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

Abstract

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 microg/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.

Central effects of the somatotropic system

“…In a placebo-controlled trial, Papadakis et al examined the effects of GH administration for 6 months (0.27 IU/kg/week) in healthy elderly men (mean age 75 years) with low IGF-I levels (90) and Friedlander et al studied the effects of IGF-I in postmenopausal women over 60 years of age for one year in a placebo-controlled study (91). In both trials, no effect Figure 2 Effect of GH replacement on measures of attention.…”

Prevalent and Emerging Therapies for Osteoporosis

“…These conflicting results plus the necessity for administration by injection make it unlikely that GH will become a therapeutic option for patients with osteoporosis who are not GH deficient. IGF-1 therapy does not appear to be effective [21].…”

“…These conflicting results plus the necessity for administration by injection make it unlikely that GH will become a therapeutic option for patients with osteoporosis who are not GH deficient. IGF-1 therapy does not appear to be effective [21].Androgens: Because men have higher bone density than women, it has been suggested that treatment with androgens might benefit women with osteoporosis. However, the effect of treatment with androgen plus estrogen on bone mineral density does not appear superior to the effect of estrogen alone and androgen has unwelcome virilizing effects [22].…”

Effects on insulin sensitivity and body composition of combination therapy with GH and IGF1 in GH deficient adults with type 2 diabetes

“…IGF1 treatment in adults has been evaluated in a few studies. In postmenopausal women treated with IGF1 alone, glucose tolerance improved (7) and in insulin-resistant individuals insulin sensitivity increased (8). IGF1 in combination with GH in healthy volunteers and patients with traumatic brain injury enhanced GH's anabolic effects (9,10) and in post-menopausal women led to fat mass reduction (11).…”