Does Aygestin (Norethindrone Acetate) Increase Cervical Cancer Risk?
No, Aygestin (norethindrone acetate) as a progestin-only contraceptive does not appear to increase cervical cancer risk based on current evidence. 1, 2
Key Evidence on Progestin-Only Contraceptives and Cervical Cancer
The distinction between combined hormonal contraceptives (containing both estrogen and progestin) and progestin-only formulations is critical here:
Progestin-only contraceptives show no increased cervical cancer risk. The CDC's Medical Eligibility Criteria found that among women with persistent HPV infection, long-term use (≥5 years) of combined hormonal contraceptives may increase risk, but this applies specifically to estrogen-containing products. 1
A large South African case-control study of 524 cervical cancer cases found no increased risk with injectable progestogen contraceptives (primarily depot medroxyprogesterone acetate), with an adjusted relative risk of 1.0 (95% CI 0.8-1.3), even with duration extending to ≥15 years. 2
Recent Danish cohort data (2021) involving over 20 million person-years showed current or recent users of progestin-only contraception had a relative risk of 0.91 (95% CI 0.78-1.07)—actually suggesting no increased risk and possibly a protective trend. 3
Why Combined Contraceptives Show Different Results
The cervical cancer risk associated with hormonal contraception appears confined to combined estrogen-progestin products:
Combined oral contraceptives show a modest duration-dependent increase in cervical cancer risk among HPV-positive women. Current or recent users of combined contraceptives had a relative risk of 1.40 (95% CI 1.28-1.53), translating to approximately 1 extra cervical cancer per 14,700 women using combined contraceptives for 1 year. 3
The risk increases with duration of combined contraceptive use: relative risks of 1.1 for <5 years, 1.6 for 5-9 years, and 2.2 for ≥10 years among all women, with similar patterns in HPV-positive women (2.5 for ≥10 years). 4
This risk appears to decline after discontinuation, disappearing approximately 10 years after stopping combined contraceptives. 1
Clinical Context: HPV as the Primary Driver
Persistent high-risk HPV infection remains the primary cause of cervical cancer, far outweighing any hormonal influence. 5 The mechanism by which combined contraceptives may increase risk is thought to involve potentiation of HPV oncogenicity in the presence of estrogen, which is absent in progestin-only formulations like Aygestin. 4
Practical Recommendations for Aygestin Users
Women using Aygestin should follow standard cervical cancer screening guidelines (beginning at age 25 for average-risk women, or age 21 for those with HIV). 1, 6
HPV vaccination and regular screening remain the cornerstone prevention strategies, regardless of contraceptive choice. 5
Women with cervical intraepithelial neoplasia (CIN) can use progestin-only contraceptives (Category 2 per CDC criteria), as there is no evidence of worsening outcomes. 1
Important Caveat
The evidence base specifically examining norethindrone acetate (Aygestin) and cervical cancer is limited. Most studies examine depot medroxyprogesterone acetate or do not distinguish between different progestin-only formulations. 7 However, the consistent finding across multiple progestin-only products is reassuring that this class does not increase cervical cancer risk. 3, 2