title: Effect of progestins on immunity: medroxyprogesterone but not norethisterone or levonorgestrel suppresses the function of T cells and pDCs.
abstract: OBJECTIVE
  The potential effect of hormonal contraception on HIV-1 acquisition and transmission represents an important public health issue. Several observational studies have suggested an association between the use of hormonal contraception, in particular injectable depot medroxyprogesterone acetate (DMPA), and an increased risk of HIV-1 acquisition and transmission. We and others have previously demonstrated that DMPA acts as a potent inhibitor of innate and adaptive immune mechanisms. The study presented here addresses the immunomodulatory properties of several common progestins with a potential to replace DMPA.
  
  
  METHODS
  To identify safe alternatives to DMPA, we tested the effect of commonly used progestins on the function of human primary T cells and plasmacytoid dendritic cells (pDCs) obtained from the blood of healthy premenopausal women.
  
  
  RESULTS
  Medroxyprogesterone acetate (MPA) inhibited the activation of T cells and pDCs in response to T cell receptor- and Toll-like receptor-mediated activation at physiological concentrations. Etonogestrel exerted a partial suppressive activity at high concentrations. In sharp contrast, norethisterone (NET) and levonorgestrel (LNG) did not exhibit detectable immunosuppressive activity.
  
  
  CONCLUSIONS
  Evidence indicating the immunosuppressive properties of DMPA strongly suggests that DMPA should be discontinued and replaced with other forms of long-term contraception. Since NET and LNG do not exert immunosuppressive properties at physiological concentrations, these progestins should be considered as alternative contraceptives for women at high risk for HIV-1 infection.
  
  
  CONCLUSIONS
  The presented data suggest that, at physiological levels, the progestins NET and LNG do not suppress cytokine production by immune cells and should be considered as alternatives to DMPA; however, more in vivo testing is needed to confirm this data.
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Richard P H
authors.initials: RP
authors.lastname: Huijbregts
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Katherine G
authors.initials: KG
authors.lastname: Michel
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA; Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA; Center for AIDS Research, University of Alabama at Birmingham, Birmingham, AL, USA. Electronic address: zhel@uab.edu.
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Hel
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D003271:Contraceptive Agents, Female / Q000009:adverse effects / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D003692:Delayed-Action Preparations / Q000009:adverse effects / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D017135:Desogestrel / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007108:Immune Tolerance / Q000187:drug effects*; D016912:Levonorgestrel / Q000009:adverse effects / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D017258:Medroxyprogesterone Acetate / Q000009:adverse effects / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D009640:Norethindrone / Q000009:adverse effects / Q000494:pharmacology; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D011372:Progestins / Q000009:adverse effects / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D051217:Toll-Like Receptor 9 / Q000819:agonists; D051193:Toll-Like Receptors / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D003271:Contraceptive Agents, Female; C526902:CpG ODN 2216; D016207:Cytokines; D003692:Delayed-Action Preparations; D007093:Imidazoles; D009838:Oligodeoxyribonucleotides; D011372:Progestins; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors; C044815:etonogestrel; D016912:Levonorgestrel; D017135:Desogestrel; D017258:Medroxyprogesterone Acetate; D009640:Norethindrone; C402365:resiquimod
keywords: AIDS; DMPA; ETG; HIV-1; Hormonal contraception; LNG; NET; Progestins