Is it safe to continue progesterone (oral, injectable, transdermal, or intra‑uterine) during the peri‑operative period for patients undergoing non‑obstetric surgery, and what specific contraindications require its discontinuation?

Progesterone Perioperative Management in Non-Obstetric Surgery

Direct Recommendation

All progestogen-only therapy (oral progesterone, injectable progestins, transdermal progestins, and levonorgestrel IUDs) should be continued throughout the perioperative period for non-obstetric surgery, as these agents do not increase venous thromboembolism risk and discontinuation provides no safety benefit. 1

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Absolute Contraindications Requiring Discontinuation

Progesterone must be discontinued if any of the following conditions exist:

• Known, suspected, or history of breast cancer (including hormone receptor-positive breast cancers) 2, 3
• Active arterial thromboembolic disease (stroke or myocardial infarction) or history of these conditions 2, 3
• Active deep vein thrombosis or pulmonary embolism, or history of these conditions 3
• Known liver dysfunction or disease 3
• Severe peanut allergy (for micronized progesterone formulations containing peanut oil; vaginal gel formulations can be used as alternative) 2, 3

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Specific Surgical Context: Cardiac Surgery

For patients undergoing coronary artery bypass graft (CABG) surgery, postmenopausal hormone therapy containing progesterone carries a Class III: HARM recommendation and must be discontinued preoperatively. 1 This represents the highest level of evidence against continuation in this specific surgical population.

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Risk-Stratified Approach for Other Non-Cardiac Surgeries

Continue Progesterone-Only Therapy

The following formulations should be continued regardless of surgery type 1:

• Progestogen-only contraceptive pills
• Depot medroxyprogesterone acetate (DMPA) injections
• Subdermal progestin implants
• Levonorgestrel intrauterine devices

These agents lack the thrombogenic effects of estrogen-containing preparations and do not require discontinuation 4.

Combined Estrogen-Progesterone Therapy Considerations

For combined hormone therapy (estrogen plus progesterone), hold therapy 3-4 weeks preoperatively only in these specific scenarios 1:

• Major surgery with prolonged immobility expected
• Patients with additional VTE risk factors (personal/family history of VTE, obesity, systemic lupus erythematosus)
• Patients with severe hypercortisolism (Cushing's disease) awaiting surgery

The thrombogenic risk in combined therapy is primarily driven by the estrogen component, not progesterone. 4

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Thromboprophylaxis Strategy When Continuing Therapy

When progesterone-containing therapy is continued perioperatively, implement 1:

• Low molecular weight heparin (with individualized timing of discontinuation before surgery to minimize bleeding risk)
• Early ambulation protocols
• Compression stockings

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Special Populations

Gender-Affirming Hormone Therapy

Hormone therapy should be continued throughout the perioperative period unless specific contraindications exist. 5 The physical and mental health benefits of continuing therapy may outweigh thrombotic risk, particularly given the psychological harm from discontinuation (exacerbation of gender dysphoria, depression, anxiety) 5. Recent evidence from facial feminization surgery showed no increased VTE risk with continued feminizing hormone therapy (0.10% VTE rate, comparable to similar cosmetic procedures) 6.

Hepatic Disease

Avoid estrogen-containing agents (but not necessarily progesterone-only therapy) in patients with 1:

• Decompensated cirrhosis
• Budd-Chiari syndrome
• Hepatocellular adenomas
• Transplant recipients with graft failure

Prefer progestogen-only methods in these populations.

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Critical Clinical Caveats

Lack of Definitive Evidence

No clear randomized controlled trial evidence exists for perioperative management of hormone therapy. 7, 8 The recommendation to discontinue combined hormone therapy is based primarily on manufacturer recommendations and extrapolation from non-surgical VTE data, not perioperative-specific studies 7.

Pregnancy Risk vs. VTE Risk

The decision to discontinue must weigh the risk of fetal harm from unwanted pregnancy in reproductive-age patients preparing for surgery against the theoretical increased VTE risk 7. For progesterone-only methods, this calculation strongly favors continuation given the lack of VTE risk.

Monitoring Requirements

For patients receiving progestin therapy for endometrial conditions (not contraception), endometrial sampling every 3-6 months is recommended 2. This does not apply to standard contraceptive use.

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Algorithm for Decision-Making

1. Identify formulation type:

   • Progesterone-only → Continue (proceed to step 2 for contraindication check)
   • Combined estrogen-progesterone → Assess surgery type and VTE risk factors

2. Screen for absolute contraindications (breast cancer, active/history of arterial thrombosis, active/history of VTE, liver disease, peanut allergy for oral formulations) 2, 3

   • If present → Discontinue
   • If absent → Proceed to step 3

3. Assess surgical context:

   • CABG surgery → Discontinue combined therapy 1
   • Major surgery with prolonged immobility + additional VTE risk factors → Hold combined therapy 3-4 weeks preoperatively 1
   • All other surgeries → Continue with appropriate thromboprophylaxis 1

4. Implement thromboprophylaxis when continuing therapy (LMWH, early ambulation, compression stockings) 1