Endometriosis
Endometriosis is a chronic, estrogen-dependent inflammatory disease characterized by the presence of endometrial-like tissue outside the uterine cavity, most commonly on pelvic organs and the peritoneum. The ectopic endometrial tissue responds to hormonal cycles, resulting in cyclical bleeding, inflammation, and subsequent fibrosis and adhesions. The pathogenesis is multifactorial and not fully elucidated but is believed to involve retrograde menstruation, coelomic metaplasia, immune dysfunction, and genetic predisposition. The disease impacts health through chronic pelvic pain, dysmenorrhea, dyspareunia, infertility, and a significant reduction in quality of life. Complications can include adhesions, ovarian cysts (endometriomas), and, rarely, malignant transformation of lesions.
This type consists of small, flat or raised lesions located on the surface of the peritoneum. These lesions are typically found on the pelvic peritoneum, ovaries, uterosacral ligaments, and pouch of Douglas. They are thought to arise from retrograde menstruation and implantation of endometrial cells onto the peritoneal surface. Superficial peritoneal endometriosis is often associated with pain symptoms but may be less likely to cause severe organ damage or infertility than deeper forms.
Also known as 'chocolate cysts,' ovarian endometriomas are cystic masses within the ovary filled with old, hemolyzed blood. These cysts form when endometrial tissue invades the ovarian cortex and encapsulates, leading to repeated bleeding and cyst formation. Ovarian endometriomas are associated with a higher risk of ovarian adhesions, distortion of pelvic anatomy, and infertility. They may also be more resistant to medical therapy and can recur after surgical removal.
DIE is defined by the presence of endometrial tissue infiltrating more than 5 mm beneath the peritoneal surface. It commonly affects the uterosacral ligaments, rectovaginal septum, bladder, bowel, and other pelvic structures. This type is associated with severe pain, including deep dyspareunia, dyschezia, and urinary symptoms, as well as significant fibrosis and anatomical distortion. DIE is often the most challenging to treat and is linked to a higher risk of complications and reduced fertility.
Endometriosis affects approximately 10% of women of reproductive age globally, translating to an estimated 190 million individuals worldwide. The prevalence is higher, up to 35–50%, in women with infertility or chronic pelvic pain. The disease can occur in adolescents and persist until menopause, with the highest incidence between ages 25 and 35. Diagnosis is often delayed by 7–10 years after symptom onset due to the variable presentation and lack of noninvasive diagnostic markers. There is no established racial or ethnic predilection, though some studies suggest differences in prevalence and presentation among populations. Family history is a significant risk factor, with first-degree relatives of affected individuals having a 5–7-fold increased risk. Endometriosis is also associated with an increased risk of certain comorbidities, including autoimmune diseases, ovarian cancer, and mood disorders.
The diagnosis of endometriosis is based on a combination of clinical evaluation, imaging, and, when necessary, surgical assessment. Clinical suspicion arises from a history of chronic pelvic pain, dysmenorrhea, dyspareunia, infertility, and other cyclic symptoms. Pelvic examination may reveal nodularity, tenderness, or adnexal masses. Transvaginal ultrasound is the first-line imaging modality, particularly effective for detecting ovarian endometriomas and deep infiltrating lesions, though superficial peritoneal lesions are often not visualized. Magnetic resonance imaging (MRI) can provide additional detail on deep infiltrating disease. Definitive diagnosis traditionally requires direct visualization of lesions via laparoscopy, often with histopathological confirmation of endometrial glands and stroma in ectopic locations. Noninvasive biomarkers are under investigation but not yet validated for routine use. Diagnostic criteria include the presence of characteristic lesions on imaging or at surgery, supported by clinical symptoms and, when possible, histology. Differential diagnoses include pelvic inflammatory disease, irritable bowel syndrome, and other causes of chronic pelvic pain.
A range of pharmacological therapies is available for the management of endometriosis, each targeting different aspects of the disease's pathophysiology. Linzagolix choline is an oral gonadotropin-releasing hormone (GnRH) receptor antagonist that reduces estrogen production, thereby decreasing endometrial lesion activity and alleviating symptoms. Combination therapy with estradiol hemihydrate, norethisterone acetate, and relugolix offers a regimen that combines estrogen and progestin with a GnRH antagonist to suppress ovarian function while mitigating hypoestrogenic side effects. Relugolix alone, another oral GnRH antagonist, is used to suppress pituitary gonadotropin secretion, leading to reduced ovarian estrogen production and symptom relief. Elagolix sodium is also an oral GnRH antagonist that provides dose-dependent suppression of ovarian hormone production, offering flexible control of endometriosis-associated pain. Dienogest, a progestin, is utilized for its anti-androgenic and anti-estrogenic effects, directly inhibiting endometrial tissue proliferation and reducing inflammation. Combined oral contraceptives, such as drospirenone with ethinylestradiol, are employed to create a hypoestrogenic environment, suppress ovulation, and reduce menstrual flow, thereby alleviating symptoms. Leuprolide acetate depot and leuprorelin acetate depot are long-acting GnRH agonists that induce a hypoestrogenic state by downregulating pituitary GnRH receptors, leading to decreased ovarian hormone production and symptom improvement. Goserelin, a GnRH agonist, is administered as a subcutaneous implant to achieve similar pituitary suppression and hypoestrogenism. Triptorelin, another GnRH agonist, is used for its ability to achieve sustained suppression of gonadotropin secretion and ovarian function. Danazol, a synthetic androgen, exerts its effect by inhibiting the mid-cycle surge of luteinizing hormone, suppressing ovarian estrogen production, and inducing endometrial atrophy, though its use may be limited by androgenic side effects.
| Structure | Generic Name | CAS Registry Number | Molecular Formula | Molecular Weight |
|---|---|---|---|---|
 | linzagolix choline (Rec INNM; USAN) | 935283-04-8 (free acid) | C22 H14 F3 N2 O7 S . C5 H14 N O | 611.587 |
| estradiol hemihydrate/norethisterone acetate/relugolix | ||||
 | relugolix (Rec INN; USAN) | 737789-87-6 | C29 H27 F2 N7 O5 S | 623.63 |
 | elagolix sodium (Prop INNM; USAN) | 832720-36-2; 834153-87-6 (free acid) | C32 H29 F5 N3 O5 . Na | 653.572 |
 | dienogest (Rec INN) | 65928-58-7 | C20 H25 N O2 | 311.418 |
| drospirenone/ethinylestradiol | ||||
| leuprolide acetate depot; leuprorelin acetate depot | ||||
 | goserelin (Rec INN; USAN; BAN) | 65807-02-5 | C59 H84 N18 O14 | 1269.41 |
 | triptorelin (Rec INN; USAN; BAN) | 57773-63-4 | C64 H82 N18 O13 | 1311.449 |
 | danazol | 17230-88-5 | C22 H27 N O2 | 337.455 |
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