EFA Medical Conference 2017: "Hormone and Cytokine Sensitivity in Endometriosis" Presentation by Dr. Robert Taylor

Dr. Robert Taylor discussed a hormone-based mechanism for endometriosis disease progression and listed various drugs that could target this signaling pathway.

Key Points

Highlights:

• This presentation by Dr. Robert Taylor delves into the hormone-regulated mechanism by which endometriosis develops. Dr. Taylor also talks about potential therapies that target this mechanism to stop disease progression.

Importance:

• The mechanism that causes endometriosis development is still at large. Understanding the entire system, or at least a part of it will enable researchers to create targeted therapies to eradicate the disease in the future.

Key Points:

• Estradiol and Progesterone are the two hormones associated with endometrium growth. Estradiol has been shown to promote inflammation; Progesterone has been found to have an anti-inflammatory effect.
• The hypothalamic pituitary gonadal axis is very important in endometriosis and many drug target this axis.
  • Opiates work outside of this axis.
  • There is a class of drugs that can be characterized as non-peptidergic, orally active, small molecules that have been shown to suppress the axis. This treatment that could potentially be used to treat endometriosis-related pain. Elagolix is projected to be the first drug of this kind to hit the market.
• Estrogen receptor beta is highly expressed in endometriotic cells.
• A prior study showed the progestins could be used for pain relief post-surgery, but later studies showed that progestins could not activate anti-inflammatory pathways in endometriotic cells.
• Macrophages are critical cells when it comes to endometriosis.
  • They are part of the pathway that occurs after retrograde menstruation.
  • They can secrete Interleukin-1 beta, a type of inflammatory protein.
• Interleukin-1 (IL-1) beta activates various pro-inflammatory responses within the cells.
  • IL-1 beta produces nuclear factor kappa B subunits.
  • Endometriosis cells are much more sensitive to IL-1 beta.
• Many drugs have NF kappa B inhibitory activity. Examples include:
  • Bortezomib – a protozoan inhibitor / Digitoxin – a cardiac glycoside / Sunitinib – a tyrosine kinase inhibitor / Tioconazole – an antifungal agent
• Many natural compounds can also potentially treat endometriosis.
  • Lycopene / Resveratrol / Curcumin
• Drugs are being developed that seek to inhibit interleukin-1 activity.
  • Monoclonal antibodies to bind interleukin one / Oxciobal receptors / Endogenous and naturally occurring antagonists to IL-1.
• Estradiol stimulates vascular endothelial growth factor messenger RNA in lesions; however, two estrogen receptor blockers occlude them.
• Selective estrogen receptor modulators have the ability to induce apoptosis.
• The Raloxifene trial proved that sometimes drug trials might not go as planned in that the effect is contrary to what was hypothesized.

Lay Summary

The first presenter of the “Estrogen from Inflammation to Cancer: A Distant Link?” section of EFA 2017 Medical Conference was Dr. Robert Taylor from Wake Forest University Health Sciences. Dr. Taylor’s presentation was titled “Hormone and Cytokine Sensitivity in Endometriosis.”

Dr. Taylor begins his presentation by discussing the two hormones known to promote endometriosis disease progression, namely estradiol, and progesterone. He then talks about the importance of the hypothalamic pituitary gonadal axis in developing therapies for endometriosis. He then proceeds to discuss a new class of drugs that could be used to suppress the axis above and lessen endometriosis-related pain.

Dr. Taylor also discusses a mechanism by which endometriosis can develop. This mechanism relies on the idea of retrograde menstruation and looks at the role of macrophages, Interleukin-1 beta, and nuclear factor kappa B. In short, macrophages can secrete Interleukin-1 beta, which can then activate nuclear factor kappa B that can subsequently turn on genes that promote endometriosis development. Dr. Taylor then delineates the types of drugs, artificially created and natural, that have the ability to target specific parts of the mechanism mentioned above.

Dr. Taylor’s presentation also focuses on the role of receptors, namely estrogen receptor alpha and estrogen receptor beta, as well as Selective estrogen receptor modulators in endometriosis disease progression. He ends by talking about the Raloxifene trial where the experimental group fared worse than the control group. This anecdote is to serve as a warning for future clinical trials.

Dr. Taylor’s entire presentation can be found at the following URL: https://www.endofound.org/video/hormone-and-cytokine-sensitivity-in-endometriosis-robert-taylor-md-phd/1549.