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Impact of Growth Hormone (GH) Treatment on Cardiovascular Risk Factors in GH-Deficient Adults: A Metaanalysis of Blinded, Randomized, Placebo-Controlled Trials

Clinical Pharmacology (P.M.), Clinical Research Unit, Assistance Pubique-Hôpitaux de Paris, Henri Mondor University Hospital, F-94010 Créteil, France; Institut National de la Santé et de la Recherche Médicale U258 (P.M., M.N.-B., N.H., B.B.), F-94807 Villejuif, France; Institute of Public Health (S.G.), CB2 2SR Cambridge, United Kingdom; and Endocrinology and Reproductive Diseases (P.C.), Assistance Publique-Hôpitaux de Paris, Bicêtre University Hospital, and University Paris XI, F-94275 Le Kremlin-Bicêtre, France

Address all correspondence and requests for reprints to: P. Chanson, M.D., Endocrinology, Bicêtre University Hospital, 78 rue du Général Leclerc, F-94275 Le Kremlin-Bicêtre, France. E-mail: philippe.chanson{at}bct.ap-hop-paris.fr.

Patients with hypopituitarism have an increased risk of cardiovascular mortality. GH treatment could modify the cardiovascular risk in adults with GH deficiency, but most published clinical trials involved few patients and the results are variable.

We conducted a systematic review of blinded, randomized, placebo-controlled trials of GH treatment in adult patients with GH deficiency published up to August 2003. Thirty-seven trials were identified. We combined the results for effects on lean and fat body mass; body mass index; triglyceride and cholesterol [high-density lipoprotein, low-density lipoprotein (LDL), and total] levels; blood pressure; glycemia; and insulinemia. Overall effect size was used to evaluate significance, and weighted differences between GH and placebo were used to appreciate the size of the effect.

GH treatment significantly reduced LDL cholesterol [–0.5 (SD 0.3) mmol/liter], total cholesterol [–0.3 (0.3) mmol/liter], fat mass [–3.1 (3.3) kg], and diastolic blood pressure [–1.8 (3.8) mm Hg] and significantly increased lean body mass [+2.7 (2.6) kg], fasting plasma glucose [+0.2 (0.1) mmol/liter], and insulin [+8.7 (7.0) pmol/liter]. All effect sizes remained significant in trials with low doses and long-duration GH treatment.

Thus, GH treatment has beneficial effects on lean and fat body mass, total and LDL cholesterol levels, and diastolic blood pressure but reduces insulin sensitivity. The global cardiovascular benefit remains to be determined in large trials with appropriate clinical endpoints.

Abbreviations: BMI, Body mass index; GHD, GH deficiency; LDL, low-density lipoprotein.

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