Received: 30 October 2016 Revised: 26 February 2017 Accepted: 27 February 2017

DOI: 10.1111/jep.12745

ORIGINAL ARTICLE

“Real‐world” pediatric endocrine practice; how much is it

influenced by physician's gender and region of practice. Results
of an international survey
Keren Smuel MD1 | Yonatan Yeshayahu MD, MHA2,3

1
Physician, Pediatrics A, The Edmond & Lily
Safra Children's Hospital, Sheba Medical
Center, Israel
2
Physician/Lecturer, Pediatrics A and Pediatric
Endocrinology Division, The Edmond & Lily
Safra Children's Hospital, Sheba Medical
Center, Israel
3
Physician/Lecturer, School of Medicine,
Tel‐Aviv University, Israel
Correspondence
Yonatan Yeshayahu, Pediatrics A and Pediatric
Endocrinology Division, The Edmond & Lily
Safra Children's Hospital, Sheba Medical
Center, Israel.
Email: yonatan.yeshayahu@sheba.health.gov.il
Abstract
Objective: To determine whether hormonal treatments for frequent clinical cases (short
stature, delayed and precocious puberty) are prescribed strictly according to clinical guidelines
or based on personal tendencies, and whether the decisions correlate with physician's personal
demographics (age, sex, and place of practice).
Methods: Cross‐sectional survey, with made‐up clinical cases, distributed to pediatric
endocrinologists using 2 web‐based professional forums, Israeli and an international. The
questionnaire included 8 clinical cases and 5 demographic questions regarding the physician.
Differences in practice between Israeli and international endocrinologists were assessed, and
correlation between the physician's gender and their decisions regarding treatment.
Results: One hundred fifty‐five physicians responded, 28% Israeli and 72% international. In
girls with early puberty, 60% of international and 26% of Israeli physicians chose not to treat with
a gonadotropin‐releasing hormone agonist. In girls with short stature, 79% of Israeli and 34% of
international physicians offered growth hormone treatment. In girls with early puberty, both male
and female physicians responded similarly in the international group, but in the Israeli group 47%
of male and 15% of female doctors would not treat. In girls with constitutional growth delay, 67%
of Israeli male doctors would not treat with growth hormone compared to 30% of Israeli female
physicians.

Conclusions: Our study demonstrated significant practice differences between Israeli and
international pediatric endocrinologists. Within the Israeli group, significant practice differences
were seen between male and female physicians. Given that Israeli physicians follow the same
clinical guidelines it is clear that a large “grey zone” of clinical cases exist and much of the
decisions on treatment are personal and influenced by personal beliefs or gender.

KEY W ORDS

clinical audit, clinical guidelines, health services research

1 | I N T RO D U CT I O N Precocious puberty is defined by the onset of secondary sexual

Changes in growth and puberty are responsible for a significant
number of referrals to pediatric endocrinologists, mostly, short stature,
delayed and precocious puberty. While clinical guidelines for managing
and treating these conditions exist, a large “grey zone” of borderline
clinical cases allows management to be influenced by personal practice
preferences of the treating physician.
characters before the age of 8 years in girls and 9 years in boys.1
Puberty is considered delayed when secondary sexual development
has not occurred by the age of 14 years in boys and 13 years in girls.2
Causes of abnormal early pubertal maturation may be divided into
gonadotropin‐releasing hormone (GnRH)‐dependent (central) and
GnRH‐independent (peripheral). The accepted treatment for central
precocious puberty is with a GnRH agonist, which desensitizes the

