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.     

Effect of tibolone on breast symptoms resulting from postmenopausal hormone replacement therapy

Objective: To evaluate the incidence of breast symptoms in a population treated with various hormone replacement therapy (HRT) regimens and to detect the variations in breast symptomatology after HRT changing to tibolone administration. Methods: This prospective placebo-controlled clinical trial was conducted on healthy women on HRT reporting breast symptoms. A questionnaire was given to each woman to detect breast symptomatology. Breast tenderness and mastalgia were evaluated using a visual analogue scale (VAS). According to the choice of the each woman with breast symptoms, the HRT was changed to tibolone (2.5 mg/day per os) or to calcium carbonate (1 tab/day, placebo group). The duration of treatment was of 12 months. After 6 and 12 months breast symptomatology was re-evaluated. Results: Among the 600 screened women, 64 (10.7%) were suffering from breast symptomatology. After 6 and 12 months of treatment with tibolone or placebo, mean VAS score for breast tenderness and for mastalgia resulted significantly (P<0.05) decreased, without differences between groups, in comparison with basal value. Only one woman had no improvement from the breast symptoms with tibolone administration. Conclusions: Shifting from classical HRT to tibolone is followed by a significant reduction of breast symptomatology in postmenopausal women with breast complaints similar to that obtained with treatment withdrawal.     

Hormone replacement therapy improves arterial stiffness in normotensive postmenopausal women

Objectives: Aortic stiffness, determined by the pulse wave velocity (PWV), is an independent marker of cardiovascular risk. PWV is mainly influenced by age-associated alterations of arterial wall structure and blood pressure (BP). To determine the impact of hormone replacement therapy (HRT) on arterial compliance in normotensive, postmenopausal women, we examined the effects of HRT on PWV. Methods: Fifty-six postmenopausal women aged 50–70 years were recruited into the present retrospective study from the patients visiting our menopause clinic. Twenty-seven women who were prescribed HRT (14 on estrogen alone and 13 on estrogen plus progestogen) for several months to 6 years and an age-matched group of 29 women not on HRT were studied (Study 1). Nine postmenopausal women were also studied before and at 4 weeks of the treatment of estrogen replacement therapy (ERT) (Study 2). Brachial to ankle PWV (baPWV), which is correlated with aortic PWV, was determined using an automatic device, BP-203PRE. Results: In Study 1, PWV was significantly correlated with age in both groups (controls: r=0.392, P=0.035; HRT group: r=0.471, P=0.013), and HRT significantly lowered the PWV value at all ages examined (Mean±S.D. of baPWV in controls: 1382.2±114.1; HRT: 1245.3±124.8, P=0.0001). In Study 2, baPWV decreased significantly after ERT (P<0.05), without a significant change in systolic BP (P=0.851). Conclusions: Estrogen appears to improve arterial compliance independently of BP within 4 weeks.     

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.     

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.     

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.     

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.     

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 HRT on hormone responses to resistance exercise in post-menopausal women

Purpose: The purpose of this study was to evaluate the effect of hormone replacement therapy (HRT) on the acute and chronic hormonal responses to resistance exercise in post-menopausal women. Methods: Thirty-two post-menopausal women were recruited for this study; 16 who were currently using HRT and 16 who were not using HRT. Subjects in both the HRT and NHRT groups were randomly assigned to either a resistance training group (N=16; 8 HRT and 8 NHRT) or a control group (N=16; 8 HRT and 8 NHRT). The training group completed a supervised resistance training program three times a week for 12 weeks. To evaluate changes in hormone levels, resting blood samples were drawn at weeks 0, 4, and 13 of the program. In addition, at weeks 0 and 13, post-exercise blood samples were drawn in order to examine the hormone response to an acute bout of resistance exercise. Samples were analyzed for serum growth hormone (GH), insulin-like growth factor-1 (IGF-1), testosterone, estradiol, dehydroepiandrosterone (DHEA), and cortisol. Results: There were no significant changes in resting hormone levels between weeks 0, 4, and 13 of the training program. There was a significant week-by-group interaction for DHEA (P<0.05) and cortisol (P<0.05) with the NHRT-training group having a greater post-exercise increase in DHEA and cortisol after training. Overall, the post-exercise GH levels were significantly greater than pre-exercise (P<0.05) or recovery levels (P<0.01). There were no significant differences between HRT and NHRT groups in the acute hormone response to exercise. Conclusion: These results indicate that HRT will not have an effect on the acute or chronic hormone response to a recreational resistance training program in post-menopausal women.     

