Evidence map›Paper›PMID 39448218›Full record

ArticleBMJ open2024

Breast and endometrial safety of micronised progesterone versus norethisterone acetate in menopausal hormone therapy (PROBES): study protocol of a double-blind randomised controlled trial.

Christina Lundell, Nikolaos Stergiopoulos, Liselott Blomberg, Dorina Ujvari, Ina Schuppe-Koistinen, Helena Kopp-Kallner, Stavros I Iliadis, Alkistis Skalkidou, Angelica Linden Hirschberg

Registry-linked trialAbstract readClinical Trial Protocol
PubMed Full text at PMC Publisher
In one paragraph

Article in BMJ open, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05586724 (Safety of Oral Micronized Progesterone Versus Norethisterone Acetate in Continuous Combination With Oral Estrogen as Menopausal Hormone Therapy - a Double-blind Randomized Study- PROBES Study), which is not on this map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT05586724 phase3recruitingnot on this map

Safety of Oral Micronized Progesterone Versus Norethisterone Acetate in Continuous Combination With Oral Estrogen as Menopausal Hormone Therapy - a Double-blind Randomized Study- PROBES Study (Progesterone Breast Endometrial Safety Study)

TypeinterventionalSponsorAngelica Lindén HirschbergRan2022 to 2027Enrolled520ConditionsMenopausal SymptomsArmsMicronized progesterone in continuous combination with oral estrogen, Norethisterone acetate in continuous combination with oral estrogen
3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Christina LundellKarolinska Institutet, Stockholm, Sweden.
Nikolaos StergiopoulosKarolinska Institutet, Stockholm, Sweden.
Liselott BlombergKarolinska Institutet, Stockholm, Sweden.
Dorina UjvariKarolinska Institute, Solna, Sweden.ORCID 0000-0002-4659-9712
Ina Schuppe-KoistinenKarolinska Institutet, Stockholm, Sweden.
Helena Kopp-KallnerKarolinska Institutet, Stockholm, Sweden.ORCID 0000-0001-7184-9165
Stavros I IliadisWomen's and Children's Health, Uppsala University, Uppsala, Sweden.
Alkistis SkalkidouUppsala University, Uppsala, Sweden.
Angelica Linden HirschbergKarolinska Institutet, Stockholm, Sweden Angelica.Hirschberg.Linden@ki.se.ORCID 0000-0001-6481-6277

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionData 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. METHODS AND ANALYSIS: 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. ETHICS AND DISSEMINATION: 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. TRIAL REGISTRATION NUMBER: NCT05586724.

Indexed as

EndometriumNorethindrone AcetateProgesteroneBreastBreast DensityDouble-Blind MethodEstradiolEstrogen Replacement TherapyFemaleHumansMiddle AgedMulticenter Studies as TopicNorethindronePostmenopauseRandomized Controlled Trials as TopicEstradiolNorethindroneNorethindrone AcetateProgesteroneCommunity gynaecologyRandomized Controlled TrialSex steroids & HRT

Identifiers

PMID39448218
PMCPMC11499784

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.