Introduction: Management of pediatric patients with short stature or short predicted adult height (PAH) is challenging. The use of aromatase inhibitors (AIs) has become a therapeutic option. Up to date, there is still scarce data about the indications of AI. Our aim was to conduct a survey on the real-world use of AI in pediatric patients with short stature or short PAH. Methods: We conducted a descriptive, cross-sectional, questionnaire-based study. Participants were collected throughout convenient sampling and by diffusion through different pediatric endocrine societies. Results: Two hundred and forty-three endocrinologists from 23 countries answered the survey, mostly from South America. 71.6% indicated AI to improve PAH. The main reason for not using AI was the lack of long-term data on effectiveness. 25.9% used AI in prepubertal patients and the most common indication in this group was in boys with congenital adrenal hyperplasia. A 92% of the survey participants used AI in pubertal patients with short stature and short PAH, regardless of the cause, mostly combined with growth hormone. Most clinicians felt confident about effectiveness of AI in reducing bone age advancement and improving PAH in pubertal male patients. One-fifth of the clinicians had to discontinue treatment due to adverse effects. Conclusion: This survey indicates that the use of AI among endocrinologists in patients with short stature or short PAH is increasing as more studies have come to light. However, questions remain regarding long-term outcomes, highlighting the need for future trials to further reassure its safety and effectiveness.

1.
Martha
PM
,
Rogol
AD
,
Veldhuis
JD
,
Kerrigan
JR
,
Goodman
DW
,
Blizzard
RM
.
Alterations in the pulsatile properties of circulating growth hormone concentrations during puberty in boys
.
J Clin Endocrinol Metab
.
1989
;
69
(
3
):
563
70
.
2.
Mauras
N
,
Ross
J
,
Mericq
V
.
Management of growth disorders in puberty: GH, GnRHa, and aromatase inhibitors: a clinical review
.
Endocr Rev
.
2023
;
44
(
1
):
1
13
.
3.
Wit
JM
,
Hero
M
,
Nunez
SB
.
Aromatase inhibitors in pediatrics
.
Nat Rev Endocrinol
.
2011
;
8
(
3
):
135
47
.
4.
Brueggemeier
RW
,
Hackett
JC
,
Diaz-Cruz
ES
.
Aromatase inhibitors in the treatment of breast cancer
.
Endocr Rev
.
2005
;
26
(
3
):
331
45
.
5.
Hero
M
.
Aromatase inhibitors in the treatment of short stature
.
Endocr Dev
.
2016
;
30
:
130
40
.
6.
Morishima
A
,
Grumbach
MM
,
Simpson
ER
,
Fisher
C
,
Qin
K
.
Aromatase deficiency in male and female siblings caused by a novel mutation and the physiological role of estrogens
.
J Clin Endocrinol Metab
.
1995
;
80
(
12
):
3689
98
.
7.
Smith
EP
,
Boyd
J
,
Frank
GR
,
Takahashi
H
,
Cohen
RM
,
Specker
B
, et al
.
Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man
.
N Engl J Med
.
1994
;
331
(
16
):
1056
61
.
8.
Hero
M
,
Toiviainen-Salo
S
,
Wickman
S
,
Mäkitie
O
,
Dunkel
L
.
Vertebral morphology in aromatase inhibitor-treated males with idiopathic short stature or constitutional delay of puberty
.
J Bone Miner Res
.
2010
;
25
(
7
):
1536
43
.
9.
Hero
M
,
Ankarberg-Lindgren
C
,
Taskinen
MR
,
Dunkel
L
.
Blockade of oestrogen biosynthesis in peripubertal boys: effects on lipid metabolism, insulin sensitivity, and body composition
.
Eur J Endocrinol
.
2006
;
155
(
3
):
453
60
.
10.
Juan
L
,
Huamei
M
,
Zhe
S
,
Yanhong
L
,
Hongshan
C
,
Qiuli
C
, et al
.
Near-final height in 82 Chinese patients with congenital adrenal hyperplasia due to classic 21-hydroxylase deficiency: a single-center study from China
.
J Pediatr Endocrinol Metab
.
2016
;
29
(
7
):
841
8
.
11.
Xi
W
,
Mao
J
,
Li
S
,
Zhao
Y
,
Nie
M
,
Yu
B
, et al
.
Aromatase inhibitor increases the height of patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency
.
Endocr Pract
.
2020
;
26
(
9
):
997
1002
.
12.
Al-Rayess
H
,
Wiersma
R
,
Turner
LE
,
Palzer
E
,
Mercado Munoz
Y
,
Sarafoglou
K
.
