What is the workup for a patient with amenorrhea (absent periods)?

Workup for Amenorrhea

Begin with a pregnancy test to exclude pregnancy, followed by hormonal assessment (FSH, LH, TSH, prolactin, estradiol) and pelvic ultrasonography to identify the underlying etiology. 1

Initial Clinical Assessment

History Taking

• Document menstrual history: age of menarche, cycle regularity, and duration of irregularity 1
• Assess weight changes, eating patterns, and exercise habits to evaluate for Female Athlete Triad or disordered eating 1
• Review medication use, including hormonal contraceptives, antipsychotics, and antiepileptics, which can cause amenorrhea 1
• Evaluate for galactorrhea, which suggests hyperprolactinemia 1

Physical Examination

• Calculate BMI, as obesity is associated with PCOS and menstrual irregularities 1
• Perform Tanner staging to assess breast and pubic hair development 1
• Conduct thyroid examination to identify enlargement or nodules 1
• Perform pelvic examination to assess for anatomical abnormalities 1

Laboratory Testing Algorithm

First-Line Tests (Perform in All Patients)

• Pregnancy test (urine or serum β-hCG) must be performed first before any other hormonal testing 1, 2, 3
• FSH and LH levels to differentiate between ovarian failure and hypothalamic/pituitary dysfunction 1, 2, 3
• TSH to exclude thyroid disorders 1, 2, 3
• Prolactin to identify hyperprolactinemia 1, 2, 3
• Estradiol to assess estrogen status 1

Interpretation by FSH Level

Elevated FSH (>40 mIU/mL):

• Confirms primary ovarian insufficiency 1
• Repeat FSH in 4 weeks (two elevated values required for diagnosis) 1
• Perform karyotype testing if age <40 years to identify Turner syndrome or other chromosomal abnormalities 1
• Important caveat: Patients with primary ovarian insufficiency can maintain unpredictable ovarian function and should not be presumed infertile 1, 2, 3

Low or Normal FSH with LH/FSH ratio >2:

• Suggests PCOS 1
• Consider additional androgen testing if hyperandrogenic features present 3

Low FSH and LH:

• Indicates hypothalamic or pituitary dysfunction (hypogonadotropic hypogonadism) 1
• Evaluate for disordered eating and low bone density in these patients 1, 2, 3

Imaging Studies

Pelvic Ultrasonography

• Transvaginal ultrasound is more sensitive than transabdominal for identifying structural abnormalities 1
• Assess endometrial thickness: thin endometrium (<5 mm) suggests estrogen deficiency; thick endometrium (>8 mm) suggests chronic anovulation with unopposed estrogen 1
• Indicated when clinical features or hormonal tests suggest ovarian pathology 1

Progesterone Challenge Test (Optional)

• Can differentiate PCOS (positive withdrawal bleed) from functional hypothalamic amenorrhea (negative), though endometrial thickness on ultrasound is more reliable 1
• Low progesterone levels (<5 ng/mL) throughout the cycle suggest anovulation 1

Common Pitfalls to Avoid

• Failing to rule out pregnancy first can lead to misinterpretation of hormonal results 1
• Do not assume infertility in primary ovarian insufficiency patients, as they can maintain unpredictable ovarian function 1, 2, 3
• Screen for eating disorders and bone density loss in patients with hypothalamic amenorrhea 1, 2, 3
• Evaluate for metabolic syndrome (glucose intolerance, dyslipidemia) in patients with PCOS 2, 3
• Perform endometrial biopsy in older patients before treatment, as the incidence of endometrial carcinoma increases with age 4

When to Refer to Specialist

Refer if:

• Laboratory testing reveals significant abnormalities 1
• Concern for eating disorder or Female Athlete Triad 1
• Turner syndrome or chromosomal abnormalities identified 1
• Patient desires fertility and requires ovulation induction 4