ENDOMETRIOSIS PAIN

Contraceptive implants reduce endometriosis-associated pain

Contraceptive implants reduce endometriosis-associated pain

By I Soussis MD

 Contraceptive implants Implanon NXT and Mirena significantly curb pelvic pain and menstrual cramping in women with endometriosis, improving their health-related quality of life, researchers from Spain report.

The study, “Control of endometriosis-associated pain with etonogestrel-releasing contraceptive implant and 52-mg levonorgestrel-releasing intrauterine system: randomized clinical trial” was published in the journal Fertility and Sterility.

Pelvic pain and debilitating menstrual cramps (dysmenorrhea) are the most common symptoms of endometriosis. One of the main objectives of endometriosis treatment is pain control. Studies have shown that Mirena is effective in controlling endometriosis-associated pain. However, few studies have focused on etonogestrel implants and on comparing the efficacy of these hormonal treatments.

In this Phase 4 clinical trial, researchers compared the efficacy of two contraceptive implants (Implanon NXT and Mirena) in alleviating pelvic pain and menstrual cramps in women with endometriosis.

Implanon NXT is an etonogestrel-releasing contraceptive implant inserted under the skin in the upper arm. Mirena is a 52-mg levonorgestrel-releasing intrauterine device.

The study included 103 women experiencing endometriosis-associated chronic pelvic pain, menstrual cramps, or both for more than six months. The patients randomly received either Implanon NXT or Mirena. The initial follow-up period of the study was six months, with a checkup every month after implantation. The patients could keep the device after completion of the study.

The women were recruited from the Department of Obstetrics and Gynecology, University of Campinas Faculty of Medical Sciences, Campinas, Sao Paolo, Brazil. They were being treated for stage I–IV endometriosis or deep endometriosis.

There were 52 patients (mean age 33.4 years) who received Implanon NXT; 51 patients (mean age 34.7 years) received Mirena.

Researchers used the patient-reported visual analogue scale (VAS; 0-10) to determine the effect of these treatments on curbing noncyclic pelvic pain and menstrual cramps. The lower the VAS score, the lesser the pain. The mean score registered in the month before implant placement was considered the baseline.

Pelvic pain was significantly eased by both treatments, with no statistical difference between the two groups. The mean VAS score for pelvic pain in the Implanon NXT group decreased from 7.6 at baseline to 2 at the six-month evaluation. Similarly, among Minera users, the mean VAS score dropped from 7.4 at baseline to 1.9 during the study period.

Both treatments also markedly alleviated menstrual cramps, the team reported. A significant reduction in the VAS score for menstrual cramps between baseline and the six-month follow-up was observed in Implanon NXT users (7.5 to 2.2) as well as the Minera users (7.3 to 1.9).

The team used the Endometriosis Health Profile-30 (EHP-30 questionnaire) to assess the impact of the treatments on the patients’ health-related quality of life (HRQoL). The patients completed EHP-30 before the start of the study and at the six-month follow-up. A lower score corresponds to a better HRQoL.

The EHP-30 core segment assesses pain, control, and powerlessness, emotional well-being, social support, and self-image. It also has a modular section that covers questions about other areas of health and emotional status that patients may or may not experience. A significant reduction was reported by both groups in the scores for core and modular segments of the EHP-30, indicating a marked improvement in their HRQoL.

Menstrual bleeding pattern disturbances were reported in patients in both groups. In the Mirena group, participants reported infrequent bleeding (30%) and spotting (22.1%), at six months follow-up. In the Implanon NXT group, 28.8% reported a complete absence of bleeding (amenorrhea) and 24.4% infrequent bleeding at the six-month follow-up. However, none of the participants discontinued the study because of these disturbances.

Although further studies with a larger study population are required to assess the efficacy of these contraceptives, “both treatments are long-term feasible options for women with endometriosis-associated pelvic pain, with few side effects,” the study concluded.

 

 

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

 

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