Effect of High Intensity Sweeteners on the Reproductive System: From the Onset of Puberty to Menstrual Health: A Comprehensive Review of Human and Animal Evidence
Abstract
Introduction: High-Intensity Sweeteners (HISs) are widely consumed as calorie-free sugar substitutes, particularly among girls and women of reproductive age. Despite their regulatory approval, growing evidence suggests potential endocrine-disrupting properties that may negatively impact women's reproductive health.
Objective: This narrative review synthesizes human and animal evidence on the Potential Pathological Effects of AS on puberty onset and menstrual health, while elucidating the underlying biological mechanisms.
Methods: A structured search of references in PubMed, Scopus, Web of Science, and Embase up to 2025 was conducted, prioritizing studies from 2015 onwards. Inclusion criteria required quantitative measurements of AS exposure and reproductive endpoints in non-pregnant, non-lactating women, or relevant animal models. Seventeen studies (12 animals, 5 humans) were thematically synthesized.
Results: Chronic exposure to AS specifically aspartame, sucralose, saccharin, and acesulfame-K-disrupts female reproductive physiology through composition-dependent and developmentally timed mechanisms. These mechanisms include (1) suppression of the hypothalamic-pituitary-gonadal (HPG) axis through downregulation of Kiss1; (2) ovarian mitochondrial dysfunction, oxidative stress, and follicular atresia; and (3) reduced estrogen production by the gut microbiota through disruption of the estrobulum. Importantly, these effects often occur independently of body weight or metabolic…
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