Endometriosis is a condition that affects some 15% of child-bearing age women in the US and millions of other women around the world. It occurs when tissue that behaves like the lining of the womb or the endometrium is found outside the womb. Now researchers show how two new compounds that target key drivers of the condition – estrogen signaling and inflammation – show promise as a new treatment for endometriosis.
The study – led by the University of Illinois at Urbana-Champaign – is published in the journal Science Translational Medicine.
The researchers hope that one day the new compounds will also treat a variety of other conditions where estrogen signaling and inflammation play a key role. These conditions include multiple sclerosis, liver fibrosis, inflammatory breast cancer, and obesity-linked cardiovascular and metabolic problems.
Current drugs for treating endometriosis suppress the condition, but they often fail to reduce the pain and inflammation that characterize it, says John Katzenellenbogen, research professor of chemistry at Illinois, and whose lab developed the new compounds.
“Current treatments also have side effects on other tissues through which estrogens work, and so they can’t be taken forever,” he adds. “There also is unfortunately a high rate of recurrence of the disease.”
Endometriosis causes painful or heavy periods. It can also cause chronic pain in the lower abdomen, pelvis or lower back. Women with the condition can also suffer from fatigue and depression. In the long term, endometriosis can lead to scarring of the ovaries, fallopian tubes and other tissues, plus inflammation and infertility.
For their study, Prof. Katzenellenbogen and colleagues tested the new compounds – chloroindazole (CLI) and oxabicycloheptene sulfonate (OBHS) – in mice with endometriosis and in human endometriotic cells.
Both compounds block estrogen receptors – signaling proteins that regulate a range of genes, including some that affect immune response and promote inflammation.
While the usual treatments for endometriosis target estrogen production, the team thought a better approach might be to target both main aspects of the condition: growth promotion and inflammation. Both of these features involve the estrogen receptor.
OBHS and CLI interact with two types of estrogen receptor – ER-alpha and ER-beta, respectively.
When they tested them on mice, the researchers found each drug reduced the amount of endometriotic tissue or prevented its growth outside the uterus. Each drug also reduced inflammation and stopped the growth of new neurons and blood vessels that support the misplaced womb tissue.
Further tests showed that the pups of mother mice that had the treatment were healthy and did not have reduced fertility.
The team also found that adding either compound to letrazole – a drug commonly used to treat endometriosis – made the treatment more effective than letrazole alone.
When they tested the drugs in human endometriotic cells cultured with macrophages – a type of immune cell that can contribute to the inflammation and growth of endometriotic tissue – the researchers found they had similar positive effects on estrogen-dependent activity and inflammation.
Benita Katzenellenbogen, a professor in the School of Molecular and Cellular Biology at Illinois, says:
“Inflammation is a driver of endometriosis. At some point, you’ve got to turn it off, and these compounds turn it off by working through the estrogen receptors.”
Although the study shows the new compounds offer a potential new approach to the treatment of endometriosis and other disorders involving estrogen signaling and inflammation, the researchers see many years of work ahead of them before they can be used in humans.
Funds for the study came from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Diabetes and Digestive and Kidney Diseases at the National Institutes of Health.
In June 2014, Medical News Today learned how the study of endometriosis took a leap forward when researchers announced they had developed a new mouse model for endometriosis.