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Genital Injury Signatures and Microbiome Alterations Associated With Depot Medroxyprogesterone Acetate Usage and Intravaginal Drying Practices

J Infect Dis. 2017 Feb 15;215(4):590-598. doi: 10.1093/infdis/jiw590.

Abstract

Background: Increasing evidence suggests depot medroxyprogesterone acetate (DMPA) and intravaginal practices may be associated with human immunodeficiency virus (HIV-1) infection risk; however, the mechanisms are not fully understood. This study evaluated the effect of DMPA and intravaginal practices on the genital proteome and microbiome to gain mechanistic insights.

Methods: Cervicovaginal secretions from 86 Kenyan women, including self-reported DMPA users (n = 23), nonhormonal contraceptive users (n = 63), and women who practice vaginal drying (n = 46), were analyzed using tandem-mass spectrometry.

Results: We identified 473 human and 486 bacterial proteins from 18 different genera. Depot medroxyprogesterone acetate use associated with increased hemoglobin and immune activation (HBD, HBB, IL36G), and decreased epithelial repair proteins (TFF3, F11R). Vaginal drying associated with increased hemoglobin and decreased phagocytosis factors (AZU1, MYH9, PLAUR). Injury signatures were exacerbated in DMPA users who also practiced vaginal drying. More diverse (H index: 0.71 vs 0.45; P = .009) bacterial communities containing Gardnerella vaginalis associated with vaginal drying, whereas DMPA showed no significant association with community composition or diversity.

Conclusions: These findings provide new insights into the impact of DMPA and vaginal drying on mucosal barriers. Future investigations are needed to confirm their relationship with HIV risk in women.

Keywords: DMPA; Depot medroxyprogesterone acetate; HIV; Mucosa; genital injury; metaproteome; microbiome; progestin; proteomics; vaginal drying.

MeSH terms

  • Adult
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism
  • Contraceptive Agents, Female / administration & dosage*
  • Contraceptive Agents, Female / adverse effects
  • Cross-Sectional Studies
  • Desiccation
  • Female
  • Gardnerella vaginalis / drug effects
  • Gardnerella vaginalis / isolation & purification
  • HIV / isolation & purification
  • HIV Infections / epidemiology*
  • Hemoglobins / metabolism
  • Humans
  • Interleukin-1 / genetics
  • Interleukin-1 / metabolism
  • Kenya
  • Medroxyprogesterone Acetate / administration & dosage*
  • Medroxyprogesterone Acetate / adverse effects
  • Microbiota*
  • Molecular Motor Proteins / genetics
  • Molecular Motor Proteins / metabolism
  • Mucous Membrane / drug effects
  • Mucous Membrane / microbiology
  • Myosin Heavy Chains / genetics
  • Myosin Heavy Chains / metabolism
  • Phagocytosis / drug effects
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism
  • Receptors, Urokinase Plasminogen Activator / genetics
  • Receptors, Urokinase Plasminogen Activator / metabolism
  • Risk Factors
  • Trefoil Factor-3 / genetics
  • Trefoil Factor-3 / metabolism
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism
  • Vagina / injuries
  • Vagina / microbiology*
  • Young Adult

Substances

  • Carrier Proteins
  • Cell Adhesion Molecules
  • Contraceptive Agents, Female
  • F11R protein, human
  • Hemoglobins
  • IL36G protein, human
  • Interleukin-1
  • MYH9 protein, human
  • Molecular Motor Proteins
  • PLAUR protein, human
  • Receptors, Cell Surface
  • Receptors, Urokinase Plasminogen Activator
  • TACC2 protein, human
  • TFF3 protein, human
  • Trefoil Factor-3
  • Tumor Suppressor Proteins
  • Medroxyprogesterone Acetate
  • Myosin Heavy Chains