Sex

Pubertal Delay

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Pubertal Delay, Delayed Puberty

  • See Also
  1. Sexual Development
  2. Male Tanner Stage
  3. Female Tanner Stage
  4. Hypogonadism
  • Definitions
  1. Delayed Puberty
    1. Delayed Adolescence in Phenotypic Male or Female
  2. Female Delayed Puberty
    1. Delayed Breast development
      1. No Breast development by age 13 years
      2. No Breast development 5 years after Menarche
    2. No Menses by age 15 years (Primary Amenorrhea)
  3. Male Delayed Puberty
    1. Testicular length under 2.5 cm by age 14 years
    2. Genital growth not complete five years from start
  • History
  1. Timing of secondary sexual characteristics
    1. Adult Body odor
    2. Breast Development or Testicular Development
    3. Pubic and axillary hair
    4. Acne
  2. Exposures
    1. Chemotherapy or Radiation Exposure (Hypogonadism)
    2. Head Trauma
  3. Conditions
    1. Cryptorchidism (Hypogonadism)
    2. Turner Syndrome (Webbed Neck, Short Stature)
    3. Family History of Delayed Puberty
  4. Symptoms
    1. Abdominal Pain (gastrointestinal disorders)
    2. Anosmia (Kallmann Syndrome)
    3. Galactorrhea (Hyperprolactinemia)
    4. Headache or Vision changes (intracranial pathology)
    5. Hyperthyroidism or Hypothyroidism symptoms
    6. Vasomotor symptoms in girls, such as Hot Flushes (ovarian insufficiency)
    7. Weight loss, decreased Caloric Intake, excessive Exercise (e.g. Eating Disorder)
  • Exam
  1. Constitutional
    1. Plot height, weight and Body Mass Index on growth curves
      1. Calculate Growth Velocity
      2. Calculate Midparental Height
      3. Compare Midparental Height with projected height from growth curve
        1. Abnormal if difference >10 cm
    2. Findings
      1. Growth Delay (Eating Disorder, systemic disease, Malnutrition)
      2. Short Stature (Turner stature)
      3. Tall Stature (Klienfelter syndrome)
  2. Head and Neck
    1. Thyromegaly (Hypogonadism)
  3. Genitourinary
    1. Sexual maturity staging (Tanner Stage) with delayed findings
    2. Asymmetric Testes (Orchitis, e.g. mumps)
    3. Small, firm Testes (Klinefelter Syndrome)
    4. Vagina
      1. Thin, red instead of dull pink mucosa due to lack of Estrogen exposure (Hypogonadism)
  4. Musculoskeletal
    1. Joint Pain (inflammatory condition)
  5. Neurologic
    1. Focal neurologic deficits (intracranial pathology)
  • Differential Diagnosis
  1. See Hypogonadism
  2. Hypogonadotropic Causes of Delayed Puberty
    1. Pituitary failure to secrete gonadotropins, results in decreased functional activity of ovaries or Testes
    2. Presents with new onset Growth Delay without pubertal growth spurt after normal growth in childhood
    3. Causes
      1. Endocrine Disorders
        1. Isolated Growth Hormone Deficiency
        2. Isolated Gonadotropin deficiency (e.g. Kallmann's Syndrome, Congenital adrenal hypoplasia)
        3. Hypothyroidism
        4. Diabetes Mellitus
        5. Glucocorticoid excess (Cushing Syndrome)
        6. Hyperprolactinemia
      2. Other Conditions
        1. CNS Infection, radiation, Head Trauma or Brain Tumor
        2. Prader-Willi Syndrome (Obesity, Short Stature, Mild Mental Retardation)
        3. Chronic conditions (e.g. CKD, Cystic Fibrosis, Sickle Cell Anemia, HIV Infection, Gaucher's Disease)
        4. Chronic Opioid use (86% of users)
        5. Nutritional deficiency OR extreme Energy Expenditure (e.g. Female Athlete Triad)
        6. Constitutional Delay in Growth and Development
  3. Hypergonadotropic Causes of Delayed Puberty
    1. Defective development of ovaries or Testes with decreased sex Hormones (Testosterone, Estradiol)
    2. Sex Hormone deficiency triggers increased gonadotropins (FSH, LH)
    3. Causes
      1. Chromosomal abnormalities
        1. Ovarian Dysgenesis (Turner's Syndrome, XO)
        2. Testicular Dysgenesis (Klinefelter Syndrome, XXY)
      2. Gonadal Toxins (Chemotherapy/Radiation)
      3. Enzyme defects
        1. Female: 17 alpha hydroxylase deficiency
        2. Male: 17 ketosteroid reductase deficiency
      4. Androgen Insensitivity (Testicular feminization)
      5. Miscellaneous (e.g. Mumps, Pelvic radiation
  4. Eugonadotropic Causes of Delayed Puberty
    1. Delayed Sexual Development and Growth Delay despite normal Pituitary Gonadotropin secretion
    2. Delayed Menarche causes
      1. Gonadal dysgenesis variants (residually functioning ovarian tissue)
      2. Abnormalities Mullerian duct development (absence of Uterus and possibly Vagina)
      3. Polycystic Ovarian disease
      4. Hyperprolactinemia
  • Labs (See Evaluation below)
  1. First-Line (early morning)
    1. Follicle Stimulating Hormone (FSH)
    2. Luteinizing Hormone (LH)
    3. Estradiol Level (in girls)
    4. Testosterone Level (in boys)
    5. Serum Thyroid Stimulating Hormone (TSH) with reflex to Free T4
    6. Serum Prolactin
  2. Additional Labs for Prepubertal range LH or FSH (Hypogonadotropic Hypogonadism)
    1. Insulinlike Growth Factor I
    2. Insulinlike Growth Factor Binding Protein 3
