Hormone replacement therapy and asthma onset in menopausal women: National cohort study.

BACKGROUND: There is uncertainty about the role of hormonal replacement therapy (HRT) in the development of asthma. OBJECTIVE: We investigated whether use of HRT and duration of use was associated with risk of development of asthma in perimenopausal and postmenopausal women. METHODS: We constructed a 17-year (from January 1, 2000, to December 31, 2016) open cohort of 353,173 women (aged 46-70 years) from the Optimum Patient Care Database, a longitudinal primary care database from across the United Kingdom. HRT use, subtypes, and duration of use; confounding variables; and asthma onset were defined by using the Read Clinical Classification System. We fitted multilevel Cox regression models to estimate hazard ratios (HRs) with 95% CIs. RESULTS: During the 17-year follow-up (1,340,423 person years), 7,614 new asthma cases occurred, giving an incidence rate of 5.7 (95% CI = 5.5-5.8) per 1,000 person years. Compared with nonuse of HRT, previous use of any (HR = 0.83; 95% CI = 0.76-0.88), estrogen-only (HR = 0.89; 95% CI = 0.84-0.95), or combined estrogen and progestogen (HR = 0.82; 95% CI = 0.76-0.88) HRT was associated with a reduced risk of asthma onset. This was also the case with current use of any (HR = 0.79; 95% CI = 0.74-0.85), estrogen-only (HR = 0.80; 95% CI = 0.73-0.87), and combined estrogen and progestogen (HR = 0.78; 95% CI = 0.70-0.87) HRT. Longer duration of HRT use (1-2 years [HR = 0.93; 95% CI = 0.87-0.99]; 3-4 years [HR = 0.77; 95% CI = 0.70-0.84]; and ≥5 years [HR = 0.71; 95% CI = 0.64-0.78]) was associated with a dose-response reduced risk of asthma onset. CONCLUSION: We found that HRT was associated with a reduced risk of development of late onset asthma in menopausal women. Further cohort studies are needed to confirm these findings.

Hormonal contraception and the risk of severe asthma exacerbation: 17-year population-based cohort study.

BACKGROUND: Longitudinal studies investigating impact of exogenous sex steroids on clinical outcomes of asthma in women are lacking. We investigated the association between use of hormonal contraceptives and risk of severe asthma exacerbation in reproductive-age women with asthma. METHODS: We used the Optimum Patient Care Research Database, a population-based, longitudinal, anonymised primary care database in the UK, to construct a 17-year (1 January 2000-31 December 2016) retrospective cohort of reproductive-age (16-45 years, n=83 084) women with asthma. Using Read codes, we defined use, subtypes and duration of use of hormonal contraceptives. Severe asthma exacerbation was defined according to recommendations of the European Respiratory Society/American Thoracic Society as asthma-related hospitalisation, accident and emergency department visits due to asthma and/or oral corticosteroid prescriptions. Analyses were done using multilevel mixed-effects Poisson regression with QR decomposition. RESULTS: The 17-year follow-up resulted in 456 803 person-years of follow-up time. At baseline, 34% of women were using any hormonal contraceptives, 25% combined (oestrogen/progestogen) and 9% progestogen-only contraceptives. Previous (incidence rate ratio (IRR) 0.94, 95% CI 0.92 to 0.97) and current (IRR 0.96, 95% CI 0.94 to 0.98) use of any, previous (IRR 0.92, 95% CI 0.87 to 0.97) and current use of combined (IRR 0.93, 95% CI 0.91 to 0.96) and longer duration of use (3-4 years: IRR 0.94, 95% CI 0.92 to 0.97; 5+ years: IRR 0.91, 95% CI 0.89 to 0.93) of hormonal contraceptives, but not progestogen-only contraceptives, were associated with reduced risk of severe asthma exacerbation compared with non-use. CONCLUSIONS: Use of hormonal contraceptives may reduce the risk of severe asthma exacerbation in reproductive-age women. Mechanistic studies investigating the biological basis for the influence of hormonal contraceptives on clinical outcomes of asthma in women are required. PROTOCOL REGISTRATION NUMBER: European Union electronic Register of Post-Authorisation Studies (EUPAS22967).

Hormonal contraceptives and onset of asthma in reproductive-age women: Population-based cohort study.

BACKGROUND: Despite well-described sex differences in asthma incidence, there remains uncertainty about the role of female sex hormones in the development of asthma. OBJECTIVE: We sought to investigate whether hormonal contraceptive use, its subtypes, and duration of use were associated with new-onset asthma in reproductive-age women. METHODS: Using the Optimum Patient Care Research Database, a UK national primary care database, we constructed an open cohort of 16- to 45-year-old women (N = 564,896) followed for up to 17 years (ie, January 1, 2000, to December 31, 2016). We fitted multilevel Cox regression models to analyze the data. RESULTS: At baseline, 26% of women were using any hormonal contraceptives. During follow-up (3,597,146 person-years), 25,288 women developed asthma, an incidence rate of 7.0 (95% CI, 6.9-7.1) per 1000 person-years. Compared with nonuse, previous use of any hormonal contraceptives (hazard ratio [HR], 0.70; 95% CI, 0.68-0.72), combined (HR, 0.70; 95% CI, 0.68-0.72), and progestogen-only therapy (HR, 0.70; 95% CI, 0.67-0.74) was associated with reduced risk of new-onset asthma. For current use, the estimates were as follows: any (HR, 0.63; 95% CI, 0.61-0.65), combined (HR, 0.65; 95% CI, 0.62-0.67), and progestogen-only therapy (HR, 0.59; 95% CI, 0.56-0.62). Longer duration of use (1-2 years: HR, 0.83; 95% CI, 0.81-0.86; 3-4 years: HR, 0.64; 95% CI, 0.61-0.67; 5+ years: HR, 0.46; 95% CI, 0.44-0.49) was associated with a lower risk of asthma onset than nonuse. CONCLUSIONS: Hormonal contraceptive use was associated with reduced risk of new-onset asthma in women of reproductive age. Mechanistic investigations to uncover the biological processes for these observations are required. Clinical trials investigating the safety and effectiveness of hormonal contraceptives for primary prevention of asthma will be helpful to confirm these results.

