TY - JOUR
T1 - Association between contemporary hormonal contraception and ovarian cancer in women of reproductive age in Denmark
T2 - prospective, nationwide cohort study
AU - Iversen, Lisa
AU - Fielding, Shona
AU - Lidegaard, Øjvind
AU - Mørch, Lina S
AU - Skovlund, Charlotte W
AU - Hannaford, Philip C
N1 - Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
PY - 2018
Y1 - 2018
N2 - Objectives 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. Design Prospective, nationwide cohort study. Setting Denmark, 1995-2014. Participants All women aged 15-49 years during 1995-2014 were eligible. Women were excluded if they immigrated after 1995, had cancer (except non-melanoma skin cancer), had venous thrombosis, or were treated for infertility before entry (final study population included 1 879 227 women). Women were categorised as never users (no record of being dispensed hormonal contraception), current or recent users (≤1 year after stopping use), or former users (>1 year after stopping use) of different hormonal contraceptives. Main outcome measures Poisson regression was used to calculate relative risk of ovarian cancer among users of any contemporary combined hormonal contraceptives and by progestogen type in combined preparations and all progestogen-only products, including non-oral preparations. Separate analyses examined women followed up to their first contraception type switch and those with full contraceptive histories. Duration, time since last use, and tumour histology were examined and the population prevented fraction were calculated. Results During 21.4 million person years, 1249 incident ovarian cancers occurred. Among ever users of hormonal contraception, 478 ovarian cancers were recorded over 13 344 531 person years. Never users had 771 ovarian cancers during 8 150 250 person years. Compared with never users, reduced risks of ovarian cancer occurred with current or recent use and former use of any hormonal contraception (relative risk 0.58 (95% confidence interval 0.49 to 0.68) and 0.77 (0.66 to 0.91), respectively). Relative risks among current or recent users decreased with increasing duration (from 0.82 (0.59 to 1.12) with ≤1 year use to 0.26 (0.16 to 0.43) with >10 years' use; P<0.001 for trend). Similar results were achieved among women followed up to their first switch in contraceptive type. Little evidence of major differences in risk estimates by tumour type or progestogen content of combined oral contraceptives was seen. Use of progestogen-only products were not associated with ovarian cancer risk. Among ever users of hormonal contraception, the reduction in the age standardised absolute rate of ovarian cancer was 3.2 per 100 000 person years. Based on the relative risk for the never use versus ever use categories of hormonal contraception (0.66), the population prevented fraction was estimated to be 21% - that is, use of hormonal contraception prevented 21% of ovarian cancers in the study population. Conclusions Use of contemporary combined hormonal contraceptives is associated with a reduction in ovarian cancer risk in women of reproductive age - an effect related to duration of use, which diminishes after stopping use. These data suggest no protective effect from progestogen-only products.
AB - Objectives 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. Design Prospective, nationwide cohort study. Setting Denmark, 1995-2014. Participants All women aged 15-49 years during 1995-2014 were eligible. Women were excluded if they immigrated after 1995, had cancer (except non-melanoma skin cancer), had venous thrombosis, or were treated for infertility before entry (final study population included 1 879 227 women). Women were categorised as never users (no record of being dispensed hormonal contraception), current or recent users (≤1 year after stopping use), or former users (>1 year after stopping use) of different hormonal contraceptives. Main outcome measures Poisson regression was used to calculate relative risk of ovarian cancer among users of any contemporary combined hormonal contraceptives and by progestogen type in combined preparations and all progestogen-only products, including non-oral preparations. Separate analyses examined women followed up to their first contraception type switch and those with full contraceptive histories. Duration, time since last use, and tumour histology were examined and the population prevented fraction were calculated. Results During 21.4 million person years, 1249 incident ovarian cancers occurred. Among ever users of hormonal contraception, 478 ovarian cancers were recorded over 13 344 531 person years. Never users had 771 ovarian cancers during 8 150 250 person years. Compared with never users, reduced risks of ovarian cancer occurred with current or recent use and former use of any hormonal contraception (relative risk 0.58 (95% confidence interval 0.49 to 0.68) and 0.77 (0.66 to 0.91), respectively). Relative risks among current or recent users decreased with increasing duration (from 0.82 (0.59 to 1.12) with ≤1 year use to 0.26 (0.16 to 0.43) with >10 years' use; P<0.001 for trend). Similar results were achieved among women followed up to their first switch in contraceptive type. Little evidence of major differences in risk estimates by tumour type or progestogen content of combined oral contraceptives was seen. Use of progestogen-only products were not associated with ovarian cancer risk. Among ever users of hormonal contraception, the reduction in the age standardised absolute rate of ovarian cancer was 3.2 per 100 000 person years. Based on the relative risk for the never use versus ever use categories of hormonal contraception (0.66), the population prevented fraction was estimated to be 21% - that is, use of hormonal contraception prevented 21% of ovarian cancers in the study population. Conclusions Use of contemporary combined hormonal contraceptives is associated with a reduction in ovarian cancer risk in women of reproductive age - an effect related to duration of use, which diminishes after stopping use. These data suggest no protective effect from progestogen-only products.
KW - Adolescent
KW - Adult
KW - Aged
KW - Cohort Studies
KW - Contraception/adverse effects
KW - Contraceptives, Oral, Combined/adverse effects
KW - Contraceptives, Oral, Hormonal/adverse effects
KW - Denmark/epidemiology
KW - Female
KW - Humans
KW - Incidence
KW - Middle Aged
KW - Ovarian Neoplasms/chemically induced
KW - Progestins/adverse effects
KW - Prospective Studies
KW - Risk Factors
KW - Young Adult
U2 - 10.1136/bmj.k3609
DO - 10.1136/bmj.k3609
M3 - Journal article
C2 - 30257920
SN - 0959-8146
VL - 362
SP - 1
EP - 9
JO - BMJ (Clinical research ed.)
JF - BMJ (Clinical research ed.)
M1 - k3609
ER -
