Effect of depot medroxyprogesterone acetate on human β-defensin production and structural integrity of the human vaginal epithelium

Abstract Background Recent studies implicate the use of hormonal contraceptives, particularly depot medroxyprogesterone acetate (DMPA; Depo-Provera), with increased risk of HIV-1 acquisition. In this study, we recruited long-term users of hormonal contraceptives to further understand the biological mechanism behind this phenomenon. Methods 83 healthy, premenopausal women using DMPA (22 participants), combined oral contraceptives (17), NuvaRing (17), or non-hormonal contraceptives (26) were recruited in Birmingham, AL, USA, for a vaginal biopsy, blood draw, and cervicovaginal lavage (CVL). Participants were excluded if they were pregnant or symptomatic for vaginitis or ulcers. Informed consent was obtained from all patients; the study was approved by the Institutional Review Board of University of Alabama at Birmingham. Vaginal epithelium was assessed with two distinct measurements: a mean thickness and shortest distance (from the lumen to the nearest lamina propria projection; minimum 100 points per biopsy). CVL antiviral content was assessed with ELISA and Luminex. RNA sequencing was performed on four DMPA and four control vaginal biopsies with use of laser capture microdissection to dissect the epithelium from the lamina propria. Findings DMPA use was significantly associated with thinner vaginal epithelium (median DMPA 290·7 μm; median control 353·8 μm; p=0·01). DMPA and NuvaRing suppressed production of human β defensin-2 (HBD2) (control 13 198 pg/mL; DMPA 741·5 pg/mL, p=0·0002; NuvaRing 326·7 pg/mL, p=0·0003) and HBD3 (control 776·4 pg/mL; DMPA 50·2 pg/mL, p