Workup for Amenorrhea in a 19-Year-Old
Begin with a pregnancy test (beta-hCG), followed by TSH, free T4, prolactin, FSH, and LH levels—these five tests identify the vast majority of amenorrhea causes in young women. 1, 2
Determine Primary vs. Secondary Amenorrhea
- Primary amenorrhea is defined as no menarche by age 15 years 3
- Secondary amenorrhea is absence of three consecutive cycles or cycle length greater than 45 days 3
- In this 19-year-old, clarify whether she ever had menarche to guide the differential diagnosis 2
Initial Laboratory Workup
Mandatory first-line tests include: 1, 2
- Pregnancy test (beta-hCG) - must be excluded first, even if patient denies sexual activity 1, 2
- TSH and free T4 - thyroid dysfunction is among the most common endocrine causes 1, 2
- Prolactin level - hyperprolactinemia frequently causes menstrual irregularity in adolescents 1, 2
- FSH and LH - distinguishes between hypergonadotropic (ovarian failure) and hypogonadotropic (hypothalamic/pituitary) causes 2
Physical Examination Priorities
Critical examination findings to document: 1, 2, 4
- Presence and stage of secondary sexual characteristics (breast development, pubic hair) - absence suggests gonadal dysgenesis 5, 4
- External genitalia examination and vaginal patency - anatomic abnormalities like Müllerian agenesis account for approximately 15% of primary amenorrhea cases 4
- Signs of androgen excess - hirsutism, acne, male-pattern hair distribution suggest PCOS 1
- Galactorrhea or nipple discharge - indicates hyperprolactinemia 1
- Body mass index and nutritional status - assess for eating disorders or relative energy deficiency 3, 1
Interpretation of Initial Labs and Next Steps
If FSH is elevated (>40 mIU/mL): 2, 5
- Indicates primary ovarian insufficiency or gonadal dysgenesis 2
- Order karyotype - Turner syndrome (45,X0) is a critical diagnosis, occurring in 1 in 2,500 to 1 in 3,000 live-born girls 5
- Pelvic ultrasound to assess ovarian and uterine anatomy 1
If FSH/LH are low or normal with low estrogen: 6, 2
- Suggests hypothalamic amenorrhea - assess for: 3, 1
- Energy availability - should be >30 kcal/kg fat-free mass/day 1
- Athletic overtraining - prevalence of primary amenorrhea in collegiate athletes is 7% overall, up to 22% in cheerleading, diving, and gymnastics 3
- Eating disorders - prevalence approximately 20% in female elite athletes 3
- Psychological stress - common contributor to hypothalamic dysfunction 6
If prolactin is elevated (>25 ng/mL): 6, 2
- Order brain MRI to evaluate for pituitary adenoma 6
- Note: Prolactin levels and menses are unreliable during tamoxifen treatment if applicable 7
If TSH is abnormal: 5
- Hypothyroidism can present with amenorrhea and multinodular goiter 5
- Treat thyroid dysfunction and reassess menstrual function 5
Imaging Considerations
Pelvic ultrasound (transvaginal if sexually active, transabdominal if not) is indicated when: 1
- Hormonal tests suggest ovarian pathology (elevated FSH) 1
- Physical examination reveals anatomic concerns 1
- Primary amenorrhea persists without clear etiology 1
Do not assume functional bleeding without excluding structural pathology, especially in primary amenorrhea. 1
Common Pitfalls to Avoid
- Never skip the genital examination - even if the patient reports "normal" sexual activity, anatomic abnormalities like Müllerian agenesis can be missed, and rare phenomena like urethral coitus have been reported 4
- Do not overlook Turner syndrome variants - patients may present with isolated findings like hypothyroidism or learning difficulties before amenorrhea is addressed 5
- Assess bone density risk early - many causes of amenorrhea result in decreased bone density that may be irreversible 8
- Screen for metabolic complications - patients with PCOS require glucose tolerance and lipid screening 2