Absolute and Relative Contraindications to Progesterone
Progesterone therapy has specific absolute contraindications defined by FDA labeling, including known hypersensitivity (particularly peanut allergy for micronized formulations), undiagnosed abnormal genital bleeding, known/suspected/history of breast cancer, active or history of venous thromboembolism, active or history of arterial thromboembolism (stroke, MI), known liver dysfunction or disease, and known/suspected pregnancy. 1
Absolute Contraindications
The FDA-approved labeling for progesterone capsules establishes the following absolute contraindications 1:
Known hypersensitivity to progesterone or its ingredients - Micronized progesterone formulations contain peanut oil and should never be used in patients with peanut allergies 2, 3, 1
- Note: Vaginal gel formulations do not contain peanut oil and can be used as an alternative in patients with peanut allergies 2
Undiagnosed abnormal genital bleeding 1
Known, suspected, or history of breast cancer - This includes hormone receptor-positive breast cancers 2, 3, 1
Active deep vein thrombosis or pulmonary embolism, or history of these conditions 1
Active arterial thromboembolic disease (stroke, myocardial infarction) or history of these conditions 2, 1
Known liver dysfunction or disease 1
Known or suspected pregnancy 1
Relative Contraindications and High-Risk Situations
The NCCN guidelines identify additional patient-specific factors that require careful consideration when prescribing progestin-based therapy 2:
Active smoking - Particularly concerning when combined with other cardiovascular risk factors 2, 4
History of thromboembolic events (even if not currently active) - Requires systematic risk-benefit analysis 4
Important Clinical Caveats
Cancer Survivors and High-Risk Populations
Endometrial cancer patients receiving fertility-sparing progestin therapy require endometrial sampling every 3-6 months to monitor for progression 2
Cancer survivors often have treatment-related complications and increased metabolic syndrome risk, requiring particularly careful assessment of contraindications 2
Formulation-Specific Considerations
Transdermal 17β-estradiol-based preparations are preferred over oral formulations in young women with iatrogenic premature ovarian insufficiency who have cardiovascular risk factors, as they avoid first-pass hepatic metabolism 2
Micronized progesterone has improved bioavailability and fewer reported side effects compared to synthetic progestins, but the peanut oil excipient remains an absolute contraindication in severe peanut allergy 2, 3, 1
Monitoring Requirements
When progesterone therapy is used despite relative contraindications, enhanced surveillance is mandatory:
Endometrial sampling every 3-6 months for patients receiving progestin monotherapy for endometrial conditions 2
Systematic assessment of disease-related metabolic profile and strength of contraindication before initiating therapy 2
Common Pitfall to Avoid
Do not confuse natural progesterone with synthetic progestins when assessing contraindications - while the absolute contraindications listed above apply to both, natural progesterone may have a more favorable safety profile for certain outcomes like breast cancer risk compared to synthetic progestins, though the absolute contraindications remain unchanged 5