New Prospective Treatment Options for Endometriosis

Posted by Phil Heler on May 4, 2021

Endometriosis is estimated to affect 176 million women worldwide and there is a significant unmet requirement for treatment options for this condition.

 

This week  I am continuing my narrative on endometriosis having departed from my promise to do so last week. If there are any emerging significant COVID-19 developments, they are hard to ignore. The better informed we are then the more valid our opinions and better our choices. But before we do dive into some science it is always fun to briefly comment on the more bizarre aspects of the week that was.

Recent news appears to be smitten with awkward relationships. Never mind Boris Johnson and Dominic Cummings (who is accused of disclosing Boris’s text messages) or David Cameron and Lex Greensill. The paint manufacturer Dulux has also had its moment.

It has apologised after making fun of the football club Tottenham Hotspur. This was a very awkward moment as the company had remarkably just signed a new  sponsorship deal with the club. It had just posted a picture of its famous English sheepdog enjoying a pretend tour of the New White Hart Lane football ground on Twitter.

 

 

Clearly the posts on Twitter soon engaged the attention of Tottenham Hotspur fans. As comments began to fly some of the replies from Dulux unfortunately appeared to be rather sarcastic (football fans can be sensitive!). One fan suggested that the English sheepdog could play right back, and Dulux replied stating ‘he might do a better job!’. Another fan asked if they could repaint the trophy cabinet and Dulux replied that all surfaces should ideally be ‘dust free’ before painting! It has been 13 years since they last won a trophy. So begins a long and illustrious relationship.

No less awkward and difficult is the national shortage of portable lavatories for outdoor events. This could of course lead to long queues and moments of personal crises as the summer turns to autumn! Given that no outdoor events have been allowed during the pandemic where have all the portable loos gone? Bizarrely this all filters back, at least in part,  to extreme weather events that occurred in Texas in February.

The state temporarily lost a large share of its energy generating infrastructure including oil. Plastic processing is big business in Texas, and it is of course centred around the large oil fields. The interruption in plastic manufacture, due to lack of oil, had consequences for the global plastic supply chain logistics. Less plastic equals fewer portable toilets.

 

 

This is also combined with the fact that construction companies throughout the pandemic have increased the ratio of portable toilets available for their workers from roughly 1 in 50 to, in some cases, 1 in 5. Huge COVID-19 testing centres also had a large portable loo requirement. An unlikely emerging popular trend for outdoor raves in a post-COVID-19 China has also exacerbated the global problem for a demand in outdoor portable toilets (remember China has a population of 1.398 billion people which is 18.5% of the world’s population). Cause and effect. But back to the day job.

Endometriosis is estimated to affect 176 million women worldwide often leading to debilitating pelvic pain.  It is a chronic, inflammatory gynaecological condition that is characterised by endometrial-like tissue migrating outside the uterus to other tissues, most often to the lining of the pelvic cavity. Currently there is a significant unmet requirement for treatment options for this condition.

Current treatment options are limited to repeated surgeries (including full hysterectomies), hormonal drugs or painkillers such as ibuprofen or paracetamol. Most available hormonal treatments have a range of unpleasant, unwanted side-effects, and serve only to further inhibit pregnancy.

 

 

There are however some particularly good examples of treatments that have been repurposed for various conditions. Dichloroacetate (or DCA) for example is now being tested for its efficacy in treating endometriosis. DCA is a non-hormonal compound previously used to treat rare metabolic disorders in children. DCA helps to control lactate levels, which have been found to be higher in patients with some cancers and endometriosis. Endometriosis cells secrete high levels of lactate. This helps develop an ideal environment for migrant endometrial cells to flourish and persist.

The University of Edinburgh is currently undertaking a randomised controlled trial (RCT) to determine if DCA is effective for the treatment of endometriosis-associated pain. Anything that helps disrupt this lactate pathway could be of some significance.

To this end the university has recruited 30 women with endometriosis-associated pain for a trial lasting 12 months. The trial results have not yet been published. Professor Horne, a lead researcher, has gone on record as commenting ‘it’s too early for any conclusive results on how well the drug works, but the findings so far are exciting’. The team is hoping to expand their investigations and receive enough funding for a much larger trial involving up to 400 volunteers. Watch this space.

There is also another interesting study by the University of Oxford which is focusing on the genetic aspects of endometriosis. The head of the research team is Professor Krina Zondervan who also co-founded the International Endometriosis Genome Consortium (IEC).

The team, allied with the consortium, are currently conducting the largest collaborative genome-wide association studies of endometriosis to date. The IEC consortium has recently expanded to 16 research centres. So far, they have collected data and tissue samples donated by 60,000 women with endometriosis from all around the world. It is the largest study of its kind ever undertaken.

 

 

Their soon-to-be published work is set to reveal new details about endometriosis, including confirmation that it is not one single condition. The study has uncovered genetic links to other inflammatory conditions such as asthma and osteoarthritis, and  conditions such as migraines and back pain.

There is hope that this body of work could speed up the development of endometriosis treatments that are non-hormonal based. For instance, this could imply that investigations can be undertaken to see if a drug used to treat asthma, because a link has now been established, could be modified to treat endometriosis.

On a different note, one large observational study published in 2018 in the American Journal of Obstetrics and Gynaecology looked specifically at modifiable risk factors in association with endometriosis: in this case meat consumption.

Consumption of meat has been shown to influence endometriosis risk through its effect on steroid hormones levels. It increases oestrogen levels and could therefore promote endometriosis. A previous study published in the New England Journal of Medicine in 2013 also discovered that changing from a diet high in animal fat to a plant-based Mediterranean diet can reduce oestrogen levels by 40%.

The Fred Hutchinson Cancer Research Centre in Seattle undertook an investigation to see if eating red meat, which is thought to influence oestrogen levels, could play a role in endometriosis. The study assessed the risk over 22 years. A total of 81,908 participants from the prospective Nurses’ Health Study II were followed up from 1991 through 2013.

The Nurses’ Health Study is one of the largest investigations into the risk factors for major chronic diseases in women. Diet was assessed via a food questionnaire every 4 years and the researchers noted any cases of surgically confirmed endometriosis. They discovered that women who ate more than two servings of red meat each day had a 56% higher risk of developing endometriosis than those who ate no more than one serving per week. Their study therefore suggested that red meat consumption may be an important modifiable risk factor especially among women with endometriosis who had not reported infertility and thus were more likely to present with pain symptoms.