ENDOMETRIOSIS PAIN

Estrogen may play role in endometriosis associated pain

Estrogen may play role in endometriosis associated pain

By I.Soussis MD

Estrogen could be responsible for endometriosis-associated chronic pain by activating a type of immune cells called macrophages and nerve cells, which increases inflammation and sensitivity, according to a review study.

The article “Villainous role of estrogen in macrophage-nerve interaction in endometriosis” was published in Reproductive Biology and Endocrinology.

Endometriosis is a chronic inflammatory disease whose specific causes are unknown. Its origin has been attributed to a combination of several factors.

Estrogen secretion is essential for disease progression, and the levels of this hormone are abnormally high in patients with endometriosis.

Researchers have found that the immune system also plays a role in this disease, increasing inflammation at the sites of injury. Additionally, the number of macrophages (the immune cells that contribute most to inflammation in the endometrium) is higher in endometriosis. This increase is thought to influence development of the disease and the frequency of endometriosis-related pain.

The findings also include the nervous system, as an abnormal distribution of nerve cells is common in endometriosis lesions, leading to an increase in nervous terminals and pain.

The review proposes that these three factors might be related and that this relationship might be the cause of endometriosis-related pain.

Estrogen can influence the action of various types of cells, as long as they express estrogen receptors. The macrophages and nerve cells on the endometrium express high numbers of estrogen receptors, which makes them more susceptible to this hormone.

The interaction of estrogen with estrogen receptors in the macrophages leads to activation and inflammatory response.

Activated macrophages produce nerve growth factors, molecules that cause the nerve cells to grow and form ramifications. This causes an increase in nerve terminals in the endometrium.

The inflammatory response lowers the threshold of the nerve cells, making them more sensitive. This combination of more sensitive cells and more nerve terminals leads to chronic pain.

Additionally, estrogen causes nerve cells to secrete migration factors that attract the macrophage to the site of injury, creating a vicious circle in which more inflammation creates more pain and the reaction to pain attracts macrophages that increase inflammation.

The villainous communication between macrophages and nerve fibers has been demonstrated to be enhanced by the aberrant level of estrogen, providing a hypothesis in endometriosis-associated pain,” researchers wrote.

This suggests that “targeting estrogen levels [or] the receptors on macrophages and nerve fibers may be a potential approach to prevent the progression of endometriosis,” they added.

There are several substances that target hormone receptors and decrease hormonal level; such treatments might help prevent chronic pain in endometriosis patients.

A better understanding of estrogen in the interaction of nerves and macrophages inspires a novel insight of endometriosis-associated pain and provides a new strategy for diagnosis and a potentially valuable target for the treatment of endometriosis-associated pain,” researchers concluded.

Source/read more:

https://rbej.biomedcentral.com/articles/10.1186/s12958-018-0441-z

https://endometriosisnews.com/2019/01/22/estrogen-role-endometriosis-associated-pain-study/

Endometriosis drug approved by the FDA to reduce pain

Endometriosis drug approved by the FDA to reduce pain

By I. Soussis MD,MSc, FRCOG, Fertility Specialist

The Food and Drug Administration announced the approval of the commercial version of the drug elagolix for the treatment of endometriosis pain.

This is the first time in over a decade that an oral treatment specifically designed for endometriosis pain has been approved.

Endometriosis is a condition affecting around 1 in 10 women (around 170 million women worldwide).

The condition is characterized by an abnormal growth of endometrium, which is the tissue that normally lines the inside of the uterus.

This tissue growth causes pain in the pelvis, lower back, and abdomen. Other symptoms include heavy periods or bleeding in-between periods, extremely painful menstrual cramps, pain during intercourse, and infertility.

There is currently no cure for the condition, but surgery is often recommended to remove the tissue, which relieves the symptoms for a while. Birth control pills are often prescribed to slow down the growth of abnormal tissue, and nonsteroidal anti-inflammatory drugs such as ibuprofen help ease the pain.

Now, the Food and Drug Administration (FDA) has approved a new drug to ease the pain of women living with moderate to severe endometriosis.

Elagolix is “the first and only oral gonadotropin-releasing hormone antagonist” designed specifically for endometriosis.

The drug -which will be marketed under the brand name Orilissa- is the first of its kind to have been approved by the FDA in more than a decade.

The drug was approved based on the results of two studies that formed the largest phase 3 clinical trial program to have ever been conducted on endometriosis.

In total, the studies examined the effects of elagolix on almost 1,700 women who had moderate to severe endometriosis pain.

In the two studies, the women were administered either 150 milligrams of elagolix once daily or 200 milligrams twice daily.

Compared with the women who received placebo, those who received the treatment reported a significant reduction in three types of pain: nonmenstrual pelvic pain, menstrual pelvic pain, and pain during intercourse.

These results were noted at 3 months and 6 months from the beginning of the treatment.

The FDA approved the following recommended dosage and duration of use: the drug can be taken for up to 24 months in a dosage of 150 milligrams per day, or up to 6 months if the dose is 200 milligrams twice per day.

However, the clinical trials also revealed a range of side effects. The most common ones were hot flashes, night sweats, headache, nausea, trouble sleeping, anxiety, joint pain, depression, and mood swings.

First study author Dr. Hugh S. Taylor,  the chair of the Department of Obstetrics, Gynecology and Reproductive Sciences at the Yale School of Medicine in New Haven, CT said “Endometriosis is often characterized by chronic pelvic pain that can impact women’s daily activities. Women with endometriosis may undergo multiple medical treatments and surgical procedures seeking pain relief and this [FDA] approval gives physicians another option for treatment based on a woman’s specific type and severity of endometriosis pain.”

My opinion:

Although endometriosis is a very common disease new drugs specifically designed for endometriosis are far and few between. This is an important development that will improve quality of life in women with endometriosis. 

It would be of interest to see if the same drug could be used as a part of the IVF antagonist protocol thus simplifying the treatment. Until now, all the antagonists used are injectable preparations. Our aim is to simplify protocols and reduce the number of injections. 

Read more: https://www.prnewswire.com/news-releases/abbvie-receives-us-fda-approval-of-orilissa-elagolix-for-the-management-of-moderate-to-severe-pain-associated-with-endometriosis-300685204.html

 

Visit Us On FacebookVisit Us On Google PlusVisit Us On Linkedin