What are the contraindications for Hormone Replacement Therapy (HRT)?

From the Guidelines

Hormone therapy is contraindicated in patients with a history of breast cancer, liver disease, myocardial infarction, known or suspected estrogen-dependent neoplasia, deep vein thrombosis, or thrombophilic disorders. These conditions are considered absolute contraindications due to the increased risk of adverse outcomes associated with hormone therapy, as outlined in the 2024 guideline for the primary prevention of stroke by the American Heart Association/American Stroke Association 1.

Key Contraindications

• History of breast cancer
• Liver disease
• History of myocardial infarction
• Known or suspected estrogen-dependent neoplasia
• History of deep vein thrombosis
• Thrombophilic disorders When these contraindications are present, the guideline recommends considering alternative nonhormonal therapy options 1. The decision to use hormone therapy should be made with caution and through shared decision-making, taking into account the individual patient's risk factors and medical history. For instance, the choice between oral and transdermal formulations may depend on the presence of certain risk factors, such as an increased risk of stroke with high-dose oral estrogen compared to low-dose estrogen or transdermal formulations 1.

From the FDA Drug Label

The following additional adverse reactions have been identified during post approval use of PREMARIN Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to drug exposure Genitourinary System Abnormal uterine bleeding, dysmenorrhea or pelvic pain, increase in size of uterine leiomyomata, vaginitis, including vaginal candidiasis, change in cervical secretion, ovarian cancer, endometrial hyperplasia, endometrial cancer, leukorrhea. Breast Tenderness, enlargement, pain, discharge, galactorrhea, fibrocystic breast changes, breast cancer, gynecomastia in males Cardiovascular Deep and superficial venous thrombosis, pulmonary embolism, thrombophlebitis, myocardial infarction, stroke, increase in blood pressure.

The hormone therapy contraindications are not explicitly stated in the provided drug label. However, based on the postmarketing experience, the following conditions may be considered as potential contraindications:

• Abnormal uterine bleeding
• Ovarian cancer
• Endometrial hyperplasia
• Endometrial cancer
• Breast cancer
• Deep and superficial venous thrombosis
• Pulmonary embolism
• Myocardial infarction
• Stroke 2

From the Research

Hormone Therapy Contraindications

• Hormone therapy is contraindicated in certain types of cancer, including:
  • Breast cancer 3, 4, 5, 6, 7
  • Endometrial stroma sarcoma 3
  • Meningioma 3
  • Glioma 3
  • Hormone receptor positive gastric and bladder cancer 3
  • Leiomyosarcoma 3
  • Certain types of ovarian tumours 3
  • Brain tumours 3
  • Advanced metastatic malignant melanoma 3
  • Lung cancer 3
  • Gastric cancer 3
  • Bladder cancer 3
• Hormone therapy may be considered in certain cases, such as:
  • Low-risk endometrial cancer 6
  • Epithelial ovarian cancer 6
  • Cervical cancer 6
  • Low-risk, non-estrogen-receptor-positive subtypes of endometrial, cervical, and ovarian cancer 6
• The decision to use hormone therapy should be made on an individual basis, taking into account factors such as age, type of hormone therapy, dose, duration of use, regimen, route, and prior exposure 6
• Systemic hormone therapy is not recommended in breast cancer survivors, whereas local low-dose estrogen therapy may be considered after discussion with the patient's oncologist 6
• The risks of hormone therapy should be assessed on an individual basis, with consideration of the specific type of cancer and the individual's overall health status 3, 4, 6, 7