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Laparoscopic surgery especially benefits endometriosis patients with pelvic pain

Laparoscopic surgery especially benefits endometriosis patients with pelvic pain

Patients with severe endometriosis and pelvic pain show the most pronounced improvements in quality of life within one year after undergoing laparoscopic surgery, a new study reports.

Laparoscopic surgery is the current gold standard to treat endometriosis. A small incision is made to allow a tool called a laparoscope, coupled with a small camera, to go inside the abdomen to guide the removal of endometriosis lesions.

Although surgery has the potential to reduce pain and improve patients’ quality of life, it is crucial to evaluate how surgery is affecting physical and mental health as well as patients’ social well-being.

Endometriosis often causes chronic pelvic pain, severe pain during menstruation (dysmenorrhea), and pain during sex (dyspareunia). Other non-gynecologic symptoms include constipation, diarrhea, and rectal bleeding. Together, these symptoms have a significant impact on patients’ quality of life.

In order to investigate which factors led to changes in patients’ quality of life, a team of researchers analyzed 981 patients from five districts in the Auvergne region of France who underwent laparoscopic treatment between 2004 and 2012.

Enrolled participants, ages 15-50, had received laparoscopic surgery or been newly diagnosed with a histological confirmation of endometriosis.

The team compared quality of life prior to surgery and one year after surgery using the 36-Item Short Form (SF-36) questionnaire, data on presence or absence of specific symptoms, and intensity of pain. Improvement in quality of life was measured using effect size method (ES), in which a value of 0.8 or higher corresponds to a significant improvement.

The SF-36 consists of eight sections covering physical functioning, energy/fatigue, bodily pain, role limitations due to physical health, general health perception, social functioning, role limitations due to emotional problems, and emotional well-being. The lower the score in the questionnaire, the greater the disability.

In total, 44% of patients with endometriosis and chronic pelvic pain had an improvement in quality of life equal to or above 0.8 ES compared to 23% of patients without pain who had similar ES scores.

Moreover, 47% of patients with stage 4 endometriosis had an ES score above 0.8, whereas only 26%, 31%, and 27.5% of patients in stage I, II, and III respectively had a similar improvement in quality of life.

Researchers observed that patients with chronic pelvic pain were more likely to improve their quality of life after surgery compared to those without it. Fertile patients also were more likely to improve quality of life compared to infertile patients.

Mental health of patients with chronic pelvic pain was also improved after surgery compared to patients without pain.

Similarly, patients with anxiety also showed better mental score compared to non-anxious patients.

Overall, researchers found that chronic pelvic pain was the most significant factor in predicting patients’ improvement in quality of life after surgery.

Patients presenting with severe endometriosis and who experience higher levels of pain are more likely to show improvement in [quality of life] after surgery,” researchers said.

[Chronic pelvic pain] is the most significant independent predictive factor for changes in QoL scores,” the study concluded.

The study, “Identification of predictive factors in endometriosis for improvement in patient quality of life,” was published in the Journal of Minimally Invasive Gynecology.

Read more: https://www.sciencedirect.com/science/article/pii/S1553465019302274?via%3Dihub

 

Medical cannabis treatment for endometriosis in clinical trial

Medical cannabis treatment for endometriosis in clinical trial

Israeli researchers have already started pre-clinical studies to examine the impact of medical cannabis in the treatment of endometriosis, which affects one in 10 women of childbearing age.

The research is led by Gynica, a company licensed by the Israeli Health Ministry to develop cannabis-based products for women, in cooperation with Lumir Lab, a cannabis research facility in the Biotechnology Park, Hadassah Ein Karem Jerusalem.

Endometriosis affects some 176 million women worldwide. In women with endometriosis, the uterine lining grows outside the uterus, in the fallopian tubes, ovaries and other areas of the abdominal cavity and in the pelvis. These women suffer from severe pain before and during menstruation, bleeding and pain during and after intercourse, dyspepsia and frequent or painful urination.

Anecdotal evidence has shown that women who smoke cannabis find relief from their pain, said Dr. Sari Sagiv, VP of research and development at Gynica. The researchers set out to find out what compounds or combination of compounds of cannabis can potentially address the problem.

