Francisco Gómez Real

Is age at menopause increasing across Europe? : results on age at menopause and determinants from two population-based studies

Objective: To investigate the variability and determinants of menopause age in two European cohort studies, the European Respiratory Health Survey and the Swiss Air Pollution and Lung Disease in Adults Cohort. Methods: Age at menopause was estimated in 5,288 women, aged 30 to 60 years, randomly selected in nine European countries between 1998 and 2002. Determinants of natural and surgically induced menopause were investigated by Cox regression and heterogeneity by meta-analysis. Follicle-stimulating hormone and luteinizing hormone levels were assessed in a subsample. Results: A quarter of the women were postmenopausal by age 50.8 years. Median age of natural menopause was 54 years. Hormone levels were within expected ranges for premenopausal and postmenopausal women. Surgically induced menopause was highly prevalent (22%-47%), associated with earlier timing of menopause. Determinants of earlier menopause were current smoking (hazard ratio [HR], 1.59; 95% CI, 1.27-1.98), body mass index greater than 30 kg/m2 (HR, 1.32; 95%, CI, 1.02-1.70), and low physical activity (HR, 1.37; 95%, CI, 1.12-1.67). The determinant for later menopause was multiparity (HR, 0.74; 95% CI, 0.62-0.89). Predictors were similar for naturally and surgically induced menopause. Oral contraceptive use yielded heterogeneous effects on timing of menopause. Later birth was associated with later menopause (HR, 0.934; 95% CI, 0.91-0.96). This evidence of a secular trend is heterogeneous across countries. Conclusions: Age at menopause varies across Europe, shifting toward higher ages. This secular trend seems paradoxical because several adult determinants, that is, overweight, smoking, sedentarity, and nulliparity, associated with early menopause are on the rise in Europe. The heterogeneity of the secular trend suggests additional country-specific factors not included in the study, such as improved childhood nutrition and health, that have an influence on reproductive aging.

Gender differences in prevalence, diagnosis and incidence of allergic and non-allergic asthma: a population-based cohort

Background Although women with severe non-allergic asthma may represent a substantial proportion of adults with asthma in clinical practice, gender differences in the incidence of allergic and non-allergic asthma have been little investigated in the general population. Methods Gender differences in asthma prevalence, reported diagnosis and incidence were investigated in 9091 men and women randomly selected from the general population and followed up after 8–10 years as part of the European Community Respiratory Health Survey. The protocol included assessment of bronchial responsiveness, IgE specific to four common allergens and skin tests to nine allergens. Results Asthma was 20% more frequent in women than in men over the age of 35 years. Possible under-diagnosis of asthma appeared to be particularly frequent among non-atopic individuals, but was as frequent in women as in men. The follow-up of subjects without asthma at baseline showed a higher incidence of asthma in women than in men (HR 1.94; 95% CI 1.40 to 2.68), which was not explained by differences in smoking, obesity or lung function. More than 60% of women and 30% of men with new-onset asthma were non-atopic. The incidence of non-allergic asthma was higher in women than in men throughout all the reproductive years (HR 3.51; 95% CI 2.21 to 5.58), whereas no gender difference was observed for the incidence of allergic asthma. Conclusions This study shows that female sex is an independent risk factor for non-allergic asthma, and stresses the need for more careful assessment of possible non-allergic asthma in clinical practice, in men and women.

Early Age at Menarche, Lung Function, and Adult Asthma

RATIONALE hormonal and metabolic status appears to influence lung health in women, and there are findings suggesting that early menarche may be related to asthma, cardiovascular disease, diabetes, and breast cancer. OBJECTIVES this study investigates whether age at menarche is related to adult lung function and asthma. METHODS among participants in the European Community Respiratory Health Survey II, 3,354 women aged 27-57 years from random population samples in 21 centers responded to a questionnaire concerning womens health (1998-2002). Of these women, 2,873 had lung function measurements, 2,136 had measurements of bronchial hyperreactivity, and 2,743 had IgE measurements. Logistic, linear, and negative binomial regression analyses included adjustment for age, height, body mass index, education, smoking, family size, and center. MEASUREMENTS AND MAIN RESULTS FEV(1) and FVC were lower and asthma was more common in women with early menarche. Women reporting menarche at age 10 years or less, as compared with women with menarche at age 13 years (reference category), had lower FEV(1) (adjusted difference, -113 ml; 95% confidence interval [CI], -196 to -33 ml) and FVC (-126 ml; 95% CI, -223 to -28 ml); also lower FEV(1) expressed as a percentage of the predicted value (-3.28%; 95% CI, -6.25 to -0.30%) and FVC expressed as a percentage of the predicted value (-3.63%; 95% CI, -6.64 to -0.62%). Women with early menarche more often had asthma symptoms (odds ratio, 1.80; 95% CI, 1.09-2.97), asthma with bronchial hyperreactivity (odds ratio, 2.79; 95% CI, 1.06-7.34), and higher asthma symptom score (mean ratio, 1.58; 95% CI, 1.12-2.21). CONCLUSIONS women with early menarche had lower lung function and more asthma in adulthood. This supports a role for metabolic and hormonal factors in womens respiratory health.

