NuvaRing Use with Heterozygous Factor V Leiden: Not Recommended
Women with heterozygous Factor V Leiden should avoid NuvaRing and all combined hormonal contraceptives (including vaginal rings containing estrogen and progestin) due to a 30-fold increased risk of venous thromboembolism compared to 4-fold risk with combined hormonal contraceptives alone. 1, 2
Why Combined Hormonal Contraceptives Are Contraindicated
The NuvaRing releases ethinyl estradiol (15 μg) and etonogestrel (120 μg), making it a combined hormonal contraceptive with the same thrombotic risks as oral contraceptive pills. 1
Quantifying the Risk
- Baseline VTE risk in women under 44: 5 events per 100,000 woman-years 1
- With combined hormonal contraceptives alone: 4-fold increased risk 1
- With Factor V Leiden heterozygosity + combined hormonal contraceptives: 30-fold increased risk 1, 2
- Absolute risk: This translates to 15 deaths per million woman-years (compared to 4 deaths per million with contraceptives alone in non-carriers) 1
Recent research confirms this synergistic effect, with one study showing an odds ratio of 20.6 for VTE in Factor V Leiden carriers using combined hormonal contraception. 3
Guideline Recommendations
The American College of Medical Genetics explicitly recommends avoiding combined oral contraceptives in women with Factor V Leiden and counseling them about alternative contraceptive methods. 2 This applies equally to all combined hormonal contraceptives, including vaginal rings. 2
The American Society of Hematology reinforces that women with thrombophilia, including Factor V Leiden, should avoid estrogen-containing contraceptives due to increased VTE risk. 4
Safer Contraceptive Alternatives
Progestin-Only Options (Preferred)
- Progestin-only pills (no estrogen component) 3
- Levonorgestrel IUD (intrauterine device) 3
- Etonogestrel implant (subdermal) 3
These progestin-only methods appear to be the least thrombogenic hormonal contraception for women with genetic hemostatic variations. 3
Important Exception
Medroxyprogesterone acetate injection carries an odds ratio of 2.2 for VTE and should be used cautiously even though it's progestin-only. 3 Women with Factor V Leiden using this method had an OR of 5.4 for VTE. 3
Non-Hormonal Options
- Copper IUD
- Barrier methods (condoms, diaphragm)
- Permanent sterilization (if family planning complete)
Critical Clinical Pitfalls to Avoid
Do not assume the vaginal ring is safer than oral contraceptives simply because it delivers lower systemic estrogen doses—the thrombotic risk remains comparable to other combined hormonal methods. 1, 5
Do not screen the general population before prescribing contraceptives, but if Factor V Leiden status is already known (as in this case), act on that information. 1, 2
Do not underestimate pregnancy risk: Denying effective contraception increases pregnancy rates, and pregnancy itself carries VTE risk (especially postpartum), along with other complications like preeclampsia and placental abruption that are also associated with Factor V Leiden. 1 However, the 30-fold increased risk with combined hormonal contraceptives still outweighs these concerns when safer contraceptive alternatives exist.
Additional Considerations
If this patient has a family history of VTE in first-degree relatives, the recommendation against combined hormonal contraceptives becomes even stronger. 1
Test for prothrombin G20210A mutation in all Factor V Leiden-positive patients, as compound heterozygosity dramatically increases thrombotic risk (OR 6.69). 2, 4
During high-risk situations (surgery, prolonged immobilization, long-distance travel), provide appropriate VTE prophylaxis regardless of contraceptive choice. 2