Endometriosis is a complicated disease,” she said, as it has a number of factors working together that need to be addressed.

I believe cannabis has enough compounds that can affect a number of factors” of the disease, she said, including reducing pain, inflammation and the risk of recurrence.

The researchers have already tested a variety of cannabis compounds of endometriosis cells in vitro to see how they react to the compounds.

We are trying single or a combination of compounds on these cells” to find out if there is an impact and what it is, she explained. “We have already seen that there are different parts of the compounds that have a lot of impact.”

The researchers are now whittling the compounds down to a “lead candidate,” with which they will start clinical trials.

We already have an indication of what can be a lead candidate to deal with a number of factors that can cure endometriosis, not just address the pain. But she declined to reveal additional details until a patent has been filed. We want to start clinical trials in the third quarter of the year,” Sagiv said.

In parallel with the research process being conducted at Lumir Lab, Gynica is collaborating with Canadian company Strainprint, a firm that specializes in data collection and analysis of the effects of cannabis on various diseases. The companies are working on setting up the world’s largest data collection platform to analyze the effects of cannabis on women.

Lumir Lab is run by Prof. Lumir Hanush, a leading cannabis researcher, who is responsible for some of the most important discoveries made in the field of cannabis active substances. Gynica is led by Prof. Moshe Hod, a gynecologist and president of the European Association of Obstetricians. The firm does R&D specializing in cannabinoids based in the field of gynecology.

Israel has one of the world’s most progressive regulatory frameworks for medical cannabis.

Source: https://www.timesofisrael.com/israeli-researchers-probe-how-cannabis-can-treat-endometriosis/

Common antibiotic may help prevent endometriosis progression

Common antibiotic may help prevent endometriosis progression

Treatment with the common antibiotic doxycycline may help prevent progression of endometriosis lesions in women who do not respond to standard therapies as recurrence of the disease and its symptoms are frequent, often requiring repeated surgeries.

Doxycycline is a widely used antibiotic, sold under several brand names.

The study was published in the journal Reproductive Biology and Endocrinology.

Many efforts have been made to better understand the underlying mechanisms involved in endometriosis. However, endometriosis still represents a medical enigma since no theory can explain all the forms of the disease.

Surgery remains the only form of treatment for a large number of women, since the medical treatment often is not effective and recurrences are common.

Enzymes, called matrix metalloproteinases (MMPs) are important regulators of organ development and tissue turnover, normally not very active in adult tissues. However, they have been found to be deregulated in several disorders, including endometriosis.

MMP-2 and MMP-9 were found to be increased in endometriosis tissue compared to healthy samples. Also, these molecules are thought to contribute to tissue remodeling mechanisms involved in endometriosis lesions’ growth and invasion.

Researchers from Switzerland’s University Hospital Zurich decided to explore the potential of doxycycline to treat endometriosis.

They found that treatment with different doses of doxycycline could prevent the production of MMP-2 and MMP-9 and reduce activity in both immortalized endometriosis cells (those manipulated in the laboratory to proliferate) and in cells collected from two patients.

Further analysis determined that treatment with low-dose doxycycline could reduce by up to 78% the number of invading cells compared to placebo-treated cells.

Next, the team evaluated doxycycline when used in combination with progesterone, often used to manage endometriosis symptoms. They found that the combo therapy further reduced the levels of activated MMP-2 compared to either of the agents alone.

Our results demonstrate the potential for use of low-dose doxycycline in the treatment of endometriosis,” researchers said.

Low-dose doxycycline has been shown to be well-tolerated in other clinical settings. So it could represent a potential treatment option for endometriosis, particularly severe forms of deep-infiltrating endometriosis that often respond poorly to current treatment options.

Also, “low-dose doxycycline might be an interesting alternative for patients who wish to have a non-hormonal medical prevention of recurrence after surgical excision of endometriosis,” researchers stated.

My opinion

This study demonstrated in-vitro the beneficial effect of doxycycline on the inhibition of proliferation of endometriosis cells alone or in combination with progesterone. It remains to be seen if this medication is useful in clinical practice. If this is proven, it would represent a cheap alternative to current medical therapies and with fewer side effects.