Oral contraception, body mass index, and asthma: a cross-sectional Nordic-Baltic population survey.

BACKGROUND Emerging evidence suggests that sex steroid hormones may influence airways obstruction, and that metabolic status may modify potential effects. OBJECTIVE This study investigated the association between use of oral contraceptive pills (OCPs) and asthma in a Nordic-Baltic population-based study, while taking into account possible interplay with body mass index (BMI). METHODS Postal questionnaires were sent to subjects in Denmark, Estonia, Iceland, Norway, and Sweden from 1999 to 2001 (response rate in women, 77%). Pregnant women, women using hormone replacement therapy, and women >45 years were excluded. Analyses included 5791 women 25 to 44 years old, of whom 961 (17%) used OCP. Logistic regression analyses included adjustment for smoking, irregular menstruation, BMI, age, type of dwelling, and center. RESULTS Oral contraceptive pills were associated with increased risk for asthma (odds ratio, 1.42; 95% CI, 1.09-1.86), asthma with hay fever (1.48; 1.08-2.03), wheeze with shortness of breath (1.27; 1.02-1.60), hay fever (1.25; 1.06-1.48), and >/=3 asthma symptoms (1.29; 1.05-1.58). The findings were consistent between centers. The associations were present only among normal weight women (BMI 20-25 kg/m(2), asthma: 1.45; 1.02-2.05) and overweight women (BMI >25kg/m(2): 1.91; 1.20-3.02), but not among lean women (BMI <20 kg/m(2): 0.41; 0.12-1.40). Interaction between BMI and OCP in association with asthma was significant (P(interaction) < .05). CONCLUSIONS Women using oral contraceptive pills had more asthma. This was found only in normal weight and overweight women, indicating interplay between sex hormones and metabolic status in effect on the airways. The findings originate from a cross-sectional postal survey and should be interpreted with caution; it is recommended that asthma symptoms are included in clinical trials of oral contraception.

Early Life Origins of Lung Ageing: Early Life Exposures and Lung Function Decline in Adulthood in Two European Cohorts Aged 28-73 Years

Objectives Early life environment is essential for lung growth and maximally attained lung function. Whether early life exposures impact on lung function decline in adulthood, an indicator of lung ageing, has scarcely been studied. Methods Spirometry data from two time points (follow-up time 9–11 years) and information on early life exposures, health and life-style were available from 12862 persons aged 28–73 years participating in the European population-based cohorts SAPALDIA (n = 5705) and ECRHS (n = 7157). The associations of early life exposures with lung function (FEV1) decline were analysed using mixed-effects linear regression. Results Early life exposures were significantly associated with FEV1 decline, with estimates almost as large as personal smoking. FEV1 declined more rapidly among subjects born during the winter season (adjusted difference in FEV1/year of follow-up [95%CI] -2.04ml [-3.29;-0.80]), of older mothers, (-1.82 ml [-3.14;-0.49]) of smoking mothers (-1.82ml [-3.30;-0.34] or with younger siblings (-2.61ml [-3.85;-1.38]). Less rapid FEV1-decline was found in subjects who had attended daycare (3.98ml [2.78;5.18]), and indicated in subjects with pets in childhood (0.97ml [-0.16;2.09]). High maternal age and maternal smoking appeared to potentiate effects of personal smoking. The effects were independent of asthma at any age. Conclusion Early life factors predicted lung function decline decades later, suggesting that some mechanisms related lung ageing may be established early in life. Early life programming of susceptibility to adult insults could be a possible pathway that should be explored further.

Respiratory health in women: from menarche to menopause

Gender differences in respiratory health have, in recent years, been the focus of considerable scientific effort. This paper reviews recent literature on respiratory health in women in relation to age at menarche, menstrual cycle, irregular menstruation, polycystic ovarian syndrome, menopause and exogenous sex hormones. This literature provides substantial evidence that hormonal status plays an important role for respiratory health in women. Effects of hormonal status on the airways often appear to be heterogeneous and recent literature in particular suggests that the interplay between hormonal and metabolic factors is important. A view to developmental factors may also be relevant for the understanding of respiratory health according to hormonal status in women. Further knowledge of respiratory health in women holds interesting potential for intervention and personalized treatment.

Menstrual cycle and respiratory symptoms in a general Nordic-Baltic population.

