[18F]2-Fluoro-2-Deoxy-d-Glucose Positron Emission Tomography Demonstration of Estrogen Negative and Positive Feedback on Luteinizing Hormone Secretion in Women

Abstract

Context: Precise regulation of the neuroendocrine components of the female reproductive axis involves both negative and positive feedback of estrogen on gonadotropin secretion. Objective: Our objective was to determine the hypothalamic and/or pituitary sites of estrogen negative and positive feedback using neuroimaging techniques. Design and Setting: A graded estrogen infusion protocol was administered at a General Clinical Research Center in an academic medical center. Subjects: Healthy postmenopausal women (n = 11) were recruited for study. Interventions: Serum samples were measured every 4 h. A structural magnetic resonance imaging was performed at baseline, and [¹⁸F]2-fluoro-2-deoxy-d-glucose (¹⁸FDG) positron emission tomography was performed at baseline and 24 and 72 h. FDG positron emission tomography was co-registered with magnetic resonance imaging scans, and region of interest analysis was performed. Main Outcome Measures: Serum LH and estradiol were assessed. Normalized values for glucose uptake were extracted from each region of interest for each subject at each time point. Results: A decrease in normalized ¹⁸FDG uptake was apparent in the hypothalamus at 24 h (P < 0.02) associated with decreased LH (P < 0.0005). The increase in LH at 72 h (P < 0.0005) was associated with increased pituitary ¹⁸FDG uptake (P < 0.02) but no change in hypothalamic uptake. Conclusions: Changes in ¹⁸FDG uptake as a measure of metabolic activity can be demonstrated in the hypothalamus and pituitary in association with discrete hormonal events. Results are consistent with mediation of estrogen negative feedback on LH at the hypothalamus, whereas estrogen positive feedback occurs at the pituitary with no evidence of increased hypothalamic activity in women.