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 receptorand 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.
progestin immunity T cell suppression, medroxyprogesterone immune function suppression, norethisterone levonorgestrel immune comparison, DMPA plasmacytoid dendritic cell function, hormonal contraception immune response, progestin-specific immunomodulation, MPA T cell pDC suppression, contraceptive progestins HIV susceptibility, differential progestin immune effects
PMID 24674041 24674041 DOI 10.1016/j.contraception.2014.02.006 10.1016/j.contraception.2014.02.006
Cite this article
Huijbregts, R. P. H., 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 RPH, 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.
Concerns about weight gain may influence contraceptive use. We compared the change in body weight over the first 12 months of use between women using the etonogestrel (ENG) implant, the levonorgestrel intrauterine system (LNG-IUS) or depot medroxyprogesterone acetate (DMPA) with women using the copper intrauterine device (IUD). This was a substudy of the Contraceptive CHOICE Project, a prospective cohort study of 9256 women provided no-cost contraception. Women who had been using the ENG implant, LNG-IUS, DMPA or copper IUD continuously for at least 11 months were eligible for participation. We obtained body weight at enrollment and at 12 months and compared the weight change for each progestin-only method to the copper IUD. We enrolled a total of 427 130 ENG implant users, 130 LNG-IUS users, 67 DMPA users and 100 copper IUD users. The mean weight change (in kilograms) over 12 months was 2.1 for ENG implant users [standard deviation (SD)=6.7]; 1.0 for LNG-IUS users (SD=5.3); 2.2 for DMPA users (SD=4.9) and 0.2 for copper IUD users (SD=5.1). The range of weight change was broad across all contraceptive methods. In the unadjusted linear regression model, ENG implant and DMPA use were associated with weight gain compared to the copper IUD. However, in the adjusted model, no difference in weight gain with the ENG implant, LNG-IUS or DMPA was observed. Only Black race was associated with significant weight gain (1.3 kg, 95% confidence interval=0.2-2.4) when compared to other racial groups. Weight change was variable among women using progestin-only contraceptives. Black race was a significant predictor of weight gain among contraceptive users.
Contraception/ComparisonReproductive Endocrinology
Open Access
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Contraception/ComparisonReproductive Endocrinology
Open Access
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Contraception/ComparisonReproductive Endocrinology
Open Access
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