Does Sugammadex Bind to Both Estrogen and Progesterone?
Sugammadex binds to progesterone but does NOT bind to estrogen. 1
Binding Specificity
Sugammadex selectively binds to progestogen (progesterone), not estrogen. The FDA label explicitly states that "in vitro binding studies indicate that BRIDION may bind to progestogen, thereby decreasing progestogen exposure." 1 There is no mention of estrogen binding in the drug label or clinical guidelines.
- The binding affinity studies using isothermal titration calorimetry screened 300 drugs, including both steroidal and nonsteroidal compounds acting on steroidal receptors, and confirmed sugammadex's selective binding to steroidal structures similar to neuromuscular blocking agents. 2
- Sugammadex is a modified γ-cyclodextrin designed to encapsulate steroidal neuromuscular blocking agents (rocuronium and vecuronium) through its lipophilic cavity, and progesterone shares structural similarities that allow binding. 2, 3
Clinical Implications for Hormonal Contraception
The FDA mandates that patients on hormonal contraceptives (containing either estrogen or progestogen) must use backup contraception for 7 days after sugammadex administration. 1 This recommendation applies because:
- Administration of sugammadex is considered equivalent to missing dose(s) of oral contraceptives containing estrogen or progestogen. 1
- For oral contraceptives taken on the same day as sugammadex, patients must use additional non-hormonal contraception (condoms and spermicides) for 7 days. 1
- For non-oral hormonal contraceptives (patches, rings, implants, IUDs), the same 7-day backup contraception rule applies. 1
The Association of Anaesthetists guideline reinforces this, stating that "after administration of sugammadex, patients taking oral hormonal contraceptives must be advised to follow 'missed pill rules.'" 4
Laboratory Interference
Sugammadex interferes with serum progesterone assays, not estrogen assays. 1 This interference occurs at sugammadex plasma concentrations of 100 mcg/mL, which may be observed for up to 30 minutes after a 16 mg/kg dose. 1
Recent Clinical Evidence
A 2023 prospective observational study found no evidence that sugammadex threatens contraceptive efficacy in women on hormonal contraception. 5 In this study of 60 women on hormonal contraception receiving sugammadex:
- Median estrogen levels decreased by approximately 40% at 240 minutes in all groups (including controls), suggesting this was unrelated to sugammadex. 5
- Progesterone levels rose significantly at 15 minutes post-sugammadex, then decreased non-significantly to 20% below baseline at 240 minutes. 5
- The authors concluded that both the decrease in estrogen and rise in progesterone could act to minimize ovulation risk and protect contraception. 5
Critical Counseling Gap
Despite clear FDA warnings, counseling about this drug interaction is severely inadequate in clinical practice. 6, 7
- A 2020 retrospective review found that only 0.7% (1 of 134 women) using hormonal contraception at the time of sugammadex exposure had documented counseling, and one patient had an unintended pregnancy within the same cycle. 6
- A 2021 survey revealed that 67% of anesthesia providers reported "rarely/never" discussing this interaction preoperatively and 80% postoperatively, despite 78% agreeing it should be discussed. 7
- Only 44% of providers correctly identified potential interference with hormonal IUDs and 55% with contraceptive implants. 7
Practical Recommendations
Anesthesia providers must actively counsel all women of childbearing potential about this interaction before sugammadex administration. 4
- Preoperatively identify all patients using any form of hormonal contraception (oral, patch, ring, implant, or hormonal IUD). 7
- Counsel that sugammadex may reduce contraceptive effectiveness equivalent to missing a dose. 1
- Provide clear instructions for 7 days of backup non-hormonal contraception (condoms, spermicides, or abstinence). 1
- Document this counseling in the medical record. 6
- For transgender and gender-diverse patients on oral contraceptives, the same counseling applies to transmasculine and nonbinary patients, but not to transfeminine patients taking estrogen for gender affirmation (as they are typically assigned male at birth and not at pregnancy risk). 4