Srouji Serene S, Pagán Yanira L, D'Amato Fernando, Dabela Amsalu, Jimenez Yarisie, Supko Jeffrey G, Hall Janet E
Reproductive Endocrine Unit, BHX-5, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, Massachusetts 02114, USA.
J Clin Endocrinol Metab. 2007 Apr;92(4):1347-52. doi: 10.1210/jc.2006-2716. Epub 2007 Jan 30.
Serum LH levels decrease with increasing body mass index (BMI) in women with polycystic ovarian syndrome (PCOS).
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 microg/kg) followed by iv recombinant human LH (rhLH; 300 IU) in the General Clinical Research Center at an academic medical center.
Pharmacokinetic parameters were estimated by modeling the LH serum concentration profiles after administration of GnRH and rhLH and related to BMI.
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).
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.
多囊卵巢综合征（PCOS）女性的血清促黄体生成素（LH）水平随体重指数（BMI）升高而降低。
本研究旨在确定药代动力学因素是否导致肥胖对PCOS患者LH产生影响。参与者/干预措施/研究地点：21名PCOS女性在一所学术医学中心的综合临床研究中心接受频繁采血、静脉注射促性腺激素释放激素（GnRH，75 ng/kg）、皮下注射NAL-GLU GnRH拮抗剂（150 μg/kg），随后静脉注射重组人LH（rhLH，300 IU）。
通过对GnRH和rhLH给药后LH血清浓度曲线进行建模来估计药代动力学参数，并将其与BMI相关联。
所有患者的LH和rhLH血清水平均呈明显的单指数下降。rhLH的表观生物半衰期不受BMI影响，全身清除率或表观分布容积也不受影响。然而，内源性LH的表观半衰期与BMI呈负相关（r = -0.46；P < 0.04），内源性LH的估计全身清除率与BMI呈正相关（r = 0.53；P < 0.02）。
PCOS女性内源性LH的估计清除率和表观半衰期受BMI影响，这导致了该人群中LH与BMI之间的负相关关系。BMI对这些受试者rhLH药代动力学无影响，这表明肥胖对内源性LH清除的影响是垂体分泌的LH同工型组成改变的结果。
