Delayed puberty medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:

Overview

Medical Therapy

General approach to pharmacological medical therapy for delayed puberty^[1]

Delayed Puberty

Initial assessment

• Clinical history
• Physical examinations
• Pubertal phenotype
• Left wrist radiograph for bone age

Unremarkable

Abnormal

Chronic disease

• Delayed puberty
• Lack of growth spurt
• Bone age delayed upon chronological age

• Possibility of chromosomal disorder
• Bone age may delayed

• Chronic disease
• Decreased growth rate or short stature
• Bone age delayed upon chronological age

Diagnosis:
• Constitutional delay of growth and puberty (CDGP)
• Gonadotropin deficiency
• Primary gonadal failure
• Extreme athletic exercise

Diagnosis:
Girls:
• Turner syndrome
Boys:
• Klinefelter syndrome

Diagnosis:
• Hypopituitarism
• Chronic systemic diseases
• Anorexia nervosa
• Malnutrition
• Kallman syndrome
• Iatrogenic

Actions:
• Evaluation hypothalamus-pituitary-gonadal axis
• Consider an MRI to exclude the CNS lesions

Actions:
• Chromosome analysis (Karyotyping)

Actions:
• Upon the underlying disease

Treatment:
1. Psychologic support
2. Observation
3. Sex hormone replacement therapy

Treatment:
1. Psychologic support
2. Sex hormone replacement
3. Excision of ovaries in Turner syndrome because of risk of malignancy

Generally, the main pharmacological medical therapy for delayed puberty is sex hormone replacement therapy.
The aim of treatment is to initiate the puberty progress and to merge the secondary sexual characteristics in patients.
Regarding that the delayed puberty involve only adolescents, all of the therapy options are for them.

Delayed puberty

1 Stage 1 - Constitutional delay of growth and puberty
- 1.1 Boys
  - Preferred regimen (1): Testosterone, not indicated before 14 years of age
    - Initial dose: 50-100 mg IM every 4 weeks for 3-6 months
    - Repeated treatment: To add 25-50 mg in dose (maximum, 100 mg per dose)
  - Preferred regimen (2): Letrozole 2.5 mg PO per day
  - Preferred regimen (3): Anastozole 1mg PO per day
- 1.2 Girls
  - Preferred regimen (1): Ethinyl estradiol (EE)
    - Initial dose: 2 μg PO per day for 6-12 months
    - Repeated treatment: Increase to 5 μg PO per day after 6-12 months
  - Preferred regimen (2): 17β-estradiol (pill)
    - Initial dose: 5 μg/kg PO per day for 6-12 months
    - Repeated treatment: Increase to 10 μg/kg PO per day after 6-12 months
  - Preferred regimen (3): 17β-estradiol (transdermal patch)
    - Initial dose: 3.1-6.2 μg (1/8-1/4 of 25 μg patch) per day for 6 months
    - Repeated treatment: Increase 3.1-6.2 μg (1/8-1/4 of 25 μg patch) per day every 6 months
  - Preferred regimen (4): Conjugated equine estrogens (CEE)
    - Initial dose: 0.1625 mg PO per day for 6-12 months
    - Repeated treatment: Titrating to 0.325 mg PO per day after 6-12 months
  - Alternative regimen (1): Progestogens/Progestins in various formulations, only if treatment last more than 12 months