A dynamic social relations model for clustered longitudinal dyadic data with continuous or ordinal responses.

Social relations models allow the identification of cluster, actor, partner, and relationship effects when analysing clustered dyadic data on interactions between individuals or other units of analysis. We propose an extension of this model which handles longitudinal data and incorporates dynamic structure, where the response may be continuous, binary, or ordinal. This allows the disentangling of the relationship effects from temporal fluctuation and measurement error and the investigation of whether individuals respond to their partner's behaviour at the previous observation. We motivate and illustrate the model with an application to Canadian data on pairs of individuals within families observed working together on a conflict discussion task.

Hormone Replacement Therapy and Risk of Severe Asthma Exacerbation in Perimenopausal and Postmenopausal Women: 17-Year National Cohort Study.

BACKGROUND: The impact of hormone replacement therapy (HRT) on clinical outcomes in menopausal women is uncertain. OBJECTIVE: To investigate the association between use of HRT and severe asthma exacerbation in perimenopausal and postmenopausal women with asthma. METHODS: We used the Optimum Patient Care Research Database, a population-based longitudinal primary care database in the United Kingdom, to construct a 17-year (January 1, 2000, to December 31, 2016) cohort of perimenopausal and postmenopausal (46-70 years, N = 31,656) women. We defined use of HRT, its subtypes, and duration of HRT use. Severe asthma exacerbation was defined as an asthma-related hospitalization, emergency department visits due to asthma, and/or prescription of oral corticosteroids. Analyses were undertaken using multilevel mixed-effects Poisson regression. RESULTS: At baseline, 22% of women were using any HRT, 11% combined HRT, and 11% estrogen-only HRT. Previous, but not current, use of any (incidence rate ratio [IRR]: 1.24, 95% confidence interval [CI]: 1.22-1.26), combined (IRR: 1.28, 95% CI: 1.25-1.31), and estrogen-only HRT (IRR: 1.18, 95% CI: 1.14-1.21), and longer duration (1-2 years: IRR: 1.16, 95% CI: 1.13-1.19; 3-4 years: IRR: 1.43, 95% CI: 1.38-1.48; 5+ years: IRR: 1.32, 95% CI: 1.28-1.36) of HRT use were associated with increased risk of severe asthma exacerbation compared with nonuse. The risk estimates were greater among lean women (body mass index [BMI] <25 kg/m2) than among heavier women (BMI 25-29.9 kg/m2 and ≥30 kg/m2) and higher among smokers than nonsmokers. CONCLUSION: Use of HRT and subtypes, particularly previous, but not current, use and use for more than 2 years, is associated with an increased risk of severe asthma exacerbation in perimenopausal/postmenopausal women with established asthma. Lean women and smokers are at greater risk than heavier women and nonsmokers, respectively.

Exogenous sex steroid hormones and asthma in females: protocol for a population-based retrospective cohort study using a UK primary care database.

INTRODUCTION: Female sex steroid hormones have been implicated in sex-related differences in the development and clinical outcomes of asthma. The role of exogenous sex steroids, however, remains unclear. Our recent systematic review highlighted the lack of high-quality population-based studies investigating this subject. We aim to investigate whether the use of hormonal contraception and hormone replacement therapy (HRT), subtypes and route of administration are associated with asthma onset and clinical outcomes in reproductive age and perimenopausal/postmenopausal females. METHODS AND ANALYSIS: Using the Optimum Patient Care Research Database (OPCRD), a national primary care database in the UK, we will construct a retrospective longitudinal cohort of reproductive age (16-45 years) and perimenopausal/postmenopausal (46-70 years) females. We will estimate the risk of new-onset asthma using Cox regression and multilevel modelling for repeated asthma outcomes, such as asthma attacks. We will adjust for confounding factors in all analyses. We will evaluate interactions between the use of exogenous sex hormones and body mass index and smoking by calculating the relative excess risk due to interaction and the attributable proportion due to interaction. With 90% power, we need 23 700 reproductive age females to detect a 20% reduction (risk ratio 0.8) in asthma attacks for use of any hormonal contraception and 6000 perimenopausal/postmenopausal females to detect a 40% (risk ratio 1.40) increased risk of asthma attacks for use of any HRT. ETHICS AND DISSEMINATION: We have obtained approval (ADEPT1317) from the Anonymised Data Ethics and Protocol Transparency Committee which grants project-specific ethics approvals for the use of OPCRD data. Optimum Patient Care has an existing NHS Health Research Authority ethics approval for the use of OPCRD data for research (15/EM/150). We will present our findings at national and international scientific meetings and publish the results in international peer-reviewed journals. TRIAL REGISTRATION NUMBER: EUPAS22967.