Endometriosis – a severely life-limiting disease affecting millions of women
Endometriosis, a painful inflammatory condition affecting approximately 190 million women worldwide, occurs when tissue similar to the uterine lining grows outside the uterus. This leads to the formation of endometriotic lesions, primarily in the abdominal cavity and on its organs, causing local inflammation and burdensome adhesions. The resulting, often excruciating pain may progress to a chronic condition. Despite its prevalence, affecting 10 percent of women of reproductive age, endometriosis remains largely underdiagnosed and undertreated, with limited novel treatment options available for patients.
Endometriosis may have a severe and wide-ranging impact on the health and quality of life of those affected. Women typically experience intense cyclic and/or chronic pelvic pain, which they describe as deeply throbbing, sharp, and cramping. This pain often accompanies daily activities, making even basic functions challenging. Menstrual pain with heavy bleeding is common, and many women experience significant discomfort during intimate relationships. Perhaps more devastatingly, endometriosis is the leading cause of female infertility and subfertility, leaving many patients struggling to conceive.
Since the persistent pain and discomfort of endometriosis may severely affect quality of life over decades, it is not surprising that it is correlated with depression and other mental health issues.
Many women find themselves withdrawing from social activities and struggling to maintain their careers. The impact on family planning and relationships can be profound, creating additional emotional strain and affecting overall life satisfaction.
The symptoms usually emerge during or shortly following adolescence – a formative time with a profound impact on the rest of life. Therefore, the disease may have long-term consequences for educational achievement, career, income, family formation, and social relationships. The time from onset of first symptoms to diagnosis is between 4 and 11 years, but many patients remain undiagnosed.
Current treatments have significant shortcomings
Standard of care for endometriosis consists mainly of pain-relieving agents and hormone-based therapies including contraceptives and other, more potent drugs. Endometriotic lesions require estrogen to grow, which is why hormone-based therapies are commonly used. Drugs which suppress estrogen production, or its effects alleviate the symptoms of endometriosis to a varying degree. However, interfering with normal variations of female hormone levels often leads to side effects, including hot flashes (vasomotor symptoms) and mood changes. Stronger anti-estrogens may also reduce bone mineral density over time, which could lead to an increased risk of osteoporosis.
In addition to hormone-based treatments, various pain-relieving agents are used. The most common painkillers are NSAIDs, such as naproxen, ibuprofen and celecoxib. They are effective for mainly the menstruation-related pain (dysmenorrhea) but unfortunately are associated with gastro-intestinal and cardiovascular side effects and should therefore be only used intermittently. Opioids are sometimes used to relieve pain, but this class of drugs carries a high risk of side effects and has a significant potential for addiction. Tricyclic antidepressants, antiepileptics, and other types of medications are also sometimes used as adjunctive therapy. As an alternative to drug treatment, surgical removal of endometriotic lesions can be effective. However, the recurrence rate is high, and many patients require repeated surgeries within a few years. More radical surgery, such as hysterectomy and oophorectomy (removal of the uterus and ovaries), may be considered as a last resort.
The enzyme mPGES-1 plays a key role in the development of endometriosis
Current treatments, including pain medications and hormonal contraceptives, provide inadequate relief for many patients or cause intolerable side effects. Therefore, major scientific efforts have been made to find new, more specific drug targets and specifically in the inflammatory cascade. Microsomal prostaglandin E synthase (mPGES-1) is an enzyme generally present only at low levels in the human body, while it is strongly upregulated in inflamed tissues, such as in the endometriosis lesions. This leads to locally increased production of proinflammatory prostaglandin E2 (PGE2), a potent biological mediator of pain and inflammation. Therefore, mPGES-1 is a compelling target for treating endometriosis. Read more about vipoglanstat in endometrios here.
Despite the key role of mPGES-1 in the pathogenesis of endometriosis, there are no pharmaceuticals available on the market that specifically inhibit this enzyme. While there are drugs that exert their mechanism of action further up in the arachidonic acid cascade, these drugs do not only target mPGES-1 but also affect the synthesis of numerous signaling substances important to many normal functions in the body.
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