Does Endometriosis Tissue Produce Its Own Estrogen?
Yes, endometriosis tissue outside the uterus produces its own estrogen locally through aberrant expression of steroidogenic enzymes, particularly aromatase, which is not normally present in healthy endometrium. 1, 2, 3
Local Estrogen Production Mechanism
Endometriotic lesions create a hyperestrogenic microenvironment through multiple aberrant mechanisms:
Aromatase expression is abnormally elevated in endometriotic tissue, converting androgens to estrogens directly within the lesions themselves—this enzyme is absent or minimally expressed in normal endometrium. 1, 2, 3
Steroid sulfatase (STS) and 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1) are overexpressed, further amplifying local estrogen production and conversion of weaker estrogens to more potent estradiol. 1, 2
Estrogen metabolizing enzymes show disturbed expression patterns, with decreased activity of enzymes that would normally inactivate estrogens, leading to accumulation of bioactive estradiol within lesions. 2, 3
Estrogen Receptor Abnormalities
The local estrogen production is compounded by altered receptor expression:
Endometriotic stromal cells express extraordinarily higher ERβ levels and significantly lower ERα levels compared to normal endometrial stromal cells, creating an abnormal hormonal response pattern. 4
This aberrant receptor expression is associated with epigenetic dysregulation, including DNA methylation changes that perpetuate the disease phenotype. 4
Clinical Implications
This local estrogen production explains key clinical features:
Endometriosis is fundamentally an estrogen-dependent disease on a background of progesterone resistance, as defined by consensus guidelines. 5, 6, 1
The disease maintains itself through autonomous local estrogen synthesis, independent of ovarian estrogen production, which is why systemic hormonal suppression alone may be insufficient. 1, 2, 3
Aromatase inhibitors targeting local estrogen synthesis represent a rational therapeutic approach, though current treatments have limitations including contraceptive effects and hypoestrogenic side effects. 1, 3
Important Caveats
The degree of local estrogen production varies between different types of endometriotic lesions (superficial peritoneal, ovarian endometriomas, deep infiltrating endometriosis), suggesting heterogeneity in the disease mechanism. 2
While local estrogen production is well-established, it represents only one component of the multifactorial pathogenesis that includes genetic factors, immune dysfunction, and environmental influences. 5, 6, 7