Reproductive factors linked with women’s COPD risk

4 minute read

Aussie research suggests ‘complex interplay’ of oestrogen levels and timing in COPD development.

Women’s reproductive history, including pregnancies and menarche, are linked with risk of chronic obstructive pulmonary disease, an Australian-led study has found.

The findings follow research showing sex-based differences in susceptibility to and severity of COPD. Women appear more likely to develop severe COPD at a younger age than men, with a higher likelihood of COPD among non-smoking women also observed.

“This study showed that female reproductive factors, including age at menarche, number of children, infertility, number of miscarriages and stillbirths, and age at natural menopause, were associated with an increased risk of COPD,” wrote the authors in Thorax.

“Health professionals should consider the potential risk of COPD among women with such reproductive histories.”

An international team, led by the University of Queensland’s Professor Gita Mishra, analysed data from three longitudinal population cohorts to explore whether reproductive factors were associated with women’s increased susceptibility to COPD.

A total of over 280,000 women were included, of whom almost 11,000 (3.8%) developed COPD after a follow-up of 10-12 years.

After adjusting for smoking, BMI, age, education and race, they discovered a U-shaped association with age of menarche and COPD, with ages 11 or younger 17% more likely and ages 16 and older 24% more likely to develop COPD.

Women with children had a 13% higher risk than those without, especially those with only one or with more than two: women with one child had an 18% higher risk than those with two, women with three children had a 14% higher risk, and having four or more carried a 34% higher risk of COPD.

Other factors linked with increased risk of COPD were infertility (13% higher than no infertility); number of miscarriages, where the risk increased with increasing number of miscarriages to 36% higher risk at three or more; experiencing still birth carried a 42% increased risk, and as with miscarriages, the greater the number, the higher the risk.

Risk of COPD decreased with age of natural menopause, with those under 40 carrying a 69% increased risk compared with that of women of average age at menopause (50-51), while those 54 or older had a 21% lower risk than those of average age.   

Drawing on other research showing a link between asthma severity and oestrogen changes, and the effects of oestrogen on the lungs, the authors suggested that a complex interplay of oestrogen levels and their timing might also influence the development of COPD.

The observational study only establishes an association between these reproductive factors, rather than causality. There are, after all, factors such as smoking, low weight and low socioeconomic status common to later menarche, low parity and pregnancy loss and COPD.

These factors were adjusted for, and explained part of the associations with reproductive histories, but even after adjustment the increased risks were still there. Data on some other factors that may influence both COPD and reproductive issues, such as air pollution and autoimmune disease, were not available.

Professor Greg King of the Woolcock Institute of Medical Research was concerned that the study used patients’ self-report for COPD, rather than gold-standard lung function testing.

“COPD really is a disease of smoking, so it was interesting that the associations with reproductive factors were there, regardless of smoking history,” Professor King told Allergy & Respiratory Republic.

“That suggests they’re looking at something broader than just COPD – the patient has been told they’ve got some form of airways disease, but I’m a bit cautious about saying it’s COPD.

“I think what it means for doctors is really keeping to general principles, rather than anything specifically that could be derived from the study, the general principles being that any sort of smoking and inhalational injury – vaping, pot smoking or cigarette smoking – is bad for you. And women are more susceptible to it than men,” said Professor King.

“If you’re suspicious of any risk factors, for example, breathlessness or cough, especially in a smoker and in women, that would really prompt you to do lung function testing.”

 Thorax 2024, online 13 February

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