medwireNews: Multiple stages in women’s reproductive history are associated with an increased risk for chronic obstructive pulmonary disease (COPD), including age at menarche and menopause, childbearing, and infertility, show a study of Australian, UK, and Swedish medical records.
A history of miscarriage or stillbirth and experiencing multiple events of this type also significantly increased the risk for COPD, report the researchers.
“Female sex hormones are crucial modulators of lung development and diseases,” write Gita Mishra, from The University of Queensland in Brisbane, Australia, and colleagues.
These hormones “may influence the development of COPD through the properties of modulating bronchodilation, inflammation, proliferation and cigarette smoke metabolism,” they suggest in Thorax.
The team analyzed data for 283,070 women from three cohorts of the InterLACE consortium including information concerning their reproductive history and COPD incidence. The women were aged a median of 54 years and followed up for a median of 11 years.
A total of 3.8% of the entire cohort developed COPD at a median of 63 years, and those with COPD were older than those without when they joined InterLACE (61 vs 54 years), were more likely to have no more than 10 years of education (68.7 vs 46.3%), have smoked for at least 10 pack–years (67.1 vs 25.3%), and have asthma (38.1 vs 10.3%).
Mishra and colleagues found a U-shaped correlation with age at menarche and development of COPD. Women who began menstruation at the age of 11 years or younger were a significant 1.17 times more likely to develop COPD than those who began menstruation at 13 years old, after adjusting for birth year, race, education, BMI, and smoking pack–years. For those who were older, the adjusted hazard ratio (HR) increased from 1.10 to 1.24 when age increased from 14 years to 16 years or older, compared with 13 years.
“In infancy and childhood, oestrogen accelerates lung maturation and termination of lung growth,” explain Mishra et al, suggesting that “[g]irls with early menarche might experience insufficient lung growth in early life, lower lung function and greater predisposition to COPD in later life.”
Women who had children had an adjusted 1.13-fold higher risk for COPD than those who did not, and those with three or more children had a significantly increased risk for developing the condition (HR=1.14 and 1.34, respectively), as did those with one child compared with those who had two (adjusted HR=1.18).
Similarly, women who had experienced infertility were a significant 1.13 times more likely to develop COPD than those who had not after adjustment, and a history of miscarriage conferred a significant 1.15 times higher risk for COPD compared with no miscarriage history.
Indeed, COPD risk increased significantly with the number of miscarriages experienced, to 1.08 times after one, 1.28 times after two, and 1.36 times after three or more, compared with women without miscarriage after adjustment. And for women who had experienced stillbirth, the risk for COPD was a significant 1.42 times higher than for those who had not, with the risk increasing to 1.67 with recurrent stillbirth compared with none.
The researchers observed an increased risk for COPD with earlier age at natural menopause, with a significant 1.69-fold increase among those who reached menopause before 40 years of age after adjustment, compared with those who were aged 50–51 years.
“In the early or middle reproductive stage, long or higher accumulated exposure to oestrogen would be detrimental to the lung, leading to a higher risk of COPD among women with early menarche or multiple live births,” write Mishra and colleagues, who conclude that “[i]n the later stage, oestrogen may be protective.”
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