Treatment with the aromatase inhibitor letrozole during adolescence increases near‐final height in boys with constitutional delay of puberty

Hero, Matti; Wickman, Sanna; Dunkel, Leo

doi:10.1111/j.1365-2265.2006.02499.x

Cited by 113 publications

(63 citation statements)

References 24 publications

(32 reference statements)

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“…This realisation prompted the development of a novel treatment for boys with short stature using aromatase inhibitors, which block oestrogen production in order to prolong the duration of growth and to increase final height. Beneficial effects of aromatase inhibitors on growth have been reported in boys with constitutional delay of puberty and growth, idiopathic short stature and GH deficiency (Wickman et al 2001, Mauras et al 2004, Hero et al 2005, 2006b). The ease of administration, low cost and lack of overt toxicity of aromatase inhibitors make them a potential attractive strategy for treatment of boys with idiopathic short stature.…”

Section: Introductionmentioning

confidence: 99%

Peripubertal aromatase inhibition in male rats has adverse long-term effects on bone strength and growth and induces prostatic hyperplasia

Bajpai¹,

Simm²,

McPherson³

et al. 2010

Journal of Endocrinology

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Aromatase inhibitors have been increasingly used in boys with growth retardation to prolong the duration of growth and increase final height. Multiple important roles of oestrogen in males point to potential adverse effects of this strategy. Although the deleterious effects of aromatase deficiency in early childhood and adulthood are well documented, there is limited information about the potential long-term adverse effects of peripubertal aromatase inhibition. To address this issue, we evaluated short-term and long-term effects of peripubertal aromatase inhibition in an animal model. Peripubertal male Wistar rats were treated with aromatase inhibitor letrozole or placebo and followed until adulthood. Letrozole treatment caused sustained reduction in bone strength and alteration in skeletal geometry, lowering of IGF1 levels, inhibition of growth resulting in significantly lower weight and length of treated animals and development of focal prostatic hyperplasia. Our observation of adverse long-term effects after peripubertal male rats were exposed to aromatase inhibitors highlights the need for further characterisation of long-term adverse effects of aromatase inhibitors in peripubertal boys before further widespread use is accepted. Furthermore, this suggests the need to develop more selective oestrogen inhibition strategies in order to inhibit oestrogen action on the growth plate, while beneficial effects in other tissues are preserved.

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Section: Introductionmentioning

confidence: 99%

Peripubertal aromatase inhibition in male rats has adverse long-term effects on bone strength and growth and induces prostatic hyperplasia

Bajpai¹,

Simm²,

McPherson³

et al. 2010

Journal of Endocrinology

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“…The delay in the tempo of bone age acceleration caused by aromatase inhibition and decreased estrogen resulted in treated with AI for twelve months, in combination with low dose testosterone therapy for 6 months [6]. The same subjects were followed until near final height [7] and the boys treated with AI attained a mean NAH 6.7 cm higher compared to the control group. Subsequent studies were done in patients with ISS and GHD [8,10,11].…”

Section: Discussionmentioning

confidence: 99%

“…The identification of one male with a point mutation in the estrogen receptor gene [3] and another male with a point mutation in the aromatase enzyme gene [4,5] confirmed that estrogen is the principal hormone causing epiphyseal closure. Studies involving AI in male patients with constitutional delay of growth and puberty [6,7], ISS [8,9], and GHD [10] suggest that AI can delay bone age acceleration and increase predicted adult height (PAH). However, data regarding adult height outcomes are limited [6][7][8][9][10][11][12].…”

Section: Introductionmentioning

confidence: 99%

The Efficacy of Anastrozole and Growth Hormone Therapy on Adult Height in Six Adolescent Males with Growth Hormone Deficiency or Idiopathic Short Stature

