Background Progestogen-only contraceptives are presented as injections, implants, oral formulations, hormone-releasing intrauterine methods, and emergency contraceptives. This study assessed the effect of different progesterone-containing contraceptive methods on safety and endogenous progesterone level. Methods This prospective cohort study included 80 healthy fertile females aged between 20 and 35 years with normal menstrual history who had at least one offspring after spontaneous pregnancy. Subjects were divided into four equal groups according to the contraceptive method: group D (Depo-Provera®) used the injectable progesterone of 150 mg every 90 days or 3 months, group I contained 68 mg of etonogestrel implant formerly known as Implanon, group N: used norgestrel (Ovrette®), (each pill contains 0.075 mg of norgestrel) once daily, and group M: used intrauterine device (IUD) (Mirena) containing 52 mg of levonorgestrel. Results Group M had a higher endogenous progesterone level compared to those who used other contraceptives with a normal follicle size. Incidence of amenorrhea was significantly lower in group M (20%) than in group D (75%), group I (65%), and group N (70%), with an insignificant difference among the other three groups. Continuation rate had significantly increased in group M than in the other three groups after 6 months. Efficacy was insignificantly different among the four groups. Conclusion Mirena had low systemic absorption of exogenous progesterone, so it had less effect on endogenous progesterone with better follicle size and low incidence of side effects (amenorrhea) compared to other contraceptives containing progesterone.