The effect of menopause on blood lipid and lipoprotein levels. The Icarus Study Group.

There is increasing evidence from epidemiological studies that exogenous estrogen (hormone replacement therapy) protects against the elevated risk of cardiovascular disease in women after the menopause. However, it is still uncertain whether the postmenopausal decrease in endogenous estrogen in itself contributes significantly to this increase in risk. Most of the studies that have provided evidence linking cardiovascular disease with menopause have involved North American women, who may differ significantly from Europeans in terms of lifestyle and diet. ICARUS (Italian Climacteric Research Group Study) is an observational study that involves Italian Menopause Clinics, with the objective of collecting observational data on menopause and its management. The results of a cross-sectional analysis of 9309 women, free from any hormonal treatment and enrolled up to March 1997, are reported here. Data show that the menopause has a marked effect on the circulating levels of lipids and lipoproteins. From pre- to post-menopause there are significant increases in total cholesterol (6.9% before and 4.4% after adjustment for covariates including chronological age, educational level, center, BMI, smoking habits, hypertension and diabetes, previous contraceptive use, and time since menopause), LDL (7.5% before, 4.0% after), and triglycerides (9.0% before, 3.2% (ns) after). However, there is no significant change in HDL. Among postmenopausal women, no effect on lipid profile of time since menopause was observed.

Determinants of age at menopause in Italy: results from a large cross-sectional study. ICARUS Study Group. Italian Climacteric Research Group Study.

OBJECTIVE: To identify the determinants of age at menopause in an Italian population, using data from the Italian Climacteric Research Group Study (ICARUS). METHODS: ICARUS is a prospective study of the effect of menopause on women's health that has been running in menopause clinics throughout Italy since 1995. A total of 4300 women with spontaneous menopause, aged 55 years or more and observed for the first time at the participating centres are included in the present analysis. RESULTS: The mean age at menopause in the total population was 50.9 years. After taking into account potential covariates, the women reported smoking, had a slightly lower mean age at menopause than non smokers 50.4 versus 50.9 years; P = 0.01. The mean age at menopause in nulliparae was 50.0 years, and, respectively 50.4, 50.6, 50.9, 51.2 and 50.9 years in those reporting 1, 2, 3, 4 and 5 or more births (P < 0.01). A low body mass index and an early age at menarche were associated with early menopause in the crude analysis, but these associations disappeared after taking into account the confounding factors. CONCLUSIONS: This study offers an estimate of the mean age at menopause of women attending menopause clinics in Italy, on the basis of the data obtained from a large sample. It also indicates that smoking and nulliparity are associated with early menopause.

The rule regulating pH changes during crystalloid infusion.

PURPOSE: To define the rule according to which crystalloid solutions characterized by different strong ion difference (SID) modify the acid-base variables of human plasma. METHODS: With a previously validated software, we computed the effects of diluting human plasma with crystalloid solutions ([SID] 0-60, 10 mEq/l stepwise). An equation was derived to compute the diluent [SID] required to maintain the baseline pH unchanged, at constant PCO2 and at every dilution fraction. The results were experimentally tested using fresh frozen plasma, re-warmed at 37°C, equilibrated at PCO2 35 and 78 mmHg, at baseline and after the infusion of crystalloid solutions with 0, 12, 24, 36, 48 mEq/l [SID]. RESULTS: The mathematical analysis showed that the diluent [SID] required to maintain unmodified the baseline pH equals the baseline bicarbonate concentration, [HCO3⁻], assuming constant PCO2 throughout the process. The experimental data confirmed the theoretical analysis. In fact, at the baseline [HCO3⁻] of 18.3 ± 0.3 mmol/l (PCO2 35 mmHg) the pH was 7.332 ± 0.004 and remained 7.333 ± 0.003 when the diluting [SID] was 18.5 ± 0.0 mEq/l. At baseline [HCO3⁻] of 19.5 ± 0.3 mmol/l (PCO2 78 mmHg) the pH was 7.010 ± 0.003 and remained 7.004 ± 0.003 when the diluting [SID] was 19.1 ± 0.1 mEq/l. At both PCO2 values infusion with [SID] lower or greater than baseline [HCO3⁻] led pH to decrease or increase, respectively. CONCLUSIONS: The baseline [HCO3⁻] dictates the pH response to crystalloid infusion. If a crystalloid [SID] equals baseline [HCO3⁻], pH remains unchanged at constant PCO2, whereas it increases or decreases if the [SID] is greater or lower, respectively.

Dilutional acidosis: where do the protons come from?

PURPOSE: To investigate the mechanism of acidosis developing after saline infusion (dilutional acidosis or hyperchloremic acidosis). METHODS: We simulated normal extracellular fluid dilution by infusing distilled water, normal saline and lactated Ringer's solution. Simulations were performed either in a closed system or in a system open to alveolar gases using software based on the standard laws of mass action and mass conservation. In vitro experiments diluting human plasma were performed to validate the model. RESULTS: In our computerized model with constant pKs, diluting extracellular fluid modeled as a closed system with distilled water, normal saline or lactated Ringer's solution is not associated with any pH modification, since all its determinants (strong ion difference, CO(2) content and weak acid concentration) decrease at the same degree, maintaining their relative proportions unchanged. Experimental data confirmed the simulation results for normal saline and lactated Ringer's solution, whereas distilled water dilution caused pH to increase. This is due to the increase of carbonic pK induced by the dramatic decrease of ionic strength. Acidosis developed only when the system was open to gases due to the increased CO(2) content, both in its dissociated (bicarbonate) and undissociated form (dissolved CO(2)). CONCLUSIONS: The increase in proton concentration observed after dilution of the extracellular system derives from the reaction of CO(2) hydration, which occurs only when the system is open to the gases. Both Stewart's approach and the traditional approach may account for these results.