Influence of psycho-social factors on climacteric symptoms

Background: It has been suggested that psycho-social factors may be crucial in the development of climacteric symptoms. Material and methods: In order to evaluate the effect of psycho-social and biological factors on menopausal symptoms, Greene (climacterical symptoms), Cooper (psychosomatic symptoms of stress), Smilkstein (family dysfunction), Duke-UNC (social support) and Israel (life events) tests were passed to 300 Chilean women between 40 and 59 years of age. Data were evaluated with ANOVA, χ² and logistic regression using the Epi-info package. Results: Perimenopausal women had a significant increase in stress and climacteric symptoms; however comparing with pre and postmenopausal women, tests for life events, family dysfunction or social support did not show any differences. A history of premenstrual syndrome was the main risk predictor f or climacteric symptoms (OR: 3.6, IC: 1.5–8.5; P<0.03), followed by perimenopausal state (OR: 2.9, IC: 1.4–6.0; P<0.001) and negative life events (OR: 2.3, IC: 1.0–5.3; P<0.05). The psycho-social factors were predictors for anxiety and depression; on the other hand, perimenopausal state was a risk factor for somatic and vasomotor symptoms. During premenopause, women with regular cycles and vasomotor symptoms have more psychological symptoms and stress. Conclusion: Climacteric symptoms that appear in the perimenopause are more intense in those women who have a biological predisposition such as premenstrual syndrome and are modulated by psycho-social factors.     

The effect of hormone replacement therapy on diastolic left ventricular function in hypertensive and normotensive postmenopausal women

Objectives: To evaluate the effect of hormone replacement therapy (HRT) on left ventricular diastolic function in a group of hypertensive and normotensive postmenopausal women. Methods: Left ventricular diastolic function at rest was evaluated by M-mode, two-dimensional and Doppler echocardiography in 19 postmenopausal women with normal blood pressure and 11 postmenopausal women with mild hypertension, before treatment and during 12 months of HRT. Transdermal estradiol was used in women with a surgical menopause and a sequential regimen of transdermal estradiol and peroral medroxyprogesterone acetate in women with a spontaneous menopause. The parameters assessed were: body mass index, heart rate, ejection fraction of the left ventricle (EF), septal (SW) and posterior wall (PW) dimensions, left ventricular end-systolic (LVsd) and end-diastolic (LVdd) dimensions and volumes (ESV, EDV), total diastolic time (DT), duration of the early (Ei) and of the late (Ai) filling phase, peak velocity of the early (E) and late mitral flow (A), A/E velocity ratio and systolic and diastolic blood pressure. Quantitative data were analyzed using unpaired t-test, MANOVA and multiple regression analysis where appropriate. Results: Hypertensive postmenopausal women had significantly higher SW (P<0.05), PW (P<0.05), A/E (P<0.05) and A (P<0.001) than normotensive postmenopausal women, before therapy. After 12 months of HRT a significant decrease in SW, PW, LVsd, ESV and increase in EF, DT, Ei and E was observed in both hypertensive and normotensive postmenopausal women. Heart rate slowed and systolic pressure decreased significantly only in normotensive postmenopausal women on HRT. Conclusion: HRT of 12 months' duration does not deteriorate left ventricular diastolic function of both hypertensive and normotensive postmenopausal women. Improvement in some parameters of diastolic function could be partially explained by the decrease in heart rate and systolic pressure, induced by therapy.     

