Tag: uterine fibroids

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Green Tea Extract may Reduce Uterine Fibroids

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In a pre-clinical, proof-of-concept study from Johns Hopkins Medicine, researchers found that epigallocatechin gallate (EGCG), a green tea compound with powerful antioxidant properties, could be promising for both treating and preventing uterine fibroids. Results of the study, appearing in Scientific Reports, add to growing evidence that EGCG may reduce fibroid cell growth, though the study is still at an early stage. The study was specifically designed to identify the biochemical mechanisms responsible for EGCG action in fibroid cells.

The investigators emphasise that their study involves in vitro human fibroid cells treated with EGCG extract to explore the possibility of oral EGCG supplementation as a therapy, rather than just drinking cups of green tea as a preventative measure for uterine fibroids.

“The purpose of this study was to examine how EGCG works to treat and prevent uterine fibroids,” says James Segars Jr., MD, professor of gynaecology and obstetrics. “There is no standard protocol for uterine fibroid disease management or prevention, no tools to prevent their growth, so finding a safe nonsurgical therapy is important.”

Uterine fibroids are the most common benign tumours of the uterus. Made up of smooth muscle cells and a large matrix of connective tissue, the fibroids range in size from nearly microscopic to bulky masses that can enlarge and distort the uterus.

An estimated 77% of women will develop fibroids in their lifetime, most of them by age 50. Black and Hispanic women develop them at 1.5 to two times the rate of white women.

While many people with uterine fibroids are symptom-free, about 25% experience significant symptoms including heavy uterine bleeding, pelvic pain and infertility. In addition to complete removal of the uterus, surgical treatment may include various means of removing fibroid tumours from the uterine wall.

For the new study, researchers used laboratory cultures of uterine fibroids collected from living patients. Because uterine fibroid cells have a large extracellular matrix compared to normal cells, researchers designed their experiments to see if treatment of cells with EGCG affects protein expression associated with this matrix. Specifically, they studied fibronectin, a matrix protein; cyclin D1, a protein involved with cell division; and connective tissue growth factor (CTGF) protein.

Cells were dosed with 100mmol/L of EGCG in growth media for 24 hours, and then a Western blot was performed. In this study, researchers looked for levels of cyclin D1 and CTGF proteins in EGCG-treated fibroid cells compared to untreated cell.

They found that EGCG reduced protein levels of fibronectin by 46% to 52%, compared with an untreated controls. They also found that EGCG disrupted pathways involved in fibroid tumour cell growth, movement, signalling and metabolism, and they saw up to an 86% decrease in CTGF proteins compared with the control group.

“The results from this study show that EGCG targets many signalling pathways involved in fibroid growth, particularly the extracellular matrix,” says study lead author Md Soriful Islam, PhD, MSc. “EGCG supplements could be an easily accessible and natural way to relieve symptoms and slow fibroid growth.”

These results lend support to the FRIEND study, an ongoing clinical trial of EGCG in women with fibroids who are seeking pregnancy. While results from this study show promise, researchers caution that more studies need to be done, and consumers should not try to self-dose with green tea supplements. Future research on EGCG will include clinical trials with large and diverse patient groups to determine optimal doses as well as possible side effects of EGCG supplementation.

Source: John Hopkins Medicine

Categories : Environmental Effects Obstetrics & GynaecologyTags :

Phthalates in Everyday Products do Cause Uterine Fibroids

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For the first time, a study published Proceedings of the National Academy of Sciences (PNAS) has shown a causal association between environmental phthalates and the increased growth of uterine fibroids, the most common tumours among women.

Manufacturers use environmental phthalates in numerous industrial and consumer products, and they’ve also been detected in medical supplies and food. Although they are known to be toxic, they are currently unbanned in the US.

“These toxic pollutants are everywhere, including food packaging, hair and makeup products, and more, and their usage is not banned,” said corresponding study author Dr Serdar Bulun at Northwestern University. “These are more than simply environmental pollutants. They can cause specific harm to human tissues.”