Prolonged bronchodilating effect of formoterol versus procaterol in bronchial asthma.

The tolerability and the duration of effect of 12 micrograms of formoterol and 25 micrograms of procaterol administered via metered-dose aerosol to 12 stable asthmatic patients were evaluated in a double-blind, placebo controlled trial. FEV1, pulse rate, and blood pressure were measured at baseline and every two hours after dosing for 12 hours. The bronchodilation peak was observed after two hours for both drugs. Formoterol induced a significant bronchodilating effect for 12 hours compared with both baseline and placebo values. With procaterol, significant bronchodilation occurred for six hours compared with baseline values and four hours compared with placebo. No significant changes were observed in pulse rate and blood pressure with either drug. Four subjects complained of muscle tremor after procaterol administration. We conclude that in subjects with stable asthma, inhaled formoterol at a dose of 12 micrograms maintains significant bronchodilation for 12 hours after dosing and is very well tolerated. Further studies are required to evaluate effectiveness and tolerability of high dose formoterol treatment in acute severe asthma therapy.

Inhaled formoterol in the prevention of exercise-induced bronchoconstriction in asthmatic children.

The duration and magnitude of the effect of inhaled formoterol (12 micrograms) against exercise-induced bronchoconstriction (EIB) was compared with that of inhaled salbutamol (200 micrograms) and that of placebo in 15 children with asthma and EIB in a double-blind, double-dummy, within-patient, placebo-controlled study. The treatments were given by metered dose aerosol on three different days. The exercise test was performed at the 3rd and the 12th hour after dosing. The magnitude of the blocking effect was assessed both by evaluating the lowest FEV1 reading obtained within an hour after each exercise test and by considering the percent decrease below the baseline FEV1 measured before drug administration. Comparison of the lowest values obtained during the hour after each exercise test shows that formoterol was significantly better than both salbutamol (p = 0.022), and placebo (p = 0.001) in limiting exercise-induced bronchoconstriction after the first exercise test (3 h after dosing), while no difference was observed between salbutamol and placebo (p = 0.198). After the second exercise test (12 h after dosing), formoterol again proved to be more effective than both salbutamol (p = 0.008) and placebo (p = 0.001), and no significant difference was observed between salbutamol and placebo (p = 0.391). The evaluation of the mean percentage decrease in FEV1 confirmed the results in favor of formoterol in both the exercise tests. No adverse effects were reported in any treatment group. The protection against EIB is significantly more prolonged after formoterol than after salbutamol, and persists for 12 h after dosing.

Sociodemographic and clinical factors associated with HRT use in women attending menopause clinics in Italy.

OBJECTIVE: The aim of this analysis is to find any association between the use of hormone replacement therapy (HRT) and sociodemographic and clinical factors among women attending 54 menopause clinics in Italy. METHODS: The analysis includes data relating to 17,851 women who attended one of 54 menopause clinics in Italy for general gynecological evaluations and counselling between 1995 and 1997. The characteristics of women reporting ever HRT use were compared with those of never users. The odds ratios (ORs) of HRT use were computed in relation to selected reference categories, together with their 95% confidence intervals (CIs). RESULTS: Of the 17,851 women interviewed, 8539 reported ever HRT use. The mean age of the never and ever HRT users was 52.8 years and 53.7 years, respectively. Higher education was associated with an increased frequency of HRT use: in comparison with women reporting no or primary-/middle-school education, the OR of HRT use of women reporting a high-school diploma or university degree was 1.3 (95% CI 1.1-1.6). HRT use tended to be less frequently reported with increasing body mass index (BMI): in comparison with women whose BMI was < 23.4 kg/m2, the OR of HRT use in those with a BMI of 23.4-26.1 kg/m2 and > or = 26.2 kg/m2 was 0.8 (95% CI 0.8-0.9) and 0.6 (95% CI 0.5-0.7), respectively. Among the postmenopausal women, those who had undergone surgical menopause had an OR of HRT use of 1.3 (95% CI 1.2-1.4). A history of breast cancer was associated with a lower frequency of HRT use (OR 0.3, 95% CI 0.2-0.4). Likewise, a history of thromboembolic disease (OR 0.5, 95% CI 0.4-0.7) or myocardial infarction (OR 0.7, 95% CI 0.6-0.9) was associated with a lower frequency of HRT use. CONCLUSIONS: In our study population, the variable most closely related to HRT use was education/social class, thus underlining the impact of information campaigns on HRT and women's health. Among the medical determinants, our analysis indicates that a history of myocardial infarction, thromboembolic disease or breast cancer is associated with less frequent use of HRT.