Horm Metab Res 2005; 37(2): 94-98
DOI: 10.1055/s-2005-861173
Original Clinical
© Georg Thieme Verlag KG Stuttgart · New York

Influence of Leptin, Androgens and Insulin Sensitivity on Increased GH Response to Clonidine in Lean Patients with Polycystic Ovary Syndrome

P.  M.  Spritzer1 , F.  V.  Comim1 , E.  Capp1 , A.  D’Avila1
  • 1Gynecological Endocrinology Unit, Division of Endocrinology, Hospital de Clínicas de Porto Alegre and Department of Physiology, Universidade Federal do Rio Grande do Sul, Rua Sarmento Leite, Porto Alegre, Brazil.
This study was presented in part as free communication at the 11th World Congress of Gynecological Endocrinology (ISGE), Florence, Italy, 26 - 29 February 2004.
Further Information

Publication History

Received 28 April 2004

Accepted after revision 12 August 2004

Publication Date:
21 March 2005 (online)

Abstract

Our aim was to investigate whether insulin sensitivity, leptin, androgen or estradiol levels are associated with disturbed GH response to clonidine in lean patients with polycystic ovary syndrome. Fourteen lean polycystic ovary syndrome patients, 11 ovulatory patients presenting idiopathic hirsutism and 10 non-hirsute, normal women with regular cycles paired for age and BMI were included in a cross-sectional study. Baseline hormonal and metabolic variables were assessed and analyzed in association with GH response to oral administration of 0.3 mg of clonidine. Delta GH was significantly higher in the PCOS group than in the IH and control groups (p = 0.014). The groups were similar in terms of body mass index, insulin, glucose, total and HDL cholesterol, triglycerides and estradiol levels. Free androgen index (r = 0. 454, p = 0.015) and leptin (r = 0.419, p = 0.023) were positively correlated with the homeostasis model assessment. The homeostasis model assessment was the only variable that significantly correlated with GH response to clonidine (r = 0.375, p = 0.029) (vs. estradiol, free androgen index, leptin and LH). Nonetheless, when the analysis was adjusted for leptin levels and free androgen index, the statistical significance of this correlation was lost. The increased GH secretion observed in our lean PCOS patients may be associated with slight changes in insulin sensitivity, even in the absence of clinical evidence of insulin resistance. This association seems to be modulated by leptin and androgen levels.

