Late female puberty

Specialty: Gynecology and breast.

• Absence of female pubertal development
• pubertal delay in girls
• female sexual infantilism

Why it occurs

• Hypergonadotropic hypogonadism due to primary ovarian failure (Turner syndrome 45,X0 is the most common genetic cause, pure gonadal dysgenesis, or post-infantile chemotherapy damage)
• Functional hypogonadotropic hypogonadism (constitutional delay in growth and development, severe malnutrition, anorexia nervosa, high-performance athletes, chronic diseases)
• Congenital hypogonadotropic hypogonadism (Kallmann syndrome with associated anosmia, panhypopituitarism)
• Severe thyroid disorders or undetected hyperprolactinemia

Initial workup

Basal serum determination of FSH, LH, Estradiol, TSH, free T4, Prolactin and antithyroid antibodies. Peripheral blood karyotype (required if FSH is elevated to rule out Turner mosaicism or dysgenesis). Wrist x-ray to assess bone age. Abdominal pelvic ultrasound to confirm presence of uterus and breasts (infantile or absent uterus suggestive of Müllerian/Rokitansky agenesis if FSH is normal). Brain MRI of the sellar region.

Standard management

• Estrogen therapy at low initial doses to induce the development of secondary sexual characteristics without prematurely accelerating epiphyseal fusion: Conjugated estrogens 0.3 mg/day orally or transdermal 17-beta-estradiol in doses of 12.5-25 micrograms/day in patch, with progressive increases over 1 to 2 years. Once the uterus has developed and after 12-18 months of estrogen therapy, micronized progesterone 100-200 mg/day orally during the last 12 days of the cycle is associated to induce regular bleeding and prevent endometrial hyperplasia (note: therapy must be individualized).