title: Altered multihormone synchrony in obese patients with polycystic ovary syndrome.
abstract: Luteinizing hormone (LH) concentrations and pulsatility are increased in obese women with polycystic ovary syndrome (PCOS). In addition, patients have hyperandrogenemia and insulin resistance. The mechanisms involved in aberrant hormone regulation in PCOS are still unclear. We investigated 15 obese PCOS women with a body mass index between 30 and 54 kg/m(2) and 9 healthy obese controls (body mass index, 31-60 kg/m(2)) with regular menstrual cycles. Subjects underwent 24-hour blood sampling at 10-minute intervals for later measurements of LH, leptin, testosterone, and insulin concentrations. Data were analyzed with a new deconvolution program, approximate entropy (and bivariate approximate entropy), and a cross-correlation network. Patients had increased LH pulse frequency and more than 2-fold greater daily LH secretion, with diminished pattern regularity. Testosterone secretion was increased 2-fold, but pattern regularity was similar to that in controls. In the network construct, insulin was correlated positively with LH, whereas leptin and testosterone were correlated negatively with LH. Bivariate synchrony of LH with insulin was decreased. Short-term caloric restriction paradoxically increased LH secretion by 1.5-fold and pattern irregularity, and reduced interpulse variability. Testosterone secretion and fasting concentrations of estradiol and sex hormone-binding globulin levels remained unchanged. Correlations between LH and insulin, leptin, and calculated free testosterone decreased. This study demonstrates marked alterations in the control of LH secretion in PCOS in the fed and calorie-restricted states. The ensemble results point to abnormal feedback control of not only the GnRH-gonadotrope complex, but also LH's relationships with leptin, insulin, and testosterone.
authors.affiliation: Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Albinusdreef 2, 2333ZA, Leiden, the Netherlands. f.roelfsema@lumc.nl
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Roelfsema
authors.forename: Petra
authors.initials: P
authors.lastname: Kok
authors.forename: Johannes D
authors.initials: JD
authors.lastname: Veldhuis
authors.forename: Hanno
authors.initials: H
authors.lastname: Pijl
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood; D007986:Luteinizing Hormone / Q000097:blood / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D011085:Polycystic Ovary Syndrome / Q000378:metabolism*; D013739:Testosterone / Q000097:blood / Q000378:metabolism
chemical_list: D007328:Insulin; D020738:Leptin; D013739:Testosterone; D007986:Luteinizing Hormone