Idiopathic central precocious

puberty: A case report*

By Mariel Anne C. dela Rea, MD and Marian C. Dichoso, MD, FPOGS
Department of Obstetrics and Gynecology, De La Salle University Medical Center

ABSTRACT

Central precocious puberty is characterized by early pubertal changes, acceleration of growth velocity, and rapid bone
maturation. It is a relatively rare disorder, with an incidence rate of about 1 : 5000 – 1 : 10 000 individuals in the general population;
it is more frequent in girls than in boys. This is a case of a 7 year-old female complaining of onset of menstruation. Physical
examination revealed advanced pubertal changes of Tanner stage 4-5 for breast and stage 3 for pubis. Diagnostic evaluation
revealed well developed internal genitalia, markedly elevated LH levels, advanced bone aging and a normal cranial MRI. Based on
clinical and diagnostic evaluations, a diagnosis of idiopathic central precocious puberty was made and the patient was started on
GnRHa therapy. It is important to initiate therapy early in patients with central precocious puberty so as to prevent compromised
adult height and psychosocial embarrassment.

Keywords: Precocious puberty, central precocious puberty, idiopathic central precocious puberty

INTRODUCTION

P
hysical changes during puberty are controlled by the
hypothalamic pituitary gonadal axis which increases
its activity before the onset of clinical puberty. The
pulsatile secretion of gonadotropin releasing hormone
(GnRH) increases and stimulates the pulsatile release of
luteinizing hormone (LH) and to a lesser extent follicle
stimulating hormone (FSH). This initially occurs at night
and then later also during the day with consequential rise
in gonadal steroid levels. Signs of pubertal maturation are
described by Tanner staging. In girls, breast development
is rated from 1 (preadolescent) to 5 (mature), and stage
2 (appearance of the breast bud) marks the onset of
pubertal development. Pubic hair stages are rated from
1 (preadolescent, no pubic hair) to 5 (adult), and stage Figure 1. In girls, breast development is rated from 1 (preadoles-
2 marks the onset of pubic hair development.1 (Figure 1) cent) to 5 (mature) and stage 2 (appearance of the breast bud)
The onset of puberty in girls is marked by breast budding marks the onset of pubertal development. Pubic hair stages are
rated from 1 (preadolescent, no pubic hair) to 5 (adult), and
(Tanner stage 2) followed by appearance of pubic and
stage 2 marks the onset of pubic hair development.
axillary hair then maximal growth velocity and finally Source: Jean-Claude Carel, MD and Juliane Leger, MD. Precocious Puberty. The N
menarche.2 Engl K Med 2008; 358:2366-77
Precocious puberty is classically defined as the onset
of secondary sexual characteristics before the age of 8 years the median age of menarche remains unchanged.
in girls and 9 years in boys. The prevalence of precocious New guidelines have been set to help in determining
puberty is about 10 times as high in girls as in boys.1 There which girls should be evaluated. These guidelines state
are controversies on the age threshold for precocious that Caucasian girls older than 7 years old and African
puberty. Pubertal changes and sexual maturation were American girls older than 6 years-old, with early breast
noted to occur earlier in African American girls however and/or pubic hair development, should be investigated
further in the following condition 1) rapid progression
of skeletal maturation (bone age >2 SD of chronological
*3rd Place, 2017 Philippine Obstetrical and Gynecological Society (POGS)
age), 2) new central nervous system (CNS) findings and
Interesting Case Paper Contest, April 6, 2017, Citystate Asturias Hotel, 3) psychosocial disturbances related to pubertal changes.3
Puerto Princesa City, Palawan Precocious puberty can be divided into central or
38 Volume 41, Number 2, PJOG March-April 2017
gonadotropin dependent precocious puberty wherein
there is early activation of pulsatile GnRH secretion. This
could be due to hypothalamic lesions but in most cases
the cause is idiopathic. Management is medical and often
directed to halting the maturation of the hypothalamic
pituitary gonadal axis. Peripheral or gonadotropin
independent precocious puberty results from sex steroid
exposure independent of hypothalamic-pituitary gonadal
activation. It may be due to gonadal or adrenal tumors
secreting exogenous sex steroids and genetic disorders
such as McCune-Albright syndrome. Surgery is indicated Uterus Endometrium
for GnRH independent precocious puberty due to
gonadal tumors. Peripheral precocious puberty can lead
to activation of pulsatile GnRH secretion and to central
precocious puberty.1

