Understanding endometriosis: Symptoms, risks, and personalized treatment
Endometriosis is a complex condition that is difficult to diagnose due to the close similarity of symptoms with other gynecological and gastrointestinal diseases. The risk and severity of endometriosis are linked to mental health status, hormones, and inflammation. Multimodal medication therapy, along with lifestyle and dietary modifications, may help manage symptoms. Pharmacogenetics helps personalize and optimize your treatment to minimize long-term health risks.
What is endometriosis?
Endometriosis is a condition in which cells similar to the lining of the uterus, or endometrium, grow outside the uterus. It can cause severe pelvic pain, irregular periods, and make it harder to get pregnant. Endometriosis affects roughly 10% of women of reproductive age worldwide and is one of the leading causes of female infertility. Despite being relatively common, it’s often underdiagnosed, with many patients experiencing a delay of several years between symptom onset and diagnosis.
Symptoms overlap with other conditions
Pain is the most common symptom. About 90% of women with endometriosis experience some form of pelvic pain, including painful periods, pelvic pain between periods, and pain during intercourse, painful bowel movements or urination, especially during periods.
Pain severity doesn’t necessarily relate to the extent of the endometriosis. Some women with mild endometriosis have severe pain, while others with extensive disease may have little pain or even no symptoms at all.
Other common symptoms include fatigue (affects about 50%), poor sleep, digestive problems worsening during periods, and infertility.
The problem is that these symptoms overlap with many other conditions:
| Alternative conditions | Dysmenorrhea | Nonmenstrual pelvic pain | Deep dyspareunia | Clinical features of alternative conditions |
|---|---|---|---|---|
| Adenomyosis | ✔ | ✔ | ✔ | Heavy menstrual bleeding; sometimes enlarged and tender uterus; commonly co-occurs with deep endometriosis |
| Uterine fibroids | ✔ | ✔ | ✔ | Heavy menstrual bleeding; enlarged or irregular uterus |
| Primary dysmenorrhea | ✔ | Often short duration (<72 h) and responsive to nonsteroidal anti-inflammatory drugs | ||
| Cervical stenosis | ✔ | Absence of menstrual period, decreased menstrual flow; history of cervical surgery or ablation of uterine lining | ||
| Müllerian anomaly with obstruction of genital tract | ✔ | Absence of a menstrual periods with cyclic pain, often symptom onset in adolescence | ||
| Pelvic floor myofascial pain | ✔ | ✔ | Pain worse with activity or at end of day; tender abdominal wall or pelvic floor muscles; can be associated with painful bowel movements, constipation, high urinary frequency | |
| Irritable bowel syndrome | ✔ | Changes in bowel frequency and stool quality with associated abdominal pain; symptoms may be worse during menses | ||
| Bladder pain syndrome/ interstitial cystitis | ✔ | ✔ | Urinary urgency, urinary frequency, and/or nocturia with normal urinalysis; symptoms may be worse during menses | |
| Pelvic venous disorder | ✔ | Pelvic heaviness that is worse when standing and at end of the day |
Because of the complexity of the condition and variability of symptoms, it can take 5 to 12 years to diagnose endometriosis after symptoms first appear. Most women see three or more healthcare providers before getting a diagnosis. A definitive diagnosis of endometriosis requires endoscopic surgery to visually identify lesions; however, an expert clinician may be able to diagnose without surgery based on your symptoms, physical examination findings, and MRI imaging and ultrasound. Normal exam results or imaging do not rule out endometriosis, especially for superficial forms.
Four main types of endometriosis:
- Superficial peritoneal: Lesions on the surface lining of the pelvis or abdominal organs
- Deep endometriosis: Tissue that penetrates deeper into organs or structures
- Ovarian endometriomas: Cysts within the ovaries (sometimes called “chocolate cysts”)
- Extrapelvic endometriosis: Lesions found outside the pelvis in areas like the diaphragm, lungs, or surgical scars
Genetics, endometriosis and mental health
There is a strong link between genetic predisposition to endometriosis and mental health issues. Women with endometriosis often report feeling unloved, experiencing abuse, or facing trauma at a young age, and they show higher rates of Post Traumatic Stress Disorder (PTSD). This suggests that mental health stressors are one of the factors that can worsen endometriosis in women with specific genetic risk variations. Research has revealed several important connections:
- Higher rates of depression: Women with endometriosis experience higher rates of depression, anxiety, and stress compared to those without the condition. Some studies show that individuals with endometriosis are 2-3 times more likely to experience anxiety and depression.
- Chronic pain and mental health: The chronic pain associated with endometriosis can contribute to psychological distress. Long-term pain is known to affect mood, sleep, and quality of life, which can lead to or worsen mental health conditions.
- Diagnostic delay impact: The often lengthy delay in diagnosis can lead to feelings of being dismissed or not believed by healthcare providers, contributing to psychological distress.
- Fertility concerns: For many with endometriosis, fertility problems can cause significant anxiety and distress.
- Treatment challenges: Hormonal treatments for endometriosis can sometimes affect mood, potentially exacerbating mental health issues.
- Relationship impacts: Chronic fatigue, poor health, pain during sex, and other symptoms can affect intimate relationships, further affecting mental well-being.
