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The Effect of Four Weeks of Supraphysiological Growth Hormone Administration on the Insulin-Like Growth Factor Axis in Women and Men¹

Department of Medicine M (Endocrinology and Diabetes), Aarhus University Hospital (R.D., J.O.L.J., J.S.C.), DK-8000 Aarhus, Denmark; Department of Clinical Medicine and Cardiovascular Sciences, University Federico II (S.L., A.C., L.S., R.N.), 80131 Naples, Italy; Research Center for Endocrinology and Metabolism, Sahlgrenska Hospital (C.E., T.R., B.A.B.), S-41345 Gothenburg, Sweden; Metabolic Research Unit, Department of Medicine, and Department of Social and Preventive Medicine, University of Queensland, Princess Alexandra Hospital (R.C.C.), 4102 Brisbane, Queensland, Australia; Department of Endocrinology, St. Thomas’s Hospital (N.K., M.A.B., P.H.S.), London, United Kingdom SE1 7EH; Institute of Mathematics and Statistics, University of Kent (E.E.B.), Canterbury, Kent, United Kingdom CT 7NF; and Kolling Institute of Medical Research, University of Sydney, Royal North Shore Hospital (R.C.B.), St. Leonards 2065, New South Wales, Australia

Address all correspondence and requests for reprints to: Rolf Dall, M.D., Aarhus Kommunehospital, Department of Medicine M (Endocrinology and Diabetes), Aarhus University Hospital, DK-8000 Aarhus, Denmark. E-mail: rd{at}dadlnet.dk

Measurements of serum insulin-like growth factor I (IGF-I) and related markers are routinely used in the diagnosis and treatment of GH deficiency and excess. The validity of these markers for assessment of exogenous GH exposure in healthy adults is, however, unknown. We therefore conducted a double blind, placebo-controlled GH treatment trial in 99 healthy subjects [49 women and 50 men; mean ± SE age, 25.6 ± 0.6 (women)/25.7 ± 0.6 yr (men)]. Blood was collected weekly during a 4-week treatment period (days 1–28), and the subjects were subsequently followed for additional 8 weeks (days 29–84). The treatment arms included: I) 0.1 IU/kg·day GH (n = 30; GH 0.1), II) 0.2 IU/kg·day GH (n = 29; GH 0.2), and III) placebo (n = 40). At baseline no gender-specific differences existed, except that the acid-labile subunit (ALS) levels were higher in females. Serum insulin-like growth factor I (IGF-I) levels in males receiving GH increased significantly through day 42 with no significant difference between the 2 doses. The absolute IGF-I response was significantly lower in females, and there was a clear dose-response relationship. ALS levels in males increased through day 30 (P < 0.001). In females ALS levels were only modestly increased on day 28 compared with those in the placebo group (P < 0.02). IGF-binding protein-3 (IGFBP-3) levels in males increased significantly in the GH 0.1 and the GH 0.2 groups on day 30 (P < 0.03), whereas no solid IGFBP-3 increase was detected in females. IGFBP-2 levels decreased insignificantly during GH exposure in both genders. A gender-specific upper normal range for each analyte was arbitrarily defined as 4 SD above the mean level at baseline. On the basis of IGF-I levels alone, GH exposure in the GH 0.2 group was detected in 86% of the males and in 50% of the females on day 21. On day 42 GH exposure was only weakly detectable in males and was not detectable in females. We conclude that 1) males are significantly more responsive than females to exogenous GH; 2) the increase in IGF-I is more robust compared with those in IGFBP-3 and ALS; 3) IGFBP-2 changes very little during GH treatment; and 4) among IGF-related substances, IGF-I is the most specific marker of supraphysiological GH exposure.

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