Up to 80% of all women may develop a fibroid tumour during their lifetime, Bulun said. One-quarter of these women become symptomatic with excessive and uncontrolled uterine bleeding, anaemia, miscarriages, infertility and large abdominal tumours necessitating technically difficult surgeries.

The new study found women with a high exposure to certain phthalates such as DEHP (used as a plasticiser to increase the durability of products such as shower curtains, car upholstery, lunchboxes, shoes and more) and its metabolites have a high risk for having a symptomatic fibroid.

Prior epidemiological studies have consistently indicated an association between phthalate exposure and uterine fibroid growth, but this study explains the mechanisms behind that link. The scientists discovered exposure to DEHP may activate a hormonal pathway that activates an environmentally responsive receptor (AHR) to bind to DNA and cause increased growth of fibroid tumors.

“Interestingly, AHR was cloned in the early ’90s as the receptor for dioxin, the key toxin in the agent orange,” Bulun said. “The use of agent orange during the Vietnam war caused significant reproductive abnormalities in the exposed populations; and dioxin and AHR were thought to be responsible for this.”

This new study, Bulun said, provides further evidence to support these theories.

Source: Northwestern University

Categories : Obstetrics & GynaecologyTags :

Trial Finds Linzagolix Safe and Effective for Uterine Fibroids

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A new, safer drug has been developed that could revolutionise the way clinicians treat some of the most common gynaecologic diseases including fibroids and endometriosis. A clinical trial published in the Lancet found that linzagolix, an oral drug that hinders oestrogen production, is an effective and customisable treatment for fibroids. Not only does linzagolix ease symptoms but also shrinks the fibroids themselves.

Professor Hugh S. Taylor, MD, co-author of the paper, said: “No treatments to date for fibroid growth are something I would ever want my patients to take for a prolonged period of time, as they did not treat the underlying cause of the problem. This is an extremely well tolerated class of drugs that can control fibroid growth. We’ve never had anything like that before.”

The suffering and inconvenience caused by uterine fibroids can have a serious impact on quality of life. “This can be an impediment to getting a good night’s sleep and being socially active, and it can even affect job performance,” said Prof Taylor.

As fibroids grow larger, they may begin putting pressure on other organs, resulting in a range of unpleasant symptoms including diarrhoea or constipation and frequent urination. Fibroids can also lead to difficulty in getting pregnant and increased risk of miscarriage. They are more common and aggressive in black patients.

Most drugs commonly used for uterine fibroids, including birth control pills, do not treat the fibroids themselves and just lighten or stop periods. And more aggressive drugs, although they treat the root of the problem are “overkill” Prof Taylor said. For example, leuprolide is an injectable drug that puts patients into a menopausal state by initially overstimulating hormonal receptors, which eventually shuts them down and completely blocks oestrogen production. Although the treatment addresses the fibroids, it also can initially exacerbate symptoms and cause harsh side effects. In more extreme cases, patients may opt for hysterectomy.

Promising clinical trial results

Linzagolix is an oral medication that works similarly to leuprolide by hindering hormone production. However, unlike its predecessor, it works by directly blocking the receptors instead of overstimulating them. The drug is also titratable, allowing reduction of oestrogen production without initiating menopause.

The new drug may however cause menopause symptoms such as hot flashes, with hormonal add-back therapy an option for mitigating these symptoms. For some patients, however, including patients with obesity, hypertension, or diabetes, this therapy has risks and may not be a suitable option. These conditions also tend to be more prevalent in Black patients. In this group, a lower dose of linzagolix without add-back therapy might be preferable.

To test the effectiveness of the drug, Prof Taylor’s team ran two large prospective, randomised, double-blind, placebo-controlled clinical trials known as PRIMROSE 1 and PRIMROSE 2. The studies enrolled patients suffering from substantial bleeding who were randomised to placebo or one of several different doses of the drug: 100mg alone, 100 mg with add-back therapy, 200mg alone, or 200mg with add-back therapy. Patients were followed for one year. The researchers considered the therapy successful if the patient’s bleeding was reduced by half and also stayed in what is considered the normal range.

