Mifepristone, but not levonorgestrel, has suppressive effect on tubal function at pharmacological dose which may contribute to emergency contraceptive action

Abstract

Emergency contraception (EC) serves as an important back-up method in cases of unprotected intercourse or unplanned failure of a regular contraceptive method. The EC pills containing levonorgestrel (LNG) 1.5 mg or mifepristone 25-50 mg taken within 72 or 120 hours respectively after unprotected intercourse are currently the recommended oral EC methods. It is currently suggested that delay or inhibition of ovulation is the main mechanism of EC action. There is limited data on whether LNG or mifepristone have modulating effects on the functions of human Fallopian tube, however, which might contribute additionally to their contraceptive actions. The current study aims at investigating the effect of the two drugs on ciliary beat frequency and muscular contractions in human Fallopian tube by in vitro experiments. This was an in-vitro study using human Fallopian tubes obtained from women who underwent hysterectomy for benign gynaecological conditions not involving the tubes. The tubal epithelium and longitudinal smooth muscle fibers of the collected tubes were dissected out into small pieces and cultured overnight in standardized medium containing estradiol 100 pmol/l and progesterone 10 nmol/l resembling the physiological early luteal phase. These tissue strips were then treated with LNG at graded concentrations of 0, 1, 10 and 100 ng/ml, and mifepristone at graded concentrations of 0, 300, 3000 and 30000 ng/ml respectively. LNG and mifepristone at concentrations of 10 ng/ml and 3000 ng/ml corresponded to their peak serum concentrations after a pharmacological dose of 1.5 mg and 25 mg respectively. Ciliary beat frequency of the treated tubal epithelium strips was measured using a photometric method. Strips of tubal smooth muscle were connected to a force transducer, and the mean contraction frequency and amplitude were determined digitally. These parameters obtained after the different treatment conditions were compared. Our results showed that there was an overall dose-dependent suppressive effect of mifepristone on ciliary beat frequency at 3000 ng/ml or above (p<0.05), but not with LNG at any of the concentrations studied. Muscular contraction amplitude and frequency were significantly reduced (p<0.05) after treatment with mifepristone at 3000 ng/ml or above, but these parameters did not differ from control (p>0.05) after treatment with LNG at any of the concentrations studied. In conclusion, our results suggested that mifepristone, but not LNG, could inhibit ciliary beat and muscular contraction of the human Fallopian tube at the pharmacological dose, which may contribute additional mechanisms of contraceptive action of mifepristone over that for LNG. This work was supported by a Seed Fund from the Centre of Reproduction, Development and Growth, The University of Hong Kong.