Causal effects of endometriosis stages and locations on menstruation, ovulation, reproductive function, and delivery modes: a two-sample Mendelian randomization study.

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  • Author(s): Shen L;Shen L;Shen L;Shen L; Li J; Li J; Zhang H; Zhang H; Zhao Y; Zhao Y
  • Source:
    Frontiers in endocrinology [Front Endocrinol (Lausanne)] 2024 Aug 02; Vol. 15, pp. 1328403. Date of Electronic Publication: 2024 Aug 02 (Print Publication: 2024).
  • Publication Type:
    Journal Article
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101555782 Publication Model: eCollection Cited Medium: Print ISSN: 1664-2392 (Print) Linking ISSN: 16642392 NLM ISO Abbreviation: Front Endocrinol (Lausanne) Subsets: MEDLINE
    • Publication Information:
      Original Publication: [Lausanne : Frontiers Research Foundation]
    • Subject Terms:
      Endometriosis*/genetics ; Mendelian Randomization Analysis* ; Ovulation*/genetics ; Menstruation* ; Reproduction*/genetics; Female ; Humans ; Pregnancy ; Adult ; Delivery, Obstetric
    • Abstract:
      Background: Endometriosis is a chronic inflammatory disease of women during their reproductive years. The relationship between the severity and location of endometriosis and menstruation, ovulation, reproductive function, and mode of delivery remains unclear.
      Methods: We explored the association between the various phenotypes of endometriosis and menstruation, ovulation, reproductive function, and mode of delivery, using two-sample Mendelian randomization (MR) and summary data on endometriosis stages and locations from the FinnGen consortium and women's menstruation, ovulation, reproductive function, and mode of delivery from OpenGWAS and ReproGen. Inverse-variance weighting was used for the primary MR analysis. In addition, a series of sensitivity analyses, confounding analyses, co-localization analyses, and multivariate MR analyses were performed.
      Results: MR analysis showed a negative effect of moderate to severe endometriosis on age at last live birth (OR = 0.973, 95% CI: 0.960-0.986) and normal delivery (OR = 0.999, 95% CI: 0.998-1.000; values for endpoint were excluded), ovarian endometriosis on age at last live birth (OR = 0.976, 95% CI: 0.965-0.988) and normal delivery (OR = 0.999, 95% CI: 0.998-1.000; values for endpoint were excluded), and fallopian tubal endometriosis on excessive irregular menstruation (OR = 0.966, 95% CI: 0.942-0.990). Bidirectional MR analysis showed that age at menarche had a negative causal effect on intestinal endometriosis (OR = 0.417, 95% CI: 0.216-0.804). All MR analyses were confirmed by sensitivity analyses, and only the genetic effects of moderate to severe endometriosis on normal delivery and age at last live birth were supported by co-localization evidence.
      Conclusion: Our findings deepen the understanding of the relationship between various types of endometriosis and menstruation, ovulation, reproductive function, and mode of delivery and clarify the important role of moderate to severe endometriosis.
      Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
      (Copyright © 2024 Shen, Li, Zhang and Zhao.)
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    • Contributed Indexing:
      Keywords: Mendelian randomization; endometriosis; menstruation; mode of delivery; ovulation; reproductive function
    • Publication Date:
      Date Created: 20240819 Date Completed: 20240819 Latest Revision: 20240820
    • Publication Date:
      20240820
    • Accession Number:
      PMC11327065
    • Accession Number:
      10.3389/fendo.2024.1328403
    • Accession Number:
      39157682