What are the side effects of tamoxifen?

Side Effects of Tamoxifen

Tamoxifen has several significant side effects including increased risk of endometrial cancer, venous thromboembolism, stroke, cataracts, and various gynecologic and vasomotor symptoms, with the severity varying by age and menopausal status. 1, 2

Common Side Effects

Vasomotor Symptoms

• Hot flashes (most common side effect, affecting 64% of women vs. 48% on placebo) 1
• Night sweats

Gynecologic Effects

• Vaginal discharge (30% vs. 15% on placebo) 1
• Vaginal dryness (35%) 3
• Irregular menses (25% vs. 19% on placebo) 1
• Amenorrhea (particularly in premenopausal women) 2

General Side Effects

• Sleep problems (36%) 3
• Fluid retention (32% vs. 30% on placebo) 2
• Nausea (26% vs. 24% on placebo) 2
• Weight changes (23% weight loss >5% vs. 18% on placebo) 2
• Depression, irritability, or mood swings (6%) 3

Serious Side Effects

Endometrial Abnormalities

• Endometrial cancer: 2 per 1,000 women per year (vs. 1 per 1,000 on placebo) 2
  • Risk is higher in women over 50 years 1
  • Risk is primarily during active treatment 1
• Uterine sarcoma (rare but increased risk) 2
• Endometrial hyperplasia and polyps 1

Thromboembolic Events

• Venous thromboembolism (1.9-fold increased risk) 1
  • Deep vein thrombosis (0.8% vs. 0.2% on placebo) 2
  • Pulmonary embolism (0.5% vs. 0.2% on placebo) 2
  • Risk factors: age ≥60 years, height ≥165 cm, diastolic BP ≥90 mmHg, immobilization, BMI ≥25 kg/m² 1
  • Risk is higher in first 3 years of treatment 1

Cardiovascular Effects

• Ischemic stroke (1.82-fold increased risk) 1
• Lower risk of fatal myocardial infarction (potential benefit) 4

Ocular Effects

• Cataracts (14 additional cases per 1,000 women) 1
• Increased need for cataract surgery (1.57-fold risk) 1

Other Serious Effects

• Liver problems (rare): jaundice, elevated liver enzymes 2
• Thrombocytopenia (rare but reported) 5

Side Effect Patterns by Age and Menopausal Status

Premenopausal Women

• Lower risk of endometrial cancer compared to postmenopausal women 1
• Lower risk of thromboembolic events 1
• Higher reporting of side effects overall 3
• May experience menstrual irregularities, amenorrhea 2
• Elevated serum estrogen levels 6

Postmenopausal Women

• Higher risk of endometrial cancer 1
• Higher risk of thromboembolic events 1
• Potential bone-preserving effects in lumbar spine 4
• Potential cholesterol-lowering effects 4

Risk Factors for Experiencing Side Effects

• Age: Women younger than 50 report more side effects 3
• Prior use of hormone therapy: Associated with more severe side effects 3
• Higher endoxifen levels (active metabolite): Associated with more side effects 3
• Duration of therapy: Side effects often decrease after 12 months of treatment 3

Monitoring Recommendations

• Baseline gynecologic examination before starting tamoxifen 1
• Annual gynecologic follow-up during and after treatment 1
• Prompt investigation of abnormal vaginal bleeding (may indicate endometrial cancer) 2
• Monitor for signs of thromboembolic events, particularly in first 3 years 1
• Be alert for visual changes that may indicate cataracts 2

Contraindications

Tamoxifen should not be used in patients with:

• Pregnancy or plans to become pregnant 2
• History of deep vein thrombosis, pulmonary embolism, stroke, or transient ischemic attack 1, 2
• Current use of anticoagulants like warfarin 2
• Limited mobility for most waking hours 2

Drug Interactions

• Avoid concurrent use of CYP2D6 inhibitors (e.g., bupropion, paroxetine, fluoxetine) as they may reduce tamoxifen efficacy 1
• Consider alternative medications when possible for patients requiring CYP2D6 inhibitors 1

Understanding these side effects and risk factors is crucial for appropriate patient counseling and monitoring during tamoxifen therapy. While the side effects can be significant, most are mild to moderate for the majority of patients, and serious adverse effects are relatively rare 1.