Read more: https://rbej.biomedcentral.com/articles/10.1186/s12958-019-0481-z

Endometriosis patients have imbalance in vaginal and cervical microbiota

Endometriosis patients have imbalance in vaginal and cervical microbiota

The population of microorganisms that reside in the vagina and cervix of patients with stage 3/4 endometriosis differs from that of healthy controls, suggesting a potential role of microorganism imbalance in this condition, according to a study.

The study, titled “The Endobiota Study: Comparison of Vaginal, Cervical and Gut Microbiota Between Women with Stage 3/4 Endometriosis and Healthy Controls,” was published in the journal Scientific Reports.

Endometriosis is a chronic condition where uterine cells are found outside of the uterus, most commonly in the pelvis. These cells can also spread to other parts such as the intestine.

Researchers believe that endometriosis likely occurs through retrograde menstruation, which causes endometrial cells to leave the uterus and implant in the pelvis. However, all women at some point experience retrograde menstruation, so researchers are looking for other possible causes of endometriosis, which affects about 10% of women of reproductive age.

Microorganisms, such as bacteria, fungi, and viruses, live and play important roles in the body. Together, they form the human microbiota.

Evidence indicates that imbalance in the human microbiota (known as dysbiosis) is associated with disease. For example, disruption of gut microbiota can lead to the development of inflammatory bowel disease as microorganisms help regulate the immune system. This phenomenon has also been associated with other conditions, such as “neuropsychiatric diseases, psoriasis, arthritis, and some cancers, especially colon cancer,” the researchers wrote.

Since inflammation and activation of immune cells have been linked to endometriosis, the researchers hypothesized that dysbiosis might also play a role in the development of the condition, and conducted a study to compare the microbiota between women with and without endometriosis.

The researchers sampled the vaginal, cervical, and gut microbiota from 14 women with stage 3/4 endometriosis and from 14 healthy controls, and they looked for the presence of different microorganisms by sequencing their genomes.

Results indicated that there was an overall similarity between the microbiota composition between the stage 3/4 endometriosis group and controls.

However, there was a difference between the two groups at the genus level, which ranks above species and below family in the hierarchy of biological classification.

There was a total lack of the genus Atopobium in the vaginal and cervical microbiota of the endometriosis group, but the researchers found an increase in the species Gardnerella, Streptococcus, Escherichia, Shigella, and Ureoplasma — all potentially pathogenic (able to cause disease) — in the cervical microbiota of stage 3/4 endometriosis patients.

More women in the disease group were also found to have a stool microbiome dominated by Shigella/Escherichia.

If confirmed in other studies, the complete absence of Atopobium in the vagina and cervix, together with the increased presence of Gardnerella, Escherichia/Shigella and Ureoplasma in cervical microbiome of patients with endometriosis could be a relevant finding of this study,” the authors wrote.

While overall microbiome composition in the cervix, vagina and gut seems similar between women with stage 3–4 endometriosis and healthy controls, there seems to be some differences at the genus level,” they said.

Further studies are needed to clarify whether the association between dysbiosis and endometriosis is causal, and whether dysbiosis leads to endometriosis or vice versa, the researchers said.

Read more:https://www.researchgate.net/publication/331170382_The_Endobiota_Study_Comparison_of_Vaginal_Cervical_and_Gut_Microbiota_Between_Women_with_Stage_34_Endometriosis_and_Healthy_Controls

Endometriosis can occur after menopause

Endometriosis can occur after menopause

Despite being rare, endometriosis can appear or come back after menopause.

Doctors should be aware of this, particularly if there are complaints of pelvic pain or heavy bleeding, and they must not underestimate the risk of the disease progressing into cancer, an opinion piece written by several obstetrician-gynecologists says.

Researchers also call attention to a major therapeutic dilemma: Should a doctor prescribe hormonal replacement therapy (HRT) to a woman experiencing menopause symptoms, given that this may raise her risk of having endometriosis come back or degenerate into cancer?

The article, “Endometriosis and the menopause: why the question merits our full attention,” appeared in the journal Hormone Molecular Biology and Clinical Investigation.

Post-menopausal endometriosis is a rare condition but is a reality,” the authors stated.

As an estrogen-dependent disease, endometriosis primarily affects women of reproductive age, its activity lessening or even regressing at the onset of menopause.

