Gastric cancer (GC) ranks as the fifth most common cancer globally and is the fourth highest in terms of mortality rate [1]. In 2020, over one million new cases were detected, and the incidence rate was 5.6% [2]. The risk factors for GC include old age, male sex, Helicobacter pylori infection, obesity, smoking, low socioeconomic status, reduced physical activity, alcohol consumption, and a high-salt diet [3]. In contrast, H. pylori eradication and menopausal hormone therapy (MHT), healthy lifestyle such as diet rich in vegetables and fruits, low in sodium, or maintaining a suitable body weight, are acknowledged as potential protective factors against GC [4], [5]. There have been several studies suggest a potential association between diabetes mellitus (DM) and an increased risk of GC [6], [7], but opposite results also have been published [8]. Moreover, research indicates that the impact of DM on the incidence of GC varies by gender [9].

GC occurs predominantly in men, with incidence rates approximately 2-fold higher in men than in women [2]. Among women, the incidence of GC increases in postmenopausal women compared to pre/peri-menopausal women after adjusting for age [10]. The lower incidence of GC in reproductive-aged women is often attributed to the presumed protective effect of female hormones against gastric carcinogenesis [11]. On the other hand, the menopausal transition, characterized by estrogen deficiency, is often associated with insulin resistance and weight gain irrespective of age [12], [13]. Obesity, itself, reinforces insulin resistance, facilitating DM [14]. The variance in estrogen exposure between genders might play a role in the differences in GC incidence and the varying impact of DM on GC development by gender. However, hormonal factors have seldom been included as covariates in GC studies.

In this study, our aim was to evaluate the influence of prediabetes and type 2 DM on GC risk among pre/peri- and postmenopausal women, while adjusting for reproductive factors. We utilized nationwide population-based data from Korea. Additionally, we conducted stratified analyses for GC risk based on body mass index (BMI), considering both glycemic and menopausal status.