    3. Early Morning Cortisol
  3. Additional Labs for suspected chromosomal abnormalities (primary gonadal failure, Step 2b below)
    1. Consider Chromosome Analysis
  4. Additional Labs for suspected Hypogonadotropic Causes of Delayed Puberty
    1. Consider GnRH Stimulation Test (Step 2a below)
  • Imaging (See Evaluation below)
  1. Left wrist radiograph for Bone Age
  2. Consider Head MRI with and without contrast (step 2a below)
  • Evaluation
  • Step 1 - Initial Evaluation
  1. Clinical history and physical (see above)
  2. Evaluate Pubertal Milestones (See Tanner Staging)
  3. Evaluate growth chart
  4. Obtain Left Hand Bone Age Film
  1. Above Prepubertal range LH or FSH
    1. Hypergonadotropic Hypogonadism (5-10% of boys, 25% of girls)
    2. Repeat FSH and LH
    3. Obtain karyotype
    4. Refer to pediatric endocrinology
  2. Pubertal range LH or FSH
    1. Constitutional delay of growth and Puberty (see above)
    2. Repeat measurements in 1-3 months
  3. Prepubertal range LH or FSH
    1. Persistent Hypogonadotropic Hypogonadism (10% of boys, 20% of girls)
      1. Consider underlying causes
        1. Dysmorphic features (e.g. Turner Syndrome)
        2. Radiation Exposure
        3. Head Trauma
        4. Brain Tumor
      2. Evaluation
        1. Pediatric Endocrinology referral
        2. MRI Brain with and without contrast
        3. Additional Labs
          1. Insulinlike Growth Factor I
          2. Insulinlike Growth Factor Binding Protein 3
          3. Early Morning Cortisol
    2. Constitutional delay of growth and Puberty (60% of boys, 30% of girls)
      1. Most common cause of Delayed Puberty (diagnosis of exclusion)
      2. Consistent findings
        1. Delayed Bone Age
        2. Family History of Delayed Puberty (75% have parental Pubertal Delay)
      3. Consider Jump Start Therapy
        1. Indications
          1. Girls over age 13 years and boys over 14 years
          2. No spontaneous Puberty after 6 months of observation
        2. Example protocol for boys
          1. Testosterone cypionate or enanthate 50 -100 mg IM per month
        3. Example protocol for girls
          1. Estradiol 6.2 mcg (25% of 25 mcg patch) applied to skin overnight for 3-6 months
      4. Consider referral to pediatric endocrinology
        1. No pubertal progression after 4-6 months after jump start therapy
    3. Functional Hypogonadotropic Hypogonadism (20% of boys, 20% of girls)
      1. Malnutrition or chronic disease (e.g. Celiac Disease, Diabetes Mellitus, Thyroid disease)
  • Evaluation
  • Step 3a - Unremarkable Evaluation in Step 1
  1. Findings
    1. Unremarkable exam except Delayed Puberty
    2. Patient has not yet experienced growth spurt
    3. Bone Age less than Chronological Age
  2. Differential Diagnosis
    1. Constitutional delay
    2. See Hypogonadotropic Causes of Delayed Puberty
    3. Primary gonadal failure
    4. Serious athletic training
  3. Further evaluation
    1. Observation
    2. Laboratory testing as above
    3. Imaging evaluation as above
  4. Management
    1. Counseling and reassurance
    2. Consider sex Hormone Replacement for some patients
  • Evaluation
  • Step 3b - Suspect Chromosomal Abnormality
  1. Findings
    1. Abnormal exam suggests chromosomal abnormality
    2. Bone Age may be less than Chronological Age
  2. Diagnosis
    1. Girls: Turner's Syndrome
    2. Boys: Klinefelter's Syndrome
    3. Noonan's Syndrome
  3. Further evaluation
    1. Chromosome analysis
  4. Management
    1. Counseling
    2. Sex Hormone Replacement
    3. Oophorectomy in Turner's Syndrome (malignancy risk)
  • Evaluation
  • Step 3c - Suspect Chronic Disease in Step 1
  1. Findings suggestive of chronic disease
    1. Overt chronic illness signs or symptoms
    2. Short Stature
    3. Slow growth rate
    4. Bone Age less than Chronological Age
  2. Differential Diagnosis
    1. Anorexia Nervosa
    2. Malnutrition
    3. Kallmann's Syndrome
      1. Hypopituitarism
      2. Anosmia or Hyposmia
      3. Hypogonadotropic Hypogonadism
    4. Iatrogenic
    5. Hypopituitarism
      1. Findings
        1. Growth failure
        2. Hypothyroidism
        3. Adrenal Insufficiency
        4. Diabetes Insipidus
        5. Delayed Puberty
      2. Causes
        1. Intracranial lesion (esp. involving pituitary)
        2. Infection of Pituitary Gland (e.g. Tuberculosis)
        3. Head Injury
    6. Chronic Systemic Illness
      1. Malignancy
      2. Chronic infection
      3. Chronic metabolic disease
      4. Celiac Disease
      5. Inflammatory Bowel Disease
      6. Cystic Fibrosis
      7. Thyroid disease
      8. Diabetes Mellitus
  3. Further evaluation
    1. Work-up suspected underlying chronic disease
  • References
  1. Blondell (1999) Am Fam Physician 60:209-24 [PubMed]
  2. Brown (2025) Am Fam Physician 112(5): 513-21 [PubMed]
  3. Foster (1992) Obstet Gynecol Clin North Am 19:59-70 [PubMed]
  4. Klein (2017) Am Fam Physician 96(9): 590-99 [PubMed]
  5. Styne (1997) Pediatr Clin North Am 44(2):505-29 [PubMed]