Injectable Progestin-Only Contraception is Associated With Increased Levels of Pro-Inflammatory Cytokines in the Female Genital Tract

Am J Reprod Immunol. 2015 Oct;74(4):357-67. doi: 10.1111/aji.12415. Epub 2015 Jul 22.


Problem: Genital inflammatory changes may be a mechanism of increased HIV risk among injectable progestin-only contraception (IPC) users.

Method of study: We conducted a cross-sectional analysis of 376 Kenyan and South African women. Genital cytokines and secretory leukocyte peptidase inhibitor concentrations in a reference population were compared to IPC users and women with reproductive tract infections.

Results: No significant variability in marker concentrations was observed by age or site. Depot medroxyprogesterone acetate (DMPA) users had significantly higher MIP-1α, MIP-1β, IL-6, IL-8, IP-10, and RANTES concentrations. Norethisterone oenanthate users had significantly higher IL-6, IL-8, and RANTES concentrations. Women with sexually transmitted infections had variable inflammation, and women with bacterial vaginosis exhibited a mixed profile of up and downregulation.

Conclusion: The finding of substantial mucosal inflammation among DMPA users provides evidence which, combined with the results of prior studies, suggests that DMPA may create an immune environment conducive to HIV target cell recruitment and inhibitory for antiviral activity.

Keywords: Cytokines; depot medroxyprogesterone acetate; mucosal; secretory leukocyte peptidase inhibitor; sexually transmitted infections.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Contraception / methods
  • Contraceptive Agents, Female / pharmacology*
  • Cross-Sectional Studies
  • Cytokines / metabolism*
  • Female
  • Genitalia, Female / metabolism*
  • HIV Infections / pathology
  • HIV Infections / virology
  • Humans
  • Inflammation / chemically induced
  • Kenya
  • Medroxyprogesterone Acetate / pharmacology
  • Norethindrone / analogs & derivatives
  • Norethindrone / pharmacology
  • Pregnancy
  • Progestins / pharmacology*
  • Sexually Transmitted Diseases, Bacterial / immunology*
  • Sexually Transmitted Diseases, Bacterial / microbiology
  • South Africa
  • Vaginosis, Bacterial / immunology*
  • Vaginosis, Bacterial / microbiology
  • Young Adult


  • Contraceptive Agents, Female
  • Cytokines
  • Progestins
  • Medroxyprogesterone Acetate
  • norethindrone enanthate
  • Norethindrone