Vaginal progesterone administration in physiological doses normalizes raised luteinizing hormone levels in patients with polycystic ovarian syndrome

A raised luteinizing hormone (LH) level is a typical finding in the polycystic ovarian syndrome (PCOS). This inappropriate elevation of LH is thought to interfere with normal follicular development and ovulation. The resulting chronic anovulation is associated with the absence of the luteal phase increase in secretion of progesterone and inhibin. Progesterone can exert both a positive and negative feedback action on LH secretion, but inhibition is thought to occur following prolonged exposure to progesterone. Therefore, the aim of this study was to see if exogenously administered progesterone in physiological doses would normalize circulating LH concentrations in patients with PCOS. Vaginal progesterone was administered twice daily in a dose of 100 mg, at 12 h intervals, to ten women with PCOS. Serum samples were taken on alternate days for radioimmunoassay of follicle stimulating hormone (FSH), LH, estradiol, progesterone and inhibin. To determine the effect of progesterone on LH secretory dynamics in PCOS, LH pulse studies were carried out prior to treatment, and on day 10 of progesterone administration in four of the ten subjects.Mean serum progesterone concentrations reached 51 nmol/l by 4 days after exogenous progesterone treatment, and remained in the mid-luteal phase range, as established in 12 normal cycles, during the use of the vaginal suppository. The mean serum LH concentration had fallen significantly (p ≤ 0.01) after 8 days of treatment, and continued to fall progressively until the end of progesterone administration. Serum LH concentrations had fallen into the normal follicular phase range by 14 days (mean 5.5, range 3.4-10.9 IU/l; normal follicular phase range 1.8-10.0 IU/l). No biphasic effect of progesterone on LH secretion was seen. There was a progressive fall in serum FSH levels during progesterone treatment, and there was no change in circulating estradiol or inhibin. There was a decrease in LH pulse frequency after 10 days of progesterone treatment from 7.5 ± 0.9 (± SD) to 5.1 ± 0.3 pulses per 6 h (p ≤ 0.01), but there was no change in LH pulse amplitude.In conclusion, vaginal progesterone administration, in a dose of 100 mg twice daily, produced circulating progesterone concentrations within the mid-luteal phase range, and this dose exerted only a negative feedback effect on LH secretion. Finally, physiological serum progesterone levels suppressed the endogenously raised serum LH level in PCOS to normal. This may be a hypothalamic effect, as LH pulse frequency is also significantly reduced, without change in pulse amplitude.