MSU researchers expand the search for hormone-free endometriosis treatments

For the nearly 200 million women and girls worldwide who suffer from endometriosis, the introduction of hormone-free treatments would be a game changer. MSU researchers are working to make this happen.

For many patients, each menstrual cycle brings days of excruciating pain that leads to missed work, school and social activities. Their suffering is compounded because endometriosis can take years to diagnosis.

Typically, this condition is treated by hormone-based medications, which have side effects and don’t allow patients to become pregnant.

“For well over 100 years, doctors have been trying to understand endometriosis,” said Asgerally Fazleabas, University Distinguished Professor and associate chair of research in the Department of Obstetrics, Gynecology and Reproductive Biology in the MSU College of Human Medicine. “We can’t yet cure endometriosis; we can only suppress it. The two main consequences of the disease are pain and difficulty getting pregnant. Our existing drug treatments only offer two choices: birth control pills or medically induced menopause. Neither is compatible with pregnancy.”

Since 2009, MSU researchers have been working to improve medical options for endometriosis patients, and a recent $3.4 million grant from the National Institutes of Child Health and Human Development will enable them to expand their work.

Fazleabas’ endometriosis research has been continuously funded by the National Institutes of Health since 1986. This grant will help his team evaluate medications that have already been approved by the U.S. Food and Drug Administration to see what could help endometriosis patients.

Endometriosis occurs when tissue from the lining of the uterus, called endometrium, grows outside of the uterus. Areas of abnormal endometrial growth are called lesions. When they become inflamed, they lead to pain.

Lesions appear in places that can’t be seen during a routine pelvic exam. Often, they’re found in the ovaries, fallopian tubes and other areas outside the uterus, but in rare cases, endometriosis lesions can appear in the lungs, skin or brain.

To help understand which FDA-approved medications might benefit women and girls who have endometriosis, researchers are now studying the communication between inflamed cells and surrounding cells. Specifically, they want to identify and decode the messages that switch on the genes that cause endometriosis. This requires RNA sequencing, and co-principal investigator Gregory Burns, assistant professor of obstetrics, gynecology and reproductive biology at the MSU College of Human Medicine explains the process with a smoothie analogy.

“If you look at a bowl with six kinds of fruit, you can see each distinct type of fruit and where each is in relation to the others — like the blueberries are next to the kiwi,” said Burns. “Put them in a blender to make a smoothie, and you can’t tell what’s what. Nor can you tell what relationships the fruits had to each other while they were in the bowl. That’s the challenge we traditionally had with analysis of endometrial lesions. We lost spatial awareness of which cells are side by side.”

A technique called spatial transcriptomics is used to identify exactly which cells are in the sample.

“If we think about our fruit bowl, it’s like taking a sample slice where the strawberry and mango touch,” Burns said. “Spatial transcriptomics lets us take a slice of tissue where we know which types of cells we’re getting. Knowing that these cell populations are next to each other allows us to see how they might be communicating. This will help us better understand the RNA sequence that turns on the genes for endometriosis lesions.”

Once the communication between the cells and the genetic switch is understood, the team will evaluate if any existing FDA-approved drugs can be repurposed to treat endometriosis.

“We’ll use an algorithm to see if the signature for the gene that leads to endometriosis matches approved drugs already in use for other conditions,” Burns said. “If the signatures match, it may be possible to prevent endometrial lesions from forming or reverse ones that are already present.”

Additional collaborators on this research include Bin Chen, associate professor at MSU, Stacey Missmer at the University of Michigan and Kathryn Terry at Brigham and Women’s Hospital.