A 28-year-old woman attends the gynaecology clinic with a 6-month history of secondary amenorrhea. She reports significant weight loss (8 kg in 3 months), intense exercise regimen (running 15 km daily), and high stress at work. Menarche was at age 13, and her cycles were regular until 6 months ago. On examination, BMI is 17.5 kg/m² (previously 20 kg/m²), and she appears anxious. Pelvic examination is normal. Serum FSH is 3.2 mIU/mL, LH is 2.1 mIU/mL, oestradiol is 25 pg/mL, prolactin is 12 ng/mL, TSH is 1.8 mIU/L, and β-hCG is negative. What is the most likely diagnosis?

Explanation

## Diagnosis: Functional Hypothalamic Amenorrhea (FHA) ### Clinical Presentation - **Secondary amenorrhea:** 6-month duration in a woman with previously regular cycles - **Triggering factors:** Rapid weight loss (8 kg in 3 months), excessive exercise (15 km daily), psychological stress - **BMI:** 17.5 kg/m² (low-normal; weight loss of 2.5 kg/m² is significant) - **Psychological signs:** Anxiety noted on examination ### Hormonal Pattern Diagnostic of FHA **Key Point:** Functional hypothalamic amenorrhea is characterized by **low or low-normal gonadotropins (FSH, LH) with low-normal oestradiol** in the absence of organic pituitary or thyroid disease. | Hormone | Value | Interpretation | | --- | --- | --- | | FSH | 3.2 mIU/mL | Low (normal follicular: 3.5–12.5) | | LH | 2.1 mIU/mL | Low (normal follicular: 2.4–12.6) | | Oestradiol | 25 pg/mL | Low-normal (normal follicular: 30–100) | | Prolactin | 12 ng/mL | Normal (<25 ng/mL) | | TSH | 1.8 mIU/L | Normal (0.4–4.0) | | β-hCG | Negative | Rules out pregnancy | **High-Yield:** The **combination of low FSH/LH + low-normal oestradiol + normal prolactin and TSH + clinical stressors** is pathognomonic for FHA. ### Pathophysiology ```mermaid flowchart TD A[Stress, weight loss, exercise]:::outcome --> B[↓ GnRH pulsatility]:::outcome B --> C[↓ FSH and LH secretion]:::outcome C --> D[↓ Follicular development]:::outcome D --> E[↓ Oestradiol]:::outcome E --> F[Amenorrhea]:::outcome classDef outcome fill:#e0f2fe,stroke:#0369a1,stroke-width:2px,color:#000 ``` FHA results from suppression of GnRH (gonadotropin-releasing hormone) pulsatility by metabolic and psychological stressors. The pituitary and ovaries remain intact and responsive; the problem is at the hypothalamic level. ### Clinical Pearl FHA is **reversible** with correction of the underlying stressor: weight gain, reduction in exercise intensity, stress management, and psychological support. Spontaneous resumption of menses occurs in >90% of cases when stressors are removed. ### Diagnostic Criteria for FHA (Consensus Statement) 1. Amenorrhea for ≥3 months 2. Low or low-normal FSH and LH 3. Low or low-normal oestradiol 4. Normal prolactin and TSH 5. Negative pregnancy test 6. Identifiable stressor(s): weight loss, exercise, stress, or combination 7. Exclusion of organic pituitary/hypothalamic disease (MRI if indicated by clinical suspicion) ### Management - **First-line:** Address underlying stressors - Weight restoration to BMI ≥19 kg/m² - Reduce exercise intensity - Psychological support / counselling for stress and anxiety - **Monitoring:** Expect return of menses within 3–6 months of intervention - **Bone health:** Consider calcium, vitamin D, and weight-bearing exercise - **Hormone replacement:** Not routinely indicated unless prolonged amenorrhea (>6–12 months) with low bone density