Patients in all four treatment groups experienced a significant reduction in menstrual bleeding. The 200 mg with add-back therapy group worked with “amazing efficacy,” said Prof Taylor: the clinical trials showed a 75.5% response rate in PRIMROSE 1 and a 93.9% rate in PRIMROSE 2. Even the lower dose of the drug still showed promising results. There were greater than 60% response rates in both trials for the 100mg group with add-back therapy, and the 100mg group without add-back showed better than 50% response rates.

“What is interesting and unique about our trials, that has not been done with other drugs in this class, is that we used a low dose with or without hormones,” said Prof Taylor. “This is a great option for patients who experience severe menopause symptoms from the high dose or have a medical problem where they can’t tolerate hormonal add-back therapy.”

Changing the treatment of gynaecologic disease

Linzagolix is one of several in this new class of drugs in development for the treatment for common gynaecologic diseases. Prof Taylor was also involved in the 2017 clinical trial for elagolix, a medication designed to suppress endometriosis that has recently become available for patients.

Linzagolix has so far been approved in Europe. Taylor says drugs in this class will radically change how clinicians treat fibroids, and he hopes linzagolix will lead to a reduction in future hysterectomies once it becomes available.

“A good medical therapy is finally here for fibroids, and I predict that what was a very common operation will dramatically decrease within the next few years,” he says. “Reducing the need for hysterectomy is very important for patients who don’t want to undergo a major surgery, especially for younger people who may still want to preserve the potential of having children in the future.”

Source: Yale University

Categories : Obstetrics & GynaecologyTags :

Tranexamic Acid Cuts Blood Loss in Myomectomies

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The use of tranexamic acid (TXA) reduced blood loss during myomectomies in women with large uterine fibroids, a retrospective cohort study has found.

Patients who underwent a myomectomy to remove uterine fibroids with a total weight greater than 173 g had lower estimated blood loss after receiving TXA compared with those who did not (205.6 mL vs 405.4 mL), reported Rachel Cullifer, MD, at the virtual American Association of Gynecologic Laparoscopists (AAGL) annual meeting. Furthermore, patients whose largest fibroid was greater than 73 mm had lower levels of blood loss with TXA (229.2 mL vs 408.3 mL).

“TXA is a highly safe hemostatic agent that gynecologic surgeons can utilize during myomectomies,” Cullifer said. “There is a role for TXA in myomectomies performed with a minimally invasive approach,” she added, noting that the treatment should be strongly considered for patients suspected of having a large fibroid burden.

When looking at all myomectomies not stratified by fibroid characteristics, there was not no significant difference in estimated blood loss between patients who received TXA and those who did not (184 mL vs 266 mL). Fibroids are the primary indication for hysterectomy in the US, Dr Cullifer noted, but myomectomy provides a safe alternative for those who want to preserve their fertility.

“Despite advances in laparoscopic techniques, blood loss and blood transfusions still remain higher in myomectomies when compared with hysterectomy,” Dr Cullifer pointed out, adding that elevated plasmin levels during surgery can result in prolonged bleeding. TXA lowers plasmin function and productivity, reducing blood loss, she stated.

Dr Cullifer and colleagues focused on fibroid characteristics to find out which patients might benefit most from TXA.

The researchers analysed patients who had a myomectomy from 2015 to 2020, compared myomectomy cases treated with TXA versus those that were not, and measured estimated blood loss, blood transfusion administration, and operative time. Of the 71 patients who had a myomectomy, 26 received TXA and 45 did not. The average estimated blood loss was 236 mL, and almost all patients underwent minimally invasive procedures, with 53% undergoing laparoscopic surgery and 40% undergoing robot-assisted procedures.

Save for age, all demographic characteristics were similar between the two groups. Patients who received TXA were an average of two and a half years younger than those who did not. Fibroid characteristics were also similar between the two groups. Additionally, adverse events were similar between the two groups. There was one case of thromboembolism in the cohort who did not receive TXA.

Source: MedPage Today