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Early menopause due to bilateral oophorectomy was associated with an increased risk of respiratory mortality, according to a secondary analysis of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening trial.

That increased risk was observed both in ever smokers (HR 1.98, 95% CI 1.34-2.92) and never smokers (HR 1.91, 95% CI 1.16-3.12), reported Shuguang Leng, MBBS, PhD, of the University of New Mexico School of Medicine in Albuquerque, and co-authors in .

Also of note, the odds of chronic bronchitis was 31% higher in never smokers with natural early menopause (OR 1.31, 95% CI 1.06-1.62) and 86% higher for those with bilateral oophorectomy (OR 1.86, 95% CI 1.45-2.38).

"We speculate that there may be shared mechanisms underlying lung and ovary maturation in early life that may subsequently lead to suboptimal development of both organs and functions," the authors wrote. "People with poorly developed lungs have higher risk for chronic obstructive pulmonary disease in later life without cigarette smoking, while poorly developed ovaries lead to pre-mature or early menopause."

Early menopause -- defined as occurring in those younger than 45 -- was also positively associated with all-cause mortality, non-cancer mortality, and cardiovascular mortality in ever smokers across menopause types. In addition, emphysema was associated with an odds ratio of 1.23 (95% CI 1.01-1.50) in those with natural early menopause, and even more strongly associated with those with bilateral oophorectomy (OR 1.99, 95% CI 1.31-3.01).

However, use of hormone therapy was associated with reduced all-cause, non-cancer, and cardiovascular mortality across menopause types regardless of smoking status, and was associated with reduced risk of non-ovarian cancer, lung cancer, and respiratory mortality in ever smokers.

"Our study provides strong evidence implicating early menopause, either naturally occurring or induced by surgery, as a risk factor for lung morbidities and mortalities in never and ever smokers during their postmenopausal life," Leng's group concluded. "Thus, smokers with early menopause should be targeted for smoking cessation and lung cancer screening regardless of menopause types."

A showed that early natural menopause was a risk factor for malignant and nonmalignant lung diseases and mortality in middle-age and older women who smoke. is also a risk factor for early menopause.

The U.S. Preventive Services Task Force (USPSTF) and the currently recommend hormone therapy to manage perimenopausal symptoms. However, their recommendations differ for primary prevention of chronic conditions like bone loss: the the use of hormone therapy for the primary prevention of chronic conditions, while NAMS recommends its use for primary prevention in specific groups, such as those younger than 60 or those within 10 years of menopause onset.

This secondary analysis included 69,706 women from the , of whom 20,163 (29%) said they had gone through menopause early: 10.2% had natural menopause, 47.2% had bilateral oophorectomy, and 75.1% had a hysterectomy alone. Women whose menopause was due to radiation or drug therapy were excluded.

Average age was 62.7, 88.8% were white, and 5.5% were Black. Just over half (52.2%) were 50-54 years old at the start of menopause, and 24.3% were 45-49.

Of the study population, 44.2% were ever smokers, while 55.8% were never smokers. Among ever smokers, the mean number of pack-years was 30.3; 37.9% smoked 1-10 cigarettes per day, and 35.9% smoked 11-20 cigarettes per day.

Women with early menopause were more likely to have ever smoked, and if they smoked, had higher numbers of cigarettes per day, longer smoking duration, and higher pack-years compared with those without early menopause, irrespective of menopause types. In addition, women with early menopause were less likely to report higher education level, at least among those with natural menopause and those with bilateral oophorectomy.

Of the 45,580 participants who reported ever using hormone therapy at baseline, 24,118 had information about type of therapy used -- 14,856 used estrogen pills; 895 used progestin pills; 6,939 used estrogen/progestin pills; 963 used estrogen creams, shots, or patches; 112 used progestin creams, shots, or patches; and 353 used estrogen/progestin creams, shots, or patches. Of those who reported natural menopause, 35.5% used estrogen pills and 47.6% used estrogen/progestin pills.

In patients who reported having ever smoked, those taking estrogen/progestin pills had reduced incidence of lung cancer (HR 0.62, 95% CI 0.40-0.97), all-cause mortality (HR 0.83, 95% CI 0.73-0.94), non-cancer mortality (HR 0.80, 95% CI 0.69-0.93), and respiratory mortality (HR 0.68, 95% CI 0.48-0.97) compared with participants who were taking estrogen-only pills.

Similarly, taking progestin-only pills was associated with reduced risks for all-cause mortality (HR 0.71, 95% CI 0.53-0.95) and non-cancer mortality (HR 0.68, 95% CI 0.47-0.98) compared with estrogen-only pill use.

Leng and team noted that lung cancer incidence and mortality, as well as emphysema, were rare among never smokers, and power was insufficient for association analyses stratified by menopause type. Other limitations included the use of self-reported information, and the somewhat limited sample size of patients who were not white in the PLCO trial.

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