Escape from chronic estrogenic suppression of ovarian function in the adult rhesus monkey: evidence for changing sensitivity of gonadotropin secretion to estrogen inhibition.

Regularly menstruating female rhesus monkeys were implanted sc with Silastic tubing packed with estrone. The implants were replaced every 6-8 months to maintain the serum estrone and estradiol concentrations constantly elevated 1.5-2.5-fold, i.e. in the midfollicular phase range, for 4 yr. Increasing the estrone and estradiol concentrations initially led to anovulation which persisted for 6 to 15 months after which three of four of the estrogen-treated animals resumed ovulatory cycles. These animals then waxed and waned between anovulation and ovulatory cycles for the remainder of the study period. The resumption of ovulatory cycles were attributed to an escape of the central nervous system-pituitary axis from the suppressive effect of the elevated estrogen concentrations, since serum estradiol concentrations did not change. During anovulatory and ovulatory months the basal LH concentration was not significantly increased in the estrogen-treated monkeys compared to the control animals, but it was significantly reduced during anovulatory months compared to ovulatory months. Furthermore, LH secretion in response to a bolus of GnRH was attenuated in the monkeys chronically exposed to the acyclic elevation of blood estrogen levels. As the sensitivity to estrogen decreased, sufficient basal concentrations of FSH and LH were achieved to support ovulatory cycles with associated midcycle surges of LH and FSH secretion and apparently normal luteal patterns of progesterone secretion. Since the daily FSH concentrations of these ovulatory cycles of the estrone-treated animals were significantly lower than that of ovulatory cycles of the control monkeys, the ovulatory cycles of the estrogen animals may not have been normal, but this was not directly documented. These studies suggest that elevated basal estrogen levels do not lead to elevated basal LH secretion in the female primate; and also in the intact adult primate the central nervous system-pituitary axis has the potential to change its sensitivity to the negative feedback effects of estrogen on gonadotropin secretion.