Huijbregts, R. P., Michel, K. G., & Hel, Z. (2014). Effect of progestins on immunity: medroxyprogesterone but not norethisterone or levonorgestrel suppresses the function of T cells and pDCs. Contraception, 90(2), 123-129. https://doi.org/10.1016/j.contraception.2014.02.006
Huijbregts RP, Michel KG, Hel Z. Effect of progestins on immunity: medroxyprogesterone but not norethisterone or levonorgestrel suppresses the function of T cells and pDCs. Contraception. 2014;90(2):123-129. doi:10.1016/j.contraception.2014.02.006
Huijbregts, Richard P. H., et al. "Effect of progestins on immunity: medroxyprogesterone but not norethisterone or levonorgestrel suppresses the function of T cells and pDCs." Contraception, vol. 90, no. 2, 2014, pp. 123-129.
Depo-Provera's Hormone Suppressed Immune Cells; Two Progestins Did Not
Medroxyprogesterone acetate (MPA), the hormone in Depo-Provera, lowered immune signals in T cells and dendritic cells in a lab dish. Two other birth control hormones, norethisterone and levonorgestrel, left those cells working normally. Researchers tested cells from healthy women against four birth control hormones and natural progesterone. MPA's effect appeared at levels found in women using the shot.
Study at a glance, lab study of blood cells from healthy women: Depo-Provera's hormone lowered immune signals; two others did not. Source: Huijbregts RP et al., 2014, PMID 24674041.
Key Findings
Medroxyprogesterone acetate, the active hormone in Depo-Provera, significantly blocked T cell signaling (p < 0.05) at concentrations within the range found in women using the injection.
Etonogestrel caused partial immune suppression, and only at concentrations the researchers describe as likely above typical contraceptive use.
Norethisterone and levonorgestrel caused no measurable drop in T cell or dendritic cell activity at any level tested.
MPA suppressed five separate immune signaling proteins together in activated immune cells, across three independent experiments.
MPA binds the glucocorticoid receptor far more strongly than the other progestins, which the researchers say may explain its distinct effect.
Interpretation
This lab study exposed blood cells from healthy women to four birth control hormones and natural progesterone in a dish, then measured immune signals directly. The findings support larger studies on how these differences affect real infection risk.
RRM Context
RRM Academy calls Depo-Provera a suppressive medication. This study shows why: its hormone reaches past birth control and dampens immune cells too. NaProTechnology and other restorative care use progesterone identical to the body's own to support a woman's cycle, a different path than the man-made hormone tested here.
Our editorial summary of this paper, not the article's abstract.
Abstract
Objectives
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.
Study Design
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.
Conclusion
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.
Implications
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.
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