CASE REPORT

The index patient is a 7 year-old gravida 0 who

presented at the clinic with the chief complaint of vaginal
bleeding of 2 days duration, using 4 moderately soaked
pads per day with no associated pelvic pain. Breast Left Ovary Right Ovary
budding was noted at 5 years of age and pubic hair Figure 2
growth at 6 years-old. The patient was born at around 28
weeks age of gestation and was admitted for 3 months
at the neonatal intensive care unit due to prematurity.
Her mother was 19 years-old at that time. Her mother’s
menarche was at 10 years of age. There was no family
history of menstrual disorder or congenital malformations.
Her parents are separated and she is being raised by her
paternal grandparents. The patient has no other siblings.
The patient denies any sexual contact. She is right handed.
On physical examination, the index patient had
Tanner staging 4 for breast (secondary mound of areola
and papilla above the breast), Tanner stage 3 for pubis
(labial hair spreads over mons pubis) and note of axillary
hair. She weighed 36kg and had a height of 137cm which
was at the 94th percentile for girls at her age. She was not
pale and had pink palpebral conjunctiva. She had a soft
flat abdomen with no palpable mass or tenderness. Pelvic
examination revealed normal appearing external genitalia
and an intact vaginal canal with passage of minimal
amount of menstrual like fluid. As the patient was a virgin,
a bimanual rectal examination was done revealing good Figure 3
sphincteric tone, smooth rectovaginal septum and no
palpable masses. stimulating hormone (FSH) and luteinizing hormone (LH)
Initial working impression was precocious puberty. were elevated with LH/FSH ratio of 3:1 (Figure 4). Serum
At the third day of menstruation, transrectal androgens levels were within normal range. Her estradiol
ultrasound showed the presence of normal sized uterus level was within pubertal range (Figure 5). An x-ray of the
with a length of 3.53 cm and endometrial thickness of patient’s non-dominant hand revealed a bone aging of 11
1.15 cm. Both ovaries were normal in size with presence years old using the Greulich-Pyle method (Figures 6 & 7).
of follicles (Figures 2 & 3). Serum thyroid function Cranial magnetic resonance imaging (MRI) with contrast
tests were within normal range. Both levels of follicle revealed a normal result (Figure 8).

Volume 41, Number 2, PJOG March-April 2017 39

 Figure 7
Figure 4

Figure 5

Figure 8

At this time, the impression was idiopathic central

precocious puberty.
After the initial cycle of menstruation which lasted for
5 days, the patient had another 2 cycles of menstruation
occurring at 35-52 days interval, lasting for 5 days. After
her third cycle and prior to initiation of therapy, the index
Figure 6 patient weighed 39 kg and had a height of 139cm (height
40 Volume 41, Number 2, PJOG March-April 2017
increase of 2 cm in 3 months). Tanner staging of the breast
had progressed to stage 5 while the pubis remained at
stage 3 (Figures 9, 10 & 11).
The patient was started on gonadotropin releasing
hormone agonist (GnRHa), leuproride acetate, 3.75 mg
given at 28 days interval. Psychosocial counseling was also
offered to the patient and her family.

