Response to clomiphene citrate challenge test in normal women through perimenopause

To identify the physiological changes that discriminate subgroups of women along the reproductive continuum.

This prospective study was carried out at the outpatient facility of George Washington University Medical Center and the outpatient clinic of the National Institutes of Health Clinical Center. Twenty-five female subjects were divided into 4 biologically distinct groups: group 1 (n = 4) regular menstrual cycles and under age 35; group 2 (n = 11) regular cycles and over age 35; group 3(n = 6) irregular cycles and over age 35, and group 4(n = 4) menopausal. Measurements of basal and stimulated gonadotropins (immunoactive LH, LH-I; bioactive LH, LH-B; immunoactive FSH, FSH-I) and E2 were obtained before and after administration of clomiphene citrate. Basal and stimulated gonadotropins and E2 were analyzed to discriminate between subject groups 1-4. The relationship of menstrual cyclicity to hormone levels was evaluated.

Basal levels of LH-I, LH-B, FSH-I could discriminate only group 4 vs. groups 1-3. Stimulated levels of FSH-I and E2 were significantly different for group 2 vs. 3 and group 2 vs. 4. Group 1 was similar to group 2. Both stimulated FSH-I and stimulated LH-I and LH-B differentiated group 4 vs. groups 1-3. The LH-B:LH-I (B:I) ratio was not discriminatory after the clomiphene citrate challenge test (CCCT).

Baseline hormone values were useful in distinguishing only group 4. CCCT unmasked differences in FSH and E2 between irregularly and regularly cycling older women; these differences were not scen with LH-B or B:I ratio. Stimulated FSH was the most useful hormone parameter and paralleled menstrual cycle regularity as a useful discriminator in older women.