EFFECTS OF NORETHISTERONE ON PITUITARY AND OVARIAN FUNCTION

Abstract

ABSTRACT The effect of norethisterone (17α-ethynyl-17β-hydroxy-19-norandrost-4-en-3-one) on certain aspects of pituitary and ovarian function has been investigated in seven healthy women. Twenty-four urine samples were collected daily throughout control cycles and subsequently during the second cycle of treatment with 0.35 mg/day of norethisterone. LH, FSH and total oestrogens were measured in all urine specimens and the level of pregnanediol-3α-glucuronoside on selected days during the luteal phase. In addition, progesterone, 17-hydroxyprogesterone and oestradiol were determined in peripheral venous plasma nine days after the peak of urinary LH. At the same time, progesterone secretion and metabolism were assessed from the analyses of urinary metabolites following the intravenous administration of labelled progesterone. The results show that, in general, norethisterone at this dose does not affect either the level or pattern of FSH, but in five subjects, there was a variable reduction in the midcycle peak of LH (to 33–85 % of the control value). In six subjects, there was a marked reduction in the levels of urinary pregnanediol (to 8–80% of the control value), plasma progesterone (16–55 %), and the urinary production rate of progesterone (3–51 %). In contrast, the level of urinary oestrogen per cycle was increased to 140–160 % in all subjects and the mean values showed an abnormal cyclical pattern. Changes in the distribution of labelled metabolites during treatment indicated the existence of at least two pools of progesterone metabolism.