Delayed Puberty –

Delayed Puberty


Delayed Puberty

Delayed puberty is clinically outlined because the absence or incomplete growth of secondary sexual traits by an age at which 95% of the inhabitants begins to mature sexually.

0For ladies, a delay in puberty is outlined as an absence of breast bud growth by age 13 or absence of menarche inside 3 yr of thelarche; for boys, delay is outlined as absence of testicular enlargement by age 14.


  • Pubertal delay

Epidemiology & Demographics


The general prevalence for kids presenting with delayed puberty is unknown. The prevalence of congenital hypogonadotropic hypogonadism, nevertheless, is estimated at 1 out of 4000 to 10,000 males and is reported to be twofold to fivefold much less frequent in females.


Constitutional delay of progress and puberty (CDGP) is usually inherited in an autosomal dominant style, with at the very least one guardian with a historical past of delayed puberty. Nevertheless, underlying genetic mechanisms are advanced.

Congenital hypogonadotropic hypogonadism may be both sporadic or familial and has a stronger genetic predisposition. These cases are linked to both defects in gonadotropin-releasing hormone (GnRH) biosynthesis, secretion, poor maturation, or lack of GnRH perform itself.

Hypergonadotropic hypogonadism from gonadal dysgenesis is commonly a results of underlying aneuploidy of intercourse chromosomes. Turner and Klinefelter syndromes are two well-known examples of this.

The beneath desk offers extra particulars on the genetic etiologies concerned in delayed puberty.

Causes of Delayed Puberty Different Than Constitutional Delay of Development and Puberty

Tailored from Sperling MA: Sperling pediatric endocrinology, ed 4, Philadelphia, 2014, Elsevier, 697-733.

Hypergonadotropic Hypogonadism Everlasting Hypogonadotropic Hypogonadism Useful Hypogonadotropic Hypogonadism
Genetic syndromes
 Noonan syndrome and associated issues
Gonadal dysgenesis
Vanishing testes syndrome
Trauma/testicular torsion
Chemotherapy/radiation remedy
Gonadal an infection
 Mumps, Coxsackie
Autoimmune orchitis
Defects in steroidogenesis
 5-alpha reductase deficiency (SR5A2)
 17, 20 lyase deficiency (CYP17A1)
 Congenital lipoid adrenal hyperplasia (StAR)
 17-hydroxysteroid dehydrogenase deficiency (HSD17B3)
Androgen insensitivity
Sertoli cell solely syndrome (Del Castillo syndrome)
CNS tumors/infiltrative illnesses
 Langerhans cell histiocytosis
Rathke’s pouch cyst
Genetic defects
 Kallmann syndrome (KAL1, FGFR1, PROK2, PROKR2, FGF8, HS6ST1, and CHD7)
—Remoted hypogonadotropic hypogonadism (KAL1, GNRHRGNRH1GPR54FGFR1FGF8PROK2PROKR2TAC3TACR3, HS6ST1NELF, and CHD7)
 HPG axis growth (DAX1, SF-1HESX-1LHX3, and PROP-1)
 Weight problems and hypogonadotropic hypogonadism (LEP, LEPR, and PC1) syndromes
Gaucher illness
Postcentral nervous system an infection
Midline defects
 Septo-optic dysplasia
 Congenital hypopituitarism
Chemotherapy/radiation remedy
Systemic sickness/situations
 Cystic fibrosis
 Bronchial asthma
 Inflammatory bowel illness
 Celiac illness
 Juvenile rheumatoid arthritis
 Anorexia nervosa/bulimia
 Sickle cell illness
 Power renal illness
 Diabetes mellitus
 Development hormone deficiency
 Cushing syndrome
Extreme train

CNS, Central nervous system.

