Context: Serum luteinizing hormone (LH) levels decrease with increasing body mass index (BMI) in women with polycystic ovarian syndrome (PCOS).

Objective: To determine whether pharmacokinetic factors contribute to the effect of obesity on LH in PCOS.

Participants/Interventions/Setting: Twenty-one women with PCOS underwent frequent blood sampling, intravenous (iv) administration of gonadotropin-releasing hormone (GnRH; 75 ng/kg) and subcutaneous administration of the NAL-GLU GnRH antagonist (150 mcg/kg) followed by iv recombinant human LH (rhLH; 300 IU) in the General Clinical Research Center at an academic medical center.

Main Outcome Measures: Pharmacokinetic parameters were estimated by modeling the LH serum concentration profiles after administration of GnRH and rhLH and related to body mass index (BMI).

Results: Serum levels of LH and rhLH decreased in a distinctly monoexponential fashion in all patients. The apparent biological half-life (t_1/2) of rhLH was not influenced by BMI, nor was the total body clearance (CL) or apparent volume of distribution. However, the t_1/2 of endogenous LH was inversely related to BMI (r = -0.46; P < 0.04) and the estimated CL of endogenous LH was positively related to BMI (r = 0.53; P < 0.02).

Conclusion: Estimated clearance and t_1/2 of endogenous LH are influenced by BMI in women with PCOS, contributing to the inverse relationship between LH and BMI in this population. The absence of an effect of BMI on the pharmacokinetics of rhLH in these subjects suggests that the effect of obesity on clearance of endogenous LH is due to alterations in the isoform composition of LH secreted by the pituitary.