CASE DISCUSSION

This is a case of a 7 year-old complaining of onset of

menstruation. Physical examination revealed advanced
pubertal changes of Tanner stage 4-5 for breast and stage
3 for pubis. Diagnostic evaluation revealed well developed
internal genitalia, markedly elevated LH levels, advanced
bone aging (>2SD of chronological age) and normal
cranial MRI. Based on clinical and diagnostic evaluation,
a diagnosis of idiopathic central precocious puberty was
made and the patient was started on GnRHa therapy.
Central precocious puberty is characterized by
hypothalamic-pituitary-gonadal axis activation leading to Figure 9
progressive pubertal development, acceleration of growth
velocity, and rapid bone maturation that often results in
reduced adult height. It is a relatively rare disorder, with
an incidence rate of about 1 : 5000 – 1 : 10 000 individuals
in the general population; it is more frequent in girls
than in boys, with the female : male ratio estimated to
be between 3 : 1 and 23 : 13. It is more common than
peripheral precocious puberty and accounts for up to 90%
of published cases4. Idiopathic central precocious puberty
is sometimes familial and occurs more frequently than
organic central precocious puberty. It is more common in
girls (74%) than in boys (60%).3 The onset of organic central
precocious puberty is earlier usually before the age of 3
in girls.3 On the other hand, organic central precocious
puberty is more common in boys than girls (40-90% vs.
8-33%).
A search for local data revealed a total of 11 reported
cases of precocious puberty, only 2 of which were central
precocious puberty - a case of hypothalamic hamartoma
and a case of 3 year-old with idiopathic central precocious
puberty.5-15
Many environmental, endocrine and genetic factors
affect the onset of puberty: 1) race 2) early maternal Figure 10
menarche 3) low birth weight 4) excessive weight gain in
infancy and early childhood 5) after international adoption
6) when no father is present in the household1.However,
these factors are associated with only a fraction of causes
of early puberty and are not considered as main etiology
of the disease. Factors noted in the index patient include
prematurity at birth (low birth weight) and the absence of
a father in the household.
Examination of a child with precocious puberty should Figure 11

Volume 41, Number 2, PJOG March-April 2017 41

start with accurate family and personal medical history, hand revealed a skeletal age of 11 years-old, much greater
physical examination and pubertal staging. A complete than her chronological age.
personal history is necessary, including the age at onset of The gold standard for evaluation of precocious
puberty and progression of pubertal manifestations which puberty is the measurement of gonadotropins at 0,
is often more rapid in precocious puberty. There also 15, 30, 45, 60 and 90 minutes after stimulation by
should be note of any evidence suggesting possible central intravenous GnRH (which is unavailable in many countries
nervous system dysfunction, such as headache, increased including the United States and the Philippines).3 Early
head circumference, visual disturbances, or seizures. activation of hypothalamic-pituitary-gonadotropin axis is
Family history should include the age at onset of puberty demonstrated by maximal luteinizing hormone level after
in parents and siblings. Growth should be evaluated since GnRH stimulation. In an attempt to simplify the GnRH test,
progressive precocious puberty is associated with a high a single determination of basal LH of > 0.3 IU/L or an LH
growth velocity. The stage of pubertal development should peak ≥ 5 IU/L at 30 to 60 minutes after GnRH stimulation
be classified as described by Tanner. Careful assessment suggest progressive central precocious puberty.3,23 Onset
is needed in obese girls to avoid overestimating breast of puberty starts with increased LH secretion compared to
development. The development of pubic hair results FSH and so an increased LH/FSH ratio may be indicative of
from the effects of androgens, which may be produced central precocious puberty. In the absence of intravenous
