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

Nwaru, Bright I.; Shah, Syed Ahmar; Tibble, Holly; Pillinger, Rebecca; McLean, Susannah; Critchley, Hilary; Hawrylowicz, Catherine M.; Simpson, Colin R; Soyiri, Ireneous N; Appiagyei, Francis; Price, David; Sheikh, Aziz

doi:10.1016/j.jaip.2021.02.052

Cited by 16 publications

(12 citation statements)

References 39 publications

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“…Our second important result was that peri/postmenopausal women who used MHT had a statistically significantly and clinically relevant lower asthma related QoL than those without MHT, also with adjustment for potential confounders. Earlier studies including a recent meta-analysis demonstrated negative or no impact on asthma symptoms in postmenopausal women using MHT [17,31]. Also, a longer use of MHT has been associated with a higher risk of exacerbation and hospital admission [32].…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Quality of life and asthma control related to hormonal transitions in women’s lives

et al. 2021

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Objectives: The aim was to investigate if menstruation and use of exogenous sex hormones influence self-reported asthma related quality of life (QoL) and asthma control. Methods:The study is based on two asthma cohorts randomly selected in primary and secondary care. A total of 622 female patients 18-65 years were included and classified as premenopausal ≤ 46 years (n = 338) and peri/postmenopausal 47-65 years (n = 284). Questionnaire data from 2012 and 2014 with demographics, asthma related issues and sex hormone status. Outcome measures were Mini Asthma Quality of Life Questionnaire (Mini-AQLQ) and asthma control including Asthma Control Test (ACT) and exacerbations last six months.Results: Premenopausal women with menstruation related asthma worsening, perimenstrual asthma (PMA) (9%), had a clinically relevant lower Mini-AQLQ mean score 4.9 vs. 5.8 (p < 0.001), lower asthma control with ACT score < 20, 72% vs. 28% (p < 0.001) and higher exacerbation frequency 44% vs. 20% (p = 0.004) compared with women without PMA. Women with irregular menstruation had higher exacerbation frequency than women with regular menstruation (p = 0.023). Hormonal contraceptives had no impact on QoL and asthma control. Peri/postmenopausal women with menopausal hormone therapy (MHT) had a clinically relevant lower Mini-AQLQ mean score compared to those without MHT, 4.9 vs 5.4 (p < 0.001), but no differences in asthma control. A c c e p t e d M a n u s c r i p tConclusion: Women with PMA had lower QoL and more uncontrolled asthma than women without PMA. Peri/postmenopausal women with MHT had lower QoL than women without MHT. Individual clinical management of women with asthma may benefit from information about their sex hormone status.

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Section: Accepted Manuscriptmentioning

confidence: 99%

Quality of life and asthma control related to hormonal transitions in women’s lives

et al. 2021

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“…The therapeutic effects of hormonal contraceptives on PMA were reported in several case reports and series, 81 , 112 , 113 but not in another case report. 114 Menopausal hormone therapy (MHT) The UK national cohort study 124 of 31,656 women with asthma found that use of MHT was associated with an increased risk of severe asthma exacerbations compared to non-use, and that longer duration of use was associated with a higher risk of asthma exacerbations than shorter duration. Several uncontrolled before-and-after studies 119–121 investigated the effects of MHT on lung function or asthma medication use in women with asthma, but reported conflicting results.…”

Section: Age- and Gender-related Disparities In Asthmamentioning

confidence: 99%

Sex Disparities in Asthma Development and Clinical Outcomes: Implications for Treatment Strategies

Gq¹,

SS²,

Rådinger³

et al. 2022

JAA

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A gender-related disparity exists in asthma morbidity and mortality, which shifts at around puberty from a male predominance to a female predominance. This is clinically reflected in the fact that asthma that occurs in childhood (childhood-onset asthma) mainly affects boys, and that asthma that occurs in adulthood (adult-onset asthma) mainly affects women. Adult-onset asthma is often non-atopic, more severe, and associated with a poorer prognosis, thus posing a marked burden to women’s health and healthcare system. Many factors have been indicated to explain this gender-related disparity, including sociocultural and environmental factors as well as biological sex differences (genetic, pulmonary and immunological factors). It has long been suggested that sex hormones may be implicated in at least these biological sex differences. Overall, the evidence remains equivocal for the role of most sex hormones in asthma pathogenesis and clinical outcomes. Well-designed randomized clinical trials are required assessing the potential preventive or therapeutic effects of hormonal contraceptives on asthma in women, thereby helping to advance the evidence to inform future practice guidelines. The mechanisms underlying the role of sex hormones in asthma are complex, and our understanding is not yet complete. Additional mechanistic studies elucidating sex hormone signaling pathways and their interactions involved in the pathogenesis and clinical manifestations of asthma will help to identify potential sex hormone-driven asthma endotypes and novel therapeutic targets, providing the basis for a more personalized asthma management strategy.

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“…Increasing BMI has also direct association with asthma severity [65]. In contrast, it was interesting that low BMI smoker women are at higher risk of asthma than the high BMI nonsmoker women [86].…”

Section: Old Age Sex Hormones and Asthmamentioning

confidence: 99%

“…Similarly, OCP is associated with increased wheezing risk in asthmatic women [90,91] and decreased wheezing in some studies [37,92]. In 2021, the role of HRT in perimenopausal and postmenopausal women with asthma has been explored, and increased risk of asthma exacerbations in perimenopausal and postmenopausal women is associated with previous history of long-term HRT of at least more than two years but not current [86].…”

Section: Old Age Sex Hormones and Asthmamentioning

confidence: 99%

Role of Sex Hormones at Different Physiobiological Conditions and Therapeutic Potential in MBD2 Mediated Severe Asthma

Wasti

Chen

et al. 2021

Oxidative Medicine and Cellular Longevity

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Sex hormone has become a “hot topic” to evaluate the hormonal therapeutic potential in severe asthma. Th17 cell is one of the main influencing factors involved in the pathogenesis of severe asthma, hence also called as kernel of severe asthma, and Th17 subtype of non-T2 asthma is less responsive (resistance) to inhaled corticosteroid (ICS), so severe in nature. Methyl-CpG binding domain protein 2 (MBD2) is overexpressed and regulates the Th17 differentiation, showing the possibility of therapeutic target in treating Th17 mediated severe asthma. Sex hormone fluctuates at the different physiobiological conditions of the human body and affects the asthma pathobiology showing its role in asthma prevalence, severity, remission, and therapy. This review briefly overviews the sex hormones, their influence in asthma at the different physiobiological conditions of human body, and MBD2 severe asthma connection with the possible therapeutic potential of sex steroids in MBD2 mediated Th17 predominant severe asthma. Male sex hormone tends to show a beneficial effect and possibly downregulates the expression of Th17 cells via regulating MBD2 through a mechanism distinct from corticosteroid treatment and guides us towards discovery of new therapeutic agent, reduces the asthma-related complications, and promotes long-term survival by lowering the risk of therapy-resistant issues of old age severe asthma.

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

Cited by 16 publications

References 39 publications

Quality of life and asthma control related to hormonal transitions in women’s lives

Quality of life and asthma control related to hormonal transitions in women’s lives

Sex Disparities in Asthma Development and Clinical Outcomes: Implications for Treatment Strategies

Role of Sex Hormones at Different Physiobiological Conditions and Therapeutic Potential in MBD2 Mediated Severe Asthma

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