title: Gender variation in leptin circadian rhythm and pulsatility in adult growth hormone deficiency: effects of growth hormone replacement.
abstract: OBJECTIVE
  Adult growth hormone deficiency (AGHD) is characterized by obesity and associated with increased leptin concentration and decreased leptin pulsatility. Growth hormone replacement (GHR) results in a decrease in leptin concentration and increase in leptin pulsatility, followed by reduction in body fat mass (BFM). In both health and AGHD, women exhibit relatively higher leptin concentrations compared to men. The effect of gender on leptin rhythm and pulse parameters in AGHD is yet to be defined and the gender difference in the response of leptin secretory pattern to GHR has not been determined. Therefore the aim of this study was to evaluate the effect of gender on circadian and pulse parameters of leptin secretion in AGHD, and examine the gender variation in response of these parameters to GHR.
  
  
  METHODS
  A prospective, open treatment design study to determine the effect of gender on leptin rhythm and pulse parameters in untreated and treated AGHD. GH was commenced at a daily dose of 0.5 IU, and titrated up by increments of 0.25 IU at 2-weekly intervals to achieve and maintain IGF-I SDs between the median and upper end of the age-related reference range.
  
  
  METHODS
  Twelve patients (six men, six women) with severe AGHD following pituitary surgery, defined as peak GH response < 9 mU/l to provocative testing were studied. All patients required additional pituitary replacement hormones following pituitary surgery and were on optimal doses at recruitment.
  
  
  METHODS
  Plasma leptin was measured at half-hourly intervals for 24 h, before and 1 month after initiation of GHR. Cosinor analysis was used to determine the circadian rhythm parameters: MESOR (rhythm-adjusted mean), acrophase and amplitude; and ULTRA algorithm used for pulse analysis. Body composition was measured using bioelectrical impedance.
  
  
  RESULTS
  BFM was higher in women than men at both visits (P < 0.05), but there was no significant change in BFM in either gender following 1 month of GHR. Women had a higher mean 24-h leptin concentration, MESOR, circadian amplitude and pulse amplitude, both before and after GHR (P < 0.05). Following treatment, mean leptin concentration and MESOR decreased significantly in both men and women (P < 0.05), with no significant difference in percentage change between the genders. Pulse frequency increased and duration decreased significantly after GHR in both groups, without any significant gender difference. IGF-I and IGF SDs were similar in both genders at baseline (P = 0.93). However, after 1 month GHR, the increase in both measurements was greater in men than women (P = 0.005) and men had significantly higher IGF-I and IGF SDs than women (P = 0.01).
  
  
  CONCLUSIONS
  As in healthy individuals, leptin levels were higher in women with AGHD than men, both prior to and after GHR. Decline in leptin concentrations and increase in leptin pulsatility following 1 month of GH treatment were similar in both genders. Changes in leptin secretory parameters appeared to occur without any significant decrease in BFM, suggesting a regulatory role for GH. Additionally, the action of GH on leptin secretory pattern does not appear to be mediated by IGF-I. Our data suggest that changes in leptin concentration and rhythm parameters following GHR are independent of gender.
authors.affiliation: Department of Diabetes, Royal Liverpool University Hospital, Liverpool, UK. h.white@ukf.net
authors.forename: H D
authors.initials: HD
authors.lastname: White
authors.forename: A M
authors.initials: AM
authors.lastname: Ahmad
authors.forename: R
authors.initials: R
authors.lastname: Guzder
authors.forename: A M
authors.initials: AM
authors.lastname: Wallace
authors.forename: W D
authors.initials: WD
authors.lastname: Fraser
authors.forename: J P
authors.initials: JP
authors.lastname: Vora
mesh_terms: D000328:Adult; D000368:Aged; D000465:Algorithms; D001823:Body Composition / Q000187:drug effects; D002940:Circadian Rhythm; D005260:Female; D013006:Growth Hormone / Q000172:deficiency* / Q000627:therapeutic use*; D020249:Hormone Replacement Therapy; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D020738:Leptin / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012636:Secretory Rate; D012723:Sex
chemical_list: D020738:Leptin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone