Oral Micronized Progesterone and Anesthesia: Perioperative Interaction Guide

Does Oral Micronized Progesterone Interact With Anesthesia?

The label does not describe an interaction with anesthetic agents. It has no separate drug-interactions section; its only interaction statement is in vitro, where ketoconazole inhibited progesterone metabolism by human liver microsomes at an IC50 of less than 0.1 micromolar. The label says this suggests CYP3A4 inhibitors may raise progesterone bioavailability, and that the clinical relevance is unknown [1].

What the label documents is a central nervous system effect: transient dizziness and drowsiness, bedtime dosing, and caution with driving or machinery [2]. How that combines with anesthetic sedation has not been measured in any study we could find.

What Does the Prometrium Label Say About Surgery and Clot Risk?

The label says, if feasible, to discontinue Prometrium at least 4 to 6 weeks before surgery of the type associated with an increased risk of thromboembolism, or during periods of prolonged immobilization. It also says to discontinue immediately if a pulmonary embolism, DVT, stroke or myocardial infarction occurs or is suspected [1]. The instruction appears in the cardiovascular warning and is not tied to sedation.

Label contraindications include active or prior DVT or PE, active or prior arterial thromboembolic disease, liver dysfunction or disease, known, suspected or prior breast cancer, abnormal genital bleeding of unknown cause, and peanut allergy, because the capsules contain peanut oil [2]. The label also says the capsules should not be used during pregnancy [2].

The label reports a DVT relative risk of 1.87 and a PE relative risk of 1.98 versus placebo from the WHI trial of conjugated estrogens 0.625 mg plus medroxyprogesterone 2.5 mg in 16,608 postmenopausal women aged 50 to 79; that progestin was medroxyprogesterone, not micronized progesterone [2][1]. In the ESTHER case-control study of 271 women with a first idiopathic VTE and 610 matched controls, micronized progesterone was not significantly associated with VTE (odds ratio 0.7, 95% CI 0.3 to 1.9) [4]. That study was not about surgery.

How Much Drowsiness and Dizziness Does the Label Report?

In the label's 400 mg/day trial in 25 estrogen-primed postmenopausal women with secondary amenorrhea versus 24 on placebo, dizziness was 24% versus 4% [1]. In the 3-year trial of 200 mg for 12 days a month plus conjugated estrogens (178 women) versus placebo (174 women), dizziness was 15% versus 9% [1]; that comparison cannot be assigned to progesterone alone, because the active group also took estrogen.