Association of celiac disease with menstrual and hormonal disturbances: a systematic review and meta-analysis.

Abstract

Background: Disturbances in the female reproductive system are known extraintestinal manifestations of celiac disease (CD). However, the reliability of the existing literature is limited by small study populations and heterogeneous study designs. This study is the first systematic review and meta-analysis to synthesize all available evidence and provide a comprehensive evaluation of the association between CD and female menstrual and hormonal parameters.

Methods: A systematic literature search was conducted in PubMed, Scopus, and Cochrane Central databases using keywords related to CD, menstrual characteristics, and hormonal markers. Studies published until August 2025 were included.

Results: Our analysis demonstrated a significantly higher mean age at menarche in girls with CD compared with controls [pooled mean difference (MD): 0.64 years, 95% confidence interval (CI): 0.32 to 0.95, p = 0.0007), as well as an increased risk of abnormal uterine bleeding [pooled odds ratio (OR): 2.11, 95% CI: 1.23 to 3.63, p < 0.05] and amenorrhea (pooled OR: 4.03, 95% CI: 1.11 to 14.65, p = 0.0394). Menopausal age was not found to be earlier in women with CD (pooled MD: -1.31 years, 95% CI: -3.02 to 0.40, p = 0.1053). Adherence to a gluten-free diet was not associated with age at menarche when adherent and non-adherent patients were compared (pooled MD: 0.56 years, 95% CI: -0.72 to 1.83, p = 0.260). Furthermore, none of the evaluated biochemical hormonal markers (FSH, LH, estradiol, prolactin, and AMH) differed significantly between women with CD and controls.

Conclusion: This systematic review and meta-analysis reinforces the existing evidence that CD may adversely affect several aspects of menstrual health in women without significantly impacting biochemical hormonal markers.