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. 2022 Mar 11;17(3):e0264909.
doi: 10.1371/journal.pone.0264909. eCollection 2022.

Beyond depression and anxiety; a systematic review about the role of corticotropin-releasing hormone antagonists in diseases of the pelvic and abdominal organs

Joshua E Pagán-Busigó  1 , Jonathan López-Carrasquillo  1 , Caroline B Appleyard  1   2 , Annelyn Torres-Reverón  1   2
Affiliations

Beyond depression and anxiety; a systematic review about the role of corticotropin-releasing hormone antagonists in diseases of the pelvic and abdominal organs

Joshua E Pagán-Busigó et al. PLoS One. .

Abstract

Evidence for beneficial effects of corticotropin releasing hormone (CRH) antagonists in abdominal and pelvic organs is emerging in preclinical studies. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement a compilation of preclinical studies using CRH receptor antagonists as a treatment for abdominal and pelvic disease was carried out. The Animal Research: Reporting of In Vivo Experiments (ARRIVE) essential 10 guidelines were used to determine quality of the included studies. A total of 40 studies from the last 15 years studying irritable bowel syndrome, inflammatory bowel disease, endometriosis, enteritis, stress impact on gastrointestinal processes and exogenous CRH administration effects were included. Blockage of the CRH receptor 1 was mainly associated with beneficial effects while that of CRH receptor 2 worsened studied effects. However, time of administration, route of administration and the animal model used, all had an impact on the beneficial outcomes. Frequency of drugs administered indicated that astressin-2B, astressin and antalarmin were among the most utilized antagonists. Of concern, studies included were predominantly carried out in male models only, representing a gender discrepancy in preclinical studies compared to the clinical scenario. The ARRIVE score average was 13 with ~60% of the studies failing to randomize or blind the experimental units. Despite the failure to date of the CRH antagonists in moving across the clinical trials pipeline, there is evidence for their beneficial effects beyond mood disorders. Future pre-clinical studies should be tailored towards effectively predicting the clinical scenario, including reduction of bias and randomization.

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Conflict of interest statement

We have read the journal’s policy and the authors of this manuscript have the following competing interests: ATR and CBA are co-founders of Sur180 Therapeutics, LLC. However, Sur 180 Therapeutics did not provide funding for the current study. ATR and CBA are named as co-inventors in the patent US-10,729,693 entitled, “Compositions and methods for the treatment of endometriosis”. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. Article search results.
Diagram depicting the number of articles found for the search strategies as established by the PRISMA guidelines.
Fig 2
Fig 2. Compounds reported in the manuscripts reviewed.
Ten compounds were used as CRH-R1 selective antagonists, while only two compounds were used as CRH-R2. Three non-selective CRH-R antagonists were reported in the studies.
Fig 3
Fig 3. Sex distribution in the animal studies.
Pie chart summarizing the percent of studies that included males, females or both sexes in their experiments. An over representation of males in the studies is evident.
See this image and copyright information in PMC

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