Early onset of menstruation and menopause associated with increased risk of COPD

By Vijay Kumar MalesuFeb 14 2024Reviewed by Lily Ramsey, LLM

In a recent study published in Thorax, a group of researchers evaluated the association between female reproductive factors such as age at menarche, stillbirth, number of children, infertility, miscarriage, and age at natural menopause—and the risk of developing chronic obstructive pulmonary disease (COPD).

Study: Female reproductive histories and the risk of chronic obstructive pulmonary disease. Image Credit: Image Point Fr/Shutterstock.com

Background 

COPD is a significant global health issue, with a prevalence of approximately 3.9% in 2017, showing slight gender differences in rates between men and women. Notably, women are more susceptible to developing severe COPD at younger ages than men, and the majority of non-smokers with COPD are women.

This suggests that female sex hormones, such as estrogen and progesterone, play crucial roles in lung development and the pathogenesis of COPD. These hormones influence bronchodilation, inflammation, and cellular proliferation, key factors in COPD development.

The variability in the female hormonal environment throughout different reproductive stages- menarche, pregnancy, menopause, and conditions like infertility or pregnancy loss- highlights the complex relationship between female reproductive health and COPD risk.

However, research specifically exploring this connection remains limited, indicating a need for further research into how reproductive history impacts COPD risk.

About the study 

The present study conducted by the Inter­national Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events (InterLACE) consortium utilized data from over 850,000 women across 12 countries.

It focused on three cohorts with information on reproductive factors and COPD: the Australian Longitudinal Study on Women’s Health, the United Kingdom (UK) Biobank, and the Swedish Women’s Lifestyle and Health Study. 

To ensure accuracy, the study excluded women who had developed COPD by age 40 from analyses involving infertility, miscarriage, stillbirths, and parity due to the absence of specific ages for these events.

Only women who had experienced natural menopause were considered for analysis regarding menopause age, and those with COPD before natural menopause were omitted.

The researchers carefully handled missing data, ensuring participants had complete records on critical factors such as race, education, smoking history, body mass index, and asthma.

To address potential biases, including the impacts of coronavirus disease 2019 (COVID-19), follow-up adjustments were made across cohorts, and reproductive histories were detailed, including menarche to menopause.

COPD was identified through diverse data, ensuring accuracy. Statistical analysis, including Cox regression and sensitivity tests, explored reproductive factors' influence on COPD risk, highlighting their importance in women's health research.

Study results 

In the present comprehensive study encompassing 283,070 women with a median age of 54 years, researchers embarked on an 11-year journey to unravel the intricate relationship between women's reproductive history and the development of COPD.

Throughout this period, 3.8% of the participants, equivalent to 10,737 women, were diagnosed with COPD at a median age of 63 years.

The identification of COPD cases varied, with 7,983 cases recognized through a singular data source—ranging from survey data to hospital records—and 2,754 through multiple sources.

The initial characteristics of these women highlighted certain risk factors, including advanced age at cohort entry, lower educational attainment, higher body mass indices, significant smoking histories, and pre-existing asthma conditions.

The researchers excluded 53,205 women due to incomplete data, particularly regarding smoking habits and body mass index, ensuring the robustness of their findings.

A nuanced pattern emerged, linking the age of menarche with COPD risk; notably, women who experienced menarche at age 11 or younger, as well as those who began menstruating after 13, saw an increased risk, with a particularly sharp rise observed in those who started menstruating at age 14 or beyond.

Furthermore, the study revealed that motherhood also influenced COPD risk, with women having one or more children facing higher risks compared to childless counterparts. This risk escalated with the number of children borne.

Additionally, experiences of infertility and miscarriages further intensified COPD risks, painting a complex picture of how reproductive history shapes respiratory health.

Women who had undergone natural menopause presented an inverse risk relationship with COPD, dependent on the age at menopause. Those entering menopause before age 40 faced the highest risk, whereas the risk diminished for women experiencing menopause at or beyond age 54.

The study also used rigorous sensitivity analyses, including random effects modeling and competing risk analysis, to validate these findings.

Notably, the association between infertility and COPD risk diminished in some analyses, yet the overarching trends remained consistent across various subgroups, including smokers and non-smokers, as well as women with and without a history of asthma.

The analysis extended to explore the impact of bilateral oophorectomy age on COPD risk, finding a heightened risk among women who underwent the procedure at younger ages.

Further, the study delved into the specific effects of reproductive history facets such as age at menarche, miscarriages, stillbirths, and menopause timing on COPD risk, with findings echoing across individual cohort studies and meta-analyses.

Despite some variability, especially concerning the age at menarche, most evidence pointed towards a consistent relationship between reproductive factors and the development of COPD.