Age, sex, and reproductive status affect the risk of MASLD development and progression.
| Author, year | Method | Findings | Comment |
|---|---|---|---|
| Lonardo et al., 2015 [84] | Narrative review. | MASLD is more common in men, increases with age, and shows sex-specific differences.In men, MASLD increases from younger to middle age and starts declining after the age of 50–60 years.In women, pre-menopausal status is relatively spared by NAFLD, whereas advancing age and menopausal status independently predict MASLD. | Age, sex, and reproductive status are major modifiers of MASLD risk. |
| Balakrishnan et al., 2021 [85] | Meta-analysis of 54 studies totaling 62,239 MASLD cases, 5,428 MASH cases, and 6,444 advanced fibrosis cases. | General population: compared to men, women had a 19% lower MASLD risk (pooled RR, 0.81; 95% CI, 0.68–0.97; I2, 97.5%). A similar risk of NASH (RR, 1.00; 95% CI, 0.88–1.14; I2, 85.1%) and 37% higher risk of advanced fibrosis (RR, 1.37; 95% CI, 1.12–1.68; I2, 74.0%).Women with average ages ≥ 50 years had higher MASH risk than men (RR, 1.17; 95% CI, 1.01–1.36) and advanced fibrosis (RR, 1.56; 95% CI, 1.36–1.80; I2 = 0). | Age and sex (and, by inference, reproductive status) affect the risk of MASLD development and progression. |
| Cholongitas et al., 2021 [86] | Meta-analysis of MASLD in Europe comprising 19 studies in adults and 9 in children/adolescents. | Pooled MASLD prevalence was significantly higher in men than women (32.8% vs. 19.6%) (P < 0.01) and in obese/overweight boys than girls [32.5% (95% CI, 22.7–44.0) vs. 15.5% (95% CI, 7.6–29.0); P = 0.04]. | The prevalence of MASLD in European adults and children/adolescents with obesity or overweight is higher in males sex. |
| Wang et al., 2021 [87] | Nested case-control study of 1,861 cases and 17,664 controls in the multiethnic cohort study. | Later age at menarche was inversely associated with MASLD (Ptrend = 0.01).Parity, irrespective of number of children or age at first birth, was associated with increased MASLD risk (OR, 1.25; 95% CI, 1.05–1.48). Oral contraceptive use was also associated with increased MASLD risk (OR, 1.14; 95% CI, 1.01–1.29; duration of use Ptrend = 0.04).Oophorectomy (OR, 1.41; 95% CI, 1.18–1.68) or hysterectomy (OR, 1.33; 95% CI, 1.11–1.60) were associated with increased MASLD risk compared to natural menopause.Longer duration of MHT* was associated with increased MASLD risk (OR per 5 years of use, 1.08; 95% CI, 1.01–1.15). | Menstrual, reproductive factors, and use of exogenous hormones modify MASLD risk. |
| Riazi et al., 2022 [88] | Meta-analysis of 72 studies totaling 1,030,160 subjects from 17 countries. | Overall, MASLD prevalence and incidence were significantly (P < 0.0001) higher in men than in women, respectively [39.7% (36.6–42.8) vs. 25.6% (22.3–28.8) and 70.8 cases per 1,000 person-years (48.7–92.8) vs. 29.6 cases per 1,000 person-years (20.2–38.9)]. | Overall, the prevalence of NAFLD is significantly higher in men than in women. |
*: only estrogen therapy; CI: confidence intervals; MASH: metabolic dysfunction-associated steatohepatitis; MASLD: metabolic dysfunction-associated steatotic liver disease; MHT: menopause hormone therapy; NAFLD: nonalcoholic fatty liver disease; NASH: nonalcoholic steatohepatitis; OR: odds ratio; RR: risk ratio.
AL and AS contributed equally: Conceptualization, Investigation, Methodology, Project administration, Validation, Writing—original draft, Writing—review & editing. Both authors read and approved the submitted version.
Amedeo Lonardo, who is the Associate Editor and Guest Editor of Exploration of Digestive Diseases, had no involvement in the decision-making or the review process of this manuscript. Ayako Suzuki declares no conflicts of interest.
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