Subscribe to RSS
DOI: 10.1055/s-0035-1564252
The Effects of Gonadotropin Replacement Therapy on Metabolic Parameters and Body Composition in Men with Idiopathic Hypogonadotropic Hypogonadism
Publication History
received 12 July 2014
accepted after second revision 21 September 2015
Publication Date:
20 October 2015 (online)
Abstract
Testosterone replacement therapy (TRT) in idiopathic hypogonadotrophic hypogonadism (IHH) slows the process of metabolic syndrome (MetS), diabetes mellitus, and cardiovascular diseases by its inversing effects on insulin resistance, dyslipidemia, and blood pressure. Since there are not enough data regarding the effects of gonadotropin replacement therapy (GRT), we aimed to investigate the impact of GRT on MetS parameters in IHH patients. Sixteen patients with IHH and 20 age and body mass index (BDI)-matched healthy controls were enrolled into the study. Patients were evaluated at baseline and 6 months after the GRT. Sex hormones, insulin like growth factor-1, prolactin, insulin, C-reactive protein (CRP), homocysteine, and lipid levels were measured at baseline and after the treatment. Anthropometric measurements, including BMI, body fat ratio (BFR), fat free mass (FFM), waist circumference, and waist-to-hip ratio (WHR), were also performed. Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) index was calculated. Body fat ratio, triglyceride, HOMA-IR, and CRP levels were higher, whereas bone age, fat free mass, and creatinine levels were lower in the patients with hypogonadism. HOMA-IR indices and basal insulin levels decreased significantly after 6 months of GRT compared with baseline levels. Triglyceride levels, and BFRs diminished significantly by an accompanying decline in WHR. FFM of the patients increased following the GRT. No significant changes were detected in CRP, homocysteine, total and LDL-cholesterol levels. Similar to TRT, hCG treatment decreases HOMA-IR, triglyceride levels, BFR and WHRs, and increases FFM in patients with IHH.
-
References
- 1 Layman LC. Hypogonadotropic hypogonadism. Endocrinol Metab Clin North Am 2007; 36: 283-296
- 2 Beg S, Al Khoury L, Cunningham GR. Testosterone replacement in men. Curr Opin Endocrinol Diabetes Obes 2008; 15: 364-370
- 3 Balasubramanian V, Naing S. Hypogonadism in chronic obstructive pulmonary disease: incidence and effects. Curr Opin Pulm Med 2012; 18: 112-117
- 4 Pitteloud N, Mootha VK, Dwyer AA, Hardin M, Lee H, Eriksson KF, Tripathy D, Yialamas M, Groop L, Elahi D, Hayes FJ. Relationship between testosterone levels, insulin sensitivity, and mitochondrial function in men. Diabetes Care 2005; 28: 1636-1642
- 5 Zitzmann M. Testosterone deficiency, insulin resistance and the metabolic syndrome. Nat Rev Endocrinol 2009; 5: 673-681
- 6 Stellato RK, Feldman HA, Hamdy O, Horton ES, McKinlay JB. Testosterone sex hormone-binding globulin, and the development of type 2 diabetes in middle-aged men: prospective results from the Massachusetts male aging study. Diabetes Care 2000; 23: 490-494
- 7 Yesilova Z, Oktenli C, Sanisoglu SY, Musabak U, Cakir E, Ozata M, Dagalp K. Evaluation of insulin sensitivity in patients with Klinefelter’s syndrome: a hyperinsulinemic euglycemic clamp study. Endocrine 2005; 27: 11-15
- 8 Laaksonen DE, Niskanen L, Punnonen K, Nyyssonen K, Tuomainen TP, Salonen R, Rauramaa R, Salonen JT. Sex hormones, inflammation and the metabolic syndrome: a population-based study. Eur J Endocrinol 2003; 149: 601-608
- 9 Haffner SM, Mykkanen L, Valdez RA, Katz MS. Relationship of sex hormones to lipids and lipoproteins in nondiabetic men. J Clin Endocrinol Metab 1993; 77: 1610-1615
- 10 Maggio M, Basaria S. Welcoming low testosterone as a cardiovascular risk factor. Int J Impot Res 2009; 21: 261-264
- 11 Shabsigh R, Katz M, Yan G, Makhsida N. Cardiovascular issues in hypogonadism and testosterone therapy. Am J Cardiol 2005; 96: 67-72
- 12 Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412-419
- 13 Theodoraki A, Bouloux PM. Testosterone therapy in men. Menopause Int 2009; 15: 87-92
- 14 Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972; 18: 499-502
- 15 Kanauchi M. A new index of insulin sensitivity obtained from the oral glucose tolerance test applicable to advanced type 2 diabetes. Diabetes Care 2002; 25: 1891-1892
- 16 Yazici M, Sahin M, Bolu E, Uckaya G, Gok DE, Taslipinar A, Ozgurtas T, Kutlu M. Prediction of testosterone response to human chorionic gonadotrophin in idiopathic hypogonadotropic hypogonadism patients. J Natl Med Assoc 2009; 101: 71-76
