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Combined GH and Aromatase Inhibitor Therapy in GHD Adolescents« Back to Volume 24, Issue 2, November 2008 - Table of Contents In this study, Mauras et al investigated whether the potent aromatase inhibitor, anastrozole, could delay bone age acceleration and increase adult predicted height in boys with growth hormone deficiency (GHD). They studied 52 GHD adolescents on recombinant human GH therapy who were randomized to co-treatment with anastrozole or placebo daily for 36 months. Fifty subjects completed 12 months, 41 completed 24 months, and 28 completed 36 months of treatment. Bone age advancement was significantly slower in the anastrozole vs the placebo group both at 2 and 3 years of therapy (1.8 ± 0.1 vs 2.7 ± 0.1 yr and 2.5 ± 0.2 vs 4.1 ± 0.1 yr, respectively [p<0.0001]). This resulted in an increase in predicted adult height of +4.5 ± 1.2 cm at 24 months and of +6.7 ± 1.4 at 36 months of therapy in the anastrozole group when compared with a 1 cm gain at both time points in the placebo group. While serum testosterone concentrations increased more in the anastrozole group after 12 months of therapy, this difference was not significant at 24 months. Estradiol and estrone concentrations increased gradually in the placebo group during the 3 years of treatment, while they remained stable in the anastrozole treated group. Insulin-like growth factor (IGF)-I levels were similar at baseline and increased in a similar fashion in both groups throughout the study. The pace of pubertal progression was similar between groups as measured both by testosterone concentrations and testicular volumes. Fasting lipids, glucose concentrations, complete blood count, urinalysis and liver profiles were normal in both groups at baseline, with no significant differences over time. There was no difference in lumbar spine bone mineral density between groups. The authors concluded that anastrozole increased the adult height potential of adolescent boys on GH therapy while maintaining a normal pubertal progression. Editor’s CommentTreatment with GH has been shown to improve the final height of GHD children. However, once puberty has begun the time available to increase linear growth in GHD patients is limited. Gonadotropin releasing hormone (GnRH) analog therapy in addition to GH treatment has proven to improve the near final height of GHD patients in puberty.1 However, this form of therapy is relatively expensive, requires long-term parenteral administration and careful follow-up, and recent studies have demonstrated substantial changes in body composition and in intermediary metabolism, with an increase in adiposity and a decrease in protein synthesis, lipid oxidation, energy expenditure and muscle strength following analog use.2 Additionally, prior studies by Mauras et al3 have demonstrated increased loss of urinary calcium and in the rate of calcium resorption, with a significant decrease in measures of bone formation in treated patients. In this study, Mauras et al demonstrated how combined anastrozole (a potent aromatase inhibitor which blocks the conversion of androstenedione to estrone and testosterone to estradiol) and GH administration to adolescent GHD boys increased their adult height potential. Growth velocity remained similar to that of GH and placebo treated children, but with a slower increase in bone maturation, resulting in a net increase in predicted adult height. Anastrozole was well tolerated and free of side effects with no negative effects on fasting lipids or glucose, liver function tests or changes in fat-free mass or percent fat mass. While the increase in lumbar bone mineral density was less in the anastrozole treated group at 24 months, this difference was not noted at 36 months and osteocalcin concentrations, a measure of bone formation, were similar during the whole treatment period in both anastrozole and placebo treated patients. The pace of pubertal progression as determined by changes in testosterone concentrations and in testicular volumes was also similar in both groups. Therefore, treatment with an aromatase inhibitor and GH may offer an alternative in promoting growth in GHD boys who have entered into puberty. However, this conclusion is based on limited data, as patients have not been followed to final height, studies have been performed only in males and in a limited number of patients, and only one randomized double-blind, placebo-controlled study has been performed in this group of patients. More long-term data regarding bone health, potential effects on spermatogenesis and sperm motility, lipid and carbohydrate metabolism will be necessary in assessing the pros and cons of aromatase inhibitor therapy in GHD children and in short boys in general. Roberto Lanes, MD References - (linked to
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Volume 26 Number 1
September 2010
www.GGHjournal.com
ISSN 1932-9032
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