by functioning ovaries in central precocious puberty. In GnRH, basal LH and FSH levels were obtained from the
girls, pubic hair in the absence of breast development is index patient on her 3rd day of menstruation. Basal LH level
suggestive of adrenal disorders, premature pubarche, or was at 15.03mIU/ml and her LH/FSH ratio was 3:1. Both
exposure to androgens.1 It would be helpful to assess results established the diagnosis of central precocious
signs of specific causes of precocious puberty, such as puberty. (IU/L=mIU/ml)
hyperpigmented skin lesions suggesting neurofibromatosis Gonadotropin levels in children younger than 3
or the McCune-Albright syndrome. years old should be interpreted with caution, because
Diagnosis of central precocious puberty is based gonadotropin levels are normally high in this age group.
on the signs of activation of the hypothalamic-pituitary- Random measurements of follicle-stimulating hormone
gonadal axis in girls younger than 8 years-old. This includes are not useful, since they vary little throughout pubertal
breast tanner stage of >1, uterine volume (longitudinal development.1
diameter >3.5cm), increased height velocity, bone age In all cases of central precocious puberty, MRI of the
>2 SD above chronological age, menstrual bleeding and brain should be performed to rule out any hypothalamic
increased basal or stimulated LH3. The course of precocious lesion. The prevalence of such lesions is higher in boys (40
puberty is considered progressive or accelerated when to 90%) than in girls (8 to 33%) presenting with precocious
tanner stage 3 is reached before 10 years of age. In the index puberty and is much lower when puberty starts after
patient, breast budding was noted at 5 years-old and pubic the age of 6 years in girls (<2%).1 The most frequent CNS
hair growth at 6 years of age. Upon initial examination lesion associated with precocious puberty is hypothalamic
tanner staging was 4 and 3 for breast and pubis, respectively hamartoma. Small and pedunculated hypothalamic
but there was progression to tanner stage 5 for breast after hamartomas are often associated with central precocious
2 months indicating possible rapid progression. Further puberty while large and sessile ones are associated with
diagnostic tests revealed uterine length of 3.53 cm, markedly seizures. The younger the child (<4 years-old), the higher
elevated LH levels and increased height velocity, all of which the possibility of a CNS lesion in central precocious puberty.
are associated with progressive precocious puberty. Cranial MRI of the index patient revealed normal result.
It is necessary to establish the degree of skeletal In at least 50% of cases of precocious puberty, pubertal
maturation. In precocious puberty, skeletal maturation manifestations will regress or stop progressing, and no
and statural growth are accelerated (the former more than treatment is necessary.1 The decision to treat depends on
the latter), so the child is mature more than they grow. the child’s age, the rate of pubertal progression and height
The child with precocious puberty is deprived, according velocity. Pubertal progression is considered slow if there
to the age of onset, of a certain period of normal pre- is no choice in Tanner staging of breast and pubis during
pubertal growth and thus final adult height is shorter than a 6 month observation. Height velocity is accelerated if
the target height. A reference atlas such as the one by it is more than 6 cm per year. In a 3 month observation
Greulich and Pyle can be used to evaluate the effect of of the index patient, tanner stage for breast progressed
sex steroids on epiphyseal maturation; the bone age of from 4 to 5 and height was increased by 2 cm. For cases
patients with precocious puberty is consistently greater in which precocious puberty progresses, concerns include
than their chronologic age (> 2 SD above chronological early menarche in girls and short adult stature due to early
age). In the index patient, bone aging of the non dominant epiphyseal fusion and adverse psychosocial outcomes.1

