Hormonal contraception and HIV-1 infection: medroxyprogesterone acetate suppresses innate and adaptive immune mechanisms

Endocrinology. 2013 Mar;154(3):1282-95. doi: 10.1210/en.2012-1850. Epub 2013 Jan 25.


Recent observational studies indicate an association between the use of hormonal contraceptives and acquisition and transmission of HIV-1. The biological and immunological mechanisms underlying the observed association are unknown. Depot medroxyprogesterone acetate (DMPA) is a progestin-only injectable contraceptive that is commonly used in regions with high HIV-1 prevalence. Here we show that medroxyprogesterone acetate (MPA) suppresses the production of key regulators of cellular and humoral immunity involved in orchestrating the immune response to invading pathogens. MPA inhibited the production of interferon (IFN)-γ, IL-2, IL-4, IL-6, IL-12, TNFα, macrophage inflammatory protein-1α (MIP-1α), and other cytokines and chemokines by peripheral blood cells and activated T cells and reduced the production of IFNα and TNFα by plasmacytoid dendritic cells in response to Toll-like receptor-7, -8, and -9 ligands. Women using DMPA displayed lower levels of IFNα in plasma and genital secretions compared with controls with no hormonal contraception. In addition, MPA prevented the down-regulation of HIV-1 coreceptors CXCR4 and CCR5 on the surface of T cells after activation and increased HIV-1 replication in activated peripheral blood mononuclear cell cultures. The presented results suggest that MPA suppresses both innate and adaptive arms of the immune system resulting in a reduction of host resistance to invading pathogens.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adaptive Immunity / drug effects*
  • Adult
  • Animals
  • Chemokines / biosynthesis
  • Contraceptive Agents, Female / adverse effects*
  • Cytokines / biosynthesis
  • Female
  • HIV Infections / immunology*
  • HIV-1* / drug effects
  • HIV-1* / physiology
  • Humans
  • Immunity, Innate / drug effects*
  • Immunosuppressive Agents / adverse effects
  • Lymphocyte Activation / drug effects
  • Medroxyprogesterone Acetate / adverse effects*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Receptors, CCR5 / metabolism
  • Receptors, CXCR4 / metabolism
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • Vagina / drug effects
  • Vagina / immunology
  • Virus Replication / drug effects
  • Young Adult


  • CXCR4 protein, human
  • Chemokines
  • Contraceptive Agents, Female
  • Cytokines
  • Immunosuppressive Agents
  • Receptors, CCR5
  • Receptors, CXCR4
  • Medroxyprogesterone Acetate