Inverse Relationship between Luteinizing Hormone and Body Mass Index in Polycystic Ovarian Syndrome: Investigation of Hypothalamic and Pituitary Contributions

Context: Patients with polycystic ovarian syndrome (PCOS) have increased LH relative to FSH, but LH is modified by body mass index (BMI). Objective: The objective of the study was to determine whether the impact of BMI on neuroendocrine dysregulation in PCOS is mediated at the hypothalamic or pituitary level. Participants/Interventions/Setting: Twenty-four women with PCOS across a spectrum of BMIs underwent frequent blood sampling, iv administration of GnRH (75 ng/kg), and sc administration of the NAL-GLU GnRH antagonist (5 μg/kg) in the General Clinical Research Center at an academic hospital. Main Outcome Measures: LH pulse frequency and LH response to submaximal GnRH receptor blockade were used as measures of hypothalamic function; LH response to GnRH was used as a measure of pituitary responsiveness. Results: BMI was negatively correlated with mean LH, LH/FSH, and LH pulse amplitude. There was no effect of BMI on LH pulse frequency. Percent inhibition of LH was decreased in PCOS, compared with normal women (53.9 ± 1.5 vs. 63.1 ± 4.1, respectively; P < 0.01), suggesting an increase in the amount of endogenous GnRH, but was not influenced by BMI. Pituitary responsiveness to GnRH was inversely correlated with BMI (peak LH, R = −0.475, P < 0.02; and LH area under the curve R = −0.412, P < 0.02). Conclusions: LH pulse frequency and quantity of GnRH are increased in PCOS, but there is no influence of BMI on either marker of hypothalamic function. The pituitary response to a weight-based dose of GnRH is inversely related to BMI in PCOS. These studies suggest that the effect of BMI on LH is mediated at a pituitary and not a hypothalamic level in PCOS.