New diagnostic and treatment modalities could drastically cut the time to endometriosis diagnosis, help prevent complex pelvic pain and preserve fertility, experts say​​​​.

Laparoscopy won’t be needed to make a diagnosis

Under new endometriosis guidelines, slated for release in the next couple of months, diagnosis will no longer rely on surgery. Instead, it can be made provisionally via history, physical examination and investigations (usually an ultrasound scan), says Associate Professor Anusch Yazdani, a subspecialist in reproductive endocrinology and infertility, reproductive endosurgeon and medical director for Endometriosis Australia.

The ultrasound should ideally be transvaginal, he says. “And preferably it’s done in a specialist service where they have the capacity to perform an endometriosis type of ultrasound scan. But those services are not available everywhere in Australia, so that’s not mandated.”

“And if a woman has extensive endometriosis, even a non-endometriosis-specific scan is very likely to demonstrate that—it has a sensitivity of over 90% for demonstrating deep and particularly extensive disease.”

While definitive diagnosis will still be by histology, the need for a laparoscopy “should no longer now be the bottleneck to instituting appropriate treatment,” Associate Professor Yazdani says.

AI imaging tools could accelerate diagnosis and reduce need for laparoscopies

Definitive non-surgical diagnosis may be a step closer with the development of AI-enabled imaging tools.

Obstetrician and gynaecologist Professor Louise Hull from Adelaide Medical School, who has a PhD in endometriosis from Cambridge University, is leading a team ​developing​ IMAGENDO® – a technology that combines specialised transvaginal ultrasound and MRI to look for endometriosis markers. “And we use AI to detect them,” Professor Hull says.

“We use very good scanners, and we annotate the images first, but after a while the AI can automate that process,” she explains.

“And we’re picking up nodules on the uterosacrals, but also sometimes we can pick up superficial markers now, so the scanning’s got much better, and the AI is improving it.”

MRI results are used to pre-train the ultrasound AI model and vice versa, helping make both better, she adds.

If all goes well, ​​​​GPs would be able to order the​se​ scans, and the AI could help automate the rebate process by confirming that an endometriosis assessment had been completed.

Professor Hull hopes this will mean women need fewer imaging tests.

“I see patients with eight scans, none of which have looked in the posterior fornix,” she says. “And then we get a proper scan, and there were clearly nodules that should have been detected.”

Imaging-based diagnosis could not only reduce the need for laparoscopies, it could also lead to the discovery of evidence-based treatment pathways in primary care.

“We have no treatment that’s got evidence in general practice because we’ve never done any trials on anyone before they’ve had surgery,” Professor Hull says. “So the whole next step is going to be how can we start running trials in general practice to show which are the best treatments.”

Blood tests may support endometriosis identification

Associate Professor Yazdani says several companies are developing blood tests that look for different endometriosis markers—including enzymes, vesicular changes and proteins—and which vary in terms of their sensitivity and specificity.

“Some of them are better for more extensive disease; some of them are better for less extensive disease, but then also pick up a whole lot of things that are not endometriosis,” he says.

Some companies are using artificial intelligence to develop their tests, enabling them to “better distinguish the noise from the actual signal” to improve diagnostic accuracy, he says.

These tests are still under investigation, but one thing we do know is that tumour markers like CA-125 don’t work particularly well, Associate Professor Yazdani says.

New drugs to manage symptoms

Long available as a contraceptive, dienogest (Visanne) was PBS-listed for endometriosis treatment last December.

Professor Hull says it “can be quite effective,” but importantly, it does not provide contraceptive cover. “It’s a selective receptor modulator,” she explains. “It only interacts with one of the progesterone receptors that’s more prevalent in the endo lesions. So it won’t block ovulation.”

Drospirenone (Slinda) is a progesterone-only oral contraceptive pill, “so the usefulness there is you can try it and stop if you get too many side effects,” she says. It will be PBS-listed from 1 May.

Likewise, Yas and Yasmin were PBS-listed earlier this year, providing more cost-effective options.

“First line management of endometriosis is hormonal, and that’s the oral contraceptive pill and progestins,” Associate Professor Yazdani explains. “There is actually no evidence that one particular hormonal treatment is better than another. It’s just a matter of tailoring the side effect profile of all of those if the patient is happy to do that.”

Second and third line management

This month the Government announced that Ryeqo would also be PBS-listed beginning in May. It was approved for endometriosis last year and must initially be prescribed by a specialist, but can then be managed by GPs.

It contains GnRH receptor antagonist relugolix, which blocks GnRH receptors in the pituitary gland, thereby reducing production of gonadotropins (particularly luteinizing hormone and follicle-stimulating hormone), inducing a menopause-like state.

“Ryeqo suppresses ovulation, so it’s got a contraceptive effect. And essentially, you just use it all the time and don’t have periods,” Professor Hull explains.

It also contains oestradiol and norethisterone acetate to help prevent or reduce the side effects of GnRH receptor blockade (called ‘add-back’ therapy).

Associate Professor Yazdani says Ryeqo “is very very good at reducing pain,” and while the GnRH analogues goserelin (Zoladex) and nafarelin acetate (Synarel) are also PBS-listed and effective, they can only be used for six months or less.

“Zoladex and Synarel have been used for a very long time in Australia. They are as effective as Ryeqo, but the difference is they’re more likely to lead to bone mineral density loss and therefore they are limited to six months,” he explains, whereas Ryeqo can be used for up to two years.

Zoladex, Synarel and Ryeqo all need to be initiated by a specialist, he adds. “They’re really second- and third-line drugs, but they can be managed by GPs in the community.”

Professor Hull says while Ryeqo already contains oestradiol, you need to test bone density before commencing it. “And then after a year you check it again.”

You don’t necessarily need to stop it if bone density drops, she explains, but you may need to implement other bone-preserving strategies—such as additional oestrogen or weight training.

As an oral medication, you can stop it if ​​the patient is bothered by side effects, she adds.

“And I probably wouldn’t use it in the younger girls first, but for people that have trialled lots of things, it can make a real difference.”

Other treatments

Other researchers are looking into potential endometriosis therapies, including non-hormonal treatments and immunobiologicals, Professor Hull says.

She explains research has proven the immune system and inflammation (largely linked to the prostaglandin response) are involved in endometriosis, “which is why you get the bloating and things like that.”

While the exact aetiology remains elusive, “we know what’s going on,” she says, noting this offers scope for treatment and even prevention.

“And we might not be able to prevent the lesions, but we might be able to prevent the complex pain syndrome that is a complication of repeated pain triggers that we haven’t treated.”

For example, the EndoChill trial is looking at cold water immersion, mindfulness and breathing exercises to manage pain, she says. Another trial is looking at an IUD with an embedded neural modifier for pain relief and period suppression.

“And we might be able to prevent infertility because we’ve frozen your eggs when you were young, or you’ve thought of freezing embryos,” she adds.

Key takeaways:

• Under new guidelines to be released soon, doctors will be able to make a provisional endometriosis diagnosis via history, examination and ultrasound scan.
• AI-enabled imaging tools could help diagnose endometriosis earlier, with less surgery.
• Earlier diagnosis means earlier treatment and less chronic pain and fertility issues.
• Various blood tests are under development and may be helpful for diagnosis.
• Visanne is now PBS listed but it does not provide contraceptive cover.
• Ryeqo allows for longer GnRH suppression than isolated GnRH analogues with less likelihood of bone sequelae, although bone density must still be monitored.