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Pharmacokinetic Factors Contribute to the Inverse Relationship between Luteinizing Hormone and Body Mass Index in Polycystic Ovarian Syndrome

Reproductive Endocrine Unit (S.S.S., Y.L.P., A.D., Y.J., J.E.H.), Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; Center for Reproductive Medicine, Department of Obstetrics and Gynecology (S.S.S.), Brigham and Women’s Hospital, Boston, Massachusetts 02115; and Division of Hematology/Oncology (F.D., J.G.S.), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114

Address all correspondence and requests for reprints to: Janet E. Hall, Reproductive Endocrine Unit, BHX-5, Massachusetts General Hospital, 55 Fruit Street, Boston, Massachusetts 02114. E-mail: hall.janet{at}mgh.harvard.edu.

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

Objective: The objective of this study was 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, iv administration of GnRH (75 ng/kg), and sc administration of the NAL-GLU GnRH antagonist (150 µg/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 BMI.

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

Conclusion: Estimated clearance and apparent half-life 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 the result of alterations in the isoform composition of LH secreted by the pituitary.

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