Abdominal pain during your period that progressively worsens from month to month is not just normal menstrual cramps. Endometriosis is a common, chronic gynecological disease that causes pain and infertility, but a recent Yale study has found evidence of a genetic variant that puts those with the condition at higher risk of depression, anxiety, and eating disorders. 

What is endometriosis?  

Endometriosis causes tissue similar to the lining of the uterus (the endometrium) to grow outside of the uterus in the abdominopelvic cavity. While these growths are not cancerous, they are problematic. During a normal menstrual cycle, the lining within the uterus swells, breaks down, and is shed from the vagina through bleeding. When this material grows outside the uterus, the tissue behaves similarly but has no means of exiting the body, which irritates the surrounding organs and eventually forms scar tissue and bands of fibrous material called adhesions. These cobweb-like adhesions cause pelvic tissues and organs to adhere (“stick”) to each other. 

Endometriosis can cause a wide range of symptoms, including bloating, constipation, diarrhea, nausea, and fatigue. Endometriosis is often painful, producing pain in the abdomen, pelvis, and lower back, pain with sex, pain with bowel movements or urination, and painful periods with cramping that may start before menstrual bleeding and last for days. But it’s not always painful. Some people with endometriosis may have no symptoms and only learn they have the condition during surgery for another reason or when they can’t get pregnant. 

Endometriosis and infertility

According to a 2022 Yale School of Medicine study, nearly one in ten women of reproductive age experience endometriosis, with one-third of them having difficulty getting pregnant (almost twice the rate of women without the disease). It’s estimated that up to half of women experiencing infertility have endometriosis. While the exact reasons why endometriosis affects fertility are still unclear, there are several theories, including pelvic anatomy distortion due to adhesions, scarred fallopian tubes, pelvic organ inflammation, changes in ovarian hormones, altered egg quality, and impaired immune system functioning. 

Treating infertility caused by endometriosis must be customized to each person, taking into account factors such as how severe the endometriosis is, where it’s located, the age of the patient, and how long they have been unable to get pregnant. For people with mild to moderate disease, using medication to trigger the ovary to release an egg or eggs (controlled ovarian hyperstimulation) in combination with inserting specially prepared sperm directly into the uterus around the time the ovary releases the egg (intrauterine insemination) can approximate the usual success rate of 20% per month seen in fertile couples. If the above method has not resulted in pregnancy after three cycles, in vitro fertilization should be considered.  In vitro fertilization bypasses the endometriosis-damaged reproductive organs by combining egg and sperm outside of the body and then placing the fertilized egg directly in the uterus. 

Endometriosis has physical and mental effects

While infertility and pain have historically been considered the main somatic effects of endometriosis, a Yale School of Medicine study released in 2023 found the condition is not just a gynecologic issue limited to the pelvic area and reproductive organs. Instead, it affects the whole body, including the brain. The year-long study was conducted on over 200,000 women with a mean age of 53 years old; 8,200 of the study participants had endometriosis and 194,000 did not. The study found those with endometriosis had a higher risk of depression, anxiety, and eating disorders, even when accounting for risk factors such as chronic pain, age, body mass index, socioeconomic status, irritable bowel syndrome, other psychiatric comorbidities, and medication use, including birth control. 

Before this study, clinicians have often explained the correlation between endometriosis and the depressive symptoms some patients experience as being linked to the chronic pain of the condition. The recent findings suggest that while chronic pain undoubtedly plays a role, it is not the sole factor or even the defining one. Worldwide data analyzed from participants from over a dozen countries found a genetic variant linked to both endometriosis and depression. That gene is related to the production of estradiol – the hormone primarily responsible for endometriosis disease progression. “The biological basis is not just chronic pain, and there is much more that we need to understand,” said Renato Polimanti, Ph.D., Yale associate professor of psychiatry and the study’s principal investigator. “The relationship between endometriosis and mental health is more complicated than we expected.” 

According to Yale endometriosis expert Hugh Taylor, M.D., another study researcher, endometriosis may even alter pain signals sent to the brain. His team observed differences in nerve conduction to the brain within a few weeks of inducing endometriosis in lab mice. According to Taylor, “The mice became more depressed, more anxious, and more sensitive to painful stimuli than they were prior to the induction [of endometriosis].” People with endometriosis experience a similar phenomenon. “They have what’s called ‘central sensitization of pain’ … being more sensitive to the same painful stimuli than they were before having the endometriosis,” Taylor said. 

Endometriosis diagnosis is often delayed

Endometriosis takes, on average, 10 years to diagnose because physicians often do not understand the systemic effects of the condition; therefore, patients get bounced around from specialist to specialist: to a psychiatrist for anxiety, to a nutritionist to help gain weight, to a gastroenterologist for abdominal pain. However, according to Taylor, if a patient notices symptoms only around their menstrual cycle, that would generally not indicate a primary bladder or bowel problem. “When the pain is cyclic, coming mostly around the menses, physicians should first think of endometriosis,” he said.

Another part of the problem is there is no simple, noninvasive test to diagnose endometriosis because unless the disease is extensive, endometrial tissue is generally not visible on imaging tests. Endometriosis may be discovered as an incidental finding during surgery for another reason. However, looking specifically for endometriosis requires a laparoscopic procedure in which a tiny camera is inserted through the belly button to view inside the abdominal cavity.  

Taylor feels in many cases, a diagnosis can be made simply by listening to the patient, focusing on symptoms and their history of pain, especially if it worsens over time. “Your first period at age 12 might set the baseline for what your periods will feel like in terms of pain. If menstrual cramps are getting more painful, that is not normal,” Taylor said. “Cyclic pain that is progressive over time is almost always endometriosis.”

There is no cure for endometriosis, but treatments are available for the symptoms and the problems it causes. Talk with your health care provider about your treatment options.

Learn more about endometriosis diagnosis and treatment at the following resources.