What are the contraindications for progesterone use?

Contraindications for Progesterone Use

Progesterone should not be used in patients with known hypersensitivity to its ingredients, undiagnosed abnormal genital bleeding, known/suspected/history of breast cancer, active deep vein thrombosis or pulmonary embolism, active arterial thromboembolic disease, known liver dysfunction or disease, or known/suspected pregnancy. 1

Absolute Contraindications

• Hypersensitivity reactions:

  • Allergic reactions to progesterone components
  • Peanut allergy (for formulations containing peanut oil) 1, 2

• Reproductive system conditions:

  • Undiagnosed abnormal genital bleeding 1
  • Known, suspected, or history of breast cancer 1
  • Hormone receptor-positive breast cancer (especially for rectal progesterone) 2
  • Low-grade serous epithelial ovarian cancer 2
  • Granulosa cell tumors 2
  • Certain types of sarcoma (leiomyosarcoma and stromal sarcoma) 2
  • Advanced endometrioid uterine adenocarcinoma 2

• Cardiovascular and thromboembolic conditions:

  • Active deep vein thrombosis or pulmonary embolism 1
  • History of thromboembolic disorders 2
  • Active arterial thromboembolic disease (stroke, myocardial infarction) 1

• Hepatic conditions:

  • Known liver dysfunction or disease 1
  • Hepatic adenomas or carcinomas 2
  • Cholestatic jaundice of pregnancy 2
  • Jaundice with previous hormonal therapy 2

• Pregnancy:

  • Known or suspected pregnancy 1

Relative Contraindications/Use with Caution

• Cardiovascular risk factors:

  • Uncontrolled hypertension 2
  • Cerebrovascular disease 2
  • Coronary artery disease 2
  • Thrombogenic valvular or rhythm diseases 2
  • Hypercoagulopathies 2

• Other conditions requiring monitoring:

  • Smokers over 35 years old 2
  • Headaches with focal neurologic symptoms 2
  • Migraine headaches with aura 2
  • Renal dysfunction 2
  • Adrenal insufficiency 2
  • Myeloproliferative neoplasms (requires individualized risk-benefit assessment) 2

Special Considerations for Different Formulations

• Vaginal progesterone:

  • Consider alternative routes when vaginal administration causes discomfort or is contraindicated 2
  • May be contraindicated in cases of vaginal infections or lesions

• Rectal progesterone:

  • Avoid in patients with hormone receptor-positive breast cancer 2
  • Avoid in patients with history of thromboembolic disorders or liver dysfunction 2
  • Ensure appropriate formulation suitable for rectal administration 2

• Oral progesterone:

  • Higher risk of systemic side effects compared to local administration
  • Particular caution with liver dysfunction due to first-pass metabolism 1

Clinical Pitfalls and Caveats

• Distinguish between natural progesterone and synthetic progestins when evaluating contraindications, as they have different risk profiles 3
• Carefully assess breast cancer risk before prescribing progesterone, especially in high-risk patients
• For patients requiring contraception with progesterone contraindications, consider non-hormonal methods such as copper IUDs, barrier methods, or male contraception 4
• In breast cancer survivors, exogenous hormonal contraception is generally contraindicated 4
• The safety of levonorgestrel-releasing IUD remains controversial in breast cancer patients 4
• For patients with severe peanut allergies requiring progesterone therapy, use alternative gel formulations that don't contain peanut oil 2

By carefully screening for these contraindications and using appropriate caution in at-risk populations, the safety profile of progesterone therapy can be optimized while minimizing potential adverse outcomes.