Effect of minipills on physiologic responses of human cervical mucus, endometrium and ovary.
To evaluate the action of 4 different low-dose progestogen oral contraceptive preparations on in vitro sperm penetrability by their effect on the cervical mucus, endometrial histology, and ovarian function, 42 normal healthy multiparous women, 21-43 years old, were divided into 4 random groups and administered daily either cingestol .25 mg, quingestanol acetate .3 mg, chlormadinone acetate .5 mg, or megestrol acetate .5 mg for 6-18 months, for a total of 370 studied cycles. 23 untreated women served as controls. Cervical mucus samples were obtained on Day 14 of the cycle and tested for receptivity with fresh semen samples. Endometrial biopsies were obtained on Day 20 of the cycle at 6-month intervals and 14 ovarian biopsies were performed during the course of tubal ligation in treated patients. Urinary pregnanediol levels were also tested in 20 patients on Cycle Day 22. Irregularities in the menstrual pattern occurred in 12%-19% of the minipill users during the first 6 months of contraceptive therapy, but later disappeared. Cervical mucus samples revealed decreased spinnbarkheit and modified crystallization patterns. In vitro sperm penetration depths were remarkably lower in the treated groups than in the controls, the means ranging from .6 cm (megestrol) to .8 cm (cingestol) compared with 3.4 cm in the control group. Spermatozoa were poorly motile or immotile. In the endometrial samples, atypical rhythmic development of the glands and stroma were observed. Secretory changes occurred in 42% (megestrol) to 60% (cingestol) of the patients, and proliferative pattern changes occurred in 31% (chlormadinone) to 44% (quingestanol). Normal corpora lutea were seen in 9 of the 14 ovarian biopsies, but distended follicular cysts with or without luteinization were seen in half of these cases. Ovarian changes and 24-hour pregnanediol levels were in contradiction with endometrial patterns. No significant differences were noted between the different minipill compounds and their functional alterations. It is concluded that low-dose progestogens achieve their contraceptive effect through interference with sperm migration in the cervical mucus, alteration of endometrial morphology, and possible interference with hormonal equilibrium.