The association between different hormone replacement therapy use and the incidence of lung cancer: a systematic review and meta-analysis

BACKGROUND: Many peri- and postmenopausal women use hormone replacement therapy (HRT) to relieve menopausal symptoms. However, the side effects of different HRT use (ever/current/former vs. never HRT use) on lung cancer risk in women were not completely consistent. Thus, we conducted this meta-analysis to examine the connection between current, former or ever HRT use and the incidence of lung cancer among women. METHODS: We systematically searched the PubMed, Web of Science, EMBASE, Cochrane Library, SCOPUS, China National Knowledge Infrastructure, Wanfang and VIP databases to identify relevant articles published from the inception of the respective databases to February 18, 2022. On the relationship between different HRT use and the incidence of lung cancer among women. Relevant risk estimates [relative risks (RRs), odds ratio (OR)] were combined based on specific study types. The Newcastle-Ottawa Scale was used to evaluate the quality of included studies. This analysis has been registered in the International prospective register of systematic reviews (PROSPERO; CRD42020219728). Publication bias was tested based on Egger’s and Begg’s tests. RESULTS: A total of 22 studies (13 prospective cohort studies and 9 case-control studies) were included, comprising 911,194 participants and 17,329 patients. Compared to never HRT users, in pooled cohort studies, current HRT users had a statistically decreased risk of lung cancer [RR 0.91, 95% confidence interval (CI): 0.86–0.97, I(2)=22.9%], and similar results were found among the postmenopausal women with current HRT use (RR 0.91, 95 CI: 0.85–0.98, I(2)=36%), while in pooled case-control studies, ever HRT users had a decreased risk of incidence of lung cancer [odds ratio (OR) 0.75, 95% CI: 0.69–0.81, I(2)=0%] as did female non-smokers with ever HRT use (OR 0.76, 95% CI: 0.66–0.87, I(2)=36.8%). CONCLUSIONS: Current or ever HRT use is partly correlated with the decreased incidence of lung cancer in women. Concerns about the incidence of lung cancer can be reduced when perimenopausal and postmenopausal women use current HRT to reduce menopausal symptoms. Meanwhile, given the roles of hormone receptors and relevant genes single nucleotide polymorphism (SNPs) among females, HRT use should be cautiously administered and individualized.