Bodily Findings & Scientific Presentation

  • •Women with pubertal delay have an absence of breast growth by age 13.
  • •Boys with pubertal delay can have testes <2.5 cm or <4 ml by age 14. Different indicators in boys might embody cryptorchidism, hypospadias, and micropenis.
  • •Quick stature and/or lack of pubertal progress spurt is commonly famous, particularly in CDGP.
  • •Anosmia (in Kallman syndrome); webbed neck, extensively spaced nipples, elevated pigmented nevi (in Turner syndrome); and low IQ, gynecomastia in males, and irregular facial/pubic hair distribution (in Klinefelter syndrome) are generally current with another causes of pubertal delay.
  • •Markers of persistent illness, dietary standing, neurologic abnormalities, and thyroid abnormalities needs to be assessed as effectively.


Causes for pubertal delay may be separated into 4 classes (from most to least frequent):

  • 1.CDGP: A self-limited delay in puberty that’s extra frequent in boys than in ladies (60% vs. 30%). Sufferers usually have progress deceleration through the first few yr of life adopted by a standard progress fee (4 to six cm per yr) alongside decrease top percentiles. Pubertal progress spurt is commonly delayed, and spontaneous pubertal onset happens by age 18 typically.
  • 2.Useful hypogonadotropic hypogonadism (FHH): It is a transient type of delayed puberty brought on by delayed maturation of hypothalamic-pituitary-gonadal (HPG) axis. FHH could also be secondary to malnutrition from extreme weight reduction (beneath the extent of 80% of splendid physique weight), persistent illness, extreme train, or stress resulting in elevated cortisol and proinflammatory cytokines. Kids with FHH have a decrease than regular progress fee for chronologic age and low ranges of gonadotropins and intercourse steroids. As soon as the illness state and/or diet stage is corrected, puberty is commonly reinstated.
  • 3.Hypergonadotropic hypogonadism: That is brought on by major gonadal failure; natural dysfunctions that end in gonadal failure regardless of sufficient hypothalamic-pituitary perform. Serum gonadotropins are elevated by the point of puberty with low intercourse steroids, resulting in absence or developmental arrest of secondary intercourse traits.
  • 4.Everlasting hypogonadotropic hypogonadism (PHH): This class could also be congenital (secondary to genetic defects) or acquired, resulting in suppression of the HPG axis. Serum gonadotropins are often low with low ranges of intercourse steroids, resulting in the absence or developmental arrest of secondary intercourse traits.


  • •Given the in depth differential analysis for pubertal delay, a scientific and targeted method is important. A cautious historical past, together with household and social historical past, can determine consuming and train habits, persistent sicknesses, weight reduction or poor weight acquire, modifications in bowel habits, and parental historical past of pubertal delay.
  • •Auxologic measurement ought to embody top and weight, a progress chart to evaluate progress velocity, and calculation of the sex-adjusted mid-parental top

Laboratory Exams

  • •Testing serum luteinizing hormone, follicle-stimulating hormone, testosterone (in males), and estradiol (in females) may help set up delayed puberty in addition to distinguish between issues of hypogonadotropic and hypergonadotropic hypogonadism. Laboratory exams alone might not be capable to distinguish between CDGP and PHH, though a low inhibin B stage in males might level to a analysis of PHH over CDGP.
  • •Full blood rely, full metabolic panel, erythrocyte sedimentation fee, thyroid-stimulating hormone, free thyroxine, prolactin, testosterone (males), estradiol (females), cortisol, and insulin-like progress issue 1 needs to be drawn when indicated.
  • •Chromosomal evaluation is indicated if there’s suspicion of gonadal dysgenesis.

Imaging Research

Bone age skeletal radiograph of the left hand and wrist determines skeletal age, which may be delayed in kids with CDGP and PHH. MRI of the top needs to be thought of if there’s excessive scientific suspicion for intracranial tumors or structural abnormalities. Pelvic ultrasound may be useful in detecting intraabdominal testes and for evaluating pelvic anatomy and maturity.