2 Stage 2 - Hypogonadism
- 2.1 Pediatric
  - 2.1.1 Boys
    - Preferred regimen (1): Testosterone, can be started after 12 years of age
      - Initial dose of 50 mg IM per month
      - Increase with 50 mg in dose IM every 6-12 months
      - After reaching 100-150 mg IM monthly, decrease interval to every 2 weeks
    - Preferred regimen (2): Pulsatile GnRH
      - Initial dose: 5-25 ng/kg/pulse SC every 90-120 min
      - Continued treatment: Increase to 25-600 ng/kg/pulse SC every 90-120 min
    - Alternative regimen (1): Testosterone undecanoate 1000 mg IM every 10-14 weeks
    - Alternative regimen (2): Testosterone gel, apply at bed time
      - Started when approximately 50% adult dose has been achieved with intramuscular testosterone
      - Adult dose 50-80 mg transdermal per day
    - Alternative regimen (3): hCG plus recombinant FSH
      - hCG: 500 to 3000 IU SC or IM twice weekly, increased to every 2 days
      - rhFSH: 75 to 225 IU SC 2-3 times weekly
  - 2.1.2 Girls
    - Preferred regimen (1): Ethinyl estradiol (EE)
      - Initial dose: 2 μg PO per day for 6-12 months
      - Repeated treatment: Increase every 6-12 months to 5 μg, 10 μg, and 20 μg PO per day
      - Adult dose 20 μg PO per day
    - Preferred regimen (2): 17β-estradiol (pill)
      - Initial dose: 5 μg/kg PO per day for 6-12 months
      - Repeated treatment: Increase to 10 μg/kg PO per day after 6-12 months, then to 15 μg/kg, and to 20μg/kg per day
      - Adult dose 1-2 mg PO per day
    - Preferred regimen (3): 17β-estradiol (transdermal patch)
      - Initial dose: 3.1-6.2 μg (1/8-1/4 of 25 μg patch) per day for 6 months
      - Repeated treatment: Increase 3.1-6.2 μg (1/8-1/4 of 25 μg patch) per day every 6 months
      - Adult dose 50-100 μg transdermal per day
    - Preferred regimen (4): Conjugated equine estrogens (CEE)
      - Initial dose: 0.1625 mg PO per day for 6-12 months
      - Repeated treatment: increase every 6-12 months to 0.325, 0.45, and 0.625 mg PO per day
      - Adult dose 0.625 mg PO per day
    - Alternative regimen (1): Progestogens/Progestins in various formulations, only if treatment last more than 12 months
    - Adult dose 5-10 mg of medroxyprogesterone acetate (MPA) PO per day during the last 7 days of menstrual cycle.
    - Alternative regimen (2): Micronized progesterone 100-200 μg PO per day
- 2.1 Adults
  - 2.1.1 Male
    - Preferred regimen (1): Testosterone 200 mg IM every 2 weeks
    - Preferred regimen (2): Pulsatile GnRH
      - Initial dose: 5-25 ng/kg/pulse SC every 90-120 min
      - Continued treatment: Increase to 25-600 ng/kg/pulse SC every 90-120 min
    - Alternative regimen (3): hCG plus recombinant FSH
      - hCG: 500 to 3000 IU SC or IM twice weekly, increased to every 2 days
      - rhFSH: 75 to 225 IU SC 2-3 times weekly
  - 2.1.2 Female
    - Preferred regimen (1): Ethinyl estradiol (EE)
      - Initial dose: 2 μg PO per day for 6-12 months
      - Repeated treatment: Increase every 6-12 months to 5 μg, 10 μg, and 20 μg PO per day
      - Adult dose 20 μg PO per day
    - Preferred regimen (2): 17β-estradiol (pill)
      - Initial dose: 5 μg/kg PO per day for 6-12 months
      - Repeated treatment: Increase to 10 μg/kg PO per day after 6-12 months, then to 15 μg/kg, and to 20μg/kg per day
      - Adult dose 1-2 mg PO per day
    - Preferred regimen (3): 17β-estradiol (transdermal patch)
      - Initial dose: 3.1-6.2 μg (1/8-1/4 of 25 μg patch) per day for 6 months
      - Repeated treatment: Increase 3.1-6.2 μg (1/8-1/4 of 25 μg patch) per day every 6 months
      - Adult dose 50-100 μg transdermal per day
    - Preferred regimen (4): Conjugated equine estrogens (CEE)
      - Initial dose: 0.1625 mg PO per day for 6-12 months
      - Repeated treatment: increase every 6-12 months to 0.325, 0.45, and 0.625 mg PO per day
      - Adult dose 0.625 mg PO per day
    - Alternative regimen (1): Progestogens/Progestins in various formulations, only if treatment last more than 12 months
    - Adult dose 5-10 mg of medroxyprogesterone acetate (MPA) PO per day during the last 7 days of menstrual cycle.
    - Alternative regimen (2): Micronized progesterone 100-200 μg PO per day

Reference

↑ Blondell RD, Foster MB, Dave KC (1999). "Disorders of puberty". Am Fam Physician. 60 (1): 209–18, 223–4. PMID 10414639.

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[pmid10414639-1] Blondell RD, Foster MB, Dave KC (1999). "Disorders of puberty". Am Fam Physician. 60 (1): 209–18, 223–4. PMID 10414639.

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