The effect of luteal phase estrogen antagonism on luteinizing hormone pulsatility and luteal function in women.

Pulsatile LH secretion was studied to determine if the frequency of LH pulses was altered by the administration of clomiphene citrate (CC; 150 mg) for 5 days during the midluteal phase of the menstrual cycle. Seven normal women received CC or placebo in alternate cycles in a randomized double blind fashion. On the day after drug administration, blood samples were obtained at 15-min intervals for 8 h for serum LH determinations. Daily blood samples were also obtained throughout the luteal phase for determination of serum LH, estradiol (E2), and progesterone. LH pulse frequency increased from 2.4 +/- 0.5 (+/- SEM)/8 h after placebo to 3.9 +/- 0.6/8 h (P less than 0.01) after CC treatment, but pulse amplitude did not change. The transverse mean of serum LH was higher after CC (13.6 +/- 0.5 mIU/ml) than after placebo (8.4 +/- 0.3 mIU/ml; P less than 0.001), and luteal phase length was increased from 13.5 +/- 0.5 to 16.0 +/- 0.4 days (P less than 0.001) by administration of CC. Luteal phase levels of E2 and progesterone measured daily were significantly elevated (P less than 0.01) in CC-treated cycles. These findings suggest that CC increases the frequency of hypothalamic GnRH secretory episodes, perhaps by an action involving a decrease in endogenous opioid peptide activity. Since peripheral progesterone levels were elevated in the CC-treated cycles, E2 may play a permissive role in the ability of progesterone to increase endogenous opioid peptide activity acutely. Furthermore, since the luteal phase was significantly prolonged by an increase in endogenous LH pulse frequency, the slow frequency of LH pulses in the normal late luteal phase may contribute to the onset of luteolysis in the human.