  • •CDGP may be managed with reassurance and longitudinal assessments. Nevertheless, short-term remedy with both low-dose testosterone (in boys) or estrogen (in ladies) may help to hasten puberty and enhance psychological well-being. In boys, intramuscular depot testosterone in doses of fifty to 100 mg each 4 wk for 3 to six mo is taken into account secure and subsequently mostly used. For ladies, there are 4 choices for the induction of puberty: Oral ethinylestradiol, oral conjugated estrogens, and oral or transdermal types of 17β-estradiol.
  • •Malnutrition and persistent illness can greatest be handled by correcting the underlying trigger. A brief (3-6 months) therapy course, as beforehand described, could also be indicated for kids with psychosocial difficulties.
  • •Everlasting causes of pubertal delay are handled as with CDGP, however dosages are step by step elevated to grownup doses over 3 to 4 yr. In ladies, cyclic progesterone is added roughly 2 yr from the beginning of estrogen remedy, or sooner, on the time of menarche.
  • •The beneath desk summarizes hormonal substitution remedy in hypogonadism.

Hormonal Substitution Remedy in Hypogonadism

From Melmed S et al: Williams textbook of endocrinology, ed 14, Philadelphia, 2019, Elsevier, 2019.

•Purpose: To approximate regular adolescent growth when analysis is established•Preliminary remedy: At 13 yr of age, testosterone enanthate (or different long-acting testosterone ester) 50 mg IM each month for ∼9 mo (6-12 mo)•Over the subsequent 3-4 yr: Progressively improve dose to grownup alternative dose of 200 mg q2-3wk•Testosterone gel is coming into widespread use, as mentioned within the textual content•Start alternative remedy in boys with suspected hypogonadotropic hypogonadism by bone age ≤14 yr•To induce fertility at acceptable time in hypogonadotropic hypogonadism: Pulsatile GnRH or FSH and hCG remedy
With a firmly established analysis of hypogonadism (e.g., ladies with 45,X gonadal dysgenesis), start hormonal substitution remedy at age 12-13 yr•Purpose: To approximate regular adolescent growth•Preliminary remedy: Ethinylestradiol 5 mg PO or conjugated estrogen 0.3 mg (or much less) PO each day for 4-6 mo or ideally estradiol transdermally•After 6 mo of remedy (or sooner if breakthrough bleeding happens), start cyclic remedy:1.Estrogen: First 21 days of month2.Progestogen (e.g., medroxyprogesterone acetate 5 mg PO) days 12-21 monthly3.Progressively improve dose of estrogen over subsequent 2-3 yr to conjugated estrogen 0.6-1.25 mg or ethinylestradiol 10-20 mg each day for first 21 days of month, or estradiol patch•In hypogonadotropic hypogonadism, to induce ovulation at acceptable time: Pulsatile GnRH or FSH and hCG remedy

FSH, Follicle-stimulating hormone; GnRH, gonadotropin-releasing hormone; hCG, human chorionic gonadotropin; PO, orally; q, each.


Pediatric endocrinology

Affected person & Household Training

Search Extra Data

  • Harrington J., Palmert M.R.: Scientific evaluation: distinguishing constitutional delay of progress and puberty from remoted hypogonadotropic hypogonadism: essential appraisal of obtainable diagnostic exams. J Clin Endocrinol Metab 2012; 97: pp. 3056-3067.
  • Howard S.R., Dunkel L.: Delayed puberty-phenotypic range, molecular genetic mechanisms, and up to date discoveries [published correction appears in Endocr Rev. 2020 Feb 1;41(1)]. Endocr Rev 2019; 40 (5): pp. 1285-1317.
  • Lazar L., Phillip M.: Pubertal issues and bone maturation. Endocrinol Metab Clin North Am 2012; 41 (4): pp. 805-825.
  • Palmert M.R., Dunkel L.: Delayed puberty. N Engl J Med 2012; 166: pp. 443-453.
  • Wei C., Crowne E.C.: Latest advances within the understanding and administration of delayed puberty. Arch Dis Youngster 2016; 101 (5): pp. 481-488.