Increased Period Pain in Endometriosis Is Linked to Estrogen


Increased Period Pain in Endometriosis Is Linked to Estrogen

Researchers in China shed light on the biological mechanism of how estrogen may lead to increased period pain in endometriosis.

Key Points

Highlights:

  • Estrogen may increase endometriosis-associated period pain via the activation of immune cells, called mast cells. 

Importance:

  • A better understanding of the biological events associated with increased period pain in endometriosis could help researchers develop new and better treatments to decrease the pain.

What’s done here?

  • Researchers analyzed ovarian endometriomas using tissue imaging techniques and enzyme assays.

Key results:

  • The concentration of estrogen and the number and activity of mast cells were significantly higher in ovarian endometriomas compared to controls.
  • These parameters were correlated with the severity of endometriosis-associated period pain.
  • Estrogen increased the degranulation (or activation) of mast cells.
  • Estrogen-activated mast cells released biologically active nerve growth factor (NGF), a protein thought to be involved in endometriosis-associated pelvic pain.
  • Estrogen-treated endometriotic cells could promote mast cell recruitment by increasing the production of proteins such as stem cell factor, transforming growth factor-β, and monocyte chemoattractant protein-1.

Limitations of the study:

  • The experiments were conducted in the laboratory using cell culture. More research is needed to understand whether the same mechanisms are in place in living organisms and women with endometriosis. 

Lay Summary

Researchers in China shed light on the mechanism of how the female sex hormone estrogen may be linked to increased period pain in women with endometriosis. A better understanding of the biological mechanism leading to pelvic pain in endometriosis could help researchers develop better treatments to reduce the pain in the future.

It was already known that abnormal enzymes associated with estrogen and an increased number of immune cells, called mast cells were implicated in endometriosis. 

In order to better understand whether estrogen is associated with the number and activity of mast cells during the pathogenesis of endometriosis, and whether this could be linked to increased pain, a team of researchers led by Dr. Xinmei Zhang at Zhejiang University School of Medicine in China analyzed ovarian endometriomas (or endometriotic cysts) using tissue imaging techniques and enzyme assays.

They found that the concentration of estrogen and the number and activity of mast cells were significantly higher in ovarian endometriomas compared to controls. Moreover, the higher the concentration of estrogen was and the more active the mast cells were, the more severe, endometriosis-associated period pain was.

In order to see whether estrogen can directly affect mast cells, the researchers treated mast cells obtained from rats called RBL2H3 cells with estrogen. Mast cells contain many granules that are rich in histamine and heparin, compounds involved in the immune response. 

They saw that estrogen increased the rate of degranulation, or release of histamine- and heparin-containing granules from these RBL2H3 mast cells. In other words, estrogen increased the activity of the mast cells.

The researchers also found that the activation of RBL2H3 cells by estrogen triggered the release of biologically active nerve growth factor (NGF), a protein that is thought to be involved in endometriosis-associated pelvic pain.

When they treated endometriotic cells with estrogen in the laboratory, the researchers found that these cells were able to attract mast cells to themselves by increasing the production of certain proteins such as stem cell factor, transforming growth factor-β, and monocyte chemoattractant protein-1. Interestingly, control endometrial cells did not do this. 

“…Elevated [estrogen] concentrations may be a key factor for degranulation and recruitment of [mast cells] in ovarian endometriomas, which play a key role in endometriosis-associated [period pain],” the researchers concluded.

The study is published in the scientific journal Reproduction.


Research Source: https://www.ncbi.nlm.nih.gov/pubmed/29074615


estrogen mast cells period pain

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