Balancing Cancer Risks and Benefits of Oral Contraceptives

Hormonal contraceptives are widely used for reproductive health and family planning but carry a complex risk-benefit profile in relation to cancer. Evidence from large studies, including Oxford and US cohorts, consistently shows a small, short-term increase in breast and cervical cancer risk with current or recent use, but substantial, long-term reductions in ovarian and endometrial cancers.^1,2

A landmark UK nested case-control study published in PLOS Medicine analyzed nearly 9500 women younger than 50 years diagnosed with invasive breast cancer and over 18,000 matched controls.² Findings show that current or recent use of any hormonal method, including combined oral contraceptives, oral progestagen-only pills, injectable progestagens, implants, and intrauterine devices (IUDs), was associated with a 20% to 30% relative increase in breast cancer risk. Absolute excess risks were age dependent, estimated at 8 cases per 100,000 users aged 16 to 20 years, and up to 265 per 100,000 at age 35 to 39 years, after 5 years of use. Elevated risk declined and returned to baseline within 10 to 15 years post discontinuation. Risk magnitude was similar across delivery methods from pills to IUDs, highlighting that progestagen-only and combined formulations confer comparable breast cancer risk.^2,3

Image Credit: New Africa | stock.adobe.com

Ovarian and Endometrial Cancer

Evidence from large meta-analyses confirms that hormonal contraceptive use yields approximately 40% to 50% reduced risk of both ovarian and endometrial cancers, with protection lasting at least 20 years post-cessation.^3,4 The Collaborative Group’s meta-analysis encompassing 36 epidemiologic studies involving over 27,000 women with endometrial cancer found that each 5-year use was associated with a 24% lower risk, and that reduction persisted for more than 30 years after stopping.⁴ Nurses’ Health Study II also showed nearly 57% lower risk for endometrial cancer among women using contraceptives for over 10 years.³ These long-term benefits must be weighed against short-term risks when counseling patients.

Strategies for Pharmacists

When educating patients, pharmacists should communicate both relative and absolute risks clearly. Although hormonal contraceptive use is linked to a relative 20% to 30% increase in breast cancer risk, absolute excess risk remains low, especially in younger women.² Visual tools and age-based risk charts, such as illustrating that at ages 35 to 39 years, 5 years of use raises breast cancer rates from 2.0% to 2.2%, can help clarify risk. Meanwhile, protective effects such as reducing the risk of ovarian and endometrial cancer remain durable and clinically significant.^3,4

Screening for contraindications and co–risk factors like smoking, hypertension, migraines with aura, or coagulation disorders is essential. While estrogen-containing contraceptives carry a small venous thrombosis risk, progestagen-only methods may reduce vascular risk, though they maintain an equivalent breast cancer risk compared to combined contraceptives.² Method selection should therefore reflect each patient’s health background and reproductive goals.

Pharmacists can develop patient education materials that present short-term trade-offs and long-term benefits of contraceptive use. Incorporate electronic medical record alerts for cervical and breast cancer screening, risk assessment prompts, and follow-up planning. Collaboration with ob-gyns and primary care providers ensures contraceptive planning aligns with broader health considerations and cancer risk reduction strategies.

Conclusion

Both combined and progestagen-only hormonal contraceptives are associated with a slight, time-limited increase in breast cancer risk, particularly during current or recent use, with risk normalizing within a decade after stopping. Conversely, these methods provide powerful and enduring protection against ovarian and endometrial cancers.^3,4 Pharmacists equipped with accurate, evidence-based information can guide women toward informed contraceptive choices that prioritize both reproductive autonomy and long-term health.

REFERENCES

1. National Cancer Institute. Oral contraceptives and cancer risk. National Cancer Institute. Published February 22, 2018. Accessed July 30, 2025 https://www.cancer.gov/about-cancer/causes-prevention/risk/hormones/oral-contraceptives-fact-sheet

2. Fitzpatrick D, Pirie K, Reeves G, Green J, Beral V. Combined and progestagen-only hormonal contraceptives and breast cancer risk: a UK nested case-control study and meta-analysis. PLOS Med. 2023;20(3):e1004188. doi:10.1371/journal.pmed.1004188

3. Burchardt NA, Shafrir AL, Kaaks R, Tworoger SS, Fortner RT. Oral contraceptive use by formulation and endometrial cancer risk among women born in 1947-1964: the Nurses' Health Study II, a prospective cohort study. Eur J Epidemiol. 2021;36(8):827-839. doi:10.1007/s10654-020-00705-5

4. Collaborative Group on Epidemiological Studies on Endometrial Cancer. Endometrial cancer and oral contraceptives: an individual participant meta-analysis of 27 276 women with endometrial cancer from 36 epidemiological studies. Lancet Oncol. 2015;16(9):1061-1070. doi:10.1016/S1470-2045(15)00212-0