References

  • 1 Azziz R. Polycystic ovary syndrome, insulin resistance, and molecular defects of insulin signaling.   J Clin Endocrinol Metab. 2002;  87 4085-4087
  • 2 Legro R S. Polycystic ovary syndrome: the new millennium.   Mol Cell Endocrinol. 2001;  184 87-93
  • 3 Legro R S, Kunselman A R, Dodson W C, Dunaif A. Prevalence and predictors of risk for type 2 diabetes mellitus and impaired glucose tolerance in polycystic ovary syndrome: a prospective, controlled study in 254 affected women.   J Clin Endocrinol Metab. 1999;  84 165-169
  • 4 Ehrmann D A, Barnes R B, Rosenfield R L, Cavaghan M K, Imperial J. Prevalence of impaired glucose tolerance and diabetes in women with polycystic ovary syndrome.   Diabetes Care. 1999;  22 141-146
  • 5 Morin-Papunem L C, Vauhkonem I, Koivunem R, Ruokonem A, Tapanainem J S. Insulin sensitivity, insulin secretion, and metabolic and hormonal parameters in healthy women and women with polycystic ovarian syndrome.   Hum Reprod. 2000;  15 1266-1274
  • 6 Spritzer P M, Poy M, Wiltgen D, Mylius L S, Capp E. Leptin concentrations in hirsute women with polycystic ovary syndrome or idiopathic hirsutism: influence on LH and relationship with hormonal, metabolic and anthropometric measurements.   Hum Reprod. 2001;  16 1340-1346
  • 7 Zournatzi V, Koios G, Vavilis D, Saravelos H, Tarlatzis V, Bontis J. Growth hormone response to oral glucose tolerance and insulin tolerance tests in patients with PCOS.   Clin Exp Obstet Gynecol. 1999;  26 109-111
  • 8 Barreca A, Del Monte P, Ponzani P, Artini P G, Genazzani A R, Minuto F. Intrafollicular insulin-like growth factor-II levels in normally ovulating women and in patients with polycystic ovary syndrome.   Fertil Steril. 1996;  65 739-745
  • 9 Acar B, Kadanalli S. Diminished growth hormone responses to L-dopa in polycystic ovarian disease.   Fertil Steril. 1993;  60 984-987
  • 10 Kazer R R, Unterman T G, Glick R P. An abnormality of the growth hormone/insulin-like growth factor-I axis in women with polycystic ovary syndrome.   J Clin Endocrinol Metab. 1990;  71 958-962
  • 11 Insler V, Shoham Z, Barash A, Koistinen R, Seppala M, Hen M, Lunenfeld B, Zadik Z. Polycystic ovaries in non-obese and obese patients: possible pathophysiological mechanism based on new interpretation of facts and findings.   Hum Reprod. 1993;  8 379-384
  • 12 Morales A J, Laughlin G A, Butzow T, Maheshwari H, Baumann G, Yen S S. Insulin, somatotropic, and luteinizing hormone axes in lean and obese women with polycystic ovary syndrome: common and distinct features.   J Clin Endocrinol Metab. 1996;  81 2854-2864
  • 13 Wasko R, Komarowska H, Warenik-Szymankiewicz A, Sowinski J. Elevated Ghrelin plasma levels in patients with polycystic ovary syndrome.   Horm Metab Res. 2004;  36 170-173
  • 14 Veldhuis J D, Pincus S M, Garcia-Rudaz M C, Ropelato M G, Escobar M E, Barontini M. Disruption of the synchronous secretion of leptin, LH, and ovarian androgens in nonobese adolescents with the polycystic ovarian syndrome.   J Clin Endocrinol Metab. 2001;  86 3772-3778
  • 15 Hull K L, Harvey S. GH as a co-gonadotropin: the relevance of correlative changes in GH secretion and reproductive state.   J Endocrinol. 2002;  172 1-19
  • 16 Comim F V, Spritzer P M. Increased growth hormone response to clonidine in nonobese normoinsulinemic patients with polycystic ovary syndrome.   Fertil Steril. 2004;  81 108-113
  • 17 Spritzer PM, Billaud L, Thalabard J C, Birman P, Mowszowicz I, Raux-Demay M C, Clair F, Kuttenn F, Mauvais-Jarvis P. Cyproterone acetate versus hydrocortisone treatment in late-onset adrenal hyperplasia.   J Clin Endocrinol Metab. 1990;  70 642-645
  • 18 Azziz R, Dewailly D, Owerbach D. Nonclassical adrenal hyperplasia: current concepts.   J Clin Endocrinol Metab. 1994;  78 810-815
  • 19 Spritzer P M, Lisboa K O, Mattiello S, Lhullier F. Spironolactone as a single agent for long-term therapy of hirsute patients.   Clin Endocrinol. 2000;  52 587-594
  • 20 Matthews D R, Hosker J P, Rudenski A S, Naylor B A, Treacher D F, Turner R C. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man.   Diabetologia. 1985;  28 412-419
  • 21 Katz A, Nambi S S, Mather K, Baron A D, Follmann D A, Sullivan G, Quon M J. Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans.   J Clin Endocrinol Metab. 2000;  85 2402-2410
  • 22 Ferriman D, Gallwey J D. Clinical assessment of body hair growth in women.   J Clin Endocrinol Metab. 1961;  21 1140-1148
  • 23 Rossato P, Minuto F, Garrone S, Ragni N. Growth hormone response to clonidine in anovulatory infertile women resistant to clomiphene citrate stimulation.   Fertil Steril. 2000;  73 78-84
  • 24 Salat-Baroux J, Rotten D, Alvarez S, Marie Antonie  J. Comparison of growth hormone responses to growth hormone releasing factor and clonidine in women with normal or poor ovarian response to gonadotropin stimulation.  Fertil Steril. 1993;  60 791-799
  • 25 Matussek N, Ackenheil M, Herz M. The dependence of the clonidine growth hormone test on alcohol drinking habits and the menstrual cycle.  Psychoneuroendocrinology. 1984;  9 173-177
  • 26 Garcia-Rudaz M C, Ropelato M G, Escobar M E, Veldhuis J D, Barontini M. Clinical study: amplified and orderly growth hormone (GH) secretion characterizes lean adolescents with polycystic ovarian syndrome.  Eur J Endocrinol. 2002;  147 207-216
  • 27 Takeuchi T, Tsutsumi O. Basal leptin concentrations in women with normal and dysfunctional ovarian conditions.  Int J Gynecol Obstet. 2000;  69 127-133
  • 28 Carro E, Senaris R, Considine R V, Casanueva F F, Dieguez C. Regulation of in vivo growth hormone secretion by leptin.  Endocrinology. 1997;  138 2203-2206
  • 29 Laughlin G A, Morales A J, Yen S SC. Serum leptin concentrations in women with PCOS: the role of insulin resistance/hyperinsulinemia.  J Clin Endocrinol Metab. 1997;  82 1692-1696
  • 30 Yu W H, Kimura M, Walczewska A, Karanth S, McCann S M. Role of leptin in hypothalamic-pituitary function.  Proc Natl Acad Sci USA. 1997;  94 1023-1028
  • 31 Bjarnason R, Boguszewski M, Dahlgren J, Gelander L, Kristrom B, Rosberg S, Carlsson B, Albertsson-Wikland K, Carlsson L M. Leptin levels are strongly correlated with those of GH-binding protein in prepubertal children.  Eur J Endocrinol. 1997;  137 68-73
  • 32 Skrha J, Haas T, Sindelka G, Prazny M, Widimsky J, Cibula D, Svacina S. Comparison of the insulin action parameters from hyperinsulinemic clamps with homeostasis model assessment and QUICKI indexes in subjects with different endocrine disorders.  J Clin Endocrinol Metab. 2004;  89 135-141
  • 33 Diamanti-Kandarakis E, Kouli C, Alexandraki K, Spina G. Failure of mathematical indices to accurately assess insulin resistance in lean, overweight, or obese women with polycystic ovary syndrome.  J Clin Endocrinol Metab. 2004;  89 1273-1276
  • 34 Cibula D, Skrha J, Hill M, Fanta M, Haakova L, VrbIkova J, Zivny J. Prediction of insulin sensitivity in nonobese women with polycystic ovary syndrome.  J Clin Endocrinol Metab. 2002;  87 5821-5825
  • 35 Genazzani A D, Battaglia C, Malavasi B, Strucchi C, Tortolani F, Gamba O. Metformin administration modulates and restores luteinizing hormone spontaneous episodic secretion and ovarian function in nonobese patients with polycystic ovary syndrome.  Fertil Steril. 2004;  81 114-119
  • 36 Bengtsson B A, Brummer R J, Bosaeus I. Growth hormone and body composition.  Horm Res. 1990;  33 19-24

P. M. Spritzer, M. D., Ph. D

Department of Physiology, Universidade Federal do Rio Grande do Sul

Rua Sarmento Leite, 500 · 90050-170 · Porto Alegre, RS · Brazil

Phone: +55-51-3316-3671

Fax: +55-51-3316-3656 ·

Email: spritzer@ufrgs.br

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