RATIONALE There is little knowledge of variations in respiratory symptoms during the menstrual cycle in a general population, and potential modifying factors are not investigated. OBJECTIVES To investigate menstrual cycle variation in respiratory symptoms in a large general population, using chronobiology methodology, and stratifying by body mass index (BMI), smoking, and asthma status. METHODS A total of 3,926 women with regular cycles less than or equal to 28 days and not taking exogenous sex hormones answered a postal questionnaire regarding the first day of their last menstruation and respiratory symptoms in the last 3 days. Moving 4-day means were computed to smooth uneven records of daily sampling; best-fitting 28-day composite cosine curves were applied to each time series to describe rhythmicity. MEASUREMENTS AND MAIN RESULTS Significant rhythmic variations over the menstrual cycle were found in each symptom for all subjects and subgroups. Wheezing was higher on cycle Days 10-22, with a midcycle dip near the time of putative ovulation (approximately Days 14-16) in most subgroups. Shortness of breath was higher on days 7-21, with a dip just before midcycle in many subgroups. Cough was higher just after putative ovulation for subjects with asthma, BMI greater than or equal to 23 kg/m(2), and smokers, or just before ovulation and menses onset for low symptomatic subgroups. CONCLUSIONS Respiratory symptoms varied significantly during the menstrual cycle and were most frequent from the midluteal to midfollicular stages, often with a dip near the time of ovulation. The patterns varied by BMI, smoking, and asthma status. These relations link respiratory symptoms with hormonal changes through the menstrual cycle and imply a potential for individualized chronotherapy for respiratory diseases.

Respiratory health in cleaners in Northern Europe : is susceptibility established in early life?

Rationale There is some evidence that maternal smoking increases susceptibility to personal smoking’s detrimental effects. One might question whether early life disadvantage might influence susceptibility to occupational exposure. Objectives In this cross-sectional study we investigated respiratory symptoms, asthma and self-reported chronic obstructive pulmonary disease (COPD) as related to working as a cleaner in Northern European populations, and whether early life factors influenced susceptibility to occupational cleaning’s unhealthy effects. Methods The RHINE III questionnaire study assessed occupational cleaning in 13,499 participants. Associations with respiratory symptoms, asthma and self-reported COPD were analysed with multiple logistic regressions, adjusting for sex, age, smoking, educational level, parent´s educational level, BMI and participating centre. Interaction of occupational cleaning with early life disadvantage (maternal smoking, severe respiratory infection <5 years, born during winter months, maternal age at birth >35 years) was investigated. Main Results Among 2138 ever-cleaners the risks of wheeze (OR 1.4, 95% CI 1.3–1.6), adult-onset asthma (1.5 [1.2–1.8]) and self-reported COPD (1.7 [1.3–2.2]) were increased. The risk increased with years in occupational cleaning (adult-onset asthma: ≤1 year 0.9 [0.7–1.3]; 1–4 years 1.5 [1.1–2.0]; ≥4 years 1.6 [1.2–2.1]). The association of wheeze with cleaning activity ≥4 years was significantly stronger for those with early life disadvantage than in those without (1.8 [1.5–2.3] vs. 1.3 [0.96–1.8]; pinteraction 0.035). Conclusions Occupational cleaners had increased risk of asthma and self-reported COPD. Respiratory symptom risk was particularly increased in persons with factors suggestive of early life disadvantage. We hypothesize that early life disadvantage may increase airway vulnerability to harmful exposure from cleaning agents later in life.

Hormonal factors and respiratory health in women – a review

Sex hormones appear to play an important role in the lung health of women. This is, however, poorly understood and, in most aspects, poorly investigated; and the literature has been contradictory and confusing. This review presents recent research concerning the involvement of sex hormones in respiratory health of adult women, using the population surveys European Community Respiratory Health Survey and Respiratory Health in Northern Europe.

Menopause Is Associated with Accelerated Lung Function Decline.

Rationale: Menopause is associated with changes in sex hormones, which affect immunity, inflammation, and osteoporosis and may impair lung function. Lung function decline has not previously been investigated in relation to menopause. Objectives: To study whether lung function decline, assessed by FVC and FEV1, is accelerated in women who undergo menopause. Methods: The population‐based longitudinal European Community Respiratory Health Survey provided serum samples, spirometry, and questionnaire data about respiratory and reproductive health from three study waves (n = 1,438). We measured follicle‐stimulating hormone and luteinizing hormone and added information on menstrual patterns to determine menopausal status using latent class analysis. Associations with lung function decline were investigated using linear mixed effects models, adjusting for age, height, weight, pack‐years, current smoking, age at completed full‐time education, spirometer, and including study center as random effect. Measurements and Main Results: Menopausal status was associated with accelerated lung function decline. The adjusted mean FVC decline was increased by −10.2 ml/yr (95% confidence interval [CI], −13.1 to −7.2) in transitional women and −12.5 ml/yr (95% CI, −16.2 to −8.9) in post‐menopausal women, compared with women menstruating regularly. The adjusted mean FEV1 decline increased by −3.8 ml/yr (95% CI, −6.3 to −2.9) in transitional women and −5.2 ml/yr (95% CI, −8.3 to −2.0) in post‐menopausal women. Conclusions: Lung function declined more rapidly among transitional and post‐menopausal women, in particular for FVC, beyond the expected age change. Clinicians should be aware that respiratory health often deteriorates during reproductive aging.