Clinicians face hurdles in treating endometriosis from a ‘head-to-toe perspective’

Key takeaways :

• Spreading awareness about endometriosis can help improve diagnosis and patients’ quality of life.
• Determining the root cause of endometriosis could be the key to more effective treatments and diagnostic tools.

Endometriosis affects roughly 10% of reproductive-aged women and accounts for 40% to 50% of unexplained infertility cases, yet experts disagree about what causes it and how best to treat it.

Healio spoke with Iris Kerin Orbuch, MD, director of the Advanced Gynecologic Laparoscopy Center in Los Angeles and New York City, and Hugh Taylor, MD, professor and chair at the department of obstetrics gynecology and reproductive sciences at Yale School of Medicine and chief of obstetrics and gynecology at Yale-New Haven Hospital, to discuss diagnosing and treating endometriosis.

Taylor and Kerin Orbuch said every specialty must be more aware of endometriosis and how it affects the entire body.

“We need to pick it up early and approach it from a head-to-toe perspective,” Kerin Orbuch said.

Hugh Taylor

Despite its prevalence and impact on patients, many misconceptions among both patients and clinicians about endometriosis continue to exist, and diagnostic delays can take an average of 6 to 11 years in the United States, according to experts.

Searching for a cause

Researchers are still investigating the cause of endometriosis, with several theories contentiously debated among gynecologists, from embryonic cell transformation to the induction theory.

One common misconception is that pregnancy or hysterectomy can cure endometriosis, which stems from the theory that retrograde menstruation causes endometriosis, according to Kerin Orbuch. Also known as Sampson’s theory, this idea is that endometriosis is caused by menstrual blood flowing back through the fallopian tubes and into the pelvic cavity.

Although this is one of the oldest and most popular theories to explain how endometriosis occurs, the concept of retrograde menstruation is false, according to Kerin Orbuch.

“The only way we’re going to find a treatment is if we recognize that that’s not true,” Kerin Orbuch said. “The reason we know that can’t be true is a 2012 study looked at female fetuses, where they did autopsies, and found that 9% of these fetuses had endometriosis. Crazy similar number to the 10% or so we quote in the general population. Do you think a fetus is having retrograde menstruation?”

Kerin Orbuch noted that she would recommend a hysterectomy only if a patient also has adenomyosis, which is when the endometriosis tissue grows into the muscle wall of the uterus, and has completed childbearing or does not desire childbearing. Hysterectomy is not the treatment for endometriosis because endometriosis by definition is found external to the uterus and would not be removed during a hysterectomy. Thus, patients who undergo a hysterectomy for endometriosis are likely to continue to experience endometriosis symptoms. Another misconception is that endometriosis affects only the reproductive system.

“The implants of endometriosis are not only pulling the anatomy, but they’re also pro-inflammatory, so the inflammation is still there sending messages throughout the entire body, all over, wreaking havoc on the whole body,” Kerin Orbuch said.

Taylor has been involved in research examining how endometriosis can directly affect the brain, impacting the mental health of patients.

“We’ve done some studies that show that endometriosis, even without pain, directly affects the brain,” he said. “So, it’s not just that they’re in pain and become depressed because of the pain. Endometriosis itself causes changes in the brain that make depression and anxiety more likely or exacerbate subtle underlying depression or anxiety.”

Diagnostic delays

Several reasons underlie the substantial diagnostic delays that people with endometriosis experience, according to both Taylor and Kerin Orbuch.

“We don’t have imaging or bloodwork to diagnose the disease like so many other diseases can be diagnosed,” Kerin Orbuch told Healio. “Also, the symptoms of endometriosis vary even within sisters or mothers and daughters. Some people have gynecologic symptoms, some people have more gastrointestinal symptoms, some people have urological symptoms, and some people are asymptomatic. Symptoms are all over the map.”

A wide range of symptoms throughout the body coupled with a cultural taboo about discussing menstrual pain, pain with sex and painful bowel movements can make it challenging for individuals to seek care.

“It isn’t until these people have some significant pain where they’re doubled over, missing school or missing work, that people start to take it seriously,” Taylor told Healio.

Both Taylor and Kerin Orbuch noted that shortening diagnostic delays can have a great impact on quality of life.

“For too long we’ve been distracted by these red herrings and not focused on endometriosis diagnosis,” Taylor said.

Definitively diagnosing endometriosis is no small feat. As Healio previously reported, a study published in Fertility and Sterility in 2023 of 308 adolescents aged 12 to 20 years with NSAID-resistant severe dysmenorrhea who underwent MRI found that 39.3% had visible endometriosis. These findings suggested that pelvic MRI could hold a key to closing the gap in diagnosis. That solution is not perfect, however, because MRI findings depend on human interpretation, according to Kerin Orbuch.

