/The latest in endometriosis research: Ways forward

The latest in endometriosis research: Ways forward


Endometriosis affects many women worldwide, but treatments for this chronic condition are few and sometimes insufficiently effective. In this Special Feature, we look at what recent research has to say about the most promising ways forward for endometriosis treatment.

This issue can affect all people assigned as female at birth, but it often goes undiagnosed, partly due to gender stereotyping.

Endometriosis is a chronic condition that causes the tissues lining the uterus to grow outside the uterine cavity.

March is Endometriosis Awareness month, so in this Special Feature, Medical News Today explore endometriosis basics, what is currently known about potential causes of endometriosis, and existing and emerging treatments.

The most common symptom of endometriosis is pain. This usually occurs when growths that characterize the condition bleed and swell in a similar way to regular uterine tissues during menstruation.

This often causes very painful, heavy periods that may worsen over time as well as chronic lower back or pelvis pain.

Endometriosis may also trigger:

  • spotting or bleeding between periods
  • pain when going to the bathroom or during sex
  • bloating
  • nausea
  • constipation
  • diarrhea

In excess of 11% of women in the United States between the ages of 15–44 years, which equates to more than 6.5 million, may have endometriosis.

A formal diagnosis of endometriosis requires laparoscopic surgery, which can lead to pain and discomfort immediately after the procedure.

Those without symptoms often learn of their endometriosis when they are unable to conceive. As many as 4 in 10 women with infertility have endometriosis. Many are not formally diagnosed until their 30s or 40s, a diagnosis that takes 8 years, on average.

According to a study by Endometriosis UK., around 62% of women between the ages of 16–54 years would also delay treatment because they think their symptoms are not serious, normal, or they believe doctors will not take them seriously. Many also delay treatment due to embarrassment.

Endometriosis, and the growths that characterize the condition, may cause infertility by:

  • negatively impacting egg and sperm function and movement, fertilization, implantation, and embryo development
  • making it harder for the egg and sperm to unite by changing the shape of the reproductive organs or pelvis
  • causing issues with the development of the uterine lining, making egg implantation difficult
  • blocking the fallopian tubes or causing fluid-filled ovarian cysts called endometriomas to form that may cause the ovaries to rupture or twist, which can cut off blood supply to the organs and kill them
  • causing the immune system to harm a healthy embryo mistakenly

Researchers are still trying to uncover the precise reason — or reasons — for which endometriosis occurs.

According to the Office on Women’s Health, it most likely occurs when tissues shed during menstruation flow into other parts of the body, such as the pelvis.

Endometriosis growths may also develop due to elevated levels of hormones and immune cells, such as prostaglandins, cytokines, and estrogen, and a reduced response to the hormone progesterone.

It also runs in families and may have a genetic basis. However, there is some speculation that it may also be due to an immune system issue that means it does not find or destroy growths that characterize endometriosis.

Endometriosis is also more common in people with ovarian or breast cancer. It may also occur when doctors accidentally move endometrial tissues to other parts of the body during surgeries.

Several factors are also linked with the development of the condition in some cases. These include:

  • periods that last longer than 1 week
  • menstrual cycles that last 27 days or fewer
  • health problems that block menstrual flow
  • never having children

Researchers continue to find new reasons to explain why endometriosis occurs and what influences its severity.

Some recent research — published in PLOS Genetics in 2020 — found that people with endometriosis have certain chemical modifications to their DNA, while those without the condition do not.

These differences involve DNA methylation, a process by which methyl group compounds bind to DNA, which can change gene activity. And these methyl changes seem to vary based on the severity of endometriosis.

In the future, these DNA modifications could be used to help diagnose endometriosis without surgery.

There is also some evidence that environmental factors may play a role in the development or severity of endometriosis.

A very large study — published in Human Reproduction in 2018 — found that severe-chronic sexual and physical abuse of several types increased the risk of a formal endometriosis diagnosis by 79%.

Research in animals has also found that toxins in the environment, such as dioxin, may impact the reproductive system, hormone functioning, and the immune system in a way that increases the risk of developing endometriosis. However, researchers have not yet proven these links in humans.

In addition, several studies have explored the potential link between endometriosis and exposure to toxins such as polychlorinated biphenyls, bisphenol A, and phthalate esters. But scientists need to conduct more studies to determine if this link exists and how strong it is.

Researchers are also exploring whether other health conditions may be linked to endometriosis in some way, including:

  • fibromyalgia
  • chronic fatigue syndrome
  • allergies
  • chemical sensitivities
  • asthma

Currently, there is no cure for endometriosis. However, in most cases, symptoms may improve with the use of medications, surgery, or both.

Over-the-counter pain medications, such as nonsteroidal anti-inflammatory medications, may help manage endometriosis pain.

Doctors often prescribe hormonal medications to help manage endometriosis symptoms. They most commonly take the form of birth control pills, progestin-only medications, and gonadotropin-releasing hormone (GnRH) medications.

