Endometriosis: Why Is Research Funding So Low?

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Endometriosis is an age-old disease described in medical texts dating back to the papyri of ancient Egypt. But despite the condition's long history, from the pharaohs to Freud, and the broad prevalence, this inflammatory illness does not get the attention it deserves.

Today, usual estimates of the prevalence of the condition vary from about 6% to 15% of females globally, with at least 1 in 10 generally thought to have this life-disrupting condition, according to the World Health Organization. That proportion translates to at least 190 million women worldwide and 6.5 million women in the U.S. The prevalence is higher in women with chronic pelvic pain and those who are infertile. While most commonly affecting those ages 25 to 40, endometriosis can occur in girls as young as age 9 and can persist or develop after menopause when it may be related to hormonal therapies.

"The current best working estimate is around 1 in 9 or 10 of women and those assigned female sex at birth, during their reproductive years," said Mike Armour, PhD, a senior research fellow in reproductive health at Western Sydney University in Australia.

Estimates from multiple prevalence analyses do vary, however. In one systematic review in 2021, for example, of literature published from January 1990 to December 2018, the researchers found a substantial overall prevalence of 18%, with the prevalence by stage ranging from 2% for stage 4 disease to 20% for stage 1.

The prevalence levels in women with infertility, chronic pelvic pain, and asymptomatic disease were found to be 31%, 42%, and 23%, respectively, and prevalence appeared to be high in developing countries.

Armour said he is not aware of any prevalence research comparing low- and middle-income counties (LMIC) with high-income countries. "It is likely that prevalence rates are similar, as we don't have any reliable evidence otherwise," he said. "Given that diagnosis until recently required laparoscopic surgery and this is likely to be less accessible in LMIC, historically it would have been difficult to determine if the prevalence is different or not. You can't determine prevalence if you don't have access to tools to determine if the disease is there."

Among 127,476 affected women in Canada and the U.S., the reported incidence was 5-15% in those of reproductive age and 2-5% in postmenopausal women. By continent, endometriosis ranged from 17% in Europe to 36% in Asia, and by the sample size from 28% for studies with fewer than 1,000 individuals to 7% for studies with more than 1,000 individuals.

In subgroup analyses, the prevalence rates were as follows:

• 31% in women with infertility

• 42% in women with chronic pelvic pain

• 23% in women with no symptoms

A large 2017 database study from Israel sought to describe the real-world disease burden, showing a point prevalence of endometriosis of 1% in women ages 15 to 55 and 2% in the highest-prevalence age group. Interestingly, a small but significant increase in incidence was noted over time, although it is unclear if this relates to a true increase in the incidence of the disease or simply to an increased awareness of the disease and thus an increase in its diagnosis, the authors said.

Healthcare and Economic Costs

Definitive up-to-date figures on related costs are sparse. The 2008 U.S. healthcare costs for endometriosis were estimated in one 2012 review by Steven Simoens, PhD, of Katholieke University Leuven in Belgium, and colleagues at approximately $4,000 per affected woman, analogous to costs for other chronic conditions such as type 2 diabetes, Crohn's disease, and rheumatoid arthritis. The management of symptoms further increases the financial burden because of the effect on physical, mental, sexual, and social well-being, as well as on school and workplace productivity.

"Many of the cost data used stem from Simoens EndoCost tool, but this is about 10 years old now," Armour said. "In Australia, our direct healthcare costs are quite low due to our mostly public healthcare system – around $2,600 USD per person, per year." In the U.S. healthcare system, direct medical costs are likely higher.

A more recent review, published in 2018 and involving 113,506 patients and 927,599 matched controls, found that endometriosis was associated with significantly higher healthcare usage during both the pre- and post-index periods. Approximately two-thirds of patients underwent an endometriosis-related surgical procedure such as laparotomy, laparoscopy, hysterectomy, oophorectomy, or other excision/ablation procedures in the first 12 months post-index.

Mean annual total adjusted direct costs per endometriosis patient during the 12-month post-index period were more than three times those for a non-endometriosis control: $16,573 vs $4733. On average, incremental direct and indirect 12-month costs per endometriosis patient were $10,002 and $2,132 compared with those for matched controls.

Moreover, the well-known delay in diagnosis of endometriosis contributes to costs. A 2020 study found that patients with intermediate or long diagnostic delays had consistently more all-cause and endometriosis-related emergency visits and inpatient hospitalizations in the pre-diagnosis period than patients with short delays.

