Hormone patterns after induction of ovulation with clomiphene citrate: an age-related phenomenon

Since the introduction of clomiphene citrate (CC), more than three decades ago, a discrepancy has been observed between ovulation and pregnancy rates for which as yet no explanation exists. To investigate if ovulation disorders or abnormal hormonal patterns occur more often in CC-stimulated seemingly ovulatory cycles, we performed hormonal and sonographic monitoring in first cycles of oligo- or amenorrheic patients who were stimulated with 50 mg CC, and compared the hormonal patterns to those in natural cycles of age-matched proven fertile women. Twenty-four first CC cycles were monitored. Twelve cycles appeared to be ovulatory, eleven showed no follicle development and one cycle exhibited the luteinized unruptured follicle (LUF) phenomenon. Ten ovulatory cycles were compared with 27 unstimulated control cycles. In four cycles stimulated by CC, a temporary decline in estradiol levels was apparent. In these cycles, estradiol reached a higher level on cycle day (CD) 7 or 8 compared to cycles without a decline. Such an estradiol decline was seen in only one control cycle. Furthermore, the estradiol levels on CD 7 or 8 appeared to be age-related. We conclude that the estradiol decline in CC-stimulated ovulatory cycles may be a consequence of a sharp rise after CC stimulation, and such a rise may be age-related and coincide with a diminished follicle quality. If this phenomenon is associated with a suboptimal cycle, and so contributes to the suboptimal pregnancy rates after ovulation-induction treatment with clomiphene citrate, is still unknown.