Anastrozole improves height outcomes in growing children with congenital adrenal hyperplasia due to 21-OHD
.
J Clin Endocrinol Metab
.
2024
:
dgae771
.
13.
Merke
DP
,
Mallappa
A
,
Parker
M
,
Sukin
C
,
Kulkarni
SE
,
Keil
MF
, et al
.
Adult height following prepubertal treatment with antiandrogen, aromatase inhibitor, and reduced hydrocortisone in CAH
.
J Clin Endocrinol Metab
.
2024
:
dgae824
.
14.
Salehpour
S
,
Alipour
P
,
Razzaghy-Azar
M
,
Ardeshirpour
L
,
Shamshiri
A
,
Monfared
MF
, et al
.
A double-blind, placebo-controlled comparison of letrozole to oxandrolone effects upon growth and puberty of children with constitutional delay of puberty and idiopathic short stature
.
Horm Res Paediatr
.
2010
;
74
(
6
):
428
35
.
15.
Wickman
S
,
Sipilä
I
,
Ankarberg-Lindgren
C
,
Norjavaara
E
,
Dunkel
L
.
A specific aromatase inhibitor and potential increase in adult height in boys with delayed puberty: a randomised controlled trial
.
Lancet
.
2001
;
357
(
9270
):
1743
8
.
16.
Leschek
EW
,
Flor
AC
,
Bryant
JC
,
Jones
JV
,
Barnes
KM
,
Cutler
GB
Jr
.
Effect of antiandrogen, aromatase inhibitor, and gonadotropin-releasing hormone analog on adult height in familial male precocious puberty
.
J Pediatr
.
2017
;
190
:
229
35
.
17.
Akın Kağızmanlı
G
,
Özalp Kızılay
D
,
Besci
Ö
,
Yüksek Acinikli
K
,
Özen
S
,
Demir
K
, et al
.
Aromatase inhibitors: a useful additional therapeutic option for slowing down advanced bone age in boys with growth hormone deficiency
.
J Endocrinol Investig
.
2024
;
47
(
5
):
1227
35
.
18.
Mauras
N
,
Gonzalez de Pijem
L
,
Hsiang
HY
,
Desrosiers
P
,
Rapaport
R
,
Schwartz
ID
, et al
.
Anastrozole increases predicted adult height of short adolescent males treated with growth hormone: a randomized, placebo-controlled, multicenter trial for one to three years
.
J Clin Endocrinol Metab
.
2008
;
93
(
3
):
823
31
.
19.
Miller
BS
,
Ross
J
,
Ostrow
V
.
Height outcomes in children with growth hormone deficiency and idiopathic short stature treated concomitantly with growth hormone and aromatase inhibitor therapy: data from the ANSWER program
.
Int J Pediatr Endocrinol
.
2020
;
2020
:
19
.
20.
Pollock
NI
,
Song
M
,
Wolf
AJ
,
Li
Y
,
Hawkes
CP
,
Motamedi
N
, et al
.
Exploring height outcomes with adjuvant aromatase inhibition in growth hormone-deficient male survivors of childhood cancer
.
Pediatr Blood Cancer
.
2024
;
71
(
8
):
e31117
.
21.
Varimo
T
,
Toiviainen-Salo
S
,
Raivio
T
,
Kerttula
L
,
Dunkel
L
,
Hero
M
.
Letrozole monotherapy in pre- and early-pubertal boys does not increase adult height
.
Front Endocrinol
.
2019
;
10
:
201
.
22.
Mauras
N
,
Ross
JL
,
Gagliardi
P
,
Yu
YM
,
Hossain
J
,
Permuy
J
, et al
.
Randomized trial of aromatase inhibitors, growth hormone, or combination in pubertal boys with idiopathic, short stature
.
J Clin Endocrinol Metab
.
2016
;
101
(
12
):
4984
93
.
23.
Rothenbuhler
A
,
Linglart
A
,
Bougnères
P
.
A randomized pilot trial of growth hormone with anastrozole versus growth hormone alone, starting at the very end of puberty in adolescents with idiopathic short stature
.
Int J Pediatr Endocrinol
.
2015
;
2015
(
1
):
4
.
24.
Zegarra
W
,
Ranadive
S
,
Toulan
D
,
Neely
EK
.
Anastrozole vs letrozole to augment height in pubertal males with idiopathic short stature: a 3-year randomized trial
.
J Endocr Soc
.
2024
;
8
(
10
):
bvae141
.
25.
