Can clomiphene therapy be individualized?

A meta-analysis on the relationship between clomiphene dosage and patient response suggests the answer may be yes. The authors caution, however, that prospective studies are necessary to confirm that dosing can be tailored and outcomes improved by monitoring plasma levels of zuclomiphene, an active metabolite of the drug.

Researchers from the University of Sheffield, Sheffield, UK, performed a meta-analysis of 13 published reports on results with clomiphene citrate therapy, which typically is given in 50-mg doses orally on days 2 to 5 of the menstrual cycle. Doses of 100 or 150 mg/day are given to women who do not respond in the first cycle, leading to a 1-month or longer delay in success in these individuals.

The analysis suggests metabolism of the key components of clomiphene citrate—zuclomiphene and enclomiphene—may vary from patient to patient. Women who more rapidly absorb and eliminate zuclomiphene may need higher drug dosages to trigger ovulation. The converse may be true for women who are slow to metabolize the isomer, i.e., those who absorb and eliminate zuclomiphene more slowly may need lower doses.

Monitoring plasma concentrations of zuclomiphene during therapy may help clinicians more quickly identify patients who are likely to respond only to higher-than-normal doses of clomiphene, need lower-than-normal dosages, or are unlikely to respond to clomiphene whatever the dosage. This more individualized approach, the researchers say, could reduce the need for multiple clinic visits, increase the likelihood of singleton pregnancy, and decrease the risk of multiples.

Rostami-Hodjegan A, Lennard MS, Tucker GT, Ledger WL. Monitoring plasma concentrations to individualize treatment with clomiphene citrate. Fertil Steril. 2004;81:1187-1193.