What laboratory tests should be ordered for a woman with a missed menstrual period?

Laboratory Testing for Missed Menstrual Period

The initial laboratory workup for a woman with a missed period must begin with a urine or serum β-hCG pregnancy test, followed by serum FSH, TSH, free T4, prolactin, LH, estradiol (E2), and anti-Müllerian hormone (AMH) if pregnancy is excluded 1.

First-Line Essential Tests

Immediate Priority: Rule Out Pregnancy

• β-human chorionic gonadotropin (β-hCG) - This is the mandatory first test for any woman with amenorrhea 1, 2
  • Can be performed on urine or serum
  • Note that approximately 10% of clinical pregnancies may not be detectable on the first day of missed menses even with sensitive assays 3
  • If negative and amenorrhea persists, proceed with endocrine evaluation

Core Endocrine Panel (After Excluding Pregnancy)

Once pregnancy is ruled out, obtain the following hormone panel 1:

• FSH (Follicle-Stimulating Hormone) - Elevated FSH >25 IU/L suggests primary ovarian insufficiency 2

  • If elevated, repeat in 1 month to confirm diagnosis 2
  • Important caveat: FSH will be falsely suppressed if patient is on combined oral contraceptives or macro-progestins; must discontinue for at least 3 months before retesting 2

• Estradiol (E2) - Low levels confirm hypoestrogenism; helps distinguish from mid-cycle LH surge 1

• TSH and free T4 - Screens for thyroid dysfunction, a common reversible cause 1

• Prolactin - Elevated levels suggest hyperprolactinemia or prolactinoma 1

• LH (Luteinizing Hormone) - Pattern interpretation with FSH is critical 1

• AMH (Anti-Müllerian Hormone) - Reflects ovarian follicle reserve 1

Additional Screening Tests for Specific Clinical Contexts

General Health Screening (Recommended for Suspected Functional Hypothalamic Amenorrhea)

The following tests help identify systemic illness or nutritional deficiency 1:

• Complete blood count (CBC)
• Electrolytes, glucose, bicarbonate
• Blood urea nitrogen (BUN), creatinine
• Liver function panel
• When appropriate: ESR and/or C-reactive protein (if chronic illness suspected)

Tests for Clinical Hyperandrogenism

If patient presents with hirsutism, acne, or other signs of androgen excess 1:

• Total testosterone
• DHEA-S
• 8 AM 17-hydroxyprogesterone (if late-onset congenital adrenal hyperplasia suspected)

Algorithmic Approach to Interpretation

Pattern recognition is more critical than absolute values 1:

1. High FSH (>25 IU/L) + Low estradiol = Primary ovarian insufficiency

   • Repeat in 1 month to confirm 2
   • Consider karyotype, FMR1 premutation testing, autoimmune screening

2. Low/normal FSH + Low estradiol = Functional hypothalamic amenorrhea or pituitary pathology

   • Assess for eating disorders, excessive exercise, stress, weight loss
   • Consider brain MRI if red flags present 1

3. Elevated prolactin = Hyperprolactinemia

   • Brain MRI with pituitary cuts indicated

4. Normal FSH + Normal estradiol + Hyperandrogenism = Consider PCOS or other androgen excess disorders

Critical Pitfalls to Avoid

• Do not rely on a single FSH measurement - Ovarian function can fluctuate, particularly in early primary ovarian insufficiency; confirmation testing is essential 2

• Timing matters for oral contraceptive users - Hormonal contraception suppresses FSH and masks the diagnosis; must discontinue for ≥3 months before meaningful interpretation 2

• Pregnancy testing limitations - Home pregnancy tests may miss up to 84-90% of pregnancies at the time of missed menses due to variable implantation timing 3, 4; clinical judgment should prevail if suspicion remains high

• Mid-cycle FSH surge - An isolated elevated FSH with high estradiol (>150-200 pg/mL) likely represents pre-ovulation peak, not pathology 2