What labs and imaging should I order for a 34-year-old woman taking zuclopenthixol (Clopixol) who has amenorrhea with a negative pregnancy test?

Amenorrhea in a 34-Year-Old Woman on Zuclopenthixol (Clopixol)

Order serum prolactin as the first-line test, followed by TSH and FSH/LH, because antipsychotic medications like zuclopenthixol commonly cause hyperprolactinemia-induced amenorrhea, and these tests will identify the most likely endocrine causes in this clinical scenario. 1

Initial Laboratory Workup

Essential First-Line Tests

• Serum prolactin level (morning, resting sample—not post-ictal) is the single most important test, as antipsychotic medications frequently elevate prolactin and cause amenorrhea; levels >20 μg/L are abnormal and warrant further evaluation 1
• Thyroid-stimulating hormone (TSH) to rule out hypothyroidism, which commonly causes menstrual irregularity and must be excluded before attributing amenorrhea to medication 1
• Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) measured between cycle day 3-6 (or at any time given amenorrhea); FSH >35 IU/L suggests premature ovarian insufficiency, while LH/FSH ratio >2 suggests polycystic ovary syndrome 1

Additional Hormonal Assessment

• Progesterone level (mid-luteal phase if cycles resume, or baseline) to assess ovulation; levels <6 nmol/L indicate anovulation, which is common with hyperprolactinemia 1
• Testosterone and androstenedione if hirsutism or other signs of hyperandrogenism are present; testosterone >2.5 nmol/L or androstenedione >10.0 nmol/L warrant investigation for PCOS or adrenal pathology 1

Imaging Studies

When to Order Pelvic Ultrasound

• Transvaginal ultrasound is indicated if hormonal tests suggest ovarian pathology (elevated LH/FSH ratio, elevated androgens) or if clinical features suggest polycystic ovary syndrome 1
• Transvaginal ultrasound is more sensitive than transabdominal for identifying structural ovarian abnormalities including cysts and tumors 1

When to Order Brain Imaging

• Pituitary MRI is indicated if prolactin is markedly elevated (typically >100 μg/L) or if galactorrhea is present, to rule out prolactinoma; however, small lactotroph adenomas may be beyond MRI resolution 1
• Note that mild prolactin elevation (20-50 μg/L) is expected with antipsychotic use and does not require imaging 1

Clinical Assessment Before Testing

Key History Elements

• Menstrual chart for at least 6 months prior to amenorrhea to document baseline cycle pattern 1
• Document galactorrhea (crusting on nipples, expressible breast milk), which strongly suggests hyperprolactinemia 1
• Assess for hirsutism (male escutcheon pattern), weight gain, and calculate BMI (>25 is obese) and waist-hip ratio (>0.9 indicates truncal obesity) 1
• Review zuclopenthixol dose and duration, as prolactin elevation is dose-dependent with antipsychotics 1

Diagnostic Algorithm

1. Confirm pregnancy is excluded (already done per your question) 1
2. Order serum prolactin, TSH, FSH, and LH as the initial panel 1
3. If prolactin is elevated (>20 μg/L):
   • Rule out hypothyroidism (TSH) as this can also elevate prolactin 1
   • If prolactin >100 μg/L or galactorrhea present, order pituitary MRI 1
   • If prolactin 20-50 μg/L without galactorrhea, attribute to medication and consider dose reduction or switching antipsychotic 1
4. If FSH >35 IU/L: diagnose premature ovarian insufficiency and refer to endocrinology 1
5. If LH/FSH ratio >2 with clinical features: order pelvic ultrasound to evaluate for polycystic ovary syndrome 1
6. If all hormonal tests are normal: consider hypothalamic amenorrhea (stress, weight loss, excessive exercise) or refer to gynecology/endocrinology for further evaluation 1

Common Pitfalls to Avoid

• Do not assume amenorrhea is solely medication-related without checking prolactin and thyroid function, as multiple endocrine disorders can coexist 1
• Do not order pituitary MRI for mild prolactin elevation (20-50 μg/L) in the setting of antipsychotic use, as this is expected and does not indicate a tumor 1
• Do not defer evaluation because the patient is on an antipsychotic; serious conditions like premature ovarian insufficiency or thyroid disease require prompt diagnosis 1
• Remember that zuclopenthixol can cause hematologic abnormalities (neutropenia, thrombocytopenia), so consider checking a complete blood count if the patient has other systemic symptoms 2