Uysal

Hodax

Topor

et al. 2017

Advances in Endocrinology

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Background. Data on adult height outcomes of the use of Anastrozole and Growth Hormone (GH) in pubertal males with Growth hormone deficiency (GHD) and Idiopathic short stature (ISS) are limited. Objective. We examined the effect of Anastrozole and GH therapy on near adult height (NAH) with pubertal males with GHD or ISS. Methods. Retrospective review of 419 charts from 2008 to 2015. The primary outcomes are NAH compared to mid-parental target height (MPTH) and predicted adult height (PAH). Results. We identified 23 patients (5 SGA/IUGR, 1 Noonan syndrome, 6 GHD, and 11 ISS). Six patients (4 GHD; 2 ISS) achieved NAH. Prior to Anastrozole treatment, the mean chronological age was 13.9±0.2 years (range 13.7–14.4), bone age was 13.6±0.6 years (range 12.5–14), mean height SDS was -1.5±0.5 (range −0.8 to −2.3), and mean PAH was 162.6±5.9 cm (range 153.5–168.6). MPTH was 173.6 cm ± 7 (range 161.8–181.6). Patients received Anastrozole for an average of 30.5 months (range 19–36 months). At NAH, the mean chronological age was 16.7±0.8 years (range 15.9–18.1 years) and height was 170±1.8 cm (range 168.5–173.4 cm). The mean height SDS improved to +0.81±0.6 (range +0.08 to +1.92, p=0.002). Net height gain was 7.3 cm compared to pretreatment PAH (p<0.01) and overall the mean adult height remained 3.5 cm below MPTH. Conclusion. Anastrozole and GH therapy can be effective in augmenting adult height without significant side effects. However, the long-term safety and efficacy of aromatase inhibitor use in pediatrics remain limited.

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“…Normal pubertal progression and bone health were found after 2 -3 years with this combination therapy (11) . Another randomized, placebo-controlled study could show that boys with constitutional delay of puberty who received the AI letrozole in combination with low-dose testosterone reached a higher mean near-fi nal height than boys on testosterone monotherapy (12) . Considering the positive effects of GH on BMD, the use of GH, together with an AI, might also be a treatment option in adolescents with ISS.…”

Section: Discussionmentioning

confidence: 99%

Marked increase of final height by long-term aromatase inhibition in a boy with idiopathic short stature

Krebs

Moske-Eick

Doerfer

et al. 2012

Journal of Pediatric Endocrinology and Metabolism

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Growth hormone (GH) is the most frequently used treatment in children with idiopathic short stature (ISS). Aromatase inhibitor (AI) therapy is still in an experimental state, and both fi nal height (FH) and long-term effi cacy data in ISS have not been published. We present a 14.5-year-old boy with ISS and a height of 142.7 cm [standard deviation score (SDS) -2.79]. Based on the baseline bone age (BA) of 13.5 -14 years, his predicted adult height (PAH) by Bayley/Pinneau was 154 cm (SDS -3.77) -158.2 (SDS -3.15). After a 5-year letrozole monotherapy, FH was 169 cm (SDS -1.57) showing a height difference between PAH and FH from 10.8 to 15 cm. No permanent side effects of the medication have been observed. Both a transient occurrence and a spontaneous recovery of decreased bone mineral apparent density were seen, verifi ed by dual-energy X-ray absorptiometry. Spinal magnetic resonance imaging revealed no vertebral abnormalities. AI therapy might be an effective and low-cost alternative to the use of GH. Further controlled trials should prove effi cacy and safety of long-term AI therapy in boys with ISS.

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Treatment with the aromatase inhibitor letrozole during adolescence increases near‐final height in boys with constitutional delay of puberty

Abstract: Our findings indicate that in adolescent boys an increase in adult height can be attained by use of aromatase inhibitors.

Cited by 113 publications

References 24 publications

Peripubertal aromatase inhibition in male rats has adverse long-term effects on bone strength and growth and induces prostatic hyperplasia

Peripubertal aromatase inhibition in male rats has adverse long-term effects on bone strength and growth and induces prostatic hyperplasia

The Efficacy of Anastrozole and Growth Hormone Therapy on Adult Height in Six Adolescent Males with Growth Hormone Deficiency or Idiopathic Short Stature

Marked increase of final height by long-term aromatase inhibition in a boy with idiopathic short stature

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