What tests should be done for delayed menarche (first menstrual cycle)?

Delayed Menarche: Diagnostic Testing Algorithm

For delayed menarche (no menstruation by age 16), begin with pregnancy testing, followed by FSH, LH, estradiol, TSH, and prolactin levels, then proceed to pelvic ultrasound if hormonal abnormalities are detected or anatomic causes are suspected. 1, 2

Initial Clinical Evaluation

Detailed menstrual and pubertal history:

• Age and presence/absence of secondary sexual characteristics (breast development, pubic hair) using Tanner staging 3, 1
• No signs of puberty by age 13 or primary amenorrhea by age 16 requires immediate evaluation 3
• Failure of pubertal progression for ≥12 months warrants investigation 3

Physical examination must include:

• Height, weight, and BMI calculation 3, 1
• Thyroid examination for enlargement or nodules 3, 1
• Assessment of breast and pubic hair development (Tanner staging) 3, 4
• Pelvic examination to assess for anatomic abnormalities, particularly in patients with normal pubertal development 5

Medical history focus:

• Family history of delayed puberty or genetic conditions 4
• Weight changes, eating patterns, and exercise habits to identify Female Athlete Triad or disordered eating 1
• Medication use, particularly antipsychotics, antiepileptics, or hormonal agents 1
• History of chemotherapy or pelvic radiation exposure 3

Laboratory Testing Algorithm

First-line hormonal assessment:

• Pregnancy test - mandatory first step to exclude pregnancy 1, 2
• FSH and LH levels - distinguish between primary ovarian insufficiency (elevated FSH >40 mIU/mL) and hypothalamic/pituitary causes (low/normal FSH) 1, 2
• Estradiol level - low levels suggest hypoestrogenism from hypothalamic amenorrhea or ovarian failure 1
• TSH - screen for thyroid disorders 1, 2
• Prolactin - evaluate for hyperprolactinemia 1, 2

Interpretation of FSH results:

• Elevated FSH (>40 mIU/mL) indicates primary ovarian insufficiency and requires repeat testing 4 weeks later for confirmation (two elevated values required) 1
• If FSH elevated and age <40 years, obtain karyotype to identify Turner syndrome or chromosomal abnormalities 1, 2
• LH/FSH ratio >2 suggests polycystic ovary syndrome 1

Imaging Studies

Pelvic ultrasonography indications:

• When hormonal tests suggest ovarian pathology 1
• In patients with normal pubertal development to rule out anatomic obstruction (transverse vaginal septum, imperforate hymen) 5
• Transvaginal ultrasound is more sensitive than transabdominal for structural abnormalities 1
• Assess endometrial thickness: thin (<5 mm) suggests estrogen deficiency; thick (>8 mm) suggests chronic anovulation 1

Brain MRI indications:

• Failure to initiate puberty by age 13 with low FSH/LH 4
• Neurological symptoms (severe headaches, visual changes, seizures) 4
• Central precocious puberty evaluation requires MRI of hypothalamic-pituitary axis 4

Referral Criteria

Immediate referral to pediatric endocrinology/gynecology:

• No signs of puberty by age 13 3
• Primary amenorrhea by age 16 3
• Failure of pubertal progression for ≥12 months 3
• Confirmed primary ovarian insufficiency requiring sex steroid replacement therapy 3

Critical Pitfalls to Avoid

• Do not assume irregular menses in adolescents are always physiologic immaturity of the hypothalamic-pituitary-ovarian axis; pathology requiring treatment may be present 6, 7
• Do not presume infertility in patients with primary ovarian insufficiency, as unpredictable ovarian function can persist 1, 2
• Discontinue hormone replacement therapy at least 2 months before laboratory evaluation to avoid falsely reassuring results 3
• Screen for eating disorders and assess bone density in patients with hypothalamic amenorrhea 1, 2
• AMH testing is not recommended as the primary surveillance modality for delayed menarche evaluation 3