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Aromatase inhibitors: a useful additional therapeutic option for slowing down advanced bone age in boys with growth hormone deficiency

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Abstract

Introduction

Aromatase inhibitors (AIs) have been used to slow down estrogen-dependent skeletal maturation in pubertal boys with short stature. In the literature, few data evaluate the effectiveness and safety of AIs in boys with growth hormone deficiency (GHD). This study aimed to evaluate the auxologic effects and short-term laboratory profiles of combined AI and rhGH therapy for 1 year in adolescent males with GHD.

Subjects and methods

Male subjects between the ages of 10 and 16 with GHD from two different centers were included in the study. Patients were divided into two groups: (i) those who only used recombinant human growth hormone (rhGH) therapy (Group I; G-I) and (ii) those who also used AI therapy (anastrozole or letrozole) along with rhGH (Group II; G-II).

Results

Forty-one patients (G-I, 46%; G-II, 54%) were included in the study. All the subjects had isolated GHD. At the beginning of the treatment, the chronological ages (CAs) of the patients in the G-I and G-II groups were 11.8 (10.9–13.7) and 12.8 (12.0–14.3) years, respectively. The ratios of bone age (BA)/CA for the two groups were 0.8 (0.8–0.9) and 1.0 (0.9–1.1), respectively (p < 0.001). After the treatment, the height standard deviation (SD) scores and predicted adult height (PAH) significantly increased from baseline in all subjects in the G-I and G-II groups (p < 0.001; p < 0.001, respectively). There was no significant change in the ratio of BA/CA post-therapy in the G-I group (p = 0.1), while there was a significant decrease in the G-II group (p < 0.001). The growth velocities of the patients in the G-I and G-II groups were 9.1 (7.4–10.1) cm/year [1.5 (0.8–5.0) SD score] and 8.7 (7.5–9.9) cm/year [1.1 (0.3–3.1) SD score], respectively (p = 0.6). While post-therapy serum testosterone concentrations were seen to increase in the G-II group, none of the patients exhibited hematocrit above 50 percent, and the fasting glucose concentrations were normal.

Conclusions

When used in addition to rhGH therapy in boys with GHD and advanced BA, AIs were observed to slow down the tempo of BA maturation after 1 year, compared to those who received rhGH treatment alone. AI therapy was found to be safe during the 1-year observation period and thus could be considered for preserving growth potential in these patients.

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Data availability

The datasets used and/or analyzed for the study are available from the corresponding author on reasonable request.

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Funding

No funds, grants, or other support was received.

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Authors and Affiliations

  1. Department of Pediatric Endocrinology, Dokuz Eylül University Faculty of Medicine, İzmir, Turkey

    G. Akın Kağızmanlı, Ö. Besci, K. Yüksek Acinikli, K. Demir, E. Böber & A. Abacı

  2. Department of Pediatric Endocrinology, Ege University Faculty of Medicine, İzmir, Turkey

    D. Özalp Kızılay, S. Özen, R. D. Gökşen Şimşek & Ş. Darcan

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  1. G. Akın Kağızmanlı
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Contributions

GAK and AA made substantial contributions to the conception and design of the work; GAK, DOK, OB, and KYA to the data acquisition; SO, KD, RDGS, EB, SD and AA to the analysis; and SO, KD, RDGS, EB, SD and AA to the interpretation. GAK, DOK, SO, KD, and AA helped in drafting the article and AA provided a critical revision of the manuscript. All the authors gave their final approval of the version to be published and agreed to the accuracy or integrity of any part of the work.

Corresponding author

Correspondence to A. Abacı.

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Conflict of interest

The authors have no conflicts of interest to declare.

Ethical statement

This research complies with the guidelines for human studies and is conducted ethically in accordance with the World Medical Association Declaration of Helsinki.

Research involving human participants and/or animals

The research involved only human participants. No animals were included.

Study approval statement

Institutional approval was granted by the Ethics Committee of Dokuz Eylül University Faculty of Medicine (Ethics Approval Number: 2022/36-15).

Informed consent

Both patients and parents were required to sign the informed consent form to participate in the study.

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Akın Kağızmanlı, G., Özalp Kızılay, D., Besci, Ö. et al. Aromatase inhibitors: a useful additional therapeutic option for slowing down advanced bone age in boys with growth hormone deficiency. J Endocrinol Invest 47, 1227–1235 (2024). https://doi.org/10.1007/s40618-023-02242-w

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