Determinants of the intention to adopt hormone replacement therapy among premenopausal women

Objective: To identify the psychosocial factors that influence the intention to adopt hormone replacement therapy (HRT) at menopause. Methods: Random Digit Dialing was used to recruit 644 premenopausal non-hysterectomized women aged 45–54. Data were collected using a telephone questionnaire previously developed according to the theory of planned behaviour. Variables measured were: intention to adopt HRT (INT); attitude towards HRT (Aact); perceived social norm (SN); perceived behavioural control (PBC); and personal normative belief (PNB). Socio-demographic data were also obtained. Results: Stepwise multiple regression of INT on the theoretical variables yielded an R² of 0.70. The determinants were Aact (β=0.39, P<0.001), PNB (β=0.25, P<0.001), PBC (β=0.23, P<0.001) and SN (β=0.12, P<0.001). Women with a strong intention to adopt HRT represented 25% of the sample. These women were more likely to believe that adopting HRT would have the following positive consequences: an improvement in general well-being, the prevention of health problems, an improvement in interpersonal relationships, an increase in productivity, the regulation of mood swings and a reduction of hot flashes. They were also more likely to believe in the following negative consequences: side-effects, an increased risk of cancer, the likelihood of weight gain, and interference in the natural course of menopause (all at P<0.001). Conclusion: Actions that target behaviourial beliefs regarding HRT and perceived barriers to its adoption are most likely to influence adoption of HRT.     

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.     

Effect of hormone replacement therapy on lipids in perimenopausal and early postmenopausal women

Objective: To determine the effects of oral sequential hormone replacement therapy (HRT) on lipid-profile in perimenopausal and early postmenopausal women. Methods: We performed a single-center, randomized, placebo-controlled trial. The trial was double blind with respect to 17β-estradiol/desogestrel (17β-E-D) and placebo and open with respect to conjugated estrogens/norgestrel (CEE-N). A total of 125 healthy perimenopausal and early postmenopausal women, aged 43–58 years, were recruited from the general population in Zoetermeer, the Netherlands. The intervention consisted of 6 months treatment with 1.5 mg 17β-estradiol/0.15 mg desogestrel (n=53), 0.625 mg conjugated estrogens/0.15 mg norgestrel (n=36) or placebo (n=36). At baseline, cycle 1, 3 and 6, overnight fasting blood samples were obtained in which lipids were determined. We used linear regression analysis to calculate differences in mean change from baseline in lipids in the active treatment groups compared to placebo. Results: In both treatment groups significant (P<0.05) falls in low-density-lipoprotein (LDL)-cholesterol (17β-E-D: −7.8% and CEE-N: −8.4%) and lipoprotein(a) (17β-E-D: −11.7% and CEE-N: −28.3%) were found compared to placebo. Apolipoprotein A1 (17β-E-D: 6.8% and CEE-N: 7.3%) and HDL-cholesterol (17β-E-D: 6.4% and CEE-N: 8.0%) significantly increased compared to placebo. No significant changes were found in the other lipids. Mean changes from baseline in total cholesterol, LDL-cholesterol and apolipoprotein B were significantly more pronounced in postmenopausal women compared to perimenopausal women, adjustment for age-differences did not change the results. Conclusion: Treatment of perimenopausal and early postmenopausal women with 17β-E-D or CEE-N changes their lipid-profile in a potentially anti-atherogenic direction. Changes appear to be more pronounced in postmenopausal women compared to perimenopausal women.     

Efficacy and safety of a soy isoflavone extract in postmenopausal women: a randomized, double-blind, and placebo-controlled study

