Feasibility, safety and tolerability of estrogen and/or probiotics for improving vaginal health in Canadian African, Caribbean, and Black women: A pilot phase 1 clinical trial

Biban Gill; Jocelyn M Wessels; Christina L Hayes; Jenna Ratcliffe; Junic Wokuri; Elizabeth Ball; Gregor Reid; Rupert Kaul; Jesleen Rana; Muna Alkhaifi; Wangari Tharao; Fiona Smaill; Charu Kaushic

doi:10.1371/journal.pone.0315576

Feasibility, safety and tolerability of estrogen and/or probiotics for improving vaginal health in Canadian African, Caribbean, and Black women: A pilot phase 1 clinical trial

PLoS One. 2025 Jan 21;20(1):e0315576. doi: 10.1371/journal.pone.0315576. eCollection 2025.

Authors

Biban Gill¹, Jocelyn M Wessels^{1

2}, Christina L Hayes¹, Jenna Ratcliffe¹, Junic Wokuri³, Elizabeth Ball¹, Gregor Reid⁴, Rupert Kaul^{5

6}, Jesleen Rana³, Muna Alkhaifi³, Wangari Tharao³, Fiona Smaill⁷, Charu Kaushic¹

Affiliations

¹ McMaster Immunology Research Centre and Department of Medicine, McMaster University, Hamilton, ON, Canada.
² Afynia Laboratories, Hamilton, ON, Canada.
³ Women's Health in Women's Hands Community Health Centre, Toronto, ON, Canada.
⁴ Departments of Microbiology & Immunology and Surgery, Western University, and Canadian Research and Development Centre for Human Microbiome and Probiotics, The Lawson Health Research Institute, London, ON, Canada.
⁵ Departments of Immunology and Medicine, University of Toronto, Toronto, ON, Canada.
⁶ Department of Medicine, University Health Network, Toronto, ON, Canada.
⁷ Department of Pathology and Molecular Medicine and Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON, Canada.

Abstract

Background: A dysbiotic vaginal microbiome (VMB) is associated with clinical conditions such as bacterial vaginosis (BV) and an increased risk of human immunodeficiency virus (HIV-1) infection. Considering the high prevalence of BV among African, Caribbean and Black (ACB) women, we conducted a prospective, randomized, open-label phase 1 clinical trial to determine the feasibility, safety and tolerability of administering low-dose estrogen, probiotics or both in combination to improve vaginal health and decrease HIV-1 susceptibility.

Methods: ACB women aged 18-49 from the Greater Toronto Area (GTA) were randomized to one of four study arms: intravaginal estradiol (Estring©; 7.5mg/day); a vaginal probiotic (RepHresh™ Pro-B™) administered twice daily; a combination of Estring© and vaginal RepHresh™ Pro-B™ (twice daily); or the Estring© and oral RepHresh™ Pro-B™ (twice daily), for a duration of 30 days. Feasibility was evaluated through enrolment, retention, and adherence rates, while safety and tolerability were determined by a pre- and post-treatment blood panel and reported adverse events (AEs).

Results: Overall, 63 ACB women were screened, 50 were enrolled and received the intervention while 41 completed the study, resulting in 80% enrollment and 82% retention rates. Overall adherence to the study protocol was high at 93%, with an adherence of 92% for RepHresh™ Pro-B™ and 97% for Estring©. A total of 88 AEs were reported by 29 participants which were mild (66/88; 75%) and largely resolved (82/88;93%) by the end of the study, with no serious AEs (SAEs) noted. In addition, a panel of safety blood markers measured pre- and post-intervention confirmed no clinically significant changes in blood chemistry or blood cell count.

Conclusion: Overall, the administration of intravaginal estrogen and/or probiotics in pre-menopausal ACB women is feasible, safe, and well tolerated.

Trial registration: The trial was registered with Clinicaltrials.gov (NCT03837015) and CIHR HIV Clinical Trials (CTN308).

Copyright: © 2025 Gill et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Publication types

Clinical Trial, Phase I
Randomized Controlled Trial

MeSH terms

Administration, Intravaginal
Adolescent
Adult
Black People
Canada
Caribbean Region
Estrogens* / administration & dosage
Feasibility Studies
Female
HIV Infections
Humans
Middle Aged
Pilot Projects
Probiotics* / administration & dosage
Probiotics* / adverse effects
Prospective Studies
Vagina* / microbiology
Vaginosis, Bacterial / drug therapy
Young Adult

Substances

Estrogens

Associated data

ClinicalTrials.gov/NCT03837015

Grants and funding

This study was funded by CIHR Grants FRN#159229 and FRN#154047 (CK) and in-kind contributions from CIHR HIV Clinical Trials Network (FS, CK). B.G was partially supported by a Post-doctoral Award from CIHR FRN#181875. There was no additional external funding received for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.