Inhaled anti-asthma therapies following hormone therapy in women: a nationwide cohort study.

Research question: Does menopausal hormone therapy (HT) with exogenous oestrogens and progestogens change the use of inhaled anti-asthma medications in women with asthma? Methods: In a population-based matched cohort study using the Danish registries, we included women with asthma aged 45-65 years from 1 June 1995 to 30 June 2018. We investigated whether HT with oestrogen and/or progestogens was associated with changes in use of inhaled anti-asthma therapies in the 12 months following initiation. We used exposure density matching to match exposed subjects with unexposed subjects on age, household income and level of education. An exposed subject was defined as receiving HT. We calculated mean dose of medications and odds ratios of increases in the 12 months following HT initiation. Results: We included 139 483 women with asthma, of whom 116 014 (83.2%) were unexposed subjects and 23 469 (16.8%) exposed subjects. Mean±sd age was 53.0±5.2 years. Initiation of HT was not consistently associated with increased mean doses of inhaled corticosteroids (ICS), or long- and short-acting ß2-agonists. Women receiving systemic oestrogens had increased odds ratios of large increases (>100 µg) in ICS at 6 months (OR 1.09; 95% CI 1.04-1.13; p<0.001) and 9 months (OR 1.07; 95% CI 1.03-1.12; p<0.001). Progestogens were protective against increases in ICS at 6 and 9 months (OR 0.87; 95% CI 0.82-0.93; p<0.001; and OR 0.86; 95% CI 0.81-0.91; p<0.001). Conclusion: Initiation of HT did not change the use of inhaled medications in asthma. However, detrimental effects of oestrogen, as well as beneficial effects of progestogens, cannot be excluded.

Hormone Replacement Therapy and Development of New Asthma.

BACKGROUND: Hormone replacement therapy (HRT) is prescribed to millions of women worldwide. Previous studies have suggested that HRT has both protective and harmful effects in asthma. RESEARCH QUESTION: Is HRT in menopause associated with new development of asthma? STUDY DESIGN AND METHODS: We undertook a nested case-control study based on the Danish registers from June 1, 1995, through December 31, 2018. A diagnosis of asthma was defined as two redeemed prescriptions of inhaled corticosteroids within 2 years. HRT was defined as two redeemed prescriptions of female sex hormones within 6 months. Data were analyzed using a conditional logistic regression model. RESULTS: We included 34,533 women with asthma vs 345,116 women without asthma between 40 and 65 years of age. In a multivariate analysis adjusted for age, household income, and educational level, active HRT resulted in a hazard ratio (HR) of 1.63 (95% CI, 1.55-1.71; P < .001) of new asthma development. Women with asthma who terminated HRT were likely to discontinue their asthma treatment subsequently (HR, 2.12; 95% CI, 1.94-2.33; P < .001). INTERPRETATION: HRT seems to play a role in the development of asthma in mature women. Clinicians prescribing HRT and women receiving HRT should be aware that new airway symptoms can develop, and discontinuation of HRT should be considered.

Fertility Treatment Resulting in Live Births in Women with Asthma - Associated with Perennial Allergy?

BACKGROUND: Asthma has been linked with prolonged time to pregnancy compared to healthy controls, also asthma has been linked to a higher need for fertility treatment. However, knowledge of the possible association between allergy and need for fertility treatment is limited. Our aim was to explore a possible difference in having had fertility treatment in women with asthma and live births in those with perennial allergy (animals, fungi and dust mites) compared to no allergy/seasonal allergy. The primary outcome of interest was fertility treatment. PATIENTS AND METHODS: Women enrolled in the Management of Asthma during Pregnancy (MAP) program at Hvidovre Hospital, DK, were included in the present analysis provided they fulfilled the following criteria: 1) diagnosed with asthma and current anti-asthma therapy and 2) first visit to the respiratory outpatient clinic within the first 18 weeks of pregnancy. Participants were divided into two groups: asthma with perennial allergy (cases) and asthma with seasonal/no allergy (controls). Logistic regression analysis was applied, and findings expressed as odds ratios (OR). RESULTS: Among women with asthma and perennial allergy (n=544 cases), 13.8% (n=75) had fertility treatment, compared to only 10.1% (n=39) among women with asthma and seasonal/no allergy (n=388, controls) (OR 1.43, 95% CI 0.95-2.16, p=0.087). This association remained statistically insignificant after adjusting for confounders, including BMI (OR 1.19, 95% CI 0.77-1.84, p=0.433). In women ≥35 years of age, 28% (n=44) and 20% (n=19), respectively, among cases and controls had fertility treatment (OR 1.60, 95% CI 0.87-2.94, p=0.132), and likewise, statistically insignificant after adjusting for confounders (OR 1.41, 95% CI 0.74-2.69, p<0.293). CONCLUSION: In women with asthma and live births, our study revealed a trend towards an association between perennial allergy and a higher need for fertility treatment compared to seasonal/no allergy.

Coexistence of asthma and polycystic ovary syndrome: A concise review.