OBJECTIVE: To investigate the efficacy of soy isoflavone on climacteric symptoms in postmenopausal women. DESIGN: In this double-blind, randomized, placebo-controlled study, a total of 80 women (mean age = 55.1 years), who reported 5 or more hot flush episodes per day, were randomized to receive either 250 mg of standardized soy extract (Glycine max AT) a total of 100mg/day of isoflavone (n = 40) or placebo (n = 40). Exclusion criteria included: contra-indication for hormone therapy (HT), chronic gastrointestinal diseases, and users of HT within the preceding 6-months. For 10-months, climacteric symptoms were evaluated using a score card and the menopausal Kupperman index. Compliance and safety were also assessed. At baseline and the end of the study, lipid and hormonal profiles, as well as vaginal, mammographic and ultrasonographic parameters were measured. The t-test, Wilcoxon test and ANOVA were used in the statistical analysis. RESULTS: At baseline, the mean number of hot flushes was 9.6 +/- 3.9 per day in the isoflavone group and 10.1+/-4.9 in the placebo group (p>0.05). After 10 months, there was a significant reduction in frequency of hot flushes among isoflavone users when compared to those on placebo (3.1 +/- 2.3 and 5.9 +/- 4.3, respectively) (p<0.001). Kupperman index mean values showed a significant reduction in both groups. However, soy isoflavone was significantly superior to placebo, in reducing hot flush severity (69.9% and 33.7%, respectively) (p<0.001). Endometrial thickness, mammography, vaginal cytology, lipids and hormonal profile did not change in both groups. No serious adverse event related to isoflavone treatment was reported. CONCLUSIONS: The soy isoflavone extract exerted favorable effects on vasomotor symptoms and good compliance, providing a safe and effective alternative therapeutic for postmenopausal women.     

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.     

Value of C-reactive protein levels and IL-6 in predicting events levels in women at increased cardiovascular risk

Background: Elevated C-reactive protein (CRP) levels due to of heightened vascular inflammatory state in vascular conditions are often associated with elevated interleukin-6 (IL-6) levels since during inflammation CRP production in the liver is induced by IL-6. It has been suggested that CRP may be a predictors of unfavourable outcome in postmenopausal women (PMW) receiving hormone replacement therapy. Because of the possible metabolic effect of hormone replacement therapy (HRT) on CRP, the relative predictive importance of CRP and IL-6 levels in PMW receiving HRT remains to be elucidated. Methods: We measured plasma levels of CRP and IL-6 levels in 346 consecutive PMW (mean age 66±9 years) with cardiovascular risk >20 in 10 years followed during a 36 month period. Women underwent measurement of inflammatory cytokines at baseline and were allocated to two groups according to the willingness to take hormone replacement therapy. All women underwent a further measurement of CRP and IL-6 at 3 and 6 months. Health status was assessed by out patient visits and hospital charts. Results: During 1 year follow up, three patient died, four had a major cardiovascular event, three had a unstable angina, two had a transient ischemic attack and two patients underwent PTCA. PMW with events had higher CRP levels compared with patients with no events (1.94±0.61 versus 1.43±0.21, P<0.05) but still within the limits of normal. Also baseline IL-6 plasma levels were significantly higher in PMW with events than in those without events (0.87±0.23 versus 0.54±0.18, P<0.05). The increase in CRP and IL-6 with HRT was significantly higher in patients with events than in those with no events (CRP: 81±12% versus 76±21%, P<0.05; IL-6 9±3% versus −14±7%, P<0.05). In a stepwise multivariate analysis, IL-6 levels resulted a stronger predictor of outcome than CRP. CRP levels were predictors of future events only after removal of IL-6 levels and presence of cardiovascular symptoms from the analysis. CRP levels were associated with an unfavourable outcome only when IL-6 levels were also elevated. The increase in CRP with HRT during follow up was not associated to an increased event rate. Conclusion: Our study showed that CRP levels are increased in PMW receiving HRT. Elevated IL-6 levels may identify those PMW at increased 1 year risk. CRP levels predict events only when they are coupled with elevated IL-6 levels.     

