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Improved treatment for anovulation in polycystic ovarian disease utilizing the effect of progesterone on the inappropriate gonadotrophin release and clomiphene response.

The treatment of anovulatory, clomiphene-resistant patients with polycystic ovarian disease (PCOD) is difficult. Ten such women were given progesterone, 50 mg/day i.m. for 5 days to achieve luteal phase concentrations. Immediately following progesterone treatment, plasma concentrations of FSH were reduced in all patients (P = 0.001) and seven of the 10 had reduced plasma LH concentrations. Following the withdrawal bleeding these seven all became responsive to clomiphene as shown by ovulation, and three conceived after a single progesterone/clomiphene cycle. LH pulsatility, studied in five women over 4 h, before and immediately following progesterone treatment, showed a slowing of the pulse frequency (62 +/- 26 min to 105 +/- 51 min, P less than 0.05) and an increase in pulse amplitude (6 +/- 1.9 IU/l to 16.7 +/- 20 IU/l). The LH and FSH response to GnRH was blunted by progesterone. It would thus appear that progesterone modulates LH pulsatility and reduces pituitary sensitivity to GnRH, reducing LH levels and possibly inducing more FSH synthesis and storage, similar to its action in the normal ovulatory cycle. These changes provide a more favourable environment for ovulation induction by clomiphene and we suggest that short-term progesterone treatment may be utilized to improve the efficiency and results of clomiphene treatment in PCOD.