Pre-diagnosis all-cause healthcare costs were significantly higher among patients with longer endometriosis diagnostic delays, averaging $21,489, $30,030, and $34,460 among those with a short, intermediate, and long delay, respectively. Direct endometriosis-related costs accounted for 12.5% of all-cause costs and followed a similar pattern.

In terms of the broader, non-medical, productivity-related economic costs of endometriosis, Armour said that these come in at around 66% to 83.6% of the overall cost-of-illness burden, depending on the country. "In Australia this tends to be around $14,000 to $19,000 in USD per person per year – with those having more severe pain incurring a greater toll," he said.

Personal Costs

Unlike some chronic diseases that start later in life, symptom onset for endometriosis generally occurs at a time of life – menarche through menopause, adolescence through young adulthood -- when key life-defining decisions are made.

And although the pain, anxiety, and fatigue of endometriosis affect all aspects of a person's life, there are few good data on endometriosis-related quality-adjusted life years (QALYs), Armour said. "But we are currently working on a project to collect this information in Australia."

Earlier research suggested similar health-related quality of life for women with endometriosis. Simoens 2012 paper looking at patients in Europe and the U.K. reported an average QALY of 0.81 for those with endometriosis, a loss of 19% in quality of life relative to the fullest possible rating of 1 denoted by the absence of any possible health problem.

"However, the more standard comparison would be to look at how such a rating compares with general-population norms for a similarly aged cohort," said Richard De Abreu Lourenco, PhD, of the Centre for Health Economics Research and Evaluation at the University of Technology Sydney in New South Wales. "One 2005 U.S. study, for example, reported a QALY of 0.91 for women in the general population of a similar age to those in Simoens et al, with QoL measured using the same instrument in both studies."

The Funding Gap

Despite being about as common as diabetes and heart disease and affecting more Americans than Crohn's disease, endometriosis reflects the same gender bias in research funding seen in other female-centered diseases, garnering only a fraction of the support allocated to conditions that affect both genders.

"I think this is at least in part due to the view of period pain, often the first symptom of endometriosis, being normalized, with young people often told it's just part of being a woman and that they will grow out of it," Armour said. "We know that women's pain is not taken as seriously as men's, and I think this is why, until recently, endometriosis has not been a funding priority."

That's putting it mildly if figures from a May 2022 paper are to be believed. The researchers noted that the NIH is expected to allocate just $16 million for endometriosis research this year -- 0.038% and $2 per woman out of the $41.7 billion global research budget, despite the fact that endometriosis is expected to strike 11% of U.S. women over the course of their lifetime.

In comparison, an anticipated 12% of U.S. women will suffer from diabetes in their lifetime. Assuming that half of the diabetes research budget is allocated for female sufferers, the funding translates to $31.30 per woman, which is 1,500% more than for endometriosis.

The study also found that while fewer than 700,00 people have Crohn's disease in the U.S., or 0.21% of the population, in 2022, Crohn's disease research will receive $90 million in funding, or $130.07 per patient, which is more than 65 times per patient than for endometriosis.

Armour acknowledged that although endometriosis research funding has increased significantly over the past few years, it still remains only a fraction of what is needed. "In Australia, endometriosis costs around 21 million to 23 million Australian dollars per day, so even with all the funding received, it only equates to around 1 day of productivity and healthcare costs."

Research Priorities

The most pressing endometriosis research priorities, he said, are two: The first need is for a noninvasive definitive diagnostic technique to help reduce the multi-year diagnostic delays worldwide, and especially in LMIC countries that may lack the healthcare infrastructure to undertake diagnostic surgery.

"The second is determining the most effective method of treatment once we have a diagnosis," Armour continued. "At the moment we have very little information on when to do surgery, what the long-term outcomes are, and what kind of surgery techniques work best for different endometriosis symptoms."

Better medical treatments that control symptoms without impacting fertility are needed as well. In the meantime, clinicians can provide psychosocial support to help those coping with the disease's multifaceted consequences.

Read previous installments of this series:

Part 1: Endometriosis: Understanding the Pathogenesis and Pathophysiology

Part 2: Diagnosing Endometriosis

Part 3: Managing Endometriosis: Research and Recommendations

Part 4: Case Study: Endometriosis or Hernia?

Part 5: Endometriosis: Fertility and Pregnancy

Part 6: The Latest on What to Know About Managing Endometriomas

Part 7: Enhancing the Doctor-Patient Dialogue About Endometriosis

Part 8: Case Study Mystery: Swollen, Painful Belly Button During Menstruation