Paracetamol-associated luteinized unruptured follicle syndrome: effect on intrafollicular blood flow

We are using transvaginal ultrasonography with color Doppler imaging to study changes in intrafollicular blood flow over the periovulatory period. We report here the findings from one volunteer (subject 9), who took two tablets of paracetamol (1000 mg) twice daily (between 07.00 and 08.00, and 18.00 and 19.00) for 2 consecutive menstrual cycle days (12 and 13) to alleviate a headache, which was shown retrospectively to have occurred within the duration of the luteinizing hormone (LH) surge in peripheral plasma. The drug appeared to have a profound effect on peak systolic blood velocity within the preovulatory follicle. Color (an index of blood velocity) disappeared and flow velocity waveforms were not detectable for at least 4 h. Color then re-appeared, but the peak systolic blood velocity had reduced by 69.8% (from 18.2 to 5.5 cm/s). The peak systolic blood velocity recovered subsequently to 16.3 cm/s, but the follicle did not rupture and continued to grow to a maximum diameter > 59 mm. There was no apparent effect of the drug on expected changes in the circulating levels of estradiol, LH, follicle stimulating hormone or progesterone. The secretory phase of the menstrual cycle lasted 13 days (i. e. day of LH peak to day of next menses minus one). We suggest that paracetamol taken at the time of the LH surge may affect intrafollicular peak systolic blood velocity and might inhibit ovulation. Possible molecular mechanisms are discussed.