Endometriosis Causes and Risk Factors

Endometriosis affects about 10% of women of reproductive age worldwide, causing chronic pelvic pain, heavy menstrual bleeding, and infertility1 . This condition occurs when tissue similar to the lining of the uterus grows outside the uterus, often involving pelvic organs such as the ovaries and fallopian tubes2 . Despite extensive research, the exact cause of endometriosis remains unclear, with multiple theories and risk factors contributing to its development3 . Understanding these causes and risk factors is essential for early diagnosis and effective management.

Potential Causes of Endometriosis

Endometriosis is a complex and multifactorial disease involving genetic, hormonal, immunological, and environmental factors3 . Several leading theories explain how endometrial-like tissue may develop and spread outside the uterus.

Retrograde menstruation is the most widely accepted theory for the origin of endometriosis4 . It was first proposed by Sampson in 1927 and suggests that menstrual blood flows backward through the fallopian tubes into the pelvic cavity instead of exiting the body through the vagina5 . This backward flow carries endometrial cells that implant and grow on pelvic organs, causing inflammation and lesions5 .

However, retrograde menstruation cannot fully explain cases of endometriosis in individuals who have not menstruated, such as premenarcheal girls or males, indicating other mechanisms are involved5 . Approximately 90% of women experience retrograde menstruation, but only a subset develop endometriosis, suggesting additional factors like immune dysfunction and hormonal imbalances contribute to disease development4 .

💡 Did You Know? Researchers currently think that most cases of endometriosis result from retrograde menstruation, where menstrual blood flows back through fallopian tubes into the pelvic cavity4 .

Coelomic metaplasia refers to the transformation of one cell type into another3 . This theory proposes that peritoneal cells lining the abdominal cavity can transform into endometrial-like cells under certain stimuli, such as hormonal imbalances or immune system changes3 . These metaplastic cells can then proliferate and form endometriotic lesions on nearby organs3 .

This mechanism helps explain endometriosis cases in individuals without menstruation and those with lesions in unusual locations3 . Hormonal imbalances, particularly excess estrogen, and immune dysfunction are thought to promote this metaplastic transformation3 .

Sampson's lymphatic and vascular metastasis theory explains how endometrial cells can spread to distant sites beyond the pelvis, such as the lungs5 . According to this theory, endometrial tissue enters the lymphatic or blood vessels and travels to remote organs, where it implants and grows5 . This mechanism accounts for rare cases of endometriosis found in locations far from the reproductive organs5 .

Stem cell involvement in endometriosis pathogenesis is an emerging area of research. Stem cells from the bone marrow or uterus may migrate and differentiate into endometrial-like tissue outside the uterus3 . Dysfunction or abnormal behavior of these stem cells could contribute to the initiation and persistence of endometriotic lesions3 .

Another proposed cause involves embryonic cell remnants that transform into endometrial tissue during puberty under the influence of estrogen2 . This embryonic cell theory suggests that misplaced embryonic cells in the pelvic region can develop into endometriotic lesions when stimulated by hormones2 .

Endometriosis is an estrogen-dependent condition, with excess estrogen promoting the growth and maintenance of endometrial-like tissue outside the uterus3 . Hormonal imbalances, including a low ratio of estrogen receptor alpha to beta and progesterone resistance, contribute to disease progression6 . These imbalances can lead to chronic inflammation and impaired immune response, facilitating lesion growth3 .

Surgical procedures involving the uterus or pelvic organs may inadvertently transplant endometrial cells to other sites, causing endometriosis in surgical scars or nearby tissues2 . This direct transplantation theory explains cases of endometriosis occurring after cesarean sections or other pelvic surgeries2 .

“Endometriosis results when cells from the lining of the uterus implant, grow, and elicit an inflammatory response outside the uterine lining.”

— Dr. Peterson, American Medical Association1

Genetic Factors in Endometriosis

Endometriosis has a strong genetic component, with over 40 genetic risk factors identified to date3 . Women with a first-degree relative who has endometriosis are at significantly increased risk of developing the disease themselves3 . Genetic studies have linked several specific genes to endometriosis susceptibility, including:

• VEZT: Involved in embryo implantation; mutations are associated with endometriosis pathogenesis3 .
• NPSR1: Implicated in uterine inflammation and increased risk of endometriosis3 .
• WNT4: Associated with abnormal cell proliferation in reproductive organs3 .
• FN1/GREB1: Variants affect estrogen production and contribute to disease risk3 .

