Early Natural Menopause is a Risk Factor for Lung Disease, Mortality in Women who Smoke

Early natural menopause is a risk factor for malignant and nonmalignant lung disease and mortality in middle-age and older women who smoke, according to study findings published in the American Journal of Obstetrics & Gynecology.

Study authors, led by Shuguang Leng, MD, PhD, of the department of internal medicine School of Medicine, University of New Mexico, Albuquerque, NM, report a more than 4.5-fold greater increase in risk of lung cancer and cancer-related mortality in women who experienced early natural (vs surgical) menopause and continued to smoke.

As context for the study, the investigators note that early onset of menopause is identified as a biomarker of both reproductive and somatic aging. Cigarette smoking, the most deleterious factor for lung health, is also a known risk factor for early menopause.

To refine and target preventive strategies to the vulnerable population, they write, requires a better understanding of the effect of early menopause on health outcomes in women beyond childbearing capacity who smoke. Their study evaluated associations of early menopause with a range of lung health and aging biomarkers, lung cancer risk, and all-cause and cause-specific death in postmenopausal women who reported moderate or heavy smoking.

The community-based retrospective study drew participants from The Pittsburgh Lung Screening Study (PLuSS), a cohort of current and former smokers screened with low-dose CT and followed for lung cancer. Eligibility criteria were age 50 to 79 years, smoked half a pack of cigarettes per day or more for at least 25 years, smoking cessation no more than 10 years before enrollment (if the individual quit smoking), and no personal history of lung cancer.

FINDINGS

The final cohort for analysis numbered 1666 postmenopausal women who smoked currently (63.9%) or previously. Among the entire cohort (average age, 59.4±6.7 years; 91.2% non-Hispanic White) 1038 women had natural menopause and 628 had surgical menopause.

Early menopause was reported by 646 (39%) of the women, of whom 198 had natural menopause and 448 had surgical menopause (P <.001). Demographics were similar across early and nonearly menopause groups, both natural and surgical. Women who experienced surgical menopause, the researchers found, had a higher history of personal cancer and of reproductive cancer than women with natural menopause (P<.01 and P<.001, respectively).

Lung disease, mortality

In women with early natural menopause investigators observed higher risk of chronic bronchitis (odds ratio [OR] 1.73; P <.01), wheezing (OR 1.65; P <.01), and radiographic emphysema (OR 1.70; P <.001) vs women with early surgical menopause.

The investigators also found that early natural menopause was associated with lower baseline measures of forced expiratory volume in 1 second (FEV₁), forced vital capacity (FVC), and FEV₁:FVC ratio than surgical menopause and, importantly, with a more rapid decline of FEV₁:FVC ratio (−0.16% per year; P=.01) and incident airway obstruction (OR 2.02; P =.04).

Leng et al report a 40% increased risk of mortality (P =.023) among women with early natural menopause, driven primarily by respiratory diseases (hazard ratio 2.32; P <.001). They found also, in mediation analyses, that more than 33.3% of the magnitude of the association between early natural menopause and both all-cause and respiratory death was explained by baseline measures of FEV₁.

Early menopause status moderated the associations observed between continuous smoking and subsequent lung cancer risk and cancer mortality, the authors write, and in participants with natural menopause, those who continued smoking post-menopause had a more than 4.5-fold greater risk of lung cancer and cancer-related death. No such associations were observed in participants with early surgical menopause.

Study limitations include the lack of generalizability of findings to women who smoke of Hispanic or Black ethnicity, possible selection bias, and the retrospective study design.

Researchers concluded that “Early natural menopause was found to be a risk factor for malignant and nonmalignant lung diseases and mortality in middle-age and older female smokers.” They suggest that the findings have implications for public health measures including prevention strategies targeting women who smoke and have natural early menopause, such as chest computed tomography screening and smoking cessation.

Reference Zhai T, Diergaarde B, Wilson DO, et al. Early natural menopause is associated with poor lung health and increased mortality among female smokers. Am J Obstet Gynecol. Published online August 4, 2022. doi:10.1016/j.ajog.2022.07.031