Work

Impact of Hormonal Contraceptive Exposure on Pancreatic β-Cell Adaptation and Glucose Homeostasis: A Systematic Review

Year: 2026

Type: review

Abstract: Background: Hormonal contraceptives (HCs) modulate endocrine and metabolic function. Some formulations have been associated with reduced insulin sensitivity, increasing the functional demand on pancreatic β-cells. This systematic review synthesised evidence on pancreatic β-cell adaptation to HC exposure. Methods: In accordance with PRISMA 2020, PubMed, Scopus and Wiley Online Library were searched for records published from January 2000 to December 2025, combining terms for β-cell function and adaptation with terms for hormonal contraceptives and for glucose homeostasis and insulin resistance. Eligible studies were original investigations in humans and rodents examining β-cell structural, functional or signalling adaptation to HC exposure, with a comparison group or pre-exposure baseline. Risk of bias was assessed by design using RoB 2, NIH and Newcastle-Ottawa criteria, SYRCLE, and adapted in vitro indicators. Findings were synthesised thematically. Results: Of 502 records identified, seven studies met the criteria: four human, two rodent in vivo and one isolated islet study. In women, ethinylestradiol with norgestimate improved insulin sensitivity in lean participants but reduced it in those with obesity; a drospirenone-containing pill raised HOMA-IR; an oral levonorgestrel preparation reduced insulin sensitivity more than an etonogestrel vaginal ring, with β-cell function unaltered by either; and androgenic formulations amplified postprandial glucose and insulin responses despite unchanged fasting values. In rodents, drospirenone-containing exposure produced hyperinsulinemia with preserved glucose tolerance, attributable to enhanced secretory activity and reduced insulin clearance; levonorgestrel impaired glucose tolerance and raised HOMA-IR, HOMA-β and circulating corticosterone. In isolated rat islets, gestodene metabolites increased insulin and glucokinase expression and glucose-stimulated insulin secretion via oestrogen receptor-dependent pathways. Conclusion: Effects of HC on glucose metabolism and β-cell function appear to depend on progestin composition, route of administration and pre-existing metabolic status. Longitudinal human studies using direct measures of secretory capacity are needed to establish whether compensatory capacity is sustained under continued exposure.

Source: Open Access Journal of Contraception

DOI: 10.2147/oajc.s629161