Studies on the Effect of the Therapeutic Dosage of Indomethacin on Human Gonadotropin Secretion

Abstract

To investigate the effect of the therapeutic dosage (50 approximately 100 mg/day) of indomethacin (IDM), which is well-known to inhibit the synthesis of prostaglandins, on the human pituitary-gonadal axis, five experiments were performed. Exp. I and Exp. II: Six healthy male subjects pretreated with IDM for two days (Exp. I), and 12 male patients receiving IDM for 1 to 19 months (Exp. II) were examined. In these two IDM treated groups, resting levels of plasma LH did not change, and LH response to LH-RH (100 microgram i.v.) slightly increased as compared with nontreated control males (N=11). Resting levels of plasma FSH, and FSH response to LH-RH statistically and significantly suppressed in both IDM treated groups, except for FSH response to LH-RH in the IDM pretreated healthy male group. Exp. III: Two healthy women with regular menstrual cycles were treated with IDM for several days just before ovulation. These women's preovulatory LH surges were not blocked by IDM and were followed by a normal luteal pattern of basal body temperature. Exp. IV: Ten female patients receiving IDM for 1 to 10 months were examined. In 9 patients, normal preovulatory LH surges were observed. It was interesting that the duration of the luteal phase was shortened (less than 10 days) in 5 of the 10 patients, and mid-luteal plasma progesterone levels were less than 500 ng/dl even if some of those patients had a normal duration of the luteal phase. Exp. V: In five female patients treated with IDM for 1 to 9 months, mid-follicular gonadotropin secretions were estimated. Resting levels of plasma gonadotropins and their responses to LH-RH did not differ from the control female group (N=4). From these results, it was indicated that (1) the therapeutic dosage of IDM acted on the central nervous system and the anterior pituitary, and then suppressed FSH secretion in male subjects. There was sexual difference in the IDM effect on FSH secretion, that is, mid-follicular FSH secretion was not affected by IDM in female subjects. (2) LH secretion was not suppressed by IDM in either male or female subjects in the mid-follicular phase. (3) The therapeutic dosage of IDM did not block the preovulatory LH surge and ovulation in female subjects, but IDM might act on corpus luteum and cause luteal dysfunction.