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.
BMJ. 2018 Sep 26;362:k3609. doi: 10.1136/bmj.k3609.
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.
Prospective, nationwide cohort study.
Denmark, 1995-2014.
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.
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.
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.
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.
探讨当代复方激素避孕药（包括复方制剂中的孕激素类型和所有孕激素单一制剂）与卵巢癌总体及特定类型的相关性。
前瞻性、全国性队列研究。
丹麦，1995-2014 年。
所有在 1995-2014 年期间年龄在 15-49 岁的女性均符合条件。如果她们在 1995 年后移民、患有癌症（除非黑色素瘤皮肤癌外）、有静脉血栓或在入组前接受过不孕症治疗（最终研究人群包括 1879227 名女性），则将其排除在外。女性分为从未使用者（无激素避孕药配药记录）、当前或近期使用者（停药后 1 年内）或以前使用者（停药后 1 年以上）。使用不同的激素避孕药进行分析。
使用泊松回归计算在使用任何当代复方激素避孕药以及在复方制剂和所有孕激素单一制剂（包括非口服制剂）中使用孕激素类型的情况下，卵巢癌的相对风险。单独的分析检查了随访至首次避孕类型转换的女性和具有完整避孕史的女性。检查了持续时间、停药后时间和肿瘤组织学，并计算了人群预防分数。
在 2140 万个人年中，发生了 1249 例卵巢癌事件。在激素避孕药的既往使用者中，在 13344511 个人年中记录了 478 例卵巢癌。从未使用者在 8150250 个人年中发生了 771 例卵巢癌。与从未使用者相比，当前或近期使用和以前使用任何激素避孕药均可降低卵巢癌的风险（相对风险分别为 0.58（95%置信区间 0.49 至 0.68）和 0.77（0.66 至 0.91））。当前或近期使用者的相对风险随着持续时间的增加而降低（从 1 年内使用的 0.82（0.59 至 1.12）降至 10 年以上使用的 0.26（0.16 至 0.43）；P<0.001 趋势）。在随访至首次避孕类型转换的女性中也获得了类似的结果。关于肿瘤类型或复方口服避孕药孕激素含量的风险估计值，没有明显的差异。孕激素单一制剂的使用与卵巢癌风险无关。在激素避孕药的既往使用者中，卵巢癌年龄标准化绝对发生率降低了 3.2/100000 人年。基于从未使用与激素避孕药既往使用类别的相对风险（0.66），估计人群预防分数为 21%-也就是说，激素避孕药的使用在研究人群中预防了 21%的卵巢癌。
在生育年龄的妇女中，使用当代复方激素避孕药与降低卵巢癌风险相关-这种效果与使用时间有关，停药后使用时间减少。这些数据表明孕激素单一制剂没有保护作用。
