How Does Hormonal Contraceptive Use Affect Ovarian Cancer Risk?

A large cohort study shows that combined hormonal contraceptive use is associated with a significant reduction in the risk of ovarian cancer. There is no effect, however, associated with progestogen-only products.

Previous work has shown a reduced ovarian cancer risk with the use of combined oral contraceptives as well. “However, most of the evidence relates to the use of older and higher dose preparations of estrogen-containing older progestogens,” wrote study authors led by Philip C. Hannaford, MD, of the University of Aberdeen in Scotland. “Therefore, this evidence might not reflect the impact of substantial changes in hormonal contraception that have occurred over time.” Oral contraceptives have seen estrogen dose reduced, and newer progestogens have been introduced including desogestrel, gestodene, and drospirenone.

The researchers conducted a large study using a national cohort of Danish women to examine more recent associations between contraceptive use and ovarian cancer. The final study population included 1,879,227 women, all aged 15–49 years between 1995 and 2014; women were excluded if they had cancer prior to study entry, or if they had venous thrombosis or were treated for infertility. The results of the analysis were published in the British Medical Journal.

During the 20-year study period covering 21.4 million person-years of observation, a total of 1,249 women had incident ovarian cancer. A total of 478 incident ovarian cancers were found among ever-users of any hormonal contraception; 771 cancers occurred in never-users. The median age at cancer diagnosis was 44.4 years.

The age-adjusted incidence of ovarian cancer was highest in never-users of hormonal contraception, at 7.5 per 100,000 person-years. Ever-use of any contraception was associated with an incidence of 4.3 per 100,000 person-years, for an adjusted relative risk of 0.66 (95% CI, 0.58–0.76). The risk decreased with increasing length of contraception use: those with more than 10 years of use had a relative risk of 0.26 (95% CI, 0.16–0.43), while those with 1 year or less had a relative risk of 0.82 (95% CI, 0.59–1.12).

The reduction in risk among previous users diminished with time since stopping their use of contraception; the difference was non-significant after 10 years since last use.

Little difference was observed between different combined hormonal contraceptives, but progestogen-only formulations did not appear to reduce the risk of ovarian cancer. For example, current or recent use of norethisterone was associated with a relative risk of ovarian cancer of 0.62 (95% CI, 0.23–1.64). The authors did note, however, that there were few women who were exclusive users of these products, meaning the statistical power to detect differences in cancer risk was limited.

Vance Broach, MD, of Memorial Sloan Kettering Cancer Center in New York, who was not involved in the research, noted that "unlike previously published studies, the authors were able to report on the effect of specific hormonal contraceptives and their components. This owes to the large sample size and granularity of the data collected in this study. Specifically, the authors did not find as robust a reduction in ovarian cancer risk among women who utilized progesterone-only hormonal contraceptives. When translating the results of this study to patient care, these data are important for several reasons," noting the need to reduce risk for women with "familial or genetic predispositions for ovarian cancer."

Robert L. Coleman, MD, of the University of Texas MD Anderson Cancer Center, who was not involved in the research, told Cancer Network, “It has been known for decades that hormonal contraception was associated with a lower risk of ovarian cancer development. The exact etiology for this decreased risk has been, and is still, largely unknown, but several hypotheses, including interruption of ovulation and alteration of the microenvironment steroidal milieu, have been stated. Both preclinical and clinical data have more or less supported these contentions, including reduction in risk for women at highest risk for ovarian cancer development (eg, those carrying a germline mutation in BRCA1 or BRCA2)."

"These data are welcome news to patients and clinicians. The lack of apparent benefit extended from progestin-only therapy has been previously noted and challenges our understanding of risk modulation and mechanism; however, these agents may not interrupt ovulatory events to the same degree as combination-based contraceptives. Not addressed in the study are long-term effects from use on other conditions, including breast cancer. As such, a balance of known risks, benefits, and alternatives should be discussed with prospective users,” he noted.