Strength-Duration Characteristics of Estrogen Effects on Gonadotropin Response to Gonadotropin-Releasing Hormone in Women. II. Effects of Varying Concentrations of Estradiol

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Abstract
This study was designed to investigate the effects of varying concentrations of estradiol, administered to normal women, upon the gonadotropin response to synthetic gonadotropin-releasing hormone (GnRH or LRF). Beginning at 4 pm on the first day of the menstrual cycle, 19 studies were performed in subjects who received im injections of estradiol benzoate (E2B every 12 h for 6 days). Concentrations of E2B administered (μg/kg/12 h) were: 0.3, 0.6, 1.25, 2.5, 3.75, and 5.0. Mean serum estradiol concentrations achieved at these respective concentrations of E2B were 43, 53, 91, 145, 195, and 305 pg/ml. Twelve h after the last E2B injection, an intravenous bolus of 100 μg GnRH was administered. Gonadotropin response to this dose of GnRH after E2B was compared with each subject's response in the early follicular phase of a previous (control) cycle during which no exogenous estradiol was administered. Significant augmentation of LH and FSH response to GnRH was not seen until 1.25 μg/kg/12 h E2B was administered. Progressively greater LH responses to GnRH were seen at the 2.5 and 3.75 μg/kg/12 h concentrations, with no further increase at 5.0 μg/kg/12 h. Greater augmentation of FSH response to GnRH was seen at the 2.5 μg/kg/12 h concentration of E2B, but no further augmentation was seen at higher concentrations. These data support the concept that estradiol augmentation of pituitary responsiveness to GnRH is concentration, as well as duration, dependent. In addition, induced LH, but not FSH, surges were seen during administration of both 3.75 and 5.0 μg/kg/12 h E2B. In many respects these LH surges resembled the spontaneous LH surges seen at midcycle in women with normal menstrual cycles, as did the estradiol concentrations achieved prior to the LH surge.

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