What is the recommended workup for exercise‑induced amenorrhea?

Workup for Exercise-Induced Amenorrhea

Begin with a pregnancy test and comprehensive endocrine panel including TSH, free T4, prolactin, LH, FSH, estradiol (E2), and AMH; obtain total testosterone and DHEA-S if clinical hyperandrogenism is present, and measure bone mineral density by DXA after 6 months of amenorrhea. 1

Initial Laboratory Evaluation

The 2017 Endocrine Society guideline provides a clear algorithmic approach to workup 1:

Essential first-line tests:

• β-hCG (pregnancy test) - mandatory in all cases
• TSH and free T4
• Prolactin
• LH and FSH
• Estradiol (E2)
• AMH (anti-Müllerian hormone)

Additional tests when indicated:

• Total testosterone and DHEA-S if signs of hyperandrogenism (acne, hirsutism) are present
• 8 AM 17-hydroxyprogesterone if late-onset congenital adrenal hyperplasia is suspected
• Complete blood count, comprehensive metabolic panel, liver function tests, and inflammatory markers (ESR/CRP) if chronic illness is suspected 1

Interpreting the Hormone Pattern

Functional hypothalamic amenorrhea (FHA) typically shows:

• Low or low-normal LH with normal FSH (FSH often higher than LH)
• E2 <50 pg/mL (often <20 pg/mL indicates severe hypoestrogenism)
• Progesterone <1 ng/mL
• Normal or low-normal testosterone
• Low-normal prolactin
• TSH and free T4 in lower normal range 1

Critical distinction: This pattern differentiates FHA from primary ovarian insufficiency (elevated FSH/LH with low E2) and from organic hypothalamic causes (very low/undetectable LH and FSH suggesting pituitary/hypothalamic tumors or infiltrative lesions) 1.

Excluding PCOS as Underlying Diagnosis

Important caveat: Exercise-induced amenorrhea can mask polycystic ovary syndrome (PCOS). Pay close attention to 1:

• BMI (women with underlying PCOS tend to have higher BMI)
• Concerns about weight and appearance in history
• Signs of hyperandrogenism (acne, hirsutism)
• Elevated AMH levels (high risk marker for PCOS)

Women with FHA and underlying PCOS have higher testosterone, LH, and BMI compared to pure FHA, and may develop hyperandrogenism and irregular menses with weight gain rather than resumption of regular cycles 1.

Bone Health Assessment

DXA scan is recommended after 6 months of amenorrhea 1, 2. Earlier assessment is warranted if 1:

• History of severe nutritional deficiency
• Other energy deficit states
• Skeletal fragility or stress fractures

Key measurement sites:

• Lumbar spine (L1-L4) - most common site of low bone density in young women with amenorrhea
• Hip BMD in women >15 years old provides additional information about cortical bone 1
• Whole body (head excluded) in adolescents 2

Interpretation for athletes: A Z-score <-1.0 SD warrants attention, as athletes in weight-bearing sports should have 5-15% higher BMD than non-athletes. Low BMD is defined as Z-score between -1.0 and -2.0 SD with history of nutritional deficiencies, hypoestrogenism, or stress fractures. Below -2.0 SD with secondary risk factors indicates osteoporosis 2.

Physical Examination Priorities

Focus on:

• Anthropometry: BMI, body composition (body fat percentage <22% is concerning) 3
• Signs of energy deficit: bradycardia, hypotension, orthostasis (severe cases may require inpatient admission) 1
• Signs of eating disorders or nutritional deficiency
• Pubertal stage in adolescents
• Signs of hyperandrogenism (acne, hirsutism, male-pattern hair distribution)
• Pelvic examination may reveal hypoestrogen-related vaginal atrophy 2

For primary amenorrhea specifically, physical examination is critical to identify anatomic abnormalities like imperforate hymen 1.

Imaging Studies

Pelvic ultrasound (transabdominal or transvaginal) may be considered to 1, 2:

• Assess ovarian morphology (polycystic ovaries suggest underlying PCOS)
• Exclude anatomic abnormalities in primary amenorrhea
• Rule out other gynecological pathologies

MRI is reserved for cases where Müllerian tract anomalies are suspected 1.

Assessment of Energy Availability

Clinical evaluation should determine 1:

• Dietary energy intake (detailed nutritional history)
• Exercise energy expenditure (training volume, intensity, hours per week)
• Recent weight changes
• Eating disorder screening (the Eating Disorder Examination interview EDE-16 is the gold standard) 2

High-risk profile for bone stress injury includes 1:

• Exercise load >12 hours/week
• Participation in low-weight sports (gymnastics, long-distance running, figure skating)
• Dietary restraint

Multidisciplinary Evaluation

The workup should include assessment by 1:

• Registered dietitian - evaluate calories, vitamin D, calcium, and other nutrient intake
• Mental health professional - screen for stress, eating disorders, and psychological factors contributing to energy deficit

This is not optional; psychological factors and stress can prevent menstrual resumption even after weight stabilization 1.

Common Pitfalls to Avoid

1. Don't assume "athletic amenorrhea" without excluding other causes - pregnancy, thyroid dysfunction, hyperprolactinemia, and primary ovarian insufficiency must be ruled out 4

2. Don't overlook underlying PCOS - it can be masked by energy deficit and will emerge with weight gain 1

3. Don't delay bone density assessment - the most rapid bone loss (approximately 4%/year) occurs early after cessation of menses 4

4. Don't ignore severe cases - hemodynamic instability (hypotension, bradycardia, orthostasis) requires immediate medical attention and possible inpatient admission 1

5. Don't rely on single E2 measurement - E2 reflects a single time point; the overall hormone pattern is more informative 1