Use of newer combined hormonal contraceptives may be associated with reduced ovarian cancer risk

The risk reduction was greater with increasing duration of use and persisted for several years after discontinuation, although there was no observed effect with use of progestogen-only products.

Compared to no use of contemporary combined hormonal contraceptives, current or former use was associated with reduced risk of ovarian cancer in women of reproductive age, a recent prospective study found.

Researchers used data from 1995 to 2014 on all women ages 15 to 49 years in Denmark to assess the association between contemporary combined hormonal contraceptives (including progestogen types in combined preparations and all progestogen-only products) and ovarian cancer (both overall and specific types). Women were excluded if they immigrated after 1995, had cancer (except nonmelanoma skin cancer), had venous thrombosis, or were previously treated for infertility.

The final study population included 1,879,227 women. The researchers categorized participants as never users (no record of receiving hormonal contraception), current or recent users (≤1 year after stopping use), or former users (>1 year after stopping use) of different hormonal contraceptives. Results were published online on Sept. 26 by the BMJ.

Overall, 1,249 incident ovarian cancers occurred: 478 cases over 13,344,531 person-years among participants who ever used hormonal contraception and 771 cases over 8,150,250 person-years among never users. Compared with never users, current/recent users and former users had reduced risks of ovarian cancer (relative risks, 0.58 [95% CI, 0.49 to 0.68] and 0.77 [95% CI, 0.66 to 0.91], respectively; overall relative risk in ever users, 0.66 [95% CI, 0.58 to 0.76]).

Relative risk among current/recent users decreased with increasing duration (from 0.82 [95% CI, 0.59 to 1.12] with ≤1 year of use to 0.26 [95% CI, 0.16 to 0.43] with >10 years of use; P<0.001 for trend). The risk reduction with former use diminished with time since discontinuation and was not significant by 10 years after last use. There was little difference in risk estimates by tumor type or progestogen content of combined oral contraceptives, but use of progestogen-only products was not associated with ovarian cancer risk (although few women were exclusive users of such products, limiting statistical power).

Among ever users, the reduction in the age-standardized absolute rate of ovarian cancer was 3.2 per 100,000 person-years. Based on a relative risk of 0.66 for the never-use versus ever-use categories, hormonal contraception prevented 21% of ovarian cancers in the study population, the study authors estimated.

The authors noted limitations, such as their inability to ensure that women who were dispensed a prescription actually used it. They added that the results do not provide information on women ages 50 years and older and that they were not able to adjust for some confounding factors (e.g., breastfeeding).

“It has been suggested that recent downward trends in ovarian cancer mortality rates in North America and Europe can be partly attributed to the use of combined oral contraceptives,” the authors wrote. “We found a population prevented fraction of 21% with use of hormonal contraception, which supports the notion that these ovarian cancer mortality benefits are likely to continue.”