Diagnostic Testing for a 25-Year-Old with Chronic Fatigue and Irregular Menstrual Cycles
Begin with hormonal evaluation measuring FSH, LH, estradiol, prolactin, TSH, and mid-luteal progesterone, as these tests identify the most common and treatable causes of menstrual irregularity in young women. 1
Initial Core Laboratory Panel
Perform these tests first, as they identify >90% of endocrine causes:
- FSH and LH: Measure between cycle days 3-6 with three samples taken 20 minutes apart for accuracy; an LH/FSH ratio >2 suggests PCOS 1, 2
- Estradiol: Obtain during early follicular phase to establish baseline ovarian function 1
- Prolactin: Essential to exclude hyperprolactinemia, which causes both fatigue and menstrual irregularity; repeat as morning resting sample if elevated, as single measurements can be spurious 1, 2
- TSH and free T4: Critical first-line test since hypothyroidism causes both presenting symptoms and occurs in 43% of women with hyperprolactinemia 2
- Mid-luteal progesterone (day 21): Levels <6 nmol/L confirm anovulation, common in PCOS and hyperprolactinemia 1, 2
Androgen Assessment
If hirsutism, acne, or PCOS is suspected clinically:
- Total and free testosterone: Screen for hyperandrogenism 1, 3
- DHEAS: Primarily adrenal origin; markedly elevated levels suggest non-classical congenital adrenal hyperplasia or adrenal pathology 3, 2
- Androstenedione: Indicated if testosterone elevated; levels >10.0 nmol/L require imaging to exclude ovarian/adrenal tumors 3
Metabolic Screening
Perform if PCOS suspected or BMI elevated:
- Fasting glucose and 2-hour oral glucose tolerance test: Insulin resistance commonly accompanies hyperandrogenism and PCOS 1, 3
- Fasting lipid panel: Screen for metabolic complications associated with hyperandrogenism 3
Additional Testing Based on Initial Results
- Anti-Müllerian hormone (AMH): May provide information on ovarian reserve, though interpret cautiously in women <25 years due to significant fluctuations 4, 1
- Hemoglobin: Exclude anemia as contributing factor to fatigue 4
- Pelvic ultrasound (transvaginal): Perform between cycle days 3-9 if initial labs suggest PCOS (>10 peripheral cysts 2-8mm diameter with thickened stroma) or to exclude ovarian pathology 1, 3
- Pituitary MRI: Order if prolactin persistently elevated (>4,000 mU/L typically indicates prolactinoma) to exclude structural pituitary pathology 2
Critical Timing Considerations
Avoid these common pitfalls:
- Do not perform testing while on hormonal contraception, as this invalidates results 1
- Do not rely on single FSH or prolactin measurements, as levels fluctuate significantly 1, 2
- Do not measure hormones at incorrect cycle times; if cycles irregular, still aim for days 3-6 when possible 1
- Do not overlook thyroid dysfunction, which commonly presents with both fatigue and menstrual irregularity 4, 2
Clinical Context for This Patient
The combination of fatigue and irregular cycles suggests several possibilities:
- PCOS: Most common cause of irregular cycles in reproductive-age women, associated with anovulation and fatigue; research shows women with CFS report increased PCOS, hirsutism, and ovarian cysts 5
- Hyperprolactinemia: Causes both anovulation and fatigue; treating underlying cause (e.g., hypothyroidism) may normalize both symptoms 2
- Hypothyroidism: Presents with fatigue and menstrual irregularity; occurs in 43% of women with hyperprolactinemia 2
- Relative Energy Deficiency (RED-S): Consider if athletic or restrictive eating patterns present; causes functional hypothalamic amenorrhea with low LH and fatigue 4
When to Refer
Refer to endocrinology or gynecology if:
- Persistent abnormal hormone levels despite initial management 1
- Prolactin >4,000 mU/L or pituitary abnormality on MRI 2
- Signs of premature ovarian insufficiency (elevated FSH with amenorrhea in woman <40 years) 1
- Markedly elevated androgens suggesting tumor (androstenedione >10.0 nmol/L) 3
- Infertility concerns 1