title: Leptin substitution results in the induction of menstrual cycles in an adolescent with leptin deficiency and hypogonadotropic hypogonadism.
abstract: BACKGROUND
  Leptin deficiency leads to midluteal-phase defect or reduced testicular volume in adults, despite normal gonadotropin levels. All children documented to date with leptin deficiency were prepubertal with physiologically low gonadotropins prior to therapy. A direct effect of leptin on pubertal development in a leptin-naive adolescent has not yet been shown.
  
  
  METHODS
  In 2010, we reported the first connatal leptin-deficient adolescent girl with clinically and chemically proven hypogonadotropic hypogonadism. In this study, we evaluated the effect of recombinant methionyl human leptin substitution.
  
  
  RESULTS
  Initially, the patient had prepubertal basal and stimulated luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels, low growth hormone and insulin-like growth factor 1 (IGF1) levels and no pulsatile secretion of LH and FSH. After 11 weeks of therapy, basal and stimulated LH and FSH levels rose to pubertal values and nocturnal pulsatility was initiated. After 76 weeks of therapy, menstruation occurred at the age of 16.3 years. Pulsatile nocturnal growth hormone secretion, stimulated growth hormone secretion and IGF1 values also normalized.
  
  
  CONCLUSIONS
  We describe here the first adolescent with hypogonadotropic hypogonadism due to connatal leptin deficiency. Leptin substitution led to a rapid induction of gonadotropin secretion and menarche. These data are further proof of the concept that leptin is needed for a timely maturation of the hypothalamic/pituitary/gonadal axis.
authors.affiliation: Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Eythstrasse 24, Ulm, Germany.
authors.forename: J
authors.initials: J
authors.lastname: von Schnurbein
authors.forename: A
authors.initials: A
authors.lastname: Moss
authors.forename: S A
authors.initials: SA
authors.lastname: Nagel
authors.forename: H
authors.initials: H
authors.lastname: Muehleder
authors.forename: K M
authors.initials: KM
authors.lastname: Debatin
authors.forename: I S
authors.initials: IS
authors.lastname: Farooqi
authors.forename: M
authors.initials: M
authors.lastname: Wabitsch
mesh_terms: D000293:Adolescent; D015992:Body Mass Index; D005260:Female; D006801:Humans; D007006:Hypogonadism / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D020738:Leptin / Q000031:analogs & derivatives* / Q000172:deficiency* / Q000627:therapeutic use; D008572:Menarche / Q000187:drug effects*; D009765:Obesity / Q000150:complications / Q000517:prevention & control; D011628:Puberty, Delayed / Q000209:etiology; D016896:Treatment Outcome
chemical_list: D020738:Leptin; C122136:recombinant methionyl human leptin