Karolinska Institutet, Stockholm, Sweden.
Karolinska Institute, Solna, Sweden.
BMJ Open. 2024 Oct 23;14(10):e082749. doi: 10.1136/bmjopen-2023-082749.
Data suggest that micronised progesterone (mP) in menopausal hormone therapy is safer for the breast than synthetic progestins, while protection of the endometrium appears to be less effective. However, comparative randomised trial data are lacking. The objective of the Progesterone Breast Endometrial Safety Study is to investigate breast and endometrial safety of mP versus norethisterone acetate (NETA) in continuous combination with oral oestrogen.
This multicentre trial, conducted at three University Hospitals in Stockholm and Uppsala, Sweden, consists of two phases: part 1 focuses on breast safety and is designed as a double-blind, randomised controlled trial. 260 postmenopausal women will be randomised to 100 mg mP or 0.5 mg NETA per day in continuous combination with 1 mg oestradiol. The primary objective is to compare the treatments with respect to percentage change in mammographic breast density after 12-month treatment. Secondary outcomes are breast proliferation, endometrial histology and proliferation, bleeding pattern, gut and vaginal microbiome, hormone levels and coagulation and metabolic factors, mood, and health-related quality of life. Part 2 features an open, single-arm design to study endometrial safety of 1-year treatment with mP in continuous combination with oestradiol on endometrial pathology (hyperplasia and cancer). We will treat 260 additional women with 100 mg mP/1 mg oestradiol resulting in an endometrial safety population of 390 women. The total number of participants in part 1 and part 2 will be 520.
The study protocol was approved by the Swedish Ethical Review Authority (2021-03033) on 29 June 2021 with amendment (2023-01480-02, protocol version 3.1) on 14 March 2023. Results of the study will be published in peer-reviewed journals and presented at scientific meetings.
NCT05586724.
数据表明，米诺孕素（mP）在绝经激素治疗中的安全性优于合成孕激素，而对子宫内膜的保护作用似乎不太有效。然而，目前缺乏比较随机试验数据。孕激素乳腺子宫内膜安全性研究的目的是研究 mP 与醋酸炔诺酮（NETA）连续联合口服雌激素对乳腺和子宫内膜的安全性。
这项多中心试验在瑞典斯德哥尔摩和乌普萨拉的三所大学医院进行，分为两个阶段：第 1 部分侧重于乳腺安全性，设计为双盲、随机对照试验。260 名绝经后妇女将被随机分为每天 100mg mP 或 0.5mg NETA 与 1mg 雌二醇连续联合治疗。主要目标是比较两种治疗方法在 12 个月治疗后乳腺密度的百分比变化。次要结果是乳腺增殖、子宫内膜组织学和增殖、出血模式、肠道和阴道微生物组、激素水平以及凝血和代谢因素、情绪和健康相关生活质量。第 2 部分采用开放、单臂设计，研究 mP 连续联合雌二醇治疗 1 年的子宫内膜安全性，对子宫内膜病理（增生和癌症）进行研究。我们将用 100mg mP/1mg 雌二醇治疗另外 260 名妇女，使子宫内膜安全性人群达到 390 名妇女。第 1 部分和第 2 部分的总参与者将达到 520 名。
该研究方案于 2021 年 6 月 29 日经瑞典伦理审查局批准（2021-03033），并于 2023 年 3 月 14 日进行了修订（2023-01480-02，方案版本 3.1）。研究结果将发表在同行评议的期刊上，并在科学会议上展示。
NCT05586724。
