Delayed Puberty, Girls

Key Features

• Indications for evaluation

  • No pubertal signs by age 13 years

  • No menarche by age 16 years

• Most common cause of delayed puberty is constitutional growth delay

• Primary hypogonadism in girls refers to a primary abnormality of the ovaries

  • Most common diagnosis in this category is Turner syndrome

  • Other types of primary ovarian insufficiency include

    • 46,XY and 46,XX gonadal dysgenesis

    • Galactosemia

    • Autoimmune ovarian failure

    • Radiation, chemotherapy

  • Premutation carriers for fragile X syndrome are also at increased risk for premature ovarian failure

• Central hypogonadism

  • Refers to a hypothalamic or pituitary deficiency of gonadotrophin-releasing hormone (GnRH) or follicle-stimulating hormone/luteinizing hormone (FSH/LH), respectively

  • Can be functional (reversible), caused by stress, undernutrition, prolactinemia, excessive exercise, or chronic illness

  • Can be permanent, which is typically associated with conditions that cause multiple pituitary hormone deficiencies, such as congenital hypopituitarism, CNS tumors, or cranial irradiation

• Isolated gonadotropin deficiency is rare but may occur in Kallmann syndrome

Clinical Findings

• History should ascertain whether and when puberty commenced, level of exercise, nutritional intake, stressors, sense of smell, symptoms of chronic illness, and family history of delayed puberty

• Past growth records should be assessed to determine whether height and weight velocity have been appropriate

• Physical examination includes body proportions, breast and genital development, and stigmata of Turner syndrome

Diagnosis

• A bone age radiograph should be obtained first

• If the bone age is lower than that consistent with pubertal onset (< 12 years in girls), evaluations should focus on finding the cause of the bone age delay

• If the patient has attained a bone age of more than 12 years and there are minimal or no signs of puberty on physical examination, FSH and LH levels will distinguish between primary ovarian failure (elevated FSH/LH) and central hypogonadism (low FSH/LH)

• If gonadotropins are elevated, a karyotype should be performed to evaluate for Turner syndrome

• Central hypogonadism is characterized by low gonadotropin levels, and evaluation is geared toward determining if the hypogonadism is functional or permanent

• Laboratory tests should be directed toward identifying chronic disease and hyperprolactinemia

• Cranial MRI may be helpful

Treatment

• Replacement therapy in hypogonadal girls begins with estrogen alone at the lowest available dosage

  • Oral preparations such as estradiol or topical patches are used

  • Cyclic estrogen–progesterone therapy is started 18–24 months later, and eventually the patient may be switched over to a birth control pill for convenience

• Progesterone therapy is needed to counteract the effects of estrogen on the uterus, as unopposed estrogen promotes endometrial hyperplasia

• Estrogen is also necessary to promote bone mineralization and prevent osteoporosis