However, there have been several reports of cases that demonstrate the disease may still develop at this time, in the absence of menstrual cycles and in a low-estrogen environment. During menopause, the ovaries’ activity drops drastically, including their capacity to secrete hormones.

The fact that endometriosis can appear in such conditions sheds doubt on Sampson’s theory of retrograde bleeding in explaining the disease origin, and implicates other mechanisms, researchers say.

Doubt persists, however, as to whether endometriosis persists into the post-menopausal period, whether it comes back from a pre-existing disease or if it can develop for the first time after menopause.

In any case, researchers propose several sources of estrogen in postmenopausal women that might serve as risk factors for endometriosis: conditions such as obesity, intake of plant-derived estrogens (phytoestrogens), the use of HRT or tamoxifen, and the production of estrogen by endometriosis lesions themselves.

Tamoxifen, a medication used for breast cancer, acts as an anti-estrogen in the mammary tissue, but as an estrogen-stimulating agent in cholesterol metabolism, bone density, and cell proliferation in the endometrium.

HRT, a common treatment used to relieve menopause symptoms, consists of taking hormone supplements, including estrogen, to restore some of the hormonal levels that decrease during menopause.

Other factors that may play a role include stress, genetic factors, hypothyroidism, or fatty acids (unsaturated omega 3).

Another factor to take into account is that HRT may increase the risk of endometriosis symptoms and disease recurrence after surgery to treat severe symptoms. If there are residues of endometriosis lesions before starting HRT, this risk may increase, particularly if the disease was more severe and surgery was incomplete.

Therefore, before prescribing HRT it is imperative “to weigh the risks and benefits,” researchers say.

The authors also call clinicians’ attention to not forgetting the risk of progression into cancer with or without HRT.

Endometriosis is a benign condition, but about 1% of cases are estimated to develop into cancer, most commonly in the ovary, but also in the bowel and even the lung.

Clinicians should be particularly attentive if a woman reports pelvic pain — dysmenorrhea, dyspareunia or chronic pelvic pain — and heavy bleeding. Diagnosis can be done through patient history, clinical examinations and using ultrasound and magnetic resonance imaging (MRI). However, laparoscopy (keyhole surgery) is the only way to fully confirm a diagnosis of cancer.

The first-line treatment for new-onset symptomatic post-menopausal endometriosis should be surgery because of diagnosis uncertainty and the risk of cancer. Medical therapy can be an alternative if pain comes back after surgery or if surgery is contraindicated, including aromatase inhibitors and levonorgestrel or gestodene, two hormonal contraceptives.

Source:https://www.degruyter.com/view/j/hmbci.ahead-of-print/hmbci-2018-0071/hmbci-2018-0071.xml

https://endometriosisnews.com/2019/04/02/doctors-must-be-aware-that-endometriosis-can-occur-after-the-menopause-article-says/

First endometriosis blood test detects up to 9 out of 10 cases

First endometriosis blood test detects up to 9 out of 10 cases

 Endometriosis is notoriously difficult to diagnose. A recent study showed that it usually takes 7-12 years from first experiencing symptoms to diagnosis.

A private company (MDNA Life Sciences) announced that it is to launch the world’s first blood test for endometriosis, able to detect the disease in up to 9 out of 10 cases. Results will be available in a matter of days after the test is carried out, enabling doctors to make earlier decisions on diagnosis and treatment.

Endometriosis, a debilitating condition affecting 1 in 10 women of reproductive age, causes years of pain and distress. A surgical procedure is required to definitively diagnose the condition, resulting in an average delay to diagnosis of 7.5 years.

Using its proprietary technology, MDNA has developed techniques to exploit the unique characteristics of mutations in mitochondrial DNA, which can act as biomarkers for the presence of a range of diseases.

After successfully identifying biomarkers for different types of cancer, researchers at MDNA’s Newcastle upon Tyne laboratory have now identified biomarkers associated with endometriosis. Results of a clinical study recently published in the peer-reviewed journal Biomarkers in Medicine, show that the newly identified biomarkers can accurately detect endometriosis in blood samples in up to 9 out of 10 cases, even in its early stages.