Asthma may be associated with polycystic ovary syndrome (PCOS), and possibly patients with PCOS have a more severe type of asthma. The purpose of this systematic literature review is to summarize evidence of a coexistense of PCOS and asthma using the available literature. The search was completed on 01.01.2016. English language articles were retrieved using the search terms 'Asthma' AND 'PCOS', 'Asthma' AND 'systemic inflammation', 'Asthma' AND 'metabolic syndrome', 'asthma' AND 'gynaecology', 'PCOS' AND 'systemic inflammation', 'PCOS' AND 'metabolic syndrome', 'PCOS' AND 'allergy'. Five papers meeting prespecified search criteria were found of which two were registry studies of relevance. The current literature supports a coexistense of PCOS and asthma and gives us an indication of the causes for the possible link between PCOS and asthma. Further research in the area must be conducted to determine the exact nature and magnitude of the association.

Fertility outcomes in asthma: a clinical study of 245 women with unexplained infertility.

Evidence is increasing of an association between asthma and aspects of female reproduction. However, current knowledge is limited and furthermore relies on questionnaire studies or small populations. In a prospective observational cohort study to investigate whether time to pregnancy, the number of fertility treatments, and the number of successful pregnancies differ significantly between women with unexplained infertility with and without asthma.245 women with unexplained infertility (aged 23-45 years) underwent questionnaires and asthma and allergy testing while undergoing fertility treatment. 96 women entering the study had either a former doctor's diagnosis of asthma or were diagnosed with asthma when included. After inclusion they were followed for a minimum of 12 months in fertility treatment, until they had a successful pregnancy, stopped treatment, or the observation ended.The likelihood of achieving pregnancy was lower in women with asthma compared with those without asthma: median total time to pregnancy was 32.3 months in non-asthmatic women versus 55.6 months in those with asthma, hazard ratio 0.50 (95% confidence interval 0.34-0.74) p<0.001.Women with asthma had fewer successful pregnancies during fertility treatment, 39.6 versus 60.4% (p=0.002). Increasing age was of negative importance for expected time to pregnancy, especially among asthmatic women (interaction between age and asthma on time to pregnancy, p=0.001). Female asthmatics had a longer time to pregnancy and less often became pregnant than non-asthmatic women. Increasing age reduced the chances of conceiving especially among asthmatic women. The causal relationship between asthma and subfertility remains unclear.

Lower values of VEGF in endometrial secretion are a possible cause of subfertility in non-atopic asthmatic patients.

OBJECTIVE: Using endometrial secretion analysis, we assessed whether altered inflammatory cytokine levels can be detected in the uterine environment in asthma patients, thereby providing a possible cause of reduced fertility in asthmatics. METHODS: Forty-four unexplained infertile women (aged 28-44) underwent asthma and allergy testing, questionnaires, endometrial secretion and blood samples in the mid-secretory phase of the menstrual cycle (day 19-23) during assisted reproduction. Differences in cytokines and growth factors were analyzed. RESULTS: Mean log-VEGF in uteri was lower in asthma patients compared with controls (2.29 versus 2.70, p = 0.028). This was mainly due to lower values of VEGF among women with non-atopic asthma compared with women with atopic asthma (1.86 versus 2.72, p = 0.009) and with healthy controls (1.86 versus 2.70, p = 0.01). Asthma treatment status had no effect on VEGF levels in uteri. Serum high sensitivity CRP was negatively correlated with VEGF in endometrial secretions. No other significant correlations were observed between peripheral blood values and markers found in utero. CONCLUSION: Asthma is associated with lower values of VEGF in uterine endometrial secretions, which might affect the receptiveness of the endometrium and thereby increase time to pregnancy. The effect appears to be associated with non-atopic asthma with general increased systemic inflammation.

Age at menarche and risk of asthma: systematic review and meta-analysis.

BACKGROUND: Several studies have suggested a relationship between the age at menarche and risk of asthma development. OBJECTIVE: To conduct a systematic review and meta-analysis of the relationship between the age at menarche and the risk of asthma. METHODS: This systematic review and meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). A pre specified literature search strategy was used to identify studies of potential relevance and independent reviews were carried out by two authors. Raw data was pooled using the software package RevMan to calculate summary odds ratios. The risk of publication bias was assessed graphically by using a funnel plot and the robustness of the overall estimate obtained was assessed by using sensitivity analyses. RESULTS: The searches identified 61 potentially relevant articles of which seven articles, with a total of 22,859 subjects, matched the inclusion criteria for the meta-analysis. Pooling of the seven studies showed that girls with early menarche (<12 years) had an increased risk of asthma relative to girls with late menarche; random effects odds ratio = 1.37 (1.15-1.64), (p = 0.0005). Substantial heterogeneity was revealed (I(2) = 55%). Sensitivity analysis showed that the risk estimate was not markedly changed when excluding any of the studies. The funnel plot did not indicate publication bias. CONCLUSIONS: Early menarche appears to be associated with increased risk of asthma. Hormonal, immunological, genetic and environmental factors may act in a developmental context to explain this relationship. Future studies are warranted to further determine the mechanisms responsible for this observation.