Many hormonal medications help treat endometriosis by reducing excess tissue growth and the formation of new adhesions. Endometriosis adhesions are places where chronic inflammation causes tissues to scar — these are most often found throughout the pelvic area and around the ovaries, uterus, and bladder.

GnRH medications also prevent ovulation, menstruation, and the growths that characterize the condition.

In severe cases, or when hormonal medications are not effective enough, doctors may perform surgery to physically remove the growths that characterize the condition.

Currently, it is very difficult for doctors to find and remove all excess growths during laparoscopic procedures. This means symptoms often return or never fully go away, while additional surgery is often necessary.

But up to 80% of women experience symptoms again within 2 years of surgery. After surgery, many also go back on hormone treatments to maintain their condition and symptoms.

If all other treatment options fail and the pain is severe, healthcare professionals may perform a hysterectomy to remove the uterus and potentially the ovaries.

None of the current treatment options for endometriosis come without major drawbacks or potential risks.

Hormonal medications can cause:

And surgery always carries health risks such as scarring, infection, and excess bleeding. That is why researchers are constantly trying to come up with new treatments.

Another major problem with current treatments for endometriosis is that they usually prevent someone from becoming or remaining pregnant. That means those looking to get pregnant have few treatment options.

A clinical trial is currently underway to assess whether dichloroacetate (DCA) could be an effective, non-contraceptive treatment for endometriosis. Doctors typically use DCA to help treat metabolic disorders in children.

Recent research has shown that people with endometriosis tend to have excess lactate in their pelvis. The drug DCA seems to lower lactate production and reduce the survival rate and growth of endometriosis growths. The clinical trial is ongoing.

There is also increasing evidence that cannabis or cannabinoids may help treat endometriosis by restoring imbalances in the endocannabinoid system (ECS) that may cause endometriosis symptoms.

In particular, cannabidiol appears to interact with the ECS to reduce the production of enzymes that help cause inflammation and spread cells.

In a 2020 study, 59% of women using cannabis to self-treat endometriosis symptoms said they were able to stop using pain medications, particularly opioids, entirely.

Research is also underway to find medications that are specifically designed to target endometriotic tissues while leaving healthy tissues unharmed.

These peptide medications would work to fine-tune faulty molecular processes that lead to the growth of excess tissues. They would also help encourage the destruction of tissues that characterize endometriosis. Peptides are small strings of amino acids.

Teams are also looking to find medicines that may help treat endometriosis by altering or reducing levels of macrophages. Macrophages are immune cells that have been shown to help encourage blood flow to, innervation (nerve sensation) of, and growth of endometriosis growths.

In a 2019 study, researchers were able to reverse pain behaviors seen in mice with endometriosis by depleting macrophage levels.

Scientists are also testing noninvasive (nonsurgical) therapies to see if they can reduce endometriosis symptoms, in particular physical therapy.

In a 2021 study, regular pelvic floor physiotherapy reduced pain during intercourse, chronic pelvic pain, and improved pelvic relaxation in women with endometriosis.

Researchers are also trying to figure out if nanomedicine may be as useful for treating and diagnosing endometriosis as it has been for cancer.

Nanomedicine uses very, very small materials, such as nanoparticles or artificial nanobots, to help deliver medications or diagnostic imaging agents that include dyes to specific areas in the body.

A pilot clinical study is taking place in The Netherlands to determine whether nanomedicine, specifically fluorescence imaging, could help doctors better visualize excess tissues. Fluorescence imaging uses injectable fluorescent dyes that help illuminate internal structures, making them easier to see.

In a 2020 study, researchers used nanoparticles packaged with a dye capable of generating a fluorescent signal and cell-destroying heat when exposed to near-infrared light to identify and then destroy abnormal endometriosis growths in mice.

Researchers continue to look for ways to diagnose endometriosis earlier, improve treatment options, and ultimately reduce the risk of serious complications.

Women’s health advocates also continue to call on the research community to fill serious knowledge gaps that make the diagnosis and treatment of endometriosis difficult.

In a 2019 review by the Society for Women’s Health Research, a group of expert researchers, patients, and clinicians reported that, despite the high prevalence and emotional and economic impact associated with endometriosis, the field remains underfunded and, therefore, under-researched.

The group report that these factors slow the development of important new diagnostic and treatment options. They also claim this disparity occurs partly because of the stigma around menstrual problems and the normalization of female pain.

So this Endometriosis Awareness Month, consider taking some small actions to help end harmful stigmas and support much-needed research.

This may be as simple as openly talking to friends, family, or a doctor about endometriosis. Here are some tips for how to talk about endometriosis in different situations.

It may also mean attending one of the many awareness events taking place globally.

For support getting diagnosed with or dealing with endometriosis, check out some national endometriosis organizations available worldwide.

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