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Does a Gender-Related Effect of Growth Hormone (GH) Replacement Exist on Cardiovascular Risk Factors, Cardiac Morphology, and Performance and Atherosclerosis? Results of a Two-Year Open, Prospective Study in Young Adult Men and Women with Severe GH Deficiency

Departments of Molecular and Clinical Endocrinology and Oncology (A.Co., C.D.S., F.R., M.C.S., G.L.), Biomorphological and Functional Sciences, Nuclear Medicine Centre of the National Council of Research (A.Cu., W.A.), Internal Medicine I (L.S.), "Federico II" University of Naples, 80131 Naples, Italy; and Emergency Unit (S.S.), "S. Maria degli Incurabili" Hospital of Naples, Naples 80138, Italy

Address all correspondence and requests for reprints to: Annamaria Colao, M.D., Ph.D., Department of Molecular and Clinical Endocrinology and Oncology, "Federico II" University of Naples, via S. Pansini 5, 80131 Naples, Italy. E-mail: colao{at}unina.it.

Context: GH secretion and response to GH replacement are gender-related.

Objective: The objective of this study was to investigate the effects of GH deficiency (GHD) and replacement on the cardiovascular system according to gender.

Design: The design was open and prospective.

Setting: The study was conducted at a university hospital.

Subjects: Subjects included 36 severe adult-onset GHD patients (18 men, 20 women, aged < 45 yr); 36 gender-, age-, and body mass index-matched healthy subjects served as controls.

Interventions: Subjects received GH replacement at a median dose of 6.5 µg/kg·d in men and 7.7 µg/kg·d in women for 2 yr.

Main Outcome Measures: Homeostasis model assessment index, total to HDL cholesterol ratio, fibrinogen and C-reactive protein levels, left ventricular mass index, blood pressure, heart rate, diastolic filling, and systolic function at rest and at peak exercise and intima-media thickness (IMT) at common carotid arteries were measured.

Results: Basal prevalence and/or degree of insulin resistance, lipid alterations, compromised cardiac function, and IMT were similar in women and men. Diastolic dysfunction was more prevalent in men (61 vs. 25%, P = 0.036). After GH replacement, IGF-I levels normalized in all patients. Lipid profile, fibrinogen, and C-reactive protein levels normalized in all cases. The total to HDL ratio (P = 0.04) was higher in women than men. The homeostasis model assessment index persisted higher in GHD patients than controls and decreased only in GHD men (P = 0.017). Left ventricular mass index normalized during treatment in both women and men, abnormal diastolic function persisted in three women (P = 0.031), and abnormal systolic performance persisted in six women and one man (P = 0.13). IMT decreased similarly in women and men, persisting higher than in controls. Exercise performance normalized in all.

Conclusions: Two-year GH replacement has similar beneficial effects on cardiac and exercise performance and atherosclerosis in women and men with severe GHD.

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