What are the side effects of estradiol (estrogen) patches?

Side Effects of Estradiol Patches

Estradiol patches can cause several side effects including skin reactions (erythema, pruritus), increased risk of venous thromboembolism, breast tenderness, and fluid retention. 1, 2

Common Side Effects

Skin-Related Side Effects

• Application site reactions: Most common side effect specific to the patch delivery system
  • Erythema (redness): Occurs in up to 66% of patch users 3
  • Pruritus (itching): Common with transdermal application 1
  • Contact dermatitis: May develop at application site 1
  • Hyperpigmentation: Can occur where patch is repeatedly applied 1

Systemic Side Effects

• Breast-related effects:

  • Breast tenderness and swelling 3
  • Potential increased risk of breast cancer with long-term use 2

• Cardiovascular effects:

  • Increased risk of venous thromboembolism (VTE) 1
  • FDA black box warning indicates 1.6 times higher estrogen exposure compared to low-dose oral contraceptives 1
  • Potential increased risk of stroke and heart attack 2

• Gastrointestinal effects:

  • Nausea and vomiting 2
  • Stomach/abdominal cramps and bloating 2

• Other common effects:

  • Headache 2
  • Irregular vaginal bleeding or spotting 2
  • Fluid retention (generally mild but use with caution in patients with heart failure) 3

Less Common but Serious Side Effects

• Cardiovascular risks:

  • Blood clots in legs or lungs 2
  • Stroke 2
  • Heart attack 2

• Cancer risks:

  • Endometrial cancer (if used without progestin in women with intact uterus) 2
  • Breast cancer 2
  • Ovarian cancer 2

• Other serious risks:

  • Gallbladder disease 2
  • Liver problems 2
  • Dementia (in older women) 2
  • High blood sugar 2

Special Considerations

Hereditary Angioedema

• Estradiol patches may increase the frequency and severity of attacks in women with hereditary angioedema 3, 1

Transgender Healthcare

• In transgender women, estradiol patches may cause:
  • Breast development (desired effect) 3
  • Decreased muscle cross-sectional area 3
  • Changes in lipid profiles 3

Warning Signs Requiring Immediate Medical Attention

• Unusual vaginal bleeding
• Breast lumps
• Severe headaches
• Chest pain
• Shortness of breath
• Leg pain or swelling
• Changes in vision or speech
• Dizziness or faintness
• Vomiting 2

Pharmacokinetics

Transdermal estradiol patches deliver estradiol directly into the bloodstream, bypassing first-pass hepatic metabolism. This results in:

• More stable estradiol levels compared to oral administration 4
• Estradiol/estrone ratio closer to physiological levels seen in premenopausal women 5
• Return to baseline hormone levels within 8-24 hours after patch removal 5

The transdermal delivery system is designed to provide consistent hormone levels throughout the application period, which typically lasts 7 days for many patch formulations 6, 5.

By understanding these potential side effects, patients and healthcare providers can make informed decisions about estradiol patch therapy and monitor appropriately for adverse reactions.