Yackobovitch-Gavan
M
,
Tenenbaum
A
,
Phillip
M
,
Lazar
L
,
Oron
T
.
Aromatase-inhibitors treatment alone or with GH increases final height in short-statured pubertal boys - real-world data
.
J Clin Endocrinol Metab
.
2025
:
dgaf224
.
26.
Hero
M
,
Norjavaara
E
,
Dunkel
L
.
Inhibition of estrogen biosynthesis with a potent aromatase inhibitor increases predicted adult height in boys with idiopathic short stature: a randomized controlled trial
.
J Clin Endocrinol Metab
.
2005
;
90
(
12
):
6396
402
.
27.
Franzini
IA
,
Yamamoto
FM
,
Bolfi
F
,
Antonini
SR
,
Nunes-Nogueira
VS
.
GnRH analog is ineffective in increasing adult height in girls with puberty onset after 7 years of age: a systematic review and meta-analysis
.
Eur J Endocrinol
.
2018
;
179
(
6
):
381
90
.
28.
Yanovski
JA
,
Rose
SR
,
Municchi
G
,
Pescovitz
OH
,
Hill
SC
,
Cassorla
FG
, et al
.
Treatment with a luteinizing hormone-releasing hormone agonist in adolescents with short stature
.
N Engl J Med
.
2003
;
348
(
10
):
908
17
.
29.
Hero
M
,
Wickman
S
,
Dunkel
L
.
Treatment with the aromatase inhibitor letrozole during adolescence increases near-final height in boys with constitutional delay of puberty
.
Clin Endocrinol
.
2006
;
64
(
5
):
510
3
.
30.
Nour
MA
,
Pacaud
D
.
Height augmentation in 11β-hydroxylase deficiency congenital adrenal hyperplasia
.
Int J Pediatr Endocrinol
.
2015
;
2015
(
1
):
12
.
31.
Goedegebuure
WJ
,
Hokken-Koelega
ACS
.
Aromatase inhibitor as treatment for severely advanced bone age in congenital adrenal hyperplasia: a case report
.
Horm Res Paediatr
.
2019
;
92
(
3
):
209
13
.
32.
Hawton
K
,
Walton-Betancourth
S
,
Rumsby
G
,
Raine
J
,
Dattani
M
.
Growth hormone with aromatase inhibitor may improve height in CYP11B1 congenital adrenal hyperplasia
.
Pediatrics
.
2017
;
139
(
2
):
e20160730
.
33.
Atay
Z
,
Turan
S
,
Buğdaycı
O
,
Guran
T
,
Bereket
A
.
Restoration of height after 11 years of letrozole treatment in 11β-hydroxylase deficiency
.
Horm Res Paediatr
.
2019
;
92
(
3
):
203
8
.
34.
Papadimitriou
DT
,
Dermitzaki
E
,
Papagianni
M
,
Papaioannou
G
,
Papaevangelou
V
,
Papadimitriou
A
.
Anastrozole plus leuprorelin in early maturing girls with compromised growth: the “GAIL” study
.
J Endocrinol Investig
.
2016
;
39
(
4
):
439
46
.
35.
Papadimitriou
DT
,
Dermitzaki
E
,
Christopoulos
P
,
Livadas
S
,
Grivea
IN
,
Mastorakos
G
.
Anastrozole monotherapy further improves near-adult height after the initial combined treatment with leuprorelin and anastrozole in early-maturing girls with compromised growth prediction: results from the second phase of the GAIL study
.
Front Endocrinol
.
2024
;
15
:
1366970
.
36.
Ramadorai
U
,
Hire
J
,
DeVine
JG
,
Brodt
ED
,
Dettori
JR
.
Incidental findings on magnetic resonance imaging of the spine in the asymptomatic pediatric population: a systematic review
.
Evid Based Spine Care J
.
2014
;
5
(
2
):
95
100
.
37.
Jaremko
JL
,
Siminoski
K
,
Firth
GB
,
Matzinger
MA
,
Shenouda
N
,
Konji
VN
, et al
.
Common normal variants of pediatric vertebral development that mimic fractures: a pictorial review from a national longitudinal bone health study
.
Pediatr Radiol
.
2015
;
45
(
4
):
593
605
.
38.
Hero
M
,
Mäkitie
O
,
Kröger
H
,
Nousiainen
E
,
Toiviainen-Salo
S
,
Dunkel
L
.
Impact of aromatase inhibitor therapy on bone turnover, cortical bone growth and vertebral morphology in pre- and peripubertal boys with idiopathic short stature
.
Horm Res
.
2009
;
71
(
5
):
290
7
.
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