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Inhibition of Estrogen Biosynthesis with a Potent Aromatase Inhibitor Increases Predicted Adult Height in Boys with Idiopathic Short Stature: A Randomized Controlled Trial
Abstract
CONTEXT: In males as well as in females, estrogen is an essential regulator of bone maturation, growth plate fusion, and cessation of longitudinal growth. Therefore, an increase in predicted adult height (PAH) may be achieved in short boys by blocking estrogen biosynthesis. OBJECTIVE: We tested the hypothesis that a decrease in the rate of bone maturation and an increase in PAH can be achieved in boys with idiopathic short stature (ISS) by the method of blocking estrogen biosynthesis with an aromatase inhibitor. Secondarily, we investigated the effects of aromatase inhibition on bone mineralization. DESIGN: This was a prospective, double-blind, randomized, placebo (Pl)-controlled clinical study. SETTING: The study was performed at a university hospital out-patient clinic. PATIENTS: Thirty-one boys, aged 9.0-14.5 yr, with ISS were studied. INTERVENTION: The boys were treated with the aromatase inhibitor letrozole (Lz; 2.5 mg/d) or Pl for 2 yr. MAIN OUTCOME MEASURE: The main outcome measure was the change in PAH after 24 months of treatment. RESULTS: PAH increased by 5.9 cm (P < 0.0001), and height SD score for bone age increased by 0.7 SD score (P < 0.0001) in the Lz-treated boys, whereas no changes occurred in the respective measures in Pl-treated boys. Areal bone mineral density of the lumbar spine and femoral neck, assessed by dual-energy x-ray absorptiometry, increased in a similar fashion in both groups during the treatment, whereas bone mineral apparent density increased only in those taking Lz (median increase, 4.3%; P = 0.009). CONCLUSIONS: Treatment with the aromatase inhibitor Lz delays bone maturation and improves PAH in boys with ISS. No adverse effects on bone mineralization were evident after 2 yr of treatment.
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“Uncontrolled studies using anastrozole, testolactone or letrozole have shown some evidence for a positive effect on sperm concentration and motility [49-51].”
From Aromatase inhibitors in men: effects and therapeutic options (2011) · cites this paper as [51]
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Metadata
- Authors
- Hero, M., Norjavaara, E., & Dunkel, L.
- Affiliations
- University of Helsinki (FI)
- University of Gothenburg (SE)
- Kuopio University Hospital (FI)
- Corresponding author
- Dunkel, Leo
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2005-12
- Volume
- 90
- Issue
- 12
- Pages
- 6396-6402
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2079935466
- Cited by
- 198
- References
- 28
- Citations by year
- 2026: 6 · 2025: 11 · 2024: 16 · 2023: 6 · 2022: 9 · 2021: 11 · 2020: 10 · 2019: 12 · 2018: 8 · 2017: 9 · 2016: 2 · 2015: 12 · 2014: 10 · 2013: 9 · 2012: 5
- FWCI
- 4.99
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
- Keywords
- aromatase inhibitors, letrozole, idiopathic short stature, predicted adult height, estrogen synthesis, skeletal maturation, bone age, bone mineral density, bone mineral apparent density, linear growth, pediatric boys
- MeSH terms
- Letrozole, Adolescent, Body Height, Child, Double-Blind Method, Estrogen Antagonists, Femur Neck, Growth, Growth Disorders, Hormones, Humans, Lumbar Vertebrae, Male, Nitriles, Prognosis, Puberty, Triazoles, Absorptiometry, Photon, Bone Density, Aromatase Inhibitors
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