Low Dose Growth Hormone in Obese PCOS Women

Summary

Study hypothesis: Growth hormone (GH), through its generation of free 'bioavailable' insulin-like growth factor (IGF)-I, can improve insulin sensitivity and the metabolic profile of women with polycystic ovary syndrome. Study aims: To determine the mechanism of how low dose GH treatment affects the body's sensitivity to insulin actions and whether this low GH dose can affect the body's handling of steroid hormone levels (cortisol clearance) and testosterone (male hormones) in obese women with polycystic ovary syndrome. Study design: Obese women with polycystic ovary syndrome, but not recently been on GH treatment, and presently attending Outpatients Clinic will be invited to participate in this study. The subjects will be assessed at the initial visit to ascertain their suitability before further participating in the study. If suitable, an equal number of women will be randomized to receive either daily low dose GH or placebo injections first for 12 weeks, before exchanging over for another 12 weeks of treatment after a 4-week washout period. Before, during and after treatment, the subjects will be assessed at frequently with blood tests, scans and fat biopsies. During the study, the subjects will be studied 4 times at the Oregon Clinical and Translational Research Institute (OCTRI). At the first, second and final visit, testing will include scans to measure the amount of whole body fat and fat in the stomach area, muscle, and liver; blood tests to measure levels of cortisol, and fat tissue (taken from a biopsy) analysis to measure the density of insulin-like growth factor-I (a hormone stimulated by growth hormone in the body) in fat; whereas blood tests to examine how well insulin works in the body (insulin sensitivity) will be collected at all visits of the study.

Timeline

Start

2010-10

Primary completion

2011-10

Completion

2011-10

Publications

• Background Azziz R, Woods KS, Reyna R, Key TJ, Knochenhauer ES, Yildiz BO. The prevalence and features of the polycystic ovary syndrome in an unselected population. J Clin Endocrinol Metab. 2004 Jun;89(6):2745-9. doi: 10.1210/jc.2003-032046.
• Background Carmina E, Lobo RA. Polycystic ovary syndrome (PCOS): arguably the most common endocrinopathy is associated with significant morbidity in women. J Clin Endocrinol Metab. 1999 Jun;84(6):1897-9. doi: 10.1210/jcem.84.6.5803. No abstract available.
• Background de Boer JA, Lambalk CB, Hendriks HH, van Aken C, van der Veen EA, Schoemaker J. Growth hormone secretion is impaired but not related to insulin sensitivity in non-obese patients with polycystic ovary syndrome. Hum Reprod. 2004 Mar;19(3):504-9. doi: 10.1093/humrep/deh122. Epub 2004 Jan 29.
• Background Van Dam EW, Roelfsema F, Helmerhorst FH, Frolich M, Meinders AE, Veldhuis JD, Pijl H. Low amplitude and disorderly spontaneous growth hormone release in obese women with or without polycystic ovary syndrome. J Clin Endocrinol Metab. 2002 Sep;87(9):4225-30. doi: 10.1210/jc.2002-012006.
• Background Essah PA, Nestler JE. Metabolic syndrome in women with polycystic ovary syndrome. Fertil Steril. 2006 Jul;86 Suppl 1:S18-9. doi: 10.1016/j.fertnstert.2006.04.013.
• Background Yuen K, Wareham N, Frystyk J, Hennings S, Mitchell J, Fryklund L, Dunger D. Short-term low-dose growth hormone administration in subjects with impaired glucose tolerance and the metabolic syndrome: effects on beta-cell function and post-load glucose tolerance. Eur J Endocrinol. 2004 Jul;151(1):39-45. doi: 10.1530/eje.0.1510039.
• Background Yuen KC, Frystyk J, White DK, Twickler TB, Koppeschaar HP, Harris PE, Fryklund L, Murgatroyd PR, Dunger DB. Improvement in insulin sensitivity without concomitant changes in body composition and cardiovascular risk markers following fixed administration of a very low growth hormone (GH) dose in adults with severe GH deficiency. Clin Endocrinol (Oxf). 2005 Oct;63(4):428-36. doi: 10.1111/j.1365-2265.2005.02359.x.
• Background Yuen K, Frystyk J, Umpleby M, Fryklund L, Dunger D. Changes in free rather than total insulin-like growth factor-I enhance insulin sensitivity and suppress endogenous peak growth hormone (GH) release following short-term low-dose GH administration in young healthy adults. J Clin Endocrinol Metab. 2004 Aug;89(8):3956-64. doi: 10.1210/jc.2004-0300.

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