Women account for approximately half of all individuals living with HIV worldwide, and researchers wanted to identify the risk factors that increase susceptibility of women to genital infection.
Because HIV and other sexually transmitted viruses must penetrate the genital mucosal barrier to establish infection, researchers at The Ohio State University Wexner Medical Center sought to identify factors that weaken genital mucosal barrier defenses.
Their research, recently published in the journal of Mucosal Immunology, shows significantly increased susceptibility of female mice to genital tract viral infections after treatment with depot medroxyprogesterone acetate (DMPA) or levonorgestrel (LNG), two injectable compounds used by women for hormonal contraception.
Specifically, treatment of mice with DMPA or LNG decreased barrier protection in the female genital tract by increasing epithelial permeability. This greater permeability increased the chances that a viral pathogen could invade and establish infection.
"Our findings provide new biological plausibility for the connection between DMPA and increased susceptibility to genital infection suggested by many clinical studies," said Dr. Thomas L. Cherpes, an associate professor in the Departments of Microbial Infection and Immunity and Obstetrics and Gynecology at The Ohio State University College of Medicine. "They also identify that LNG may similarly enhance susceptibility to viral infections."
"Remarkably, our evaluation of cervical biopsy tissue from women before and one month after initiating DMPA revealed barrier protection was diminished by treatment identically to the change seen in progestin-treated mice," said Dr. Nirk Quispe Calla, lead author of the publication.
On the other hand, additional mouse studies performed by the researchers showed that combined treatment with DMPA and intravaginal estrogen prevented mice from acquiring herpes simplex virus type 2 by restoring the genital mucosal barrier, a first-line of defense against all sexually transmitted infections.
Based on the latter results, Cherpes said the ability to rescue DMPA-treated mice with local estrogen administration may offer a foundation for the development of contraceptive strategies less compromising of barrier protection, as use of an estradiol-releasing vaginal delivery device could be integrated into approaches for hormonal contraception.
"In one possible scenario, women would receive DMPA and an estradiol-releasing vaginal ring that also releases antiviral microbicides. While only a hypothetical alternative at this time, defining the safety and efficacy of such an approach warrants further study," said Dr. Rodolfo Vicetti Miguel, another study author.
Other Ohio State investigators involved in the study were Drs. Luanne Hall-Stoodley, Balveen Kaur and Wayne Trout and undergraduate researcher Stephen Pavelko.
Funding from the Eunice Kennedy Shriver National Institute for Child Health and Human Development supported this research.
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