- Intrauterine environment to rule out teratogen
- Chronologic pubertal development, including growth spurt, pubarche, and thelarche
- Dietary habits or preferences, body weight perception and changes, psychosocial stress
- Family history: pubertal delay, menstrual patterns
- Social skills, school achievement
- Physical examination
- External genitalia maturity, virilization, pubic hair distribution
- Internal genitalia, inguinal hernial sites
- Pubertal features: degree of pubic hair and breast development, galactorrhea
- Skin: consistency, acne, hair distribution, bruising and pigmentation
- Growth: height and weight
- Diagnostic procedures
Steps in the assessment of primary amenorrhea.
- Ultrasound may be used to assess internal genitalia when office examination is difficult. It will also rule out flow-tract abnormalities and assess adnexal status.
- Progesterone withdrawal: Provera 10 mg PO for 5 days (or 100 mg progesterone in oil); bleeding within 1 week indicates significant endogenous estrogen and normal outflow tract and a likely diagnosis of anovulation.
- Karyotyping (or buccal smear chromatin) should be ordered, and if necessary human Y antigen assay (occasionally leukocyte karyotyping does not detect all forms of mosaicism).
- FSH + LH (high levels = ovarian failure), thyroid-stimulating hormone (TSH), and prolactin are frequently also needed and can be used to assess pituitary status.
- Ambiguous genitalia.
- With Y chromosome presence, a gonadal biopsy is needed (differential diagnosis male pseudohermaphrodite, mixed gonadal dysgenesis, or true hermaphrodite).
- Without Y chromosome, consider virilizing tumors or 17-hydroxylase deficiency (late onset may require ACTH stimulation test).
- Elevated prolactin (>50 ng/mL) warrants magnetic resonance imaging (MRI) or a computed tomography (CT) scan.
- The cause should be treated if possible (i.e., dexamethasone for 17-OH deficiency).
- Phenotypic status should be attained with plastic surgery (i.e., clitoral recession for clitoromegaly and neovagina for blind nonfunctional vaginal pouches).
Fertility should be achieved when possible and desired (i.e., Parlodel for pituitary microadenomas, gonadotrophins for Kallmann’s syndrome, in vitro fertilization for vaginal agenesis, donor eggs for gonadal dysgenesis, etc.).
- Excision of gonads in Y chromosome-positive individuals should be performed because of the increased risk of germ cell tumors. In testicular feminization, surgeons should wait until after puberty to allow normal long bone development. In others, surgery should occur before puberty to minimize risk of malignancy and virilization.
Estrogen replacement therapy can be used for hypoestrogenic states.