. ±2.1 points) (P<0.05); 17β-estradiol 44 pg/ml (S.D. ±25 pg/ml); FSH 36.4 IU/l (S.D. ±57.3 ng/ml); we found cerebral blood flow increase in all studied slices: right cerebellar slice: 5.2%; left cerebellar slice: 4.1%; right thalamic slice: 3.8%; left thalamic slice: 3.3%; right ventricular slice: 7.5%*; left ventricular slice: 6.7%* (* P<0.05). Conclusions: Cerebral blood flow is lower in the postmenopausal women than in regularly menstruating women. HRT increases regional cerebral blood flow and this improvement coexists with an increase of serum 17β-estradiol level.     

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.     

Estrogen/progesterone replacement versus pravastatin and their sequential association in hypercholesterolemic postmenopausal women

Objectives: The objectives of this study were to assess serum lipid changes in response to an oral estrogen combined with progesterone (Group A) as compared with pravastatin (Group B) and to evaluate the additive effects of the sequential addition of statin to hormonal replacement therapy (HRT) and of HRT to statin. Methods: Thirty-seven of 63 hypercholesterolemic menopausal women initially submitted to a 4-month diet were randomised to oral conjugated estrogens (0.625 mg)/micronised progesterone (200 mg) or to pravastatin (40 mg). After 6 months, each group received both medications for another 6 months. Results: Nineteen percent of women corrected their lipids below decision levels with diet alone. Low density lipoprotein-cholesterol (LDL-C) decreased by 8±5% with HRT and by 26±3% (P<0.001) with the statin. These single medications increased high density lipoprotein-cholesterol (HDL-C) by 13±5% (P<0.01) and 11±7%, respectively. Combined interventions produced cumulative LDL-C reductions of 40±2 and 42±3% (P<0.001) and additive HDL-C augmentations of 16±4 and 23±5% (P<0.01) with proportional changes in apolipoprotein (Apo)B-100 and ApoA-1. These combined effects brought the atherogenic index (C/HDL-C) for Groups A and B, respectively, from a moderate (5.18±0.25 and 5.87±0.18) to a reduced (3.35±0.20 and 3.52±0.19) risk category. Triglycerides (TG) which were increased by HRT and decreased by the statin returned to baseline during combined treatments. No changes in diet, physical activity or anthropomorphometric measurements explained the lipid modifications. Conclusions: In menopausal patients with elevated C not responding to diet, pravastatin was most effective to decrease LDL-C, and oral estrogen–micronised progesterone most effective to increase HDL-C. Marked reduction of the atherogenic index is achieved by sequential combinations of medications resulting from beneficial cumulative effects on both C-LDL and C-HDL.     

Hysteroscopic findings in postmenopausal abnormal uterine bleeding: a comparison between HRT users and non-users

Objectives: The aim of our study was to investigate hysteroscopic findings in a sample of 410 menopausal women (hormonal replacement therapy, HRT users n=219 and HRT non-users n=191) and to evaluate the relationship between the presence of intrauterine disease, the use of HRT and the presence of AUB. Methods: Two hundred and nineteen women on HRT underwent standard office hysteroscopy by means of the Hamou hysteroscope (in 94 cases for abnormal uterine bleeding (AUB) and in 125 cases for periodic endometrium monitoring). One hundred and ninety-one women who had never received HRT were submitted to office hysteroscopy (154 for AUB and 37 for other reasons). Results: Intrauterine diseases are more frequent in patients who do not use HRT (P=0.02). Endometrial polyps is a frequent disease present in 30% of the sample (23.7% of HRT users and 30.8% of HRT non-users). Myomas were present in 8.7% of all patients examined (6.8% of HRT users and 11% of HRT non-users). Irregular bleeding in menopause is often associated with endouterine abnormalities: in symptomatic patients the frequency of endouterine diseases was 41% while in asymptomatic patients was 28% (P=0.003). In patients taking HRT (n=219) endouterine disease is demonstrated in 37% with AUB and in 26% without AUB (P=0.07). Conclusion: Benign intrauterine diseases (endometrial polyps and submucous myomas) are more frequent in postmenopausal women who do not use HRT. In patients taking HRT irregular bleeding is associated with intrauterine diseases; however, the absence of AUB does not exclude the presence of endometrial polyps or myomas.     

