Depot medroxyprogesterone acetate and norethisterone enanthate differentially impact T‐cell responses and expression of immunosuppressive markers

다국어 초록 (Multilingual Abstract)

Injectable contraceptive use may impact immune cell responsiveness and susceptibility to infection. We measured responsiveness of T‐cells from women before and after initiating depot medroxyprogesterone acetate (DMPA) or norethisterone enanthate (Net‐En).
Peripheral blood mononuclear cells collected from women aged 18‐34 years prior to, at steady state, and nadir concentrations after initiating DMPA (n = 30) or Net‐En (n = 36) and from women initiating copper intrauterine device (CU‐IUD; n = 32) were stimulated with phorbol myristate acetate and analyzed using flow cytometry. We evaluated percentage change in T‐cells expressing programmed cell death‐1 (PD‐1) and cytotoxic T‐lymphocyte associated protein‐4 (CTLA‐4).
Compared to baseline, there were decreased numbers of CD4+CTLA4+ (P < .001) and CD8+CTLA4+ (P < .01) T‐cells following ex vivo stimulation challenge at steady state DMPA concentrations and no differences at nadir concentrations (P = .781 and P = .463, respectively). In Net‐En users, no differences in CD4+CTLA4+ T‐cells at steady state (P = .087) and nadir concentrations (P = .217) were observed. DMPA users had fewer CD4+PD‐1+ (P < .001) and CD8+PD‐1+ (P < .001) T‐cells at nadir concentrations. Number of CD4+PD‐1+ and CD8+PD‐1+ T‐cells decreased at steady state concentration (P = .002 and P = .001, respectively) and at nadir concentrations after Net‐En initiation (P < .001 and P < .001). In CU‐IUD users, there were no changes in number of CD4+CTLA4+ (P = .426) and CD8+CTLA4+ (P = .169) and no changes in CD4+PD‐1+ (P = .083) and CD8+PD‐1+ (P = .936) compared to baseline.
Activation of T‐cells in response to ex vivo stimulation is suppressed at steady state DMPA concentration and resolves at nadir concentration, suggesting DMPA immunosuppressive effects may be transient.