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Association between contemporary hormonal contraception and ovarian cancer in women of reproductive age in Denmark: prospective, nationwide cohort study.

Abstract

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.

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  • Authors+Show Affiliations

    ,

    Academic Primary Care, Institute of Applied Health Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK.

    ,

    Medical Statistics Team, Institute of Applied Health Sciences, University of Aberdeen, Aberdeen, UK.

    ,

    Rigshospitalet, Juliane Marie Centre, Department of Gynaecology, University of Copenhagen, Denmark.

    ,

    Rigshospitalet, Juliane Marie Centre, Department of Gynaecology, University of Copenhagen, Denmark.

    ,

    Rigshospitalet, Juliane Marie Centre, Department of Gynaecology, University of Copenhagen, Denmark.

    Academic Primary Care, Institute of Applied Health Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK.

    Source

    BMJ (Clinical research ed.) 362: 2018 Sep 26 pg k3609

    MeSH

    Adolescent
    Adult
    Aged
    Cohort Studies
    Contraception
    Contraceptives, Oral, Combined
    Contraceptives, Oral, Hormonal
    Denmark
    Female
    Humans
    Incidence
    Middle Aged
    Ovarian Neoplasms
    Progestins
    Prospective Studies
    Risk Factors
    Young Adult

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    30257920

    Citation

    Iversen, Lisa, et al. "Association Between Contemporary Hormonal Contraception and Ovarian Cancer in Women of Reproductive Age in Denmark: Prospective, Nationwide Cohort Study." BMJ (Clinical Research Ed.), vol. 362, 2018, pp. k3609.
    Iversen L, Fielding S, Lidegaard Ø, et al. Association between contemporary hormonal contraception and ovarian cancer in women of reproductive age in Denmark: prospective, nationwide cohort study. BMJ. 2018;362:k3609.
    Iversen, L., Fielding, S., Lidegaard, Ø., Mørch, L. S., Skovlund, C. W., & Hannaford, P. C. (2018). Association between contemporary hormonal contraception and ovarian cancer in women of reproductive age in Denmark: prospective, nationwide cohort study. BMJ (Clinical Research Ed.), 362, pp. k3609. doi:10.1136/bmj.k3609.
    Iversen L, et al. Association Between Contemporary Hormonal Contraception and Ovarian Cancer in Women of Reproductive Age in Denmark: Prospective, Nationwide Cohort Study. BMJ. 2018 Sep 26;362:k3609. PubMed PMID: 30257920.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Association between contemporary hormonal contraception and ovarian cancer in women of reproductive age in Denmark: 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, Y1 - 2018/09/26/ PY - 2018/9/28/entrez PY - 2018/9/28/pubmed PY - 2019/3/20/medline SP - k3609 EP - k3609 JF - BMJ (Clinical research ed.) JO - BMJ VL - 362 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. SN - 1756-1833 UR - https://www.unboundmedicine.com/medline/citation/30257920/Association_between_contemporary_hormonal_contraception_and_ovarian_cancer_in_women_of_reproductive_age_in_Denmark:_prospective_nationwide_cohort_study_ L2 - http://www.bmj.com/cgi/pmidlookup?view=long&amp;pmid=30257920 DB - PRIME DP - Unbound Medicine ER -