MDNA has now embarked on a programme to create a CE-marked test kit to enable clinical laboratories in the UK and worldwide to carry out the test on a commercial basis. The CE process will be completed in 9-10 months.

Dr Andrew Harbottle, MDNA Life Sciences’ Chief Science Officer explains: “Mutations in mitochondrial DNA act as ideal biomarkers, providing us with a unique and detailed diary of damage to the DNA and accurately detecting many difficult to diagnose diseases and conditions, such as endometriosis”.

MDNA’s Mitomi Technology platform identifies and optimises the best biomarkers to detect a specific disease. The company has already demonstrated the accuracy of its technology in a blood test for prostate cancer. As well as the new test for endometriosis, MDNA is planning to release tests for ovarian cancer and pancreatic cancer next year. Tests for lung, liver, and stomach cancers will follow in 2021 and more tests are in the pipeline.

Harry Smart, MDNA Life Sciences’ Chairman says “Our ground-breaking test for endometriosis will fundamentally change the way this debilitating disease is detected and diagnosed. We look forward to helping women get treatment sooner, reducing their pain and distress and providing cost savings to health services”.

My opinion

The development of a reliable non-invasive test for the diagnosis of endometriosis is highly desirable and necessary since it will spare many patients of unnecessary surgical interventions and it will facilitate and speed up the diagnosis and management of endometriosis. This will immensely improve the quality of life of millions of women worldwide.

Source:

https://mdnalifesciences.com/2019/04/worlds-first-blood-test-for-endometriosis-can-detect-up-to-9-out-of-10-cases/

Red grapes, blueberries, raspberries and peanuts benefit infertile women with endometriosis

Red grapes, blueberries, raspberries and peanuts benefit infertile women with endometriosis

Resveratrol, a natural substance present in many edible plants, is able to lower the levels of two enzymes, MMP-2 and MMP-9, which have been implicated in the development of endometriosis and associated infertility, an exploratory trial suggests.

The compound has anti-inflammatory properties that may have therapeutic effects for women with endometriosis, but more studies are needed to confirm this claim, the authors caution.

The study, “The modulating effects of Resveratrol on the expression of MMP-2 and MMP-9 in endometriosis women: a randomized exploratory trial,” was published in the journal Gynecological Endocrinology.

Endometriosis is an inflammatory disease marked by an overactivation of matrix metalloproteinases (MMPs), a group of enzymes that break down several proteins that make up the extracellular matrix, a network outside cells that provides support to cells and tissues.

MMPs play an important part in the organ’s development and tissue turnover but normally are not very active in adult tissues.

However, their activity can increase significantly in various disorders such as endometriosis, where they have been associated with the failure of embryo implantation after cycles of assisted reproduction technology (ART).

Two MMPs, MMP-2 and MMP-9, in particular, have been linked to this effect.

Resveratrol, a compound naturally occurring in plants such as red grapes, blueberries, raspberries, and peanuts, is able to inhibit MMP-2 and MMP-9 and has shown signs of preventing the formation of endometriotic lesions in some studies.

The compound is also sold as a supplement and used as a medicine for high cholesterol, cancer, heart disease, and many other conditions, although there is no solid evidence to support its use for these issues.

A team of researchers at the Tehran University of Medical Sciences in Iran have now investigated the effects of resveratrol on the levels of MMP-2 and MMP-9 in endometriosis patients.

They carried out an exploratory clinical trial, which included 34 patients who had endometriosis-associated infertility. They randomly divided 17 participants into a control group given a placebo and 17 into a treatment group given 400 mg of Resveratrol for 12 to 14 weeks.

Results showed that the levels of both MMP-2 and MMP-9 significantly dropped in the endometrium tissue as well as in the endometrium fluid and blood of women treated with resveratrol, compared with the control group.

The blood and endometrial fluid levels of both MMP-2 and MMP-9 were lower following the surgical removal of endometrial lesions.

We showed that Resveratrol can modify the inflammation process in the endometrium of women with endometriosis at least in the level of MMP-2 and -9 expressions,” the researchers wrote. “All participants in this study were infertile women with endometriosis stages III and IV, which may limit the generalization of the findings to all women with endometriosis.”

