What is the recommended treatment for Turner's syndrome?

Treatment of Turner's Syndrome: Hormone Replacement Therapy and Growth Hormone

For patients with Turner's syndrome, the recommended treatment includes early initiation of growth hormone therapy followed by hormone replacement therapy with transdermal 17β-estradiol for pubertal induction starting at age 11-12 years. 1, 2

Growth Hormone Therapy

• Growth hormone (GH) therapy should be initiated as soon as growth failure is demonstrated 3
• Early initiation of GH therapy accounts for 44% of variance in height outcomes 3
• Benefits of GH therapy:
  • Increases final adult height
  • Allows for age-appropriate puberty while still achieving normal adult stature
  • Improves quality of life 4

Hormone Replacement Therapy (HRT)

Timing and Approach

• Pubertal induction should begin between ages 11-12 years 1, 2
• HRT should mimic the physiological course of puberty in tempo and magnitude
• Pubertal induction should be carried out over 2-3 years 1
• Early HRT initiation results in:
  • Better psychosocial and psychosexual adaptation
  • Larger uterine volume
  • Improved bone mass accrual
  • Reduced risk of future miscarriages 1

Recommended Formulations

• First choice: Transdermal 17β-estradiol 1, 5
  • Provides more physiological estrogen delivery
  • Better effects on bone mineral density
  • More favorable impact on lipid profile
  • Better uterine development
  • Does not suppress IGF-I levels or GH effects 3

Dosing Schedule for Pubertal Induction

Time period	Transdermal 17β-estradiol	Oral 17β-estradiol
0-6 months	1/8 patch weekly or 1/4 patch for 3-4 days/week	0.5 mg every other day
6-12 months	1/4 patch weekly	0.5 mg every other day
12-18 months	1/2 patch for 3-4 days, 1/4 patch remaining days	0.5 mg daily
18-24 months	1/2 patch weekly	0.5 mg and 1 mg alternating days
>24 months	Full patch weekly	1 mg daily

1, 2

Progestin Addition

• Add progestin after at least 2 years of estrogen therapy or when breakthrough bleeding occurs
• Recommended options:
  • Micronized progesterone (100-200 mg/day for 12-14 days of the month)
  • Dydrogesterone (5-10 mg/day for 12-14 days of the month) 2

Monitoring and Follow-up

• Initial evaluation at 3-6 months after starting therapy
• Annual clinical review thereafter, monitoring:
  • Symptom control
  • Compliance
  • Blood pressure
  • Weight 2
• Annual cardiovascular risk assessment:
  • Blood pressure
  • Smoking status
  • Weight
  • Lipid profile
  • Fasting glucose
  • HbA1c 2
• Cardiovascular imaging based on risk factors:
  • Transthoracic echocardiography
  • Cardiovascular MRI or CT if inadequate visualization of ascending aorta 1

Adjuvant Therapies

• Oxandrolone may be considered as adjuvant therapy with GH
  • Meta-analysis shows positive effect on adult height when combined with GH therapy 6
  • Consider for patients with delayed diagnosis or poor growth response

Potential Complications and Management

• Cardiovascular risks:
  • Higher risk of aortic dissection, especially with bicuspid aortic valve
  • Consider beta-blockers and/or ARBs for aortic aneurysm prevention 1
• Bone health:
  • Early estrogen replacement crucial for bone mass accrual
  • 90% of peak bone mass achieved by age 18 1
• Metabolic issues:
  • Monitor for diabetes mellitus
  • Screen for thyroid disorders 7

Important Caveats

• Oral estrogens decrease IGF-I levels and suppress GH effects, potentially compromising growth outcomes
• Delaying estrogen replacement may be deleterious to bone and uterine health
• Conjugated estrogens should be avoided 5
• Ethinyl estradiol should only be used when other options are unavailable 5

By following this comprehensive approach to treatment, patients with Turner's syndrome can achieve improved height outcomes, appropriate pubertal development, and better long-term health outcomes.