Initial Workup of Secondary Amenorrhea
The initial workup for secondary amenorrhea should include a thorough menstrual history, physical examination, pregnancy test, and laboratory assessment of luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin, thyroid-stimulating hormone (TSH), and estradiol levels. 1, 2
Definition and Timing for Evaluation
Secondary amenorrhea is defined as:
Step-by-Step Diagnostic Approach
1. History and Physical Examination
Key History Elements:
- Age of menarche
- Previous menstrual regularity
- Medications (including hormonal contraceptives)
- Weight changes
- Exercise patterns
- Dietary habits and caloric intake
- Stress levels
- Presence of other health issues
- Family menstrual history 2
Physical Examination:
- Height, weight, BMI calculation
- Vital signs
- Assessment of anthropometry
- Pubertal staging
- Signs of eating disorders
- Signs of hyperandrogenism (hirsutism, acne)
- Signs of hypoestrogen-related vaginal atrophy
- Thyroid examination
- Galactorrhea assessment 2, 1
2. Initial Laboratory Testing
First-line laboratory tests:
- Pregnancy test (to exclude pregnancy)
- Luteinizing hormone (LH)
- Follicle-stimulating hormone (FSH)
- Prolactin
- Thyroid-stimulating hormone (TSH)
- Estradiol 2, 1, 4
3. Additional Testing Based on Initial Results
If elevated FSH/LH:
- Consider primary ovarian insufficiency
- Karyotype analysis may be indicated
If elevated prolactin:
- Consider pituitary MRI to rule out prolactinoma 1
If normal/low FSH/LH with normal prolactin and TSH:
- Consider functional hypothalamic amenorrhea (FHA)
- Evaluate for energy deficiency, excessive exercise, stress 2, 1
If normal/elevated LH with normal/low FSH:
- Consider polycystic ovary syndrome (PCOS)
- Androgen profile (total testosterone, free testosterone, DHEA-S)
- Pelvic ultrasound to assess ovarian morphology 2
If normal/low FSH/LH with signs of hyperandrogenism:
- Complete androgen profile
- Consider adrenal causes 1
4. Specialized Testing When Indicated
- Pelvic ultrasound: To assess endometrial thickness, ovarian morphology, and rule out anatomical abnormalities 2
- Progestin challenge test: May help differentiate between hypoestrogenic states (no withdrawal bleed) and eustrogenic states (withdrawal bleed) 2, 1
- Bone mineral density (DXA): Indicated if amenorrhea persists for ≥6 months, especially in patients with FHA 2, 1
Common Diagnostic Scenarios
Functional Hypothalamic Amenorrhea (FHA)
- Low/normal LH, FSH
- Low estradiol
- Normal prolactin and TSH
- Often associated with energy deficiency, stress, or excessive exercise
- Diagnosis of exclusion 2, 1
Polycystic Ovary Syndrome (PCOS)
- Normal/elevated LH
- Normal/low FSH
- LH:FSH ratio often >2
- Signs of hyperandrogenism
- Polycystic ovarian morphology on ultrasound 2, 1
Hyperprolactinemia
Primary Ovarian Insufficiency
Common Pitfalls to Avoid
Misdiagnosing FHA with polycystic ovarian morphology (FHA-PCOM) as PCOS: These conditions require different treatment approaches. FHA-PCOM patients typically have lower LH:FSH ratios (<1) compared to PCOS patients (>2) 2, 1
Overlooking subtle energy deficits: Energy deficiency can lead to hypothalamic amenorrhea even without intense exercise or obvious weight loss 1
Neglecting bone health evaluation: Women with amenorrhea >6 months should have bone density assessment due to risk of osteoporosis 2, 1
Focusing only on weight rather than energy balance: Energy availability is more important than weight alone in restoring menstrual function 1
By following this systematic approach to the initial workup of secondary amenorrhea, clinicians can efficiently identify the underlying cause and develop appropriate treatment strategies to address both the amenorrhea and any associated health risks.