42 Volume 41, Number 2, PJOG March-April 2017

Thus, the two main reasons for treating patients with obtained 90 minutes after GnRH agonist administration
idiopathic central precocious puberty is to improve indicates adequate suppression with a sensitivity of 100%
psychosocial well being and to prevent compromised and specificity of 88%.22 A study by Brito et al indicated
adult height. LH level of < 6.6 IU/L obtained 2 hours after GnRH agonist
GnRH agonists are the gold standard in the administration was consistent with adequate pubertal
management of progressive central precocious puberty. suppression.20 Repeat LH level was determined in the index
They provide continuous stimulation of the pituitary patient 90 minutes after her 3rd monthly GnRH (3.75 mg)
gonadotrophs, leading to desensitization and decrease in administration. The result was 1.83 mIU/ml (basal LH level
the release of LH and, to a lesser extent, FSH. This leads to was at 15.03mIU/ml).
decreased sex steroid production. Factors affecting height Aside from laboratory evaluation, the patient must
gains include baseline bone age (markedly advanced be monitored clinically to assess gonadal suppression.
bone age associated with shorter adult height) and The patient’s BMI, tanner staging and growth velocity
duration of treatment (onset of treatment at a younger should be evaluated every 3-6 months. Bone age should
age and a longer duration of treatment associated with be evaluated every 6 months. Successful therapy would
greater height gain). Normal adult height can be achieved indicate arrest or regression of tanner staging and
if treatment is started before bone maturation is too bone aging nearing chronological age.22 At the time of
advanced and if gonadal suppression is maintained for submission of this paper, the index patient had completed
several years. 6 months of treatment. Her height remained unchanged
Most common GnRH agonist used for the treatment after her third GnRHa injection at 141 cm. Tanner staging
of central precocious puberty is the monthly 3.75 mg of the breast regressed to tanner stage 3 after the fourth
intramuscular injection. Dose can be increased depending GnRHa injection and to tanner stage 2 after the sixth
on the response of the patient to the therapy. Other injection. There was no progression of tanner staging for
forms/dosage of GnRH agonist have also been used for her pubis.
central precocious puberty-3-month depot formulations The optimal time to stop treatment has not been
(11.25 and 30 mg) and the once-yearly histrelin established, but most studies suggest that treatment
subcutaneous implants. Although these formulations beyond the age of 11 years is not associated with significant
have not been studied as extensively as the 1 month further height gain.1 Pubertal manifestations reappear
depot leuprolide acetate formulation, they have proven within months after discontinuing GnRH agonist treatment.
to be as effective and with better compliance due to the Follow up 6 months after completion of treatment is
less frequency of administration.16,17,18 Higher LH and FSH recommended to ensure puberty subsequently progresses
levels were seen with the 11.25 mg 3-month leuprolide normally.
acetate dose but no differences in final growth velocity For cases in which precocious puberty is caused by a
and bone age progression was noted. However, during central lesion (e.g., a mass or malformation), management
monitoring of treatment higher dosing was required in of the lesion generally has no effect on the course of
some circumstances.18 The index patient was offered both pubertal progression. Initial management of hypothalamic
the 1 month (3.75 mg) and 3 month (11.25 mg) dosing but hamartomas include the use of GnRH agonist since
her family opted to start the monthly leuprolide acetate significant risk is associated with surgery and removal of
administration. the lesion does not guarantee pubertal regression.23
Several methods have been proposed in monitoring No adverse effects on reproductive development
pubertal suppression during GnRH agonist therapy. or fertility have been found to be associated with GnRH
Traditionally, LH level of < 2 IU/L obtained 30-60 minutes agonist therapy. There was reversibility of hypothalamic
after GnRH stimulation indicate adequate pubertal pituitary ovarian axis suppression after cessation of GnRH
suppression.3,19,20 Other methods have been investigated agonist treatment.24 In a prospective study involving
and appear more applicable to the Philippine setting long term follow-up and adult callback after completion
since GnRH is unavailable. A study done by Zung et al of treatment with 1 month leuprolide acetate depot, all
compared basal, post GnRH agonist and first voided patients achieved pubertal hormonal response within 1
urinary LH as alternative methods to GnRH stimulation year after cessation of treatment and no impairment of
test in assessing pubertal suppression during treatment.21 reproductive function was observed in adulthood.25
The study concluded LH levels obtained 24 hours after the In contrast to adults, hypoestrogenic state induced
GnRH agonist injection was accurate enough to determine by the long term use of GnRH agonist in early pubertal
adequate pubertal suppression. Basal LH, urinary LH and stage does not result in deterioration of the bone mineral
estradiol levels did not correlate well with the degree of density.26 Pituitary-ovarian suppression by GnRH agonist
suppression.21 In another study, LH level ≤ 2.5 mIU/ml does not reverse or prevent bone mass acquisition.27

Volume 41, Number 2, PJOG March-April 2017 43

 The negative psychosocial implications of early sexual CONCLUSION
development should not be underestimated. Precocious
pubertal changes have been associated with adverse The onset of precocious puberty has important
psychosocial outcomes and psychological evaluation may physical and psychological consequences for affected
be useful. However, there is limited available data that are children and induces anxiety in their families. However,
specific to patients with precocious puberty. A study done not all girls with early signs of puberty require treatment.
by Baumann et al in 2001 showed that patients with history It is necessary to make a rapid, correct diagnosis as well
of precocious puberty had behavioral problems including as to form a judgment concerning the progression of the
neuroticism and feelings of insecurity.28 Patients suffering condition based on a combination of clinical signs and
from precocious puberty are at risk for depression, anxiety, diagnostic evaluation thus providing the appropriate
difficult socialization, early sexual activity at a young age treatment to prevent psychosocial embarrassment and
and sleep disturbances. poor height prognosis in these patients.

