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[2]
- 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
- Preferred regimen (1): Testosterone, not indicated before 14 years of age
- 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
- Preferred regimen (1): Ethinyl estradiol (EE)
- 1.1 Boys
- 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
- 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
- Preferred regimen (1): Testosterone, can be started after 12 years of age
- 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
- 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
- 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: Increase every 6-12 months to 0.325, 0.45, and 0.625 mg PO per day
- Alternative regimen (1): Progestogens/Progestins in various formulations, only if treatment last more than 12 months
- Preferred regimen (1): Ethinyl estradiol (EE)
- 2.1.1 Boys
- 2.1 Adults
- 2.1.1 Male
- Preferred regimen (1): Testosterone 200 mg IM every 2 weeks
- Preferred regimen (2): Testosterone undecanoate 1000 mg IM every 10-14 weeks
- Preferred regimen (3): Testosterone gel 50-80 mg transdermal per day
- Alternative regimen (1): 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 (2): 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) 20 μg PO per day
- Preferred regimen (2): 17β-estradiol (pill) 1-2 mg PO per day
- Preferred regimen (3): 17β-estradiol (transdermal patch) 50-100 μg transdermal per day
- Preferred regimen (4): Conjugated equine estrogens (CEE) 0.625 mg PO per day
- Alternative regimen (1): Progestogens/Progestins 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
- 2.1.1 Male
- 2.1 Pediatric