目前或最近使用含有雌激素和黄体素的口服避孕药与乳腺癌风险略有增加相关。黄体素单用药正在增加，但相关风险信息有限。我们旨在评估更年轻期妇女使用不同类型的激素避孕药与乳腺癌风险的关系，特别强调单黄体素制剂。根据英国初级保健数据库（临床实践研究数据联接（CPRD））中预先记录的激素避孕药处方，在一项巢式病例对照研究中比较9,498名年龄小于50岁，在1996年至2017年间被诊断为患有侵袭性乳腺癌的妇女和18,171名密切匹配的对照组。每个病例及其匹配的对照组在诊断日期之前平均可用于临床记录的时间为7.3年（标准偏差[SD]4.6年）。进行条件 logistic 回归，控制变量包括年龄、家庭医生诊所、体重指数、记录出生数量、上次分娩时间以及饮酒量，计算出口服避孕药、注射型黄体素、植入型黄体素和放置型子宫内节育器（IUD）作为最后一次处方对患有乳腺癌的医疗机构的比例，并计算出95%置信区间（Cl）。我们搜索了 Medline 和 Embase 上1995年1月1日至2022年11月1日的观察性研究，并从12个既往的观察性研究结果中选取结果，评估黄体素单独避孕药使用与更年轻期妇女乳腺癌风险之间的关联。我们的元分析将 CPRD 结果与以前公布的结论相结合，总的来说，与口服激素药、注射络孕酮、植入型避孕药或 IUD 相比，当最后一次处方为黄体素单独制剂时，乳腺癌 OR 值相对较高而明显：分别为1.23(95% CI [1.14-1.32]; p < 0.001)、1.26(95% CI [1.16-1.37]; p < 0.001)、1.25(95% CI [1.07-1.45]; p = 0.004) 和1.32(95% CI [1.17-1.49]; p < 0.001)。我们的元分析得出使用黄体素单独避孕药目前或最近 RR 显著提高：口服药 = 1.29(95% CI [1.21-1.37]; 杂质 χ25 = 6.7; p = 0.2)，注射药= 1.18 (95% CI [1.07-1.30]; 杂质 χ28 = 22.5; p = 0.004)，植入物 = 1.28(95% CI [1.08-1.51]; 杂质 χ23 = 7.3; p = 0.06) 和 IUD= 1.21(95% CI [1.14-1.28];杂质 χ24 = 7.9; p = 0.1)。该研究的主要局限性是，由于 CPRD 数据和大多数其他处方数据库的特性，关于避孕用途的信息仅在定义的期间内记录，一般无法获得输入数据库之前的信息。这意味着尽管我们的研究提供了有关激素避孕药与乳腺癌风险短期关联的证据，但它们不提供关于长期关联或使用避孕药时长对乳腺癌风险的影响方面的信息。这项研究提供了有关黄体素单独避孕药目前或最近使用与乳腺癌风险略有增加相关的重要新证据，这种风险似乎不会因投药途径而有所不同，且其大小与口服避孕药所引起的乳腺癌风险相似。鉴于随着年龄的增长，乳腺癌的潜在风险也增加，使用口服避孕药或黄体素单独避孕药带来的绝对风险的剩余更少的女性是使用年龄较小的女性。这些风险需要与生育年龄期间使用避孕药的优点相平衡。版权：© Fitzpatrick等人，2023。这是一篇开放获取文章，根据知识共享署名许可证分发，允许在任何媒介上无限制使用、分发和再现，只要原作者和来源得到了认可。

Current or recent use of combined oral contraceptives (containing oestrogen+progestagen) has been associated with a small increase in breast cancer risk. Progestagen-only contraceptive use is increasing, but information on associated risks is limited. We aimed to assess breast cancer risk associated with current or recent use of different types of hormonal contraceptives in premenopausal women, with particular emphasis on progestagen-only preparations.Hormonal contraceptive prescriptions recorded prospectively in a UK primary care database (Clinical Practice Research Datalink [CPRD]) were compared in a nested case-control study for 9,498 women aged <50 years with incident invasive breast cancer diagnosed in 1996 to 2017, and for 18,171 closely matched controls. On average, 7.3 (standard deviation [SD] 4.6) years of clinical records were available for each case and their matched controls prior to the date of diagnosis. Conditional logistic regression yielded odds ratios (ORs) and 95% confidence intervals (CIs) of breast cancer by the hormonal contraceptive type last prescribed, controlled for age, GP practice, body mass index, number of recorded births, time since last birth, and alcohol intake. MEDLINE and Embase were searched for observational studies published between 01 January 1995 and 01 November 2022 that reported on the association between current or recent progestagen-only contraceptive use and breast cancer risk in premenopausal women. Fixed effects meta-analyses combined the CPRD results with previously published results from 12 observational studies for progestagen-only preparations. Overall, 44% (4,195/9,498) of women with breast cancer and 39% (7,092/18,171) of matched controls had a hormonal contraceptive prescription an average of 3.1 (SD 3.7) years before breast cancer diagnosis (or equivalent date for controls). About half the prescriptions were for progestagen-only preparations. Breast cancer ORs were similarly and significantly raised if the last hormonal contraceptive prescription was for oral combined, oral progestagen-only, injected progestagen, or progestagen-releasing intrauterine devices (IUDs): ORs = 1.23 (95% CI [1.14 to 1.32]; p < 0.001), 1.26 (95% CI [1.16 to 1.37]; p < 0.001), 1.25 (95% CI [1.07 to 1.45]; p = 0.004), and 1.32 (95% CI [1.17 to 1.49]; p < 0.001), respectively. Our meta-analyses yielded significantly raised relative risks (RRs) for current or recent use of progestagen-only contraceptives: oral = 1.29 (95% CI [1.21 to 1.37]; heterogeneity χ25 = 6.7; p = 0.2), injected = 1.18 (95% CI [1.07 to 1.30]; heterogeneity χ28 = 22.5; p = 0.004), implanted = 1.28 (95% CI [1.08 to 1.51]; heterogeneity χ23 = 7.3; p = 0.06), and IUDs = 1.21 (95% CI [1.14 to 1.28]; heterogeneity χ24 = 7.9; p = 0.1). When the CPRD results were combined with those from previous published findings (which included women from a wider age range), the resulting 15-year absolute excess risk associated with 5 years use of oral combined or progestagen-only contraceptives in high-income countries was estimated at: 8 per 100,000 users from age 16 to 20 years and 265 per 100,000 users from age 35 to 39 years. The main limitation of the study design was that, due to the nature of the CPRD data and most other prescription databases, information on contraceptive use was recorded during a defined period only, with information before entry into the database generally being unavailable. This means that although our findings provide evidence about the short-term associations between hormonal contraceptives and breast cancer risk, they do not provide information regarding longer-term associations, or the impact of total duration of contraceptive use on breast cancer risk.This study provides important new evidence that current or recent use of progestagen-only contraceptives is associated with a slight increase in breast cancer risk, which does not appear to vary by mode of delivery, and is similar in magnitude to that associated with combined hormonal contraceptives. Given that the underlying risk of breast cancer increases with advancing age, the absolute excess risk associated with use of either type of oral contraceptive is estimated to be smaller in women who use it at younger rather than at older ages. Such risks need be balanced against the benefits of using contraceptives during the childbearing years.Copyright: © 2023 Fitzpatrick et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.