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SMUEL AND YESHAYAHU 867

gonadotrophic cells of the pituitary to the stimulatory effect of endog- TABLE 1 Demographics of participants
enous GnRH and halts the progression of central puberty. N‐155 N %
Delayed puberty may be constitutional and warrant clinical obser-
Gender Male 57 36.8
vation only, or can be caused by a variety of hypothalamic, pituitary, Female 98 63.2
and gonadal disorders. If a specific underlying disorder can be identi- Country North America 85 55
fied, therapy should be targeted at that disorder. Initial treatment for Israel 43 28
Europe 14 9
boys who have not started spontaneous puberty may be the use of South America 6 4
Testosterone. Africa 3 2
Asia 3 2
Short stature is defined as height below the 3rd percentile for age Australia and New Zealand 1 1
and sex. Treatment with growth hormone (GH) has been approved by Age Under 39 43 27.7
the Food and Drug Administration for growth hormone deficiency, 40‐55 years 66 42.6
Above 55 46 29.7
additional medical conditions, and idiopathic short stature (ISS), which
Practice facility Hospital clinic 129 83.2
is defined as height which is −2.25 standard deviation score (SDS)
Private clinic 26 16.8
below the mean for age and sex in an otherwise healthy child.3
Even though treatment guidelines for the above conditions are
widely known, there is great diversity among clinicians concerning endocrinologists, and therefore for purpose of statistical analysis all
the age of treatment initiation. There are other parameters concerning non‐Israeli physicians were clustered into one group.
the patient, which the doctor might take into consideration before In a case of a 9‐year‐old girl with early but not precocious
treating. Such parameters include the child's age,4,5 rate of pubertal puberty a significantly higher number of non‐Israeli endocrinologists
progression,6,7 height velocity, the estimated adult height as deter- responded that they would offer no treatment. When assessing the
mined from the rate of bone age advancement,3 and the psychosocial same age of puberty in girls but in combination with short stature,
concerns about a delay.4,8,9 the number of physicians who would not treat was lower, but still
The aim of our study was to assess whether changes in treatment significantly different between Israeli and non‐Israeli physicians.
practice exist between physicians and their adherence to clinical guide- Results were similar when assessing early puberty and short stature
lines. In addition, we wanted to assess whether demographic parame- in boys (Table 2).
ters of the physicians correlated with their clinical decisions. Our In the approach to ISS, 2.5 times more Israeli doctors would offer
hypothesis was that treatment initiation is strongly influenced by treatment with GH to both boys and girls. The same trend was seen in
factors related to the physician, such as gender, age, and country of the case of constitutional growth delay in girls and boys where twice as
practice.10-12 much non‐Israeli physicians avoided treatment with GH compared to
Israeli physicians (Table 2).
Similar approach towards a 14‐year‐old male with delayed
2 | METHODS puberty was seen worldwide, where 65% of Israeli and 70% of
non‐Israeli physicians recommended a short course of Testosterone
Questionnaires which consisted of made‐up clinical cases regarding (P = .7).
growth or pubertal development were emailed to an international When assessing differences in approaches based on the physi-
pediatric endocrine forum, and to the local Israeli pediatric endocrine cian's gender there was a significant difference between male and
group. The questionnaire was designed using “Typeform,” an electronic female physicians within the Israeli group. In the case of a girl with
web‐based questionnaire tool. early puberty, most of the non‐Israeli physicians would not offer
Statistical analysis: Categorical variables were expressed as
frequency and percentages. Chi‐square test or the Fisher exact test
TABLE 2 Decisions on treatment based on location of practice and
were used to evaluate association between categorical variables. A
patient gender
two‐tailed P < .05 was considered statistically significant. Analyses
were performed with International Business Machines SPSS Statistics P
Gender Other, n % Israel, n % value
for Windows, Version 22.0 (IBM Corp., Armonk, New York).
EP‐ would not recommend GIRLS 111 (59.9%) 42 (26.2%) 0.001
treatment
EP and ISS ‐ would not GIRLS 108 (38%) 41 (14.6%) 0.001
3 | RESULTS recommend treatment BOYS 107 (44.9%) 42 (11.9%) <0.001
CGD ‐ would not GIRLS 110 (86.4%) 42 (42.9%) <0.001
recommend treatment BOYS 111 (82%) 42 (40.5%) <0.001
One Hundred fifty‐five participants filled the questionnaire.
ISS ‐ would offer treatment GIRLS 110 (33.6%) 42 (78.6%) <0.001
Demographics are shown in Table 1. Ninety‐five percent of partici-
BOYS 109 (35.8%) 43 (79.1%) <0.001
pants were pediatric endocrinologists, and the remainders were pedia-
No differences were seen in practice based on gender of patient, but
tricians. The majority of responders were from North America and
significant differences were seen based on location, comparing Israeli to
Israel (55% and 28%, respectively) (Table 1). other physicians.
When analyzing the responses, we found a clear difference Abbreviations: EP, early puberty; ISS, idiopathic short stature; CGD,
between the clinical approaches of Israeli and non‐Israeli constitutional growth delay.

