The present systematic review and meta-analysis aimed to investigate the association between age at menopause onset and the risk of developing type 2 diabetes mellitus (T2DM). The results from the pooled analysis of the included studies provided valuable insights into this relationship.

Our findings demonstrated a significant association between early menopause age and an increased odds of T2DM. Women who experienced menopause at an earlier age had 24% higher odds of developing T2DM compared to those with a normal menopausal age. This observation is consistent with previous studies that have reported a link between early menopause and increased T2DM risk [36]. The underlying mechanisms for this association may be attributed to hormonal changes during menopause, including a decline in estrogen levels, which can affect insulin sensitivity and glucose metabolism [37].

Furthermore, early menopause is often associated with other risk factors for T2DM, such as increased body mass index (BMI) and unfavorable lifestyle behaviors [38]. These findings highlight the importance of considering early menopause as a potential risk factor for T2DM and the need for targeted preventive measures in this population. Interestingly, our results also indicated that late menopause age was associated with an increased odds of T2DM compared to the reference group with normal menopausal age. Women with a later onset of menopause had 14% higher odds of developing T2DM. This finding is somewhat unexpected, as late menopause has often been considered a protective factor against chronic diseases. However, it is important to interpret this result cautiously, as the magnitude of the association was relatively small and the heterogeneity among the included studies was moderate. Further research is needed to explore the underlying mechanisms and confirm this observation.

Regarding the secondary outcomes, our analysis assessed the hazard of developing T2DM in individuals with early or late menopausal age. The results revealed a significantly higher hazard of T2DM among women with early menopause age, indicating that they are at a greater risk of developing T2DM over time. This finding suggests that early menopause may have long-term implications for metabolic health. On the other hand, late menopause age did not show a significant association with the hazard of T2DM. However, it is important to note that the evidence for this outcome was less robust, because of the low number of studies included in the analysis. Further investigations are warranted to provide more definitive conclusions on the relationship between late menopause and T2DM hazard.

There are several systematic reviews on this topic [36, 39, 40]. The first study by Anagnostis et al. [40] explores the relationship between early menopause, premature ovarian insufficiency (POI), and the risk of developing type 2 diabetes. The findings of the meta-analysis, in line with our results, revealed a significant association between early menopause and an increased risk of type 2 diabetes. Women who experienced early menopause were found to have 15% higher odds of developing type 2 diabetes compared to those who underwent menopause at the usual age. Similarly, women with premature ovarian insufficiency had 50% increased risk of type 2 diabetes compared to those without this condition.

In a dose-response meta-analysis conducted by Guo et al. [36], it was found that for every 5-year increase in age at menopause, there was a significant 10% reduction in the risk of developing type 2 diabetes in the future. These findings differ from our own study, which indicated an increased odds of type 2 diabetes among individuals with a later age of menopause. However, it is important to note that the results reported by Guo et al. may be limited due to the inclusion of a relatively small number of studies, with only six studies being included in their analysis.

The most recent study by Liu et al. comprehensively evaluated the cardiometabolic diseases among individuals with early menopause [39]. The study analyzed data from 921,517 participants in 20 cohort studies conducted between 1998 and 2022. The findings showed that women who experienced premature menopause (PM) or early menopause (EM) had a higher risk of certain health conditions compared to women who experienced menopause at a later age (> 45 years). Women with PM or EM had a higher risk of type 2 diabetes, hyperlipidemia, coronary heart disease, stroke, and total cardiovascular events. However, there was no significant difference in the risk of hypertension between PM or EM women. Additionally, they found that PM women were associated with an increased risk of both ischemic and hemorrhagic stroke, while this association was not observed in EM women. However, the conclusion that both PM and EM women had a higher risk of total stroke was not supported by the findings.

While our study provides valuable insights into the association between age at menopause and T2DM, several limitations should be considered. First, the included studies were observational in nature. Second, there was considerable heterogeneity among the studies, potentially influenced by variations in study design, participant characteristics, and methodological approaches. Future studies on this topic are warranted in order to strength the evidence regarding late menopausal age and T2DM.