Combined oral contraceptives — containing both smaller doses of estrogens plus newer progestogens — are associated with a decreased risk of ovarian cancer in women younger than 50, a large study suggests.
Oral, intravaginal, injectable, and patch estrogen-progestogen combinations are used to prevent pregnancy. The numerous hormone-containing contraceptives available differ in the estrogen compound used and its dose, the progestogen used, the schedule of exposure to the drugs, and the means of administration.
“Previous research has shown a reduced risk of ovarian cancer in users of combined oral contraceptives, an effect that persists for many years after stopping use. However, most of the evidence relates to the use of older and higher-dose preparations of estrogen containing older progestogens,” investigators said.
Therefore, there’s a need to understand if this is also true for newer formulations of combined hormonal contraceptives, which now include lower estrogen doses and newer progestogens, and if a potential ovarian cancer risk benefit is specific to a certain formulation.
In a prospective, Danish cohort study, researchers sought to investigate the association between contemporary combined hormonal contraceptives (including progestogen types in combined preparations and all progestogen-only products) and overall and specific types of ovarian cancer.
Using national prescribing and cancer registries from 1995 until 2014, researchers at the University of Aberdeen in Scotland and the University of Copenhagen in Denmark studied a total of 1,879,227 Danish women ages 15-49.
According to their use of different hormonal contraceptives, women were classified as never users — no record of being dispensed hormonal contraception; current or recent users — up to one year after stopping use; or former users — more than one year after stopping use.
Eighty-six percent of hormonal contraceptive use was related to combined oral contraception.
The number of cases of ovarian cancer were higher in women who had never used hormonal contraceptives, compared to women who had ever used it — 7.5 cases over 100,000 person years versus 3.2 cases over 100,000 person years. The exact number of ovarian cancer cases within the ever users’ group was 478, compared to the 771 ovarian cancers that occurred in the group that never used hormonal contraception.
“Overall, ever users of any hormonal contraception had a reduced risk of ovarian cancer compared with never users,” researchers said. “Reduced risk estimates were also observed for current or recent use of any hormonal contraception … as well as for former use.”
The longer the contraceptive use, the stronger the reduced risk of ovarian cancer got among current users: ovarian cancer risk decreased by 18% after up to one year of use, and dropped by 74% with over 10 years’ use, compared to never users.
Progestogen-only products did not protect against ovarian cancer, but few women were exclusive users of these contraceptives, which statistically limits the ability to detect an effect.
Relative risk comparison between the never and ever users revealed that hormonal contraception prevented an estimated 21% of ovarian cancers in this study’s population.
In addition, a reduced risk from the use of combined contraceptives was seen in almost all studied types of ovarian cancer, including clear cell epithelial, endometrioid epithelial, mucinous epithelial and serous epithelial ovarian cancer. Findings are supported by epidemiological evidence indicative of a long-lasting protection against most ovarian cancer types from combined oral contraceptives.
“The cohort was younger than 50 years, and so few women will have used hormone replacement therapy known to increase ovarian cancer risk,” the team wrote regarding the study’s age criteria. “While this age restriction meant that we could be confident that we were examining the effects of oral contraception, it also meant that the study could not provide information on how contemporary hormonal contraceptives affected ovarian cancer risk in older women, in whom most cases of ovarian cancer occur.”
“Based on results from our prospective study, contemporary combined hormonal contraceptives are still associated with a reduced risk of ovarian cancer in women of reproductive age, with patterns similar to those seen with older combined oral products. The reduced risk seems to persist after stopping use, although it is not yet known how long for. Presently, there is insufficient evidence to suggest similar protection among exclusive users of progestogen-only products,” they concluded.