The effect of tibolone versus continuous combined norethisterone acetate and oestradiol on memory, libido and mood of postmenopausal women: a pilot study

Objective: Several studies have shown a positive effect of oestrogen on memory, mood and well-being but these data are controversial and focus particularly on the effect of oestrogen alone. In this pilot study we have investigated the effect of a continuous combination of norethisterone acetate 1 mg and oestradiol valerate 2 mg (Kliogest®) versus tibolone (Livial®) on memory, sexuality and mood. Methods: Twenty-two postmenopausal women, age range 51–57, were randomised to a 6 months single blind interventional study treatment with either continuous combined oestradiol plus norethisterone acetate, or tibolone. Computerised psychological test of memory, mood and libido were administered both before and at the end of the 6 months treatment. Results: Fourteen patients completed the study; eight on Livial® and six on Kliogest®. Recognition memory was improved by Kliogest but not by Livial (P<0.05) while either drug equally improved both the reaction time (P<0.01) and accuracy of performance (P<0.001) of categorical semantic memory. Both the treatments improved libido significantly (P<0.05), while the mood did not change with either. Conclusion: The results suggest that both these forms of hormonal replacement therapy improve the efficiency of memory performance and libido. However, a combination of oestradiol and norethisterone acetate seems to be marginally more effective on improving cognitive processes.     

B cell subsets in postmenopausal women and the effect of hormone replacement therapy

Objectives: In elderly subjects the capacity for antibody production is depressed. This immunosenescence state of humoral immunity is associated with the occurrence of autoimmune disorders involving CD5⁺ B (B-1) cells. Since estrogen is capable of stimulating the production of autoantibodies, this sex steroid hormone may be a contributing cause of the higher incidence of autoimmune diseases in women. In the present study, B cell subsets in women during the postmenopausal period was determined. The effect of hormone replacement therapy (HRT) on B cell subsets was examined to establish whether the administration of gonadal hormones influence humoral immunity in postmenopausal women. Methods: Forty six untreated pre- and postmenopausal women and 39 women on HRT were studied. The proportion of B-1 (CD5⁺) and conventional CD5⁻ B (B-2) lymphocytes was determined by two-color flow cytometry. Serum autoantibodies to a nuclear antigen and to interleukin (IL)-1 were measured by immunofluorescence and by radioimmunoassay, respectively. Thirteen women were examined prospectively before and during HRT. Results: In late postmenopausal women (≥30 years postmenopausal period), the proportion of B-2 cells was significantly reduced (p<0.01) compared to those of premenopausal and perimenopausal women. HRT induced a significant (p<0.01) increase in the percentage of B-2 cells, while that of B-1 cells remained unchanged. HRT did not affect autoantibody production. Conclusion: HRT may retard the progress of immunosenescence by increasing the production of B-2 cells. Moreover, HRT appears not to increase the risk of autoimmune diseases developing in postmenopausal women.     

Polyunsaturated fatty acids (PUFAs) might reduce hot flushes: an indication from two controlled trials on soy isoflavones alone and with a PUFA supplement

OBJECTIVES: To investigate the effect on hot flushes of a soy isoflavone extract alone (Study A) and with the addition of a supplement of polyunsaturated fatty acids, PUFAs (Study B). METHODS: Subjects were postmenopausal women (29 in Study A, 28 in Study B) with more than five troublesome hot flushes per day. Both studies were double-blind randomized placebo-controlled trials with cross-over design, of 24-week duration. After a 2-week observation period, they were randomized to receive two capsules per day providing 60mg of isoflavones or placebo for 12 weeks; thereafter, women who had taken isoflavones were given placebo for a second 12-week period, and vice-versa. Women in the Study B were given also two capsules per day containing a PUFA supplement for the entire 24-week test period. RESULTS: Both studies showed the isoflavone extract to have no greater efficacy on hot flushes than the placebo. During the 24 weeks of the Study B there was a progressive and highly significant reduction in the number of hot flushes, independent of whether the women had begun with isoflavones or with placebo. CONCLUSION: In these two trials the isoflavone extract did not show greater efficacy on the hot flushes than the placebo. The reduction of hot flushes observed in the Study B might be due to the PUFA supplement. PUFAs, particularly Omega (Omega) 3-fatty acids, could reduce hot flushes through their influence on neuronal membranes and/or the modulation of the neurotransmitter function and the serotoninergic system. Studies specifically designed to document the action of PUFAs on hot flushes would be welcome.