Emphysema, a form of chronic obstructive pulmonary disease (COPD) is a disease of significant public health importance that remains a major cause of morbidity and mortality within the US population and elsewhere in the industrialized world. An emerging body of literature appears to suggest gender differences in susceptibility to emphysema, with women showing significantly less emphysematous changes on high resolution Computed Tomography radiography compared to men. A pertinent but yet to be addressed question in the literature however, is whether these apparent differences in emphysematous structural lung disease result from differential exposures and or lifestyle choices on the one hand, or if on the other hand, these gender differences in CT-emphysema are related to certain biological mechanisms such as female hormonal influences or genetic differences in toxin metabolism. The present study evaluated differences in CT-emphysema status among 1834 women with different hormone replacement therapy (HRT) exposure profiles. In an unadjusted generalized logistic regression model, current use of HRT was statistically significantly associated with a 38% reduction in the risk of moderate to severe CT-emphysema, OR 0.62 (95% CI=0.39-0.99). After adjusting for the effects of age and smoking dose intensity, current HRT-users had a 34% reduction in the risk of mild to moderate CT-emphysema compared to never-users. Although this effect is quite sizable, it was marginally statistically insignificant, OR=0.66 (95% CI=0.41-1.07). We conclude that current use of hormone replacement therapy may be associated with a lower risk of moderate to severe CT-emphysema