868
TABLE 3 Decision not to treat, based on physician's gender
Other
Male n‐40 Female n‐70
EP in girls 60% 58.6%
EP and ISS in boys 61.50% 34.3%
CGD in girls 87.8% 85.3%
Rates of physicians choosing to offer no treatment in different clinical situations, divided by gender of physician.
Abbreviations: EP, early puberty; ISS, idiopathic short stature; CGD, constitutional growth delay.
treatment with no difference between male and female physicians. In
contrast, the number of male Israeli physicians who would not offer
treatment was 3 times higher than the female physicians who would
not treat. The same trend goes for girls with constitutional growth
delay where 29.6% of female Israeli endocrinologists would not treat
with GH compared to 66.7% of the male endocrinologists (Table 3).
There was also a significant gender difference in the management
of boys with early puberty and short stature where 61.5% of the non‐
Israeli male endocrinologists would not offer treatment and only 34.3%
of the female endocrinologists would not treat.
4 | DISCUSSION
In our study, we have shown significant differences in treatment
approaches between the 2 large groups which comprised our study
group; Israeli and non‐Israeli (mostly North American) physicians.
Israeli physicians tend to intervene more, in borderline clinical cases
that do not fall under the clear guidelines. Non‐Israeli physicians were
shown to be more conservative with hormonal treatments, in line with
clinical guidelines. The reason for this finding is unclear, given the fact
that Israeli physicians use the same guidelines used internationally, and
do not have local guidelines which are different and more proactive. In
addition, a clear difference was seen between male and female physi-
cians with regards to treating early puberty in girls with a GnRH
analogue, or short stature in girls using GH. Male physicians within
the Israeli group tended not to treat in much higher rates than their
female counterparts. The reason for this difference is unclear and
may be explained by personal beliefs, which female physicians have,
that timing of menarche should be delayed, or beliefs of male physi-
cians that short stature in girls is not “as bad” as in boys. Despite ample
evidence that initiating GnRH analogue treatment in early but not
precocious puberty does not affect final height,4 treatment is still
commonly prescribed in Israel for psychosocial reasons. It might be
that female endocrinologists are more sensitive to that aspect and
therefore tend to prescribe treatment more easily than male endocri-
nologists do. Both findings support the hypothesis that Israeli physi-
cians are more likely to prescribe or not prescribe treatment based
on personal beliefs, experience, or “gut feeling” rather than strict
guidelines.8 This was much less evident with the international physi-
cians who tended to adhere more to clinical guidelines.
In the consensus of the Pediatric Endocrine Society 2009,4
there is a recommendation for use of GnRH analogues in early onset
central precocious puberty only, since the benefit of its use in other
conditions needs further investigation. From our results, it
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SMUEL AND YESHAYAHU
Israel
P value Male n‐15 Female n‐27 P value
0.89 46.7% 14.8% 0.02
0.04 28.6% 3.6% 0.09
0.92 66.7% 29.6% 0.03
seems that most non‐Israeli endocrinologists do follow those
recommendations.
Another interesting finding was that although ISS is a Food and
Drug Administration approved indication for GH treatment in the
USA;13 most of the non‐Israeli endocrinologists that participated in
this study (75% from North America) still chose not to treat, while in
Israel, where treatment with GH for ISS is considered off‐label, most
physicians did choose to treat. The reason for these findings is unclear,
and may be attributed to medication funding, which drives different
practices. In Israel, hormonal treatments, which fall under the same
clinical indications used in North America, are fully funded within the
social health insurance. In other countries, funding of these treatments
vary. They may not be covered at all in some parts of the world, or
depend on the type of private health insurance the patient has.
In summary, hormonal treatments using GH, GnRH analogues, or
puberty induction, have clear guidelines which apply to the clear
unequivocal cases. However, in borderline cases, much of the
decision‐making is based on personal tendency, and approaches vary
worldwide.10-12,14 It would be of benefit, if cohorts of those cases,
which are treated or not, and their outcomes, would be published so
future decisions in these clinical cases could be evidence based.
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How to cite this article: Smuel K, Yeshayahu Y. “Real‐world”
pediatric endocrine practice; how much is it influenced by phy-
sician's gender and region of practice. Results of an interna-
tional survey. J Eval Clin Pract. 2017;23:866–869. https://doi.
org/10.1111/jep.12745