“Someone could have a belly full of endometriosis, and the MRI will still be read as negative. It’s not the gold standard,” Kerin Orbuch said. “If the patient is lucky and they have a good MRI machine and the radiologist can kind of pick up endometriosis, that’s if they’re lucky.”

Taylor agreed that pelvic MRI is not always the best option for diagnosing endometriosis.

“I do use MRI, but I don’t think it adds a lot of value. Most endometriosis is missed on MRI,” Taylor said. “Most endometriosis, especially early disease where the diagnosis is most needed, is small and not seen on MRI. MRI can give detail as to severity of deep infiltrating disease; however, by that stage the diagnosis is usually clear. MRI is useful to plan surgery or to monitor severe disease, but can never be used to say that someone does not have endometriosis.”

Another barrier to diagnosis is the lack of clarity as to the qualifications required to be an endometriosis specialist, according to Kerin Orbuch.

“There’s no qualifications,” Kerin Orbuch said, “There’s no board certification. There’s nothing. Someone who does one excisional biopsy but ablates the rest can call themselves an excision specialist.”

Kerin Orbuch said excisional biopsy is the only way to definitively diagnose endometriosis, a view that has long been held by most gynecologists and researchers.

Taylor agrees that excision surgery is effective in treating endometriosis, but he said surgery should not be the gold standard for diagnosis.

“That’s pretty barbaric to wait until you’re in so much pain that you need surgery before you diagnose the disease,” Taylor said. “I like to compare it to if you have a headache. We don’t say we need a brain biopsy before we can give you some Tylenol. We can make some diagnoses based on symptoms or presumptive diagnoses of what’s wrong.”

The ‘gold standard’ treatment

Although there is no cure, treatment options include medical suppression, physical therapy, pain management, temporary medical suppressants, such as gonadotropin-releasing hormone antagonists, and surgical excision to remove the endometriosis tissue. In cases of adenomyosis, hysterectomy may also be a treatment option.

The first line of treatment for endometriosis, generally, is hormonal birth control pills. These pills may help relieve symptoms, but they do not treat the endometriosis tissue itself.

For patients who do not respond to hormonal birth control pills, Taylor offers gonadotropin-releasing hormone antagonists.

“These are oral medications that lower estrogen. They’re not as extreme as the old-fashioned injectables. They’re sort of milder, gentler variants of that,” Taylor said.

Kerin Orbuch said excision surgery is the gold standard for treating endometriosis.

“I learned the wrong kind of surgery when I was a resident,” Kerin Orbuch said. “I learned how to do ablation, or burning, which is the wrong surgery. The proper technique is excision or cutting out endometriosis.”

Some clinicians use ablation to remove endometriosis tissue, but a meta-analysis of three randomized controlled trials published in the Journal of Minimally Invasive Gynecology in 2017 found that although there was no significant difference in dyspareunia symptoms between those who underwent surgical excision or ablation, surgical excision resulted in greater improvements in dysmenorrhea, dyschezia and chronic pelvic pain 12 months after surgery compared with ablation.

A common characteristic associated with endometriosis is tight abdominal muscles, whether from intense menstrual cramping, anticipation of pain during penetration, straining for bowel movements or straining to urinate.

“There’s diagnostic delay. Let’s say someone has painful periods and they’re hunched over in the fetal position. Their abdominal muscles are getting tight and they’re not even realizing it, but they’re squeezing their pelvic floor muscles in pain, meaning they’re guarding and gripping because they’re in pain,” Kerin Orbuch said. “Whether someone kicks you in the stomach or you have pain from endometriosis, you’re going to squeeze. And month after month of doing that year after year, a decade later, your muscles are going to be tight.”

Pelvic floor therapy can help resolve chronic pelvic floor dysfunction, Taylor said, but he recommends waiting until after surgery to regain control of the disease first.

However, Kerin Orbuch recommends starting patients with pelvic floor therapy before operating.

“That’s why my patients take between zero and two narcotics,” Kerin Orbuch said. “We are undoing the pain generators that happened because of endometriosis before I operate on them. By the time I operate on them, typically all I’m left with is their endometriosis.”

Focusing on diagnosis

Although diagnosing endometriosis remains a challenge, both Kerin Orbuch and Taylor said it is important that clinicians work with the tools currently available to shorten the diagnostic delay. Both experts emphasize the importance of pediatricians looking for early signs and symptoms.

Taylor said researchers are currently working on a blood test to diagnose endometriosis without invasive surgery. In the meantime, clinicians are left with the challenge of treating a disease that mimics other conditions and is often resistant to therapy.

“Until we have a better diagnostic plan, we can work pretty good at listening to people and pay attention to what they’re telling us,” Taylor said. “Think endometriosis and try a birth control pill.”

For more information:

Iris Kerin Orbuch, MD, can be reached at @dririsorbuch on Instagram.

Hugh Taylor, MD, can be reached at hugh.taylor@yale.edu.

References:

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