Impact of Contraceptive Initiation on the Cervicovaginal Mucosa: Results from the UMPALA Multicentre Partially Randomized Patient-Preference Interventional Trial

Authors

• Betty Njoroge, Kenya Medical Research Institute
• Nelly Mugo, University of Washington
• Carolina Herrera, Macon & Joan Brock Virginia Health Sciences at Old Dominion UniversityFollow
• Karen Dominguez, Macon & Joan Brock Virginia Health Sciences at Old Dominion UniversityFollow
• Louise A. Ouattara, Macon & Joan Brock Virginia Health Sciences at Old Dominion UniversityFollow
• Nazita Yousefieh, Macon & Joan Brock Virginia Health Sciences at Old Dominion UniverityFollow
• Neelima Chandra, Macon & Joan Brock Virginia Health Sciences at Old Dominion UniversityFollow
• Agnieszka Kurczewska, Macon & Joan Brock Virginia Health Sciences at Old Dominion UniversityFollow
• Stephanie Nartey, Brigham and Women's Hospital and Harvard Medical School
• Julie Lewis, Brigham and Women's Hospital and Harvard Medical School
• Andrea R. Thurman, Macon & Joan Brock Virginia Health Sciences at Old Dominion University
• Matilda Saina, Kenya Medical Research Institute
• Raina N. Fichorova, Brigham and Women's Hospital and Harvard Medical School
• Jacques Ravel, University of Maryland School of Medicine
• Reem Sharaf Alddin, Macon & Joan Brock Virginia Health Sciences at Old Dominion University
• Nicola Richardson-Harman, AlphaStat L.L.C.
• Kenneth Ngure, University of Washington
• Gustavo F. Doncel, Macon & Joan Brock Virginia Health Sciences at Old Dominion University

Document Type

Article

Publication Date

2026

DOI

10.3389/frph.2026.1882772

Publication Title

Frontiers in Reproductive Health

Volume

8

Pages

1882772 (15 pp.)

Abstract

Background: Long-acting contraceptives are widely used, providing superior efficacy and systemic safety; however, the impact of contraceptive initiation on female genital tract function and health has been understudied.

Methods: Non-pregnant, HIV-uninfected women aged 18–50 years were enrolled in a dual-centre partially randomized patient-preference interventional trial (NCT04814927) and allowed to choose one of four contraceptive options, etonogestrel contraceptive implant, depot medroxyprogesterone acetate subcutaneous injection, levonorgestrel intrauterine device, and copper IUD, with a minimum target of 12 participants per arm and site. Sampling took place at baseline, 1 and 3 months after contraceptive initiation, and 1 month post-contraceptive discontinuation. Primary outcomes focused on mucosal function and health, while secondary and tertiary outcomes pertained to systemic and mucosal susceptibility to HIV-1 and HSV-2.

Results: Cervicovaginal samples from 112 enrolled participants showed transient, statistically significant changes in endpoints comparing baseline vs. 1 and 3 months after contraceptive initiation. Changes in pH, epithelial thickness, E-cadherin expression, antimicrobial peptides, glycogen, and lactic acid varied with contraceptive type and were typically transient. Serum oestradiol level was correlated with cervicovaginal epithelial function and glycogen and lactic acid secretion. Contraceptive initiation did not result in detectable ex vivo or in vitro increase of HIV-1 and HSV-2 susceptibility in cellular and tissue models.

Conclusions: Contraceptive initiation during the first 3 months of use induced transient and variable changes in mucosal epithelial and immune markers, not leading to persistent alterations of the vaginal milieu or increased susceptibility to viral infections during the 3 months after contraception initiation.

Clinical Trial Registration: https://clinicaltrials.gov/study/NCT04814927?term=NCT04814927.&viewType=Card&rank=1, identifier NCT04814927.

Rights

© 2026 Njoroge, Mugo, Herrera, Dominguez, Ouattara, Yousefieh, Chandra, Kurczewska, Nartey, Lewis, Thurman, Saina, Fichorova, Ravel, Sharaf Alddin, Richardson-Harman, Ngure and Doncel.

This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC BY 4.0). The use, distribution or reproduction in other forums is permitted, provided the original authors and the copyright owners are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Data Availability

Article states: "The raw data supporting the conclusions of this article will be made available by the authors upon request, without undue reservation."

Original Publication Citation

Njoroge, B., Mugo, N., Herrera, C., Dominguez, K., Ouattara, L. A., Yousefieh, N., Chandra, N., Kurczewska, A., Nartey, S., Lewis, J., Thurman, A. R., Saina, M., Fichorova, R. N., Ravel, J., Sharaf Aldin, R., Richardson-Harman, N., Ngure, K., & Doncel, G. F. (2026). Impact of contraceptive initiation on the cervicovaginal mucosa: Results from the UMPALA multicentre, partially randomized patient-preference interventional trial. Frontiers in Reproductive Health, 8, Article 1882772. https://doi.org/10.3389/frph.2026.1882772

Repository Citation

Njoroge, B., Mugo, N., Herrera, C., Dominguez, K., Ouattara, L. A., Yousefieh, N., Chandra, N., Kurczewska, A., Nartey, S., Lewis, J., Thurman, A. R., Saina, M., Fichorova, R. N., Ravel, J., Sharaf Aldin, R., Richardson-Harman, N., Ngure, K., & Doncel, G. F. (2026). Impact of contraceptive initiation on the cervicovaginal mucosa: Results from the UMPALA multicentre, partially randomized patient-preference interventional trial. Frontiers in Reproductive Health, 8, Article 1882772. https://doi.org/10.3389/frph.2026.1882772