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*The aim of treatment is to initiate the [[puberty]] progress and to merge the [[secondary sexual characteristics]] in patients.
*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 [[Adolescent|adolescents]], all of the therapy options are for them.
*Regarding that the delayed [[puberty]] involve only [[Adolescent|adolescents]], all of the therapy options are for them.
===Delayed puberty===
===Delayed puberty<ref name="PalmertDunkel2012">{{cite journal|last1=Palmert|first1=Mark R.|last2=Dunkel|first2=Leo|title=Delayed Puberty|journal=New England Journal of Medicine|volume=366|issue=5|year=2012|pages=443–453|issn=0028-4793|doi=10.1056/NEJMcp1109290}}</ref>===
*'''1 Stage 1 - Constitutional delay of growth and puberty'''
*'''1 Stage 1 - Constitutional delay of growth and puberty'''
**1.1 '''Boys'''
**1.1 '''Boys'''
Line 65: Line 65:
****Alternative regimen (1): [[Testosterone]] undecanoate 1000 mg IM every 10-14 weeks
****Alternative regimen (1): [[Testosterone]] undecanoate 1000 mg IM every 10-14 weeks
****Alternative regimen (2): [[Testosterone]] gel, apply at bed time
****Alternative regimen (2): [[Testosterone]] gel, apply at bed time
*****Started when approximately 50% adult dose has been achieved with intramuscular testosterone
*****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]]  
****Alternative regimen (3): [[hCG]] plus [[recombinant]] [[FSH]]  
*****[[hCG]]: 500 to 3000 IU SC or IM twice weekly, increased to every 2 days
*****[[hCG]]: 500 to 3000 IU SC or IM twice weekly, increased to every 2 days
Line 74: Line 73:
*****Initial dose: 2 μg PO per day for 6-12 months
*****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
*****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)
****Preferred regimen (2): 17β-[[estradiol]] (pill)
*****Initial dose: 5 μg/kg PO per day for 6-12 months
*****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
*****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]])
****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  
*****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
*****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 estrogens|Conjugated equine estrogens (CEE)]]  
****Preferred regimen (4): [[Conjugated estrogens|Conjugated equine estrogens (CEE)]]  
*****Initial dose: 0.1625 mg PO per day for 6-12 months  
*****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
*****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
****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 '''Adults'''
***2.1.1 '''Male'''
***2.1.1 '''Male'''
****Preferred regimen (1): [[Testosterone]] 200 mg IM every 2 weeks
****Preferred regimen (1): [[Testosterone]] 200 mg IM every 2 weeks
****Preferred regimen (2): Pulsatile [[GnRH]]
****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
*****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
*****Continued treatment: Increase to 25-600 ng/kg/pulse SC every 90-120 min
****Alternative regimen (3): [[hCG]] plus [[recombinant]] [[FSH]]  
****Alternative regimen (2): [[hCG]] plus [[recombinant]] [[FSH]]  
*****[[hCG]]: 500 to 3000 IU SC or IM twice weekly, increased to every 2 days
*****[[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
*****rhFSH: 75 to 225 IU SC 2-3 times weekly
***2.1.2 '''Female'''
***2.1.2 '''Female'''
****Preferred regimen (1): [[Ethinyl estradiol|Ethinyl estradiol (EE)]]  
****Preferred regimen (1): [[Ethinyl estradiol|Ethinyl estradiol (EE)]] 20 μg PO per day
*****Initial dose: 2 μg PO per day for 6-12 months
****Preferred regimen (2): 17β-[[estradiol]] (pill) 1-2 mg PO per day
*****Repeated treatment: Increase every 6-12 months to 5 μg, 10 μg, and 20 μg PO per day
****Preferred regimen (3): 17β-[[estradiol]] ([[transdermal patch]]) 50-100 μg [[transdermal]] per day
*****Adult dose 20 μg PO per day
****Preferred regimen (4): [[Conjugated estrogens|Conjugated equine estrogens (CEE)]] 0.625 mg PO per day
****Preferred regimen (2): 17β-[[estradiol]] (pill)
****Alternative regimen (1): [[Progestogens]]/[[Progestins]] 5-10 mg of [[Medroxyprogesterone acetate|medroxyprogesterone acetate (MPA)]] PO per day during the last 7 days of menstrual cycle
*****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 estrogens|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
****Alternative regimen (2): Micronized [[progesterone]] 100-200 μg PO per day
==Reference==
==Reference==

Revision as of 21:21, 11 September 2017

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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
 
 
 
 
 
 
 


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
    • 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
        • 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
        • 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
    • 2.1 Adults

Reference

  1. ↑ Blondell RD, Foster MB, Dave KC (1999). "Disorders of puberty". Am Fam Physician. 60 (1): 209–18, 223–4. PMID 10414639.
  2. ↑ Palmert, Mark R.; Dunkel, Leo (2012). "Delayed Puberty". New England Journal of Medicine. 366 (5): 443–453. doi:10.1056/NEJMcp1109290. ISSN 0028-4793.

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