Despite these discoveries, genetic testing for endometriosis risk is not yet available in clinical practice3 . Ongoing research aims to develop targeted therapies based on these genetic insights.

“The largest genetic study of endometriosis included DNA from 60,600 women with endometriosis and 701,900 without. It revealed evidence of a shared genetic basis for endometriosis and other types of pain including migraine, back pain, and multi-site pain. 7”

Endometriosis Demographics and Prevalence

Endometriosis affects approximately 10% of women of reproductive age, most commonly diagnosed in individuals in their 20s and 30s1 . It can occur in any menstruating individual but is rare before menarche or after menopause unless hormone replacement therapy is used1 . The disease often involves pelvic organs such as the ovaries, fallopian tubes, and peritoneum but can also affect distant sites like the lungs or diaphragm in rare cases2 8.

Endometriosis is a chronic condition that can cause severe menstrual pain, fatigue, and infertility1 . It may take several years for a correct diagnosis due to symptom variability and the need for surgical confirmation1 . Up to 50% of women presenting with infertility have endometriosis, and up to 70% of those evaluated for chronic pelvic pain are diagnosed with the disease1 .

Key Endometriosis Risk Factors

Several risk factors have been identified that increase the likelihood of developing endometriosis. These factors are related to menstrual characteristics, reproductive history, genetics, and lifestyle3 9.

• Early menarche (starting periods before age 11) 39.
• Short menstrual cycles (less than 27 days) 39.
• Heavy or prolonged menstrual bleeding lasting more than 7 days3 9.
• Intermenstrual bleeding or spotting between periods3 .
• Nulliparity (never having given birth) 3.
• Low or high body mass index (BMI), with lean body mass possibly increasing risk3 9.
• Family history of endometriosis, especially in first-degree relatives3 9.
• Structural abnormalities of the reproductive tract that impede menstrual blood flow2 .
• Lifestyle factors such as low physical activity and high alcohol consumption3 .

Factors that may lower the risk include pregnancy, breastfeeding, late onset of menstruation, and higher fruit intake, especially citrus fruits9 .

• Family history of endometriosis3 9.
• Early age at first menstruation3 9.
• Short menstrual cycles3 9.
• Heavy or prolonged periods3 9.
• Nulliparity3 .
• Low or high BMI3 .
• Lifestyle factors: low physical activity, high alcohol use3 .

Endometriosis is a chronic inflammatory condition affecting millions worldwide, causing severe menstrual pain, fatigue, and infertility. It affects about one in 10 women of reproductive age and often takes years to diagnose due to symptom variability and the need for surgical confirmation. Early diagnosis and treatment are crucial for improving quality of life. 13

Summary of Endometriosis Causes

Endometriosis is a chronic, estrogen-dependent condition characterized by the presence of endometrial-like tissue outside the uterus, causing pain and infertility10 . Its causes are multifactorial, involving a combination of genetic predisposition, hormonal imbalances, immune dysfunction, and environmental factors3 .

“Endometriosis is a chronic condition that will likely require management for a significant portion of someone’s life.”

— Dr. Peterson, American Medical Association1

Key mechanisms include:

• Retrograde menstruation transporting endometrial cells into the pelvic cavity5 4.
• Coelomic metaplasia transforming peritoneal cells into endometrial-like tissue3 .
• Vascular and lymphatic spread allowing distant implantation of endometrial cells5 .
• Stem cell dysfunction contributing to lesion formation3 .
• Embryonic cell remnants transforming under hormonal influence2 .
• Hormonal imbalances, especially excess estrogen and progesterone resistance, promoting lesion growth3 6.
• Surgical transplantation of endometrial cells during pelvic procedures2 .

Risk factors such as early menarche, short cycles, heavy bleeding, family history, and nulliparity increase susceptibility3 9. Despite advances in understanding, the exact cause remains unknown, and diagnosis often requires surgical confirmation1 .