- 17 Kapoor D, Goodwin E, Channer KS, Jones TH. Testosterone replacement therapy improves insulin resistance, glycaemic control, visceral adiposity and hypercholesterolaemia in hypogonadal men with type 2 diabetes. Eur J Endocrinol 2006; 154: 899-906
- 18 Marin P, Holmang S, Jonsson L, Sjostrom L, Kvist H, Holm G, Lindstedt G, Bjorntorp P. The effects of testosterone treatment on body composition and metabolism in middle-aged obese men. Int J Obes Relat Metab Disord 1992; 16: 991-997
- 19 Tripathy D, Shah P, Lakshmy R, Reddy KS. Effect of testosterone replacement on whole body glucose utilisation and other cardiovascular risk factors in males with idiopathic hypogonadotrophic hypogonadism. Horm Metab Res 1998; 30: 642-645
- 20 Singh AB, Hsia S, Alaupovic P, Sinha-Hikim I, Woodhouse L, Buchanan TA, Shen R, Bross R, Berman N, Bhasin S. The effects of varying doses of T on insulin sensitivity, plasma lipids, apolipoproteins, and C-reactive protein in healthy young men. J Clin Endocrinol Metab 2002; 87: 136-143
- 21 Boyanov MA, Boneva Z, Christov VG. Testosterone supplementation in men with type 2 diabetes, visceral obesity and partial androgen deficiency. Aging Male 2003; 6: 1-7
- 22 Naharci MI, Pinar M, Bolu E, Olgun A. Effect of testosterone on insulin sensitivity in men with idiopathic hypogonadotropic hypogonadism. Endocr Pract 2007; 13: 629-635
- 23 Smith MR, Lee H, Nathan DM. Insulin sensitivity during combined androgen blockade for prostate cancer. J Clin Endocrinol Metab 2006; 91: 1305-1308
- 24 Kapoor D, Clarke S, Stanworth R, Channer KS, Jones TH. The effect of testosterone replacement therapy on adipocytokines and C-reactive protein in hypogonadal men with type 2 diabetes. Eur J Endocrinol 2007; 156: 595-602
- 25 Aydogdu A, Bolu E, Sonmez A, Tasci I, Haymana C, Acar R, Meric C, Taslipinar A, Ozgurtas T, Azal O. Effects of three different medications on metabolic parameters and testicular volume in patients with hypogonadotropic hypogonadism: 3-year experience. Clin Endocrinol (Oxf) 2013; 79: 243-251
- 26 Singh R, Artaza JN, Taylor WE, Gonzalez-Cadavid NF, Bhasin S. Androgens stimulate myogenic differentiation and inhibit adipogenesis in C3H 10T1/2 pluripotent cells through an androgen receptor-mediated pathway. Endocrinology 2003; 144: 5081-5088
- 27 Eiholzer U, Grieser J, Schlumpf M, l’Allemand D. Clinical effects of treatment for hypogonadism in male adolescents with Prader-Labhart-Willi syndrome. Horm Res 2007; 68: 178-184
- 28 Rodriguez-Tolrà J, Torremadé Barreda J, del Rio L, di Gregorio S, Franco Miranda E. Effects of testosterone treatment on body composition in males with testosterone deficiency syndrome. Aging Male 2013; 16: 184-190
- 29 Giltay EJ, Haider A, Saad F, Gooren LJ. C-reactive protein levels and ageing male symptoms in hypogonadal men treated with testosterone supplementation. Andrologia 2008; 40: 398
- 30 Mazo EB, Gamidov SI, Iremashvili VV, Gasanov RV. Efficacy of phosphodiesterase inhibitors in the treatment of patients with organic erectile dysfunction: a comparative study. Urologia 2009; 40: 43-46
- 31 Oktenli C, Yesilova Z, Ozata M, Yaman H, Tuzun A, Dundar S, Sanisoglu SY, Musabak U, Erbil MK, Dagalp K. Gonadotropin treatment increases homocysteine levels in idiopathic hypogonadotropic hypogonadism: an indirect effect mediated by changes in body composition. J Endocrinol 2003; 179: 35-39
- 32 Hagenfeldt Y, Linde K, Sjoberg HE, Zumkeller W, Arver S. Testosterone increases serum 1,25-dihydroxyvitamin D and insulin-like growth factor-I in hypogonadal men. Int J Androl 1992; 15: 93-102
- 33 MacGillivray MH. Induction of puberty in hypogonadal children. J Pediatr Endocrinol Metab 2004; Suppl 4: 1277-1287
- 34 Liu L, Merriam GR, Sherins RJ. Chronic sex steroid exposure increases mean plasma growth hormone concentration and pulse amplitude in men with isolated hypogonadotropic hypogonadism. J Clin Endocrinol Metab 1987; 64: 651-656
- 35 Prior JC, Cox TA, Fairholm D, Kostashuk E, Nugent R. Testosterone-related exacerbation of a prolactin-producing macroadenoma: possible role for estrogen. J Clin Endocrinol Metab 1987; 64: 391-394
- 36 Sodi R, Fikri R, Diver M, Ranganath L, Vora J. Testosterone replacement-induced hyperprolactinaemia: case report and review of the literature. Ann Clin Biochem 2005; 42: 153-159
- 37 Miner MM, Sadovsky R. Evolving issues in male hypogonadism: evaluation, management, and related comorbidities. Cleve Clin J Med 2007; 74 (Suppl. 03) 38-46