What is the pathophysiology of endometrioma in women of reproductive age?

Pathophysiology of Endometrioma

Endometriomas form when endometrial-like tissue (glands and stroma) becomes established within the ovary, creating blood-filled cysts that undergo cyclic hemorrhage, inflammation, and progressive fibrosis in response to hormonal fluctuations. 1, 2

Defining Characteristics

• Endometriomas are ovarian cysts containing endometrial-like tissue (both glands and stroma) located outside the normal endometrial cavity, representing the most common form of endometriosis. 1, 3
• The tissue responds to cyclical hormonal changes just as normal endometrium does, leading to monthly bleeding within the cyst followed by inflammation and scarring. 2, 4
• These lesions appear as blood-filled cysts surrounded by puckering scars, with varying degrees of fibrosis depending on size and chronicity. 5, 4

Proposed Mechanisms of Formation

Two primary theories explain endometrioma development, and different mechanisms may account for the phenotypic variability observed clinically:

Theory 1: Invagination/Metaplasia Pathway

• Endometriomas may form from endometriotic invasion or metaplasia of functional ovarian cysts (corpus luteum or follicular cysts). 5
• This mechanism suggests that endometriotic tissue infiltrates pre-existing ovarian structures and transforms them into endometriomas. 5

Theory 2: Surface Implantation Pathway

• Alternatively, endometriomas develop from ovarian surface endometriosis that bleeds into the ovarian cortex, creating an intraovarian cavity. 5
• This theory aligns with Sampson's retrograde menstruation hypothesis, where viable endometrial cells flow backward through the fallopian tubes during menstruation and implant on the ovarian surface. 2

Pathophysiologic Cascade

Initial Establishment

• Viable eutopic endometrial cells reach the peritoneal cavity through retrograde menstruation, the most widely accepted mechanism for endometriosis development. 2
• These cells implant on the ovarian surface or invade functional cysts, establishing ectopic endometrial tissue. 2, 5

Immune System Dysfunction

• The immune system paradoxically supports the viability and growth of ectopic endometriotic tissue rather than eliminating it, while simultaneously promoting chronic inflammation at lesion sites. 2
• This aberrant immune response creates a permissive microenvironment that allows endometriotic implants to survive and proliferate. 2

Cyclic Hemorrhage and Inflammation

• The ectopic endometrial tissue responds to monthly hormonal fluctuations (estrogen and progesterone), undergoing proliferation, secretory changes, and breakdown. 2, 4
• Monthly bleeding occurs within the confined ovarian space, causing accumulation of blood products and hemosiderin-laden macrophages. 2, 4
• Repeated hemorrhage triggers persistent inflammation and progressive fibrosis of the cyst wall. 2, 4

Progressive Fibrosis and Structural Changes

• Endometriomas range from small (1-3 cm) densely fibrotic cysts to large (≥20 cm) cysts with varying degrees of fibrosis. 5
• Small, densely adherent endometriomas develop thick fibrotic capsules that obliterate the normal plane between the cyst and healthy ovarian cortex. 5
• Large endometriomas may develop adhesions to surrounding pelvic structures (bowel, bladder, pelvic sidewall). 5

Impact on Ovarian Function

Ovarian Aging and Reserve Depletion

• The pelvic and local microenvironment in women with endometriomas causes detrimental effects on ovarian development and function, accelerating ovarian aging. 6
• Endometriomas are associated with poor ovarian reserve, premature ovarian insufficiency, and early menopause. 6
• The mechanism involves hyperactivation of primordial follicles and progressive deterioration of the normal ovarian reservoir. 6

Fertility Impairment

• Approximately 50% of patients with endometriosis experience infertility, with endometriomas being a major contributing factor. 1
• The combination of chronic inflammation, altered ovarian microenvironment, and mechanical distortion of pelvic anatomy impairs reproductive function. 1, 6

Hormonal Dependency

• Endometriosis is fundamentally an estrogen-dependent disease, which explains its predominance in reproductive-age women and relative rarity in postmenopausal women (2.55% prevalence). 2, 3
• The decreased estrogen levels after menopause typically lead to regression of endometriotic lesions, though rare cases of large postmenopausal endometriomas have been reported. 3
• Unopposed estrogen exposure (obesity, early menarche, late menopause, hormone replacement without progesterone) increases endometrioma risk. 7

Clinical Pitfalls and Important Caveats

• Different mechanisms of endometrioma formation may explain the significant phenotypic variability observed among endometriomas, including differences in size, fibrosis density, and adhesion patterns. 5
• The severity of symptoms does not necessarily correspond to disease stage or endometrioma size—small lesions can cause debilitating pain while large lesions may be asymptomatic. 2
• Free abdominal endometriomas (not attached to ovaries) can develop from endometriotic implants on the greater omentum, receiving blood supply from omental vessels. 3
• Endometriomas should remain in the differential diagnosis at any age, including postmenopausal women, particularly when large cystic masses are encountered. 3