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One Year of Insulin-Like Growth Factor I Treatment Does Not Affect Bone Density, Body Composition, or Psychological Measures in Postmenopausal Women¹

Medical Service, Geriatric Research Education Clinical Center, and Psychiatry Service, Palo Alto Veterans Administration Health Care System, and Departments of Medicine and Psychiatry, Stanford University, Palo Alto, California 94304

Address all correspondence and requests for reprints to: Anne L. Friedlander, Ph.D., Geriatric Research Education Clinical Center Building MB2, 182B, Palo Alto Veterans Administration Health Care System, 3801 Miranda Avenue, Palo Alto, California 94304-1207. E-mail: friedlan{at}leland.stanford.edu

The activity of the hypothalamic-GH-insulin-like growth factor I (hypothalamic-GH-IGF-I) axis declines with age, and some of the catabolic changes of aging have been attributed to the somatopause. The purpose of this investigation was to determine the impact of 1 yr of IGF-I hormone replacement therapy on body composition, bone density, and psychological parameters in healthy, nonobese, postmenopausal women over 60 yr of age. Subjects (n = 16, 70.6 ± 2.0 yr, 71.8 ± 2.8 kg) were randomly assigned to either the self-injection IGF-I (15 µg/kg twice daily) or placebo group and were studied at baseline, at 6 months, and at 1 yr of treatment. There were no significant differences between the IGF-I and placebo groups in any of the measured variables at baseline. Fasting blood IGF-I levels were significantly elevated above baseline values (65.6 ± 11.9 ng/mL) at 6 months (330.0 ± 52.8) and 12 months (297.7 ± 40.8) in the IGF-I treated group but did not change in the placebo subjects. Circulating levels of IGF-binding protein-1 and -3 were unaffected by the IGF-I treatment. Bone mineral density of the forearm, lumbar spine, hip, and whole body [as measured by dual-energy x-ray absorptiometry (DXA)] did not change in either group. Similarly, there was no difference in DXA-measured lean mass, fat mass, or percent body fat throughout the treatment intervention. Muscle strength values (grip, bench press, leg press), blood lipid parameters (cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides), and measures of postmeal glucose disposal were not altered by IGF-I treatment, although postmeal insulin levels were lower in the IGF-I subjects at 12 months. IGF-I did not affect bone turnover markers (osteocalcin and type I collagen N-teleopeptide), but subjects who were taking estrogen had significantly lower turnover markers than subjects who were not on estrogen at baseline, 6 months, and 12 months. Finally, the psychological measures of mood and memory were also not altered by the intervention. Despite the initial intent to recruit additional subjects, the study was discontinued after 16 subjects completed the protocol, because the preliminary analyses above indicated that no changes were occurring in any outcome variables, regardless of treatment regimen. Therefore, we conclude that 1 yr of IGF-I treatment, at a dose sufficient to elevate circulating IGF-I to young normal values, is not an effective means to alter body composition or blood parameters nor improve bone density, strength, mood, or memory in older women.

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