Repetitive responses to clomiphene citrate in normal women of late reproductive age.
The hormonal response to clomiphene citrate (CC) has been used to evaluate ovarian reserve. In the current study, we tested the reproducibility of response to 100 mg of CC administered for 5 days in a group of 20 women, 35 to 40 years of age, with regular menstrual cycles who completed 57 cycles during the study. Individual hormonal responses to repeated stimulation were not identical. When ovarian responsiveness to CC was categorized as "low" (E(2) and E(2)/FSH ratios =200 pg/mL and =20, respectively) or "high" (E(2) =400 pg/mL and E(2 /FSH ) =61), however, responses of individual subjects seldom spanned both categories. Specifically, only 3 of 20 subjects had both low and high E(2) and low and high E(2/FSH ) ratios (P<0.001). In addition, seven subjects were identified as FSH hyperresponsive in at least one cycle (post-CC FSH =10 IU/L). Only 2 of 21 cycles in these seven subjects had post-CC E(2)/FSH ratios =61, in comparison with 20 of 36 cycles in the other 13 subjects (P<0.01). Thus, despite the cycle-to-cycle variations, the hormonal response of an individual subject could usually be categorized as occurring at one or the other end of the spectrum of ovarian function, these two extremes probably signifying good and poor ovarian reserve. This prediction is further strengthened by the observation of a significant negative correlation between the FSH and E(2) responses after administration of CC (P=0.05).