The endometriosis-adenomyosis spectrum: shared pathophysiology and microenvironment-driven disease divergence

Area of Science:

• Gynecologic pathology
• Cellular biology
• Molecular mechanisms

Background:

• Endometriosis and adenomyosis are common gynecologic disorders causing pain and infertility.
• Shared molecular features exist, but distinct pathological phenotypes in different tissue environments are not fully understood.

Purpose of the Study:

• To review shared and divergent pathogenic mechanisms of endometriosis and adenomyosis, focusing on lesion-specific microenvironments.
• To propose a model explaining how mitochondria integrate pathogenic stimuli into distinct disease phenotypes.

Main Methods:

• Narrative review based on a PubMed literature search (publication year to December 2025).
• Keywords included endometriosis, adenomyosis, mitochondrial function, oxidative stress, fibrosis, mechanical stress, and calcium signaling.

Main Results:

• Both disorders involve tissue injury, estrogen-dependent repair, inflammation, oxidative stress, and mitochondrial dysfunction.
• Superficial endometriosis involves mitochondrial adaptation for hypoxia tolerance and angiogenesis.
• Deep infiltrating endometriosis and adenomyosis are characterized by fibrosis, ECM remodeling, and adaptation to mechanical stress, with mitochondria regulating calcium, ROS, and fibrotic signaling.

Conclusions:

• A proliferation-fibrosis divergence model is proposed, where mitochondria-dependent responses to local microenvironments dictate disease progression.
• Mitochondria act as central regulators linking various pathogenic factors, influencing proliferative or fibrotic outcomes.
• This framework may guide future precision therapeutic strategies for endometriosis and adenomyosis.