Impact of Hormonal Contraceptive Exposure on Pancreatic β-Cell Adaptation and Glucose Homeostasis: A Systematic Review.
- 1Department of Medical Physiology, School of Medicine and Pharmacy, College of Medicine and Health Sciences, University of Rwanda, Kigali, Rwanda.
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.
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BibTeX
@article{niyomugabo2026impact,
title = {{Impact of Hormonal Contraceptive Exposure on Pancreatic β-Cell Adaptation and Glucose Homeostasis: A Systematic Review.}},
author = {Aime Patrick Niyomugabo and Olufunke Onaadepo and Leopold Ntakirutimana and Muluken Walle Birhanie and Onyinye Cynthia Okeke and Abdul-Rahuf Aderemi Feyitimi and Ejike Daniel Eze and Abdulazeez Jimoh and Abdullateef Isiaka Alagbonsi and Makinde Vincent Olubiyi},
journal = {Open access journal of contraception},
year = {2026},
month = oct,
doi = {10.2147/oajc.s629161},
url = {https://europepmc.org/article/MED/42974476},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Impact of Hormonal Contraceptive Exposure on Pancreatic β-Cell Adaptation and Glucose Homeostasis: A Systematic Review.
AU - Aime Patrick Niyomugabo
AU - Olufunke Onaadepo
AU - Leopold Ntakirutimana
AU - Muluken Walle Birhanie
AU - Onyinye Cynthia Okeke
AU - Abdul-Rahuf Aderemi Feyitimi
AU - Ejike Daniel Eze
AU - Abdulazeez Jimoh
AU - Abdullateef Isiaka Alagbonsi
AU - Makinde Vincent Olubiyi
PY - 2026
DA - 2026/10/29
JO - Open access journal of contraception
DO - 10.2147/oajc.s629161
UR - https://europepmc.org/article/MED/42974476
AB - 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.
SN - 1179-1527
ER -