Effects of tamoxifen on corpus luteum function and luteal phase length in cynomolgus monkeys

Previous data in nonhuman primates have demonstrated that tamoxifen prolongs the luteal phase without altering reproductive hormone levels. A small study in humans found no effect on menstrual cycle length, but an increase in luteal ovarian steroid levels. in view of these conflicting results, we studied the effect of tamoxifen on corpus luteum (CL) function in monkeys (n = 20). Blood was obtained daily beginning cycle day 8, and sera assayed for estradiol (E₂), progesterone (P), luteinizing hormone, and follicle-stimulating hormone. Four days after the midcycle E₂ peak, laparoscopy confirmed CL formation, and the animals were administered (1) lactose (n = 7), (2) tamoxifen, 0.5 mg·kg^-1·d^-1 (n = 6), or (3) tamoxifen, 3.0 mg·kg^-1·d^-1 (n = 7) for 12 consecutive days. Serum collection continued until cycle day 50 or menses, whichever came first. Results indicate a biphasic response among tamoxifen-treated animals, with 7 or 13 developing prolonged luteal phases. There was, however, no significant difference in luteal phase length among the three groups, although when the two groups given tamoxifen were combined, the difference in luteal phase length versus controls approached significance. No differences were found among peak P levels, mean luteal phase P levels, or mean luteal phase gonadotropin levels. No variables were found to correlate significantly with luteal phase length. These results suggest that luteal phase administration of the antiestrogen tamoxifen does not alter pituitary gonadotropin secretion of CL function. However, tamoxifen does prolong luteal phase length in a subset of monkeys, perhaps via a direct effect on the endometrium.