Can a healthy, non‑smoking woman with a first‑degree relative with factor V Leiden thrombophilia and no personal history of venous thromboembolism safely use Nexplanon (etonogestrel) for contraception?

Nexplanon is Safe for Women with Family History of Factor V Leiden

A healthy, non-smoking woman with a first-degree relative with factor V Leiden thrombophilia and no personal history of VTE can safely use Nexplanon without testing for the mutation. Progestin-only contraceptives like Nexplanon do not carry the estrogen-related thrombotic risk that makes combined oral contraceptives dangerous in this population. 1

Why Nexplanon is Safe in This Context

Progestin-Only Methods Do Not Increase VTE Risk

• The 30-fold increased VTE risk associated with factor V Leiden applies exclusively to combined oral contraceptives containing estrogen, not to progestin-only methods like Nexplanon. 1

• Combined oral contraceptives alone increase thrombosis risk 4-fold in the general population, which escalates to approximately 30-fold in factor V Leiden heterozygotes—this risk is driven entirely by the estrogen component. 1, 2

• Progestin-only contraceptives do not increase venous thromboembolism risk in the same manner as estrogen-containing products, according to the American College of Medical Genetics. 1

Testing is Not Required Before Prescribing Nexplanon

• Nexplanon can be prescribed safely without factor V Leiden testing, as it does not carry estrogen-related thrombotic risk. 1

• The American College of Medical Genetics explicitly recommends against routine screening of all asymptomatic women due to cost-effectiveness concerns and potential psychosocial harms, including insurance discrimination and job-related issues. 1

• Even if testing were performed and showed factor V Leiden positive, Nexplanon would remain an appropriate choice, as progestin-only methods are not contraindicated in thrombophilia. 1

When Testing Should Be Considered

Indications for Factor V Leiden Testing

• Testing may be appropriate for women contemplating combined hormonal contraceptives (pills, patches, or vaginal rings) who have a family history of thromboembolism, according to the American College of Medical Genetics. 1

• The American College of Medical Genetics recommends factor V Leiden testing for women with a family history of thromboembolism who are specifically contemplating estrogen-containing hormonal contraception. 1

Critical Contraindication: Personal History of VTE

• If the patient has a personal history of VTE, this would be a contraindication to all hormonal contraception, including Nexplanon, and testing becomes mandatory. 1

• The FDA label for etonogestrel lists "a high risk of arterial or venous thrombotic diseases" as a contraindication. 3

Understanding the Risk Profile

Absolute Risk Remains Low in Heterozygotes

• Heterozygous factor V Leiden carriers with a family history of VTE have a low absolute antepartum VTE risk of 0.50% (95% CI, 0.06%-1.21%). 4

• The baseline venous thrombosis rate in heterozygous factor V Leiden carriers is only 0.19-0.56% per year, representing a modest absolute risk. 1

• Research data confirm that absolute VTE risk during combined oral contraceptive use in women with single thrombophilic defects (including factor V Leiden) is 0.49 per 100 person-years, compared to 0.19 in those without defects. 5

Combined Oral Contraceptives Should Be Avoided

• The American College of Medical Genetics recommends avoiding combined oral contraceptives in women with factor V Leiden, as the combination increases thrombotic risk 30-fold compared to 4-fold with oral contraceptives alone. 2

• A meta-analysis demonstrated that in COC-users with mild thrombophilia (factor V Leiden or prothrombin mutation), the risk of VTE increased almost 6-fold (rate ratio 5.89; 95% CI, 4.21-8.23). 6

• Carriers of factor V Leiden using desogestrel-containing oral contraceptives face an almost 50-fold increased risk compared with non-carrier non-users. 7

Common Pitfalls to Avoid

• Do not confuse progestin-only contraceptives with combined hormonal contraceptives—the thrombotic risk profiles are fundamentally different. 1

• Do not assume the vaginal ring (NuvaRing) is safer than oral contraceptives merely because it delivers a lower systemic estrogen dose; it remains a combined hormonal contraceptive with comparable thrombotic risk. 2

• Do not withhold effective contraception based solely on family history when progestin-only methods are available and safe. 1

• Do not order factor V Leiden testing in asymptomatic women before prescribing progestin-only contraceptives—it provides no clinical benefit and may cause psychosocial harm. 1