The impact of hormonal therapy for infertility on the age at menopause

Objectives: To look for possible association between past history of ovulation induction and age at menopause. Design: Women attending our postmenopausal outpatient clinic were asked to fill questionnaires with demographic data, obstetrical history (including treatment for infertility), and medical details related to menopause. Patients: The study group (n=31) consisted of women with a history of ovulation induction, and a control group (n=200) included women who did not experience such intervention. Results: The age at the final menstrual bleeding was 46.4±5 in the study group, and 50±4 for the control group (P<0.001). This difference was most prominent for women who had induction of ovulation prior to age 35 years: they entered menopause at age 43.8±5 years. Smoking had a weak effect on the age at menopause (48.5±4 for current, vs. 49.9±4 for non- or past-smokers; P<0.03). Conclusions: This retrospective and preliminary study raises the question whether hormonal manipulations and ovarian over-stimulation during fertility treatments could be a risk factor for premature menopause.     

Effects of progestins on estrogen-induced increase in C-reactive protein in postmenopausal women

Background: C-reactive protein (CRP) represents an independent risk factor for coronary disease and stroke. Because oral estrogens increase CRP levels, with inflammatory and thrombotic consequences, we determined whether the co-administration of a progestin might modify the estrogenic effect on CRP. Methods: In a non-randomized, non-blinded study, we measured C-reactive protein serum concentrations with high-sensitivity technique (hs-CRP) in 163 healthy postmenopausal women divided into groups as follow: 52 not taking hormones (referent group), and 111 taking hormone replacement therapy (HRT) (42 of whom treated with unopposed estrogen, and 69 with an estrogen/progestin combination). Results: Compared with non-users of hormones, median CRP levels were 66% (95% confidence interval: from 44 to 89%) higher and 112% (95% confidence interval: from 89 to 168%) higher among women using a combined estrogen/progestin regimen and, respectively, among women taking unopposed estrogen [1.54 mg/L in the referent group; 2.56 mg/L in the estrogen/progestin group (P=0.032), and 3.27 mg/L in the unopposed estrogen group (P=0.004)]. Furthermore, there was no difference in CRP distributions between women taking different types of progestins. Conclusion: concurrent progestin administration may attenuate estrogen’s pro-inflammatory effects, independently on the type of used progestin.     

Transdermal estrogen replacement therapy and plasma lipids in 693 French women

Objectives: The cardiovascular effects of transdermal estrogen are not so well established than those induced by oral estrogen. In a representative sample of French postmenopausal women, we assessed plasma lipid changes induced by transdermal 17β-estradiol. Methods: This cross-sectional study was carried out among the population sample of the third MONICA survey on cardiovascular risk factors. We selected 693 postmenopausal women according to the followed criteria; women with intact uterus and no menstruation for more than 12 months, women with bilateral oophorectomy, hysterectomized women older than 55 years and hysterectomized women who had followed hormone replacement therapy. We used multivariate linear regression models, taking into account confounding variables, to assess lipid changes induced by estrogen. Results: We compared 192 women currently taking transdermal 17β-estradiol (27 unopposed estrogen and 165 estrogen plus progestin) with 501 women without any hormonal treatment. After adjustment for living area, education level, income tax, smoking, alcohol consumption, physical activity, age and body mass index, transdermal estrogen replacement therapy (ERT) was significantly associated with lower levels of serum total cholesterol [6.10 (S.E., 0.11) vs 6.35 (0.09) mmol/l, P<0.01], triglycerides [1.06 (0.06) vs 1.23 (0.05) mmol/l, P<0.001], LDL-cholesterol [3.93 (0.11) vs 4.13 (0.09) mmol/l, P<0.05], VLDL-cholesterol [0.48 (0.03) vs 0.56 (0.02) mmol/l, P<0.001] and apolipoprotein B [1.20 (0.03) vs 1.26 (0.02) g/l, P<0.01]. Levels did not differ significantly for HDL-cholesterol [1.68 (0.05) vs 1.66 (0.04) mmol/l] and apolipoprotein A1 [1.79 (0.03) vs 1.81 (0.02) g/l]. Conclusion: Transdermal ERT may confer a cardiovascular protection by lowering atherogenic lipoproteins.