The therapeutic potency of Resveratrol in endometriosis needs more clinical studies,” they concluded.

Read more: https://www.ncbi.nlm.nih.gov/pubmed/30777471

Source: https://endometriosisnews.com/2019/03/12/resveratrol-helps-reduce-two-enzymes-endometriosis-trial/

Endometriosis diagnosis takes 7 to 12 years

Endometriosis diagnosis takes 7 to 12 years

Endometriosis may affect all aspects of a woman’s life, including sexual relations, social activities, emotional well-being and work productivity.

The disease is costly. Claims data show that average annual health care costs (medical and prescription) are more than three times higher for women with endometriosis compared to patients without endometriosis, even five years pre- and five years post-diagnosis. Τhe cost can increase in cases of greater severity of the disease, presence of pelvic pain and infertility.

However, endometriosis is still underfunded and under-researched, thus limiting scientific progress and the number of available diagnostic and treatment options, according to a new review study.

Aiming to address these concerns, the Society for Women’s Health Research (SWHR) brought together a group of researchers, clinicians, and patients as well as industry and government officials, who evaluated barriers affecting endometriosis diagnosis and treatment, reviewed current practice, and highlighted research priorities.

Multidisciplinary approaches addressing all patient needs and greater disease awareness are needed to improve care, diagnosis and development of treatments for people with endometriosis, showed the resutls of the research “Assessing Research Gaps and Unmet Needs in Endometriosis,” which was published in the American Journal of Obstetrics and Gynecology.

According to the expert group, the current lack of knowledge and awareness about the causes of endometriosis contributes to the significant delays (7 to 12 years) from first experiencing symptoms to diagnosis. These delays are even worse for women with pelvic pain and for younger women, and may cause physical and emotional damage, as well as increase costs associated with the disease.

Another contributing factor is that the current gold standard for diagnosis requires surgery (laparoscopy), warranting the development of accurate, noninvasive and less costly diagnostic tools, such as biomarkers. Also, current guidelines only recommend assessing endometrial lesions, despite reports of a questionable association between the number of lesions and disease severity, symptoms and impact on women’s quality of life.

Campaigns to educate patients, healthcare providers, and the public may also help achieve more timely and accurate diagnosis and treatment, the team noted.

Additional barriers are difficulties with insurance coverage, and the stigma around menstrual issues and society’s normalization of women’s pain, which may make patients reluctant to discuss symptoms or seek care.

“In addition, women who do bring up their symptoms may fall victim to the well-documented clinical gender bias that has resulted in some women’s pain being dismissed or inadequately treated,” Rebecca Nebel, PhD, the study’s senior author and director of scientific programs at SWHR, said.

Standardized screenings, such as those used in cases of potential violence against women, could be used as a model in endometriosis, the experts said.

Other barriers are related to healthcare providers, as women need to make an average of seven visits to their primary provider before being referred to specialists, and often are misdiagnosed.

As for current practice in treatment, most medical and surgical approaches — including hysterectomy and uterus removal — focus on managing pain and associated symptoms by suppressing or removing endometrial lesions, but may not be effective.

Physical therapy, acupuncture, and yoga are examples of non pharmacological strategies that may help ease pain. Mental health professionals may help treat depression and grieving associated with endometriosis, while also providing coping and relaxation strategies.

Available medical therapies may induce side effects such as bone loss, hot flashes, and weight gain. Also, many cannot be used when women are trying to get pregnant, often forcing them to decide on whether to minimize pain or time their attempts to conceive while off medication.

Overall, “future treatments and care should shift toward a patient-centric, multidisciplinary approach that focuses on the patient as a whole, rather than one symptom at a time,” the experts said.

Centers of expertise taking an interdisciplinary approach with experts in “laparoscopy, medical management, pain education, physical therapy, and psychological care” may help implement treatment strategies “that address all the needs of the patient, including quality-of-life issues,” the team stated.

Read more: https://www.ajog.org/article/S0002-9378(19)30385-0/pdf

https://www.ajog.org/article/S0002-9378(19)30385-0/fulltext

Source: https://endometriosisnews.com/2019/02/28/multidisciplinary-approach-awareness-will-most-benefit-endometriosis-patients-experts-say/

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/

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