Roles of Estradiol and Progesterone in Eliciting the Midcycle Luteinizing Hormone and Follicle-Stimulating Hormone Surges*

Abstract

The positive feedback effects of estradiol (E₂) and progesterone (P) on LH and FSH release were studied under novel experimental conditions in three women of reproductive age who had undergone oophorectomy and received uninterrupted E₂ replacement by subdermal implants. Basal serum E₂ levels were in the midfollicular phase range, while LH and FSH levels were normal or slightly elevated. Each volunteer underwent seven experiments at 2- to 4-week intervals, receiving im injections of increasing amounts of estradiol benzoate (E₂B) alone and in combination with P. The time and dose of P (administered via P-impregnated polysiloxane intravaginal rings) were varied. In two of the seven experiments, P was given without E₂B injections. In all three subjects, increasing serum E₂ levels mimicking the preovulatory E₂ peak were followed by a surge of LH but not of FSH. However, when serum P levels rose after an increase in serum E₂ concentrations had occurred, the LH surge occurred earlier and was accompanied by an FSH peak. When serum P levels rose before serum E₂ concentrations had risen or when P levels increased without a rise in serum E₂, neither a serum LH nor FSH peak was observed. When administered concomitantly, E₂B and P suppressed FSH but not LH levels, while P alone did not affect serum LH or FSH concentrations. These data indicate that an acute rise in serum E₂ is a necessary condition for the midcycle LH and FSH surges, that P facilitates or blocks the positive feedback response of gonadotropin release in a time-dependent manner, and that P is required for the preovulatory FSH peak.