Effect of injectable medroxyprogesterone acetate and etonogestrel implants on GABA-A and serotonin receptors in white and gray matter of the brain: experimental study in rats.

The aim of this study was to evaluate the time-dependent effect of progesterone-only contraceptives on the brain and to obtain an improved understanding of mood disorders experienced under this medication. A total of 66 Wistar albino rats were divided into three groups: etonogestrel (ENG) implant (group 1, n = 30); depot medroxyprogesterone acetate (MPA)-injectable (group 2, n = 30); and control (group 3, n = 6) groups. Groups 1 and 2 were each divided into five subgroups, which were examined every 10 d for up to 50 d after medication administration, to evaluate its time-dependent effect. There was no difference in terms of gamma-aminobutyric acid (GABA) and serotonin immunohistochemical staining in white and gray matter among the subgroups of group 1. In group 2, there was a significant decrease in serotonin receptor staining intensity in white and gray matter on day 50, when compared to the control group (p = 0.041). When the subgroups of group 2 were compared, there was a significant decrease in serotonin receptor staining intensity in white and gray matter on days 40 and 50 when compared to day 10. In conclusion, we showed that ENG and MPA have no effect on apoptosis and GABA-A receptors in the brain. We also showed that MPA has time-dependent effects on serotonin receptors, which may be a possible mechanism involved in mood disorders during long-term usage of injectable progesterone-only contraceptives.