Hormonal effects of the 300 μg norethisterone (NET) minipill

1. Daily steroid levels in 43 subjects during a pretreatment cycle alnd during the second month of NET administration
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      The ovarian effects of the 300 μg norethisterone (NET) minipill were investigated in 43 normally menstruating women by the daily analysis of the peripheral plasma levels of estradiol and progester-one in a pretreatment (control) cycle and during the second month of NET administration. During the latter period, the daily levels of NET were also measured. The assessment of normal values characterizing an ovulatory cycle was based on the results of a previous study, indicating Math Eq that in a normal luteal phase, 95 out of 100 normally menstruating women of the local study population exhibit plasma progesterone levels exceeding 16 nmol/1 for a minimum of five days.
      The present study revealed four characteristic and distinctly different types of ovarian reaction to the NET minipill; seven subjects (16%) exhibited no signs of follicular or luteal activity as evidenced by the low estradiol and progesterone levels (Math Eq), ten subjects (23%) showed a marked cyclic follicular activity, but no luteal function (group B), nine subjects (21%) had a normal follicular activity, but a significantly reduced (insufficient) luteal activity (Math Eq),and 17 subjects (40%) exhibited estradiol and progesterone profiles which were indistinguishable from those found in normally menstruating women, in general, and in their pretreatment cycles, in particular (Math Eq).
      Compared to the characteristics of the pretreatment cycles, the administration of NET resulted in a shortening of the luteal phase in group C and in a lengthening of the follicular phase together with a shortening of the luteal phase in group D.
      The plasma levels of NET closely reflected the regularity (or irregularity) of pill taking by the various subjects and the time interval elapsing between pill taking and blood withdrawal. There was no correlation between the levels of NET and the types of ovarian reaction induced, or of the bleeding profile.
      Compared to the bleeding profile of the pretreatment period, the administration of NET increased the number of episodes and the number of days with bleeding and spotting and reduced the average bleeding-free interval. In this limited study, no difference could be established in the bleeding patterns observed in the various groups.
      An important aspect of this investigation was to assess whether or not the ovarian reaction to the NET minipill can be predicted from the analysis of previous reproductive events and/or the hormonal profile of the pretreatment cycle. There was a significant excess of nulliparous women in group A. Compared to the women of the three other groups, they exhibited, in their pretreatment cycle, a diminished progesterone maximum together with a prolonged follicular phase and shortened luteal phase. On the other hand, the 17 women of group D showed a shorter follicular phase and longer luteal phase than the 26 women in groups A+B+C.
      It is concluded that the relative length of follicular and luteal phases has a predictive value for the expected ovarian reaction to the NET minipill. Hence, the efficacy of the minipill might be increased by judicious selection of women exhibiting, during the pretreatment period, a high follicular to luteal phase (Math Eq) ratio (measured, for instance, by basal body temperature, or some other simple method).
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