What could be causing severe headaches in the top left of my head while I'm taking 25mg of Clomid (clomiphene citrate) and 40mg of Nolvadex (tamoxifen) for fertility treatment?

Severe Headaches While Taking Clomid and Nolvadex

Your severe, localized headache on clomiphene citrate (Clomid) and tamoxifen (Nolvadex) requires immediate medical evaluation to rule out cerebral venous thrombosis (CVT), a rare but life-threatening complication documented with clomiphene use.

Immediate Action Required

Stop both medications immediately and seek urgent medical evaluation with MRI brain with contrast and MR venography (MRV) to evaluate for cerebral venous sinus thrombosis, as this is the gold standard imaging modality for CVT diagnosis 1. Progressive, lateralized headache (specifically left-sided in your case) is a red flag symptom that suggests increased intracranial venous pressure and potential CVT 1.

Critical Red Flags Present in Your Case

• Localized unilateral headache (top left of head) is concerning for lateral sinus thrombosis, which specifically causes localized pain and headache 1
• Clomiphene citrate has been directly associated with intracranial venous thrombosis in case reports, occurring as early as 3 weeks after starting treatment 2
• CVT presents with progressive symptoms in 56% of cases, with median delay from symptom onset to diagnosis of 7 days, and headache occurs in nearly 90% of CVT patients 1

Why This Is Dangerous

• Clomiphene citrate, while generally considered safe for ovulation induction, has been documented to cause life-threatening complications including intracranial venous thrombosis and myocardial infarction 2, 3
• After excluding common causes of intracranial venous thrombosis and hypercoagulable states, clomiphene citrate appears to be the most likely culprit in documented cases 2
• CVT can progress rapidly and requires immediate anticoagulation if confirmed, necessitating urgent neurology/neurosurgery consultation 1

Diagnostic Workup Needed

• MRI brain with contrast and MRV is the first-line imaging study, as it is superior for evaluating sigmoid venous sinuses and detecting CVT 1
• If MRI/MRV is unavailable, CT head with CT venography (CTV) is an acceptable alternative 1
• D-dimer testing has high sensitivity for CVT identification, though methodological limitations exist 1
• Urgent lumbar puncture with opening pressure measurement if increased intracranial pressure is suspected without mass effect 1

Alternative Diagnoses to Consider

• Idiopathic intracranial hypertension (pseudotumor cerebri) can show venous outflow obstruction on MRV in 52% of cases and presents with progressive headache 1
• Medication-induced headache from clomiphene itself, as headaches are a recognized adverse effect occurring in approximately 5% of patients taking clomiphene 4, 5
• Migraine headache, though the unilateral, localized nature and temporal relationship to medication initiation makes this less likely as the primary diagnosis 6

Common Adverse Effects of These Medications

• Clomiphene citrate commonly causes hot flushes (5% of patients), headache (5%), visual disturbances, and cervical mucus abnormalities 4, 5
• Tamoxifen (Nolvadex) can cause headaches as part of its adverse effect profile, though serious vascular complications are less commonly reported than with clomiphene 7
• The combination of both medications may have additive effects on headache frequency and severity

Critical Pitfalls to Avoid

• Do not dismiss this as a simple medication side effect without imaging to rule out CVT, as the consequences of missing this diagnosis are catastrophic 1
• Do not continue these medications while awaiting evaluation, as clomiphene-associated thrombotic events can progress 2, 3
• Do not treat with simple analgesics alone without first excluding secondary causes of headache, particularly given the red flag of new-onset, localized, severe headache 6
• Do not delay imaging based on normal neurologic examination, as CVT can present with isolated headache before other neurologic signs develop 1

If CVT Is Ruled Out

If imaging excludes CVT and other secondary causes, and the headache is determined to be a medication side effect:

• Consider discontinuing clomiphene citrate, as headaches occur in approximately 5% of patients and may necessitate stopping the medication 4
• For acute headache management while off these medications, NSAIDs (ibuprofen 400-800 mg or naproxen 500 mg) are first-line treatment 8
• Add metoclopramide 10 mg orally 20-30 minutes before the NSAID for synergistic analgesia if nausea is present 8
• Limit acute headache medication use to no more than 2 days per week to prevent medication-overuse headache 8, 6