Side Effects of Clomiphene Citrate
Clomiphene citrate commonly causes vasomotor symptoms, visual disturbances, and mood changes, with rare but serious risks including ovarian hyperstimulation syndrome, multiple gestation, and thromboembolic events. 1, 2
Common Side Effects
Vasomotor Symptoms
- Hot flashes (occur in approximately 10.4% of patients) 3
- Flushing
- Night sweats
Visual Disturbances
- Blurred vision
- Seeing spots or flashes
- Scotomata (blind spots in visual field)
- These symptoms are typically reversible upon discontinuation 1
Mood and Neurological Effects
- Mood swings and irritability
- Anxiety
- Depression
- Headaches
- Dizziness
- Insomnia
- In rare cases, severe psychological reactions including psychosis 4, 5
Reproductive System Effects
- Ovarian enlargement with pelvic or abdominal pain
- Ovarian cyst formation
- Abnormal uterine bleeding
- Cervical mucus abnormalities 3
- Luteal phase deficiency 3
Serious Side Effects
Ovarian Hyperstimulation Syndrome (OHSS)
- Ovarian enlargement
- Abdominal pain and distension
- Nausea and vomiting
- In severe cases: ascites, pleural effusion, electrolyte imbalances
Multiple Gestation
- Approximately 10% risk of multiple pregnancy 3
- Primarily twin pregnancies
Cardiovascular Effects
- Rare cases of thromboembolic events
- Case reports of myocardial infarction, even in young women without cardiovascular risk factors 6
Monitoring Recommendations
When prescribing clomiphene:
Before starting treatment:
- Perform baseline assessment for contraindications
- Rule out pregnancy
- Evaluate for ovarian cysts
During treatment:
- Monitor for visual symptoms (discontinue if they occur)
- Be alert for signs of OHSS (abdominal pain, rapid weight gain)
- Assess mood changes, particularly in the first few weeks 5
After treatment:
- Evaluate for pregnancy
- Monitor for multiple gestation if pregnancy occurs
Special Considerations
Long-term Use Concerns
- Some studies have raised questions about potential increased ovarian cancer risk with prolonged use, though causality has not been established 7, 3
- The ACOG recommends limiting treatment duration due to these theoretical concerns 2
Overdose Symptoms
- Nausea and vomiting
- Vasomotor flushes
- Visual blurring
- Spots or flashes
- Scotomata
- Ovarian enlargement with pelvic or abdominal pain 1
Patient Counseling Points
- Advise patients to report any visual symptoms immediately
- Inform about the possibility of mood changes and when to seek help
- Explain the risk of multiple pregnancy
- Instruct patients to report severe abdominal pain, bloating, or rapid weight gain (signs of OHSS)
- Recommend taking the medication at the same time each day
For patients experiencing significant side effects, alternative fertility treatments may be considered based on the specific clinical situation and fertility diagnosis.