Mental health support is increasingly recognized as a vital component of comprehensive endometriosis care. Psychological interventions, such as cognitive behavioural therapy and mindfulness-based approaches, have shown promise in helping patients manage both the physical symptoms and the psychological impacts of the condition.
Endometriosis treatment options
Currently, there is no cure for endometriosis; however, both surgical and non-surgical treatments can help manage symptoms. The choice of treatment depends on the severity of the symptoms, plans for pregnancy, and personal preferences.
Medications
First-line treatments:
- Combined hormonal contraceptives (birth control pills, patches, or rings)
- Progestin-only medications (pills, injections, or IUDs)
- Pain relievers like NSAIDs (ibuprofen, naproxen)
These treatments suppress hormones that fuel the growth of endometriosis and reduce inflammation. They are often effective but may cause side effects such as breakthrough bleeding, mood changes, or headaches. For many women, continuous use of birth control pills offers better pain relief than cyclical use.
Second-line treatments:
- GnRH modulating drugs – create a temporary menopausal state. These are typically prescribed by specialists after other treatments have failed.
Third-line treatment:
- Aromatase inhibitors – these medications lower estrogen levels.
Genetic factors impacting endometriosis medications
| Medication | Mechanism of action | Common side effects | Key pharmacogenes | Additional considerations |
|---|---|---|---|---|
| Combined hormonal contraceptives | Suppression of ovarian hormone production; reduces inflammatory mediators, lesion proliferation | Headache, mood changes, breast tenderness, nausea | F5 (Factor V Leiden)
F2 (Prothrombin) |
Avoid estrogen-containing drugs in women in history of thromboembolism or carrying F5 or F2 variants |
| NSAIDs
Naproxen Celecocib |
Inhibit COX enzymes to reduce inflammation and pain | GI irritation, hypersensitivity reactions, cardiovascular risk | CYP2C9 | Use with caution in those CYP2C9 deficiency, with kidney or cardiac disease |
| GnRH agonists Elagolix
Leuprolide Nafarelin |
Downregulation of GnRH receptors to suppresses estrogen | Hot flush, headache , mood swings | SLCO1B1, CYP3A4 | Bone mineral density loss |
| Aromatase inhibitors Letrozole Anastrozole | Suppress estrogen by inhibiting aromatase | Hot flush, night sweats, headache, joint pain | CYP3A4 | Combined with other hormonal drugs to prevent ovarian cysts |
In addition to the treatments outlined above, counselling and antidepressants can also be vital to improve mental health for women experiencing endometriosis.
Pharmacogenetics can assist in guiding drug therapy management for endometriosis and help ensure long-term safety. Testing for thrombophilia genes (F5, F2) can lower the risk of deep vein thrombosis and stroke in women taking estrogen-containing or similar medications. Frequent use of anti-inflammatory drugs has been linked to an increased risk of bleeding and cardiovascular events in individuals with reduced CYP2C9 activity. Elagolix and some other medications in this class are metabolized by the liver enzymes SLCO1B1 and/or CYP3A4.
Pharmacogenetic testing can help women and their doctors select appropriate medications and dosages to lower the risk of drug-induced complications. Clinical trials have shown that genetics-guided mental health management accelerates recovery from anxiety and depression.
The pharmacogenetic test results should be interpreted in conjunction with the patient’s current medications and symptoms, helping to resolve critical drug-gene interactions.
Surgery
Surgery may be recommended if:
- Hormonal treatments aren’t effective or cause intolerable side effects
- You have ovarian endometriomas that are large or have concerning features
- Deep endometriosis is causing issues with your bladder, bowels, or other organs
- You’re trying to conceive and have fertility issues
Surgery generally involves removing visible endometriosis lesions, usually through minimally invasive procedures, like laparoscopy. However, pain may return; approximately 15-25% of women experience recurrent pain within one to two years.
As women age, those suffering from persistent, severe pain who do not want future pregnancies and have not responded to other treatments may consider having a hysterectomy. However, some women still experience pain afterward.
Complementary approaches
These approaches may help manage symptoms alongside medical treatment:
- Pelvic floor physical therapy
- Pain education and psychological support
- Regular exercise
- Anti-inflammatory diets
- Acupuncture
Living with endometriosis
Endometriosis is a chronic condition that requires ongoing management. Some key points to remember:
- Find healthcare providers who listen. You deserve to have your pain taken seriously.
- Consider a multidisciplinary approach. Many women benefit from working with different specialists, including gynecologists, pain specialists, physical therapists, and counselors.
- Connect with others. Support groups and online communities can provide valuable emotional support and practical advice.
- Track your symptoms. Keeping a record of your pain and other symptoms can help identify patterns and treatment effectiveness.
- Optimize your therapy. Treatment should be tailored to your genetics, specific needs, symptoms, and life goals.
Living with endometriosis can be challenging, but with proper management and support, most women can lead full, active lives. Research continues to improve our understanding of this condition and develop better treatments.
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ORDER NOWSelected references
As-Sanie S et al., Endometriosis: A Review JAMA. Published online May 5, 2025. doi:10.1001/jama.2025.2975
Koller D et al., Observational and Genetic Analyses of Traumatic Experiences and Endometriosis JAMA Psychiatry. Published online February 5, 2025.
Mattina GF et al., Inflammation, depression and cardiovascular disease in women: the role of the immune system across critical reproductive events Therapeutic Advances in Cardiovascular Disease. 2019;13.