REFERENCES
1. Jean-Claude Carel, MD and Juliane Leger, MD. Precocious Puberty. 12. Helen Valenzona Madamba, Ma. Cristina Palaez-Crisolongo. An
The N Engl K Med. 2008; 358:2366-77. Ovarian Sex Cord Tumor with Annular Tubules. Philippine Journal
of Obstetrics and Gynecology. July 2012; Vol. 36 (3): p. 144-148.
2. Lobo R, Lentz G, Gershenson D and Katz V: Comprehensive
Gynecology, 6th ed. USA: Elsevier Mosby, 2012. 13. Arlene Tiong-Samonte. Precocious puberty. Philippine Journal of
Pediatrics; Vol. 36 (1) : p. 65-77.
3. Franco Antoniazzi and Giorgio Zamboni. Central Precocious
Puberty Current Treatment Options. Pediatr Drugs. 2004; 6 14. Cyriel Anthony I. Tingne, Agnes L. Soriano-Estrella. Juvenile
(4):211-231. Granulosa Cell Tumor of the Ovary Presenting as Isosexual
Precocious Puberty: A Case Report. Philippine Journal of Obstetrics
4. Martin Chalumeau, MD, Wassim Chemaitilly, MD, Christine Trivin and Gynecology. July 2015; Vol. 39 (3): p. 28-33.
PhD, Luis Adan, MD, Gerard Breart, MD and Raja Brauner, MD.
Central Precocious Puberty in Girls: An Evidence-Based Diagnosis 15. Manish Gutch, Sukriti Kumar, Keshav Kumar Gupta, Abhinav
Tree to Predict Central Nervous System Abnormalities. Pediatrics Kumar Gupta, Syed Mohd Razi. McCune-Albright Syndrome with
Vol. 109 No. 1 January 2002. Hypophosphatemic Rickets. Journal of the ASEAN Federation of
Endocrine Societies. May 2015; Vol. 30 (1) : p. 40-43.
5. Christine Marie Caligagan-Bucad. Precocious Puberty: A Case
Report. Philippine Scientific Journal. 2002; 35(2):44-58. 16. Lee PA, Klein K, Mauras N, Neely EK, Bloch CA, Larsen L, Mattia-
Goldberg C, Chwalisz K. Efficacy and safety of leuprolide acetate
6. Ouano MML, Gamuac RC, Ortiz MH. Isosexual Precocious Puberty 3-month depot 11.25 milligrams or 30 milligrams for the
and Gelastic Seizure with Hypothalamic Mass – Case Report and treatment of central precocious puberty. J Clin Endocrinol Metab.
Review of Literature. The PCMC Journal. 1992; 0. 2012 May; 97(5):1572-80. Epub. 2012; Feb 16.

7. Mercado-Asis LB, Gallardo LT, Reyes-Rivera CT, Araza LA. McCune- 17. Silverman LA, Neely EK, Kletter GB, Lewis K, Chitra S, Terleckyj O,
Albright Syndrome. Congress Programme and Book of Abstracts. Eugster EA. Long-Term Continuous Suppression With Once-Yearly
1996; 0. Histrelin Subcutaneous Implants for the Treatment of Central
Precocious Puberty: A Final Report of a Phase 3 Multicenter Trial.
8. Torres, JRS. Precocious Puberty in a Child with an Ovarian Sex Cord J Clin Endocrinol Metab. 2015 Jun; 100(6):2354-63. Epub. 2015
Tumor. Philippine Journal of Obstetrics and Gynecology. 1999; 0. Mar 24.

9. Madona Victoria Calderon-Domingo, Ina S. Irabon, Pure Sertoli Cell 18. Fuld K, Chi C, Neely EK. A randomized trial of 1- and 3-month
Tumor of the Ovary, A Rare Cause of Isosexual Pseudoprecocious depot leuprolide doses in the treatment of central precocious
Puberty in a Two Year Old Girl. Philippine Journal of Reproductive puberty. J Pediatr. 2011; 159(6):982.
Endocrinology and Infertility. January 2009; Vol. 6 (2): p. 68-79.
19. Nurgun Kandemir, Huseyin Demirbilek, Zeynep Alev Ozon, Nazli
10. Carmela Lapitan, Liemer R Miranda. Precocious Puberty as Gonc, Ayfer Aliasifoglu. GnRH Stimulation Test in Precocious
the Presenting Feature of Leydig Cell Tumor of the Testis. Puberty: Single Sample is Adequate for Diagnosis and Dose
PCHRDPC051089. Adjustment. J Clin Res Ped Endo. 2011; 3(1):12-17.

