Hormonal consequences of “missing the pill”

The hormonal effects of the deliberate omission of a low-dose combined oral contraceptive pill (150 μg levonorgestrel + 30 μg ethinyl estradiol) were studied in 32 apparently healthy women of the fertile age. Four groups of eight subjects each were requested to omit pill-taking on two consecutive days of the study, namely days 9 and 10 (Group I), 11 and 12 (Group II), 14 and 15 (Group III) and 17 and 18 (Group IV), respectively, and the peripheral plasma levels of progesterone (P), levonorgestrel (NOG) and estradiol (E₂) were measured daily for 29 days.The analysis of NOG levels revealed that one subject did not take any pill during the last cycle preceding the study and did not start pill-taking before day 10 of the study cycle. In this subject, a biphasic P profile with significantly, but insufficiently (up to 8.0 nmol/l), elevated P levels was found.In the remaining 31 subjects, the P levels remained invariably below 1.5 nmol/l; however, the mean P levels of days 1–15 were significantly (P < 0.01) higher than those of days 16–29.The assay of NOG levels indicated measurable values in each of the 31 subjects even six days after the discontinuation of pill-taking. From the peripheral NOG levels, an average removal half-life of 29 hours was calculated.The E₂ levels were uniformly suppressed (below 400 pmol/l) in 26 of the 31 subjects (hereafter: “low” E₂-group), whereas five subjects (“high” Eg-group) exhibited a cyclic E₂ profile, with peak levels between 530 and 1200 pmol/l. A linear increase with time in E₂ levels (P < 0.001) was found during the pill-free week in both groups of subjects.