11. Enrico Gil C. Oblepias, Margaret Joyce A. Cristi-Limson. A Rare 20. Vinicius N. Brito, Ana C Latronico, Ivo J.P. Arnhold and Bernice
Case of Isosexual Pseudoprecocious Puberty in a Patient with B. Mendonca. A Single Luteinizing Hormone Determination 2
Mixed Germ Cell Malignancy of the Ovary with Endodermal Sinus Hours After Depot Leuprolide is Useful for Therapy Monitoring
Tumor and Dysgerminoma. Philippine Journal of Obstetrics and of Gonadotropin-Dependent Precocious Puberty in Girls. The
Gynecology. October 2012; Vol. 36 (4): p. 166-174. Journal of Clinical Endocrinology & Metabolism. Novemver 2009;
89(9):4338-4342.
44 Volume 41, Number 2, PJOG March-April 2017
REFERENCES
21. Amnon, Zung, Ella Burundukov, Mira Ulman, Tamar Glaser and Zvi 27. Jung Hee Ko, Hyo Sung Lee, Jung Sub Lim, Shin Mi Kim, Jin Soon
Zadik. Monitoring Gonadotropin-Releasing Hormone Analogue Hwuang. Changes in Bone Mineral Density and Body Composition
(GnRHa) Treatment in Girls With Central Precocious Puberty: A in Children with Central Precocious Puberty and Early Puberty
Comparison of Four Methods. Pediatr Endocr Met. 2015; 28(7- Before and After One Year of Treatment with GnRH Agonist. Horm
8):885-893. Res Paediatr. 2011; 75:174-179.

22. Huseyin Demirbilek, Ayfer Alikasifoglu, Nazli E. Gonc, Alev Ozon 28. D.A. Bauann, M.A. Landolt, R. Wetterwald, J.M. Dubuis, P.C.
and Nurgun Kandemir. Assessment of Gonadotrophin suppression Sizonenko, E.A. Werder. Psychological Evaluation of Young Women
in Girls Treated with GnRH Analogue for Central Precocious After Medical Treatment for Central Precocious Puberty. Horm
Puberty; Validity of Single Luteinizing Hormone Measurement Res. 2001; 56:45-50.
After Leuprolide Acetate Injection. Clinical Endocrinology. 2012;
76, 126-130. 29. Gonul Catli, Pinar Erdem, Ahmet Anik, Ayhan Abaci, Ece Bober.
Clinical and Laboratory Findings in the Differential Diagnosis
23. Stewart L, Steinbok P, Daaboul J. Role of surgical resection in of Central Precocious Puberty and Premature Thelarche. Turk
the treatment of hypothalamic hamartomas causing precocious Pediatri Arsivi. 2015; 50:20-6.
puberty. Report of six cases. Journal Of Neurosurgery [J
Neurosurg]. 1998 Feb; Vol. 88 (2), pp. 340-5. 30. John S. Fuqua. Treatment and Outcomes of Precocious Puberty:
An Update. J Clin Enocrinol Metab. June 2013; 98(6):2198-2207.
24. Thornton P, Silverman LA, Geffner ME, Neely EK, Gould E, Danoff
TM. Review of outcomes after cessation of gonadotropin-releasing 31. Melinda Chen and Erica A. Eugster. Central Precocious Puberty:
hormone agonist treatment of girls with precocious puberty. Update on Diagnosis and Treatment. Pediatr Drugs. 2015; 17:273-
Pediatric Endocrinology Reviews: PER [Pediatr Endocrinol Rev]. 281.
2014 Mar; Vol. 11 (3), pp. 306-17.
32. P.S.N. Menon, M. Vijayakumar. Precocious Puberty – Perspectives
25. E. Kirk Neely, Peter A. Lee, Clifford A. Bloch, Lois Larsen, Di Yang, on Diagnosis and Management. Indian J Pediatr. January 2014;
CynthiaMattia-Goldberg, Kristof Chwalisz. Leuprolide Acetate 81(1):76-83.
1-Month Depot for Central Precocious Puberty: Hormonal
Suppression and Recovery International Journal of Pediatric 33. Wassim Chemaitilly, Christine Trivin, Luis Adan, Valerie Gall,
Endocrinology. Volume 2010, p. 1-9. Christian Sainte-Rose and Raja Brauner. Central Precocious
Puberty: Clinical and Laboratory Features. Clinical Endocrinology.
26. Hong K. Park, Hae S. Lee, Jung H. Ko, Il T. Hwang, Jung S. Lim and 2011; 54:289-29.
Jin S. Hwang. The effect of gonadotrophin-releasing hormone
agonisttreatment over 3 years on bone mineral density and body
composition in girls with central precocious puberty. Clinical
Endocrinology. 2012; 77:743-748.

Volume 41, Number 2, PJOG March-April 2017 45