Endometriosis link with ovarian cancer … and other research

Endometriosis and ovarian cancer risk

Endometriosis affects around 11% of women of reproductive age and is an underlying cause of up to 50% of pelvic pain and female infertility. An additional worry is that having endometriosis carries a small increased risk of developing ovarian cancer.

This large population-based cohort study from Utah found that women with incident endometriosis were 4.2 times more likely to develop ovarian cancer (7.48-fold increase in type I, 2.7-fold increase in type II) than those without endometriosis (in whom the estimated lifetime risk of ovarian cancer is around 2%). The worse the subtype of endometriosis, the higher the risk of ovarian cancer. Deep infiltrating endometriosis and/or ovarian endometriomas were associated with a 9.66-fold increased risk, whereas superficial peritoneal endometriosis and other endometriosis were associated with 2.82-fold and 2.62-fold increase respectively.

Important questions remain. Why does endometriosis apparently increase the risk of ovarian cancer? What’s the interaction with other known risk factors such as BRCA mutations? Are there novel treatment targets? And, most relevant for the women concerned, how should we advise, screen, and treat women plagued by this troublesome condition?

JAMA doi:10.1001/jama.2024.9210

STOMP against pain

Chronic pain (>3 months) is common, hard to treat, difficult for individuals, and costly for society. The opioid crisis has highlighted the urgent need for better options to offer people who live with chronic pain. Pain self management has shown some positive results in people with low back pain and fibromyalgia. Could it be helpful in people with HIV, who have a high prevalence of chronic pain (30-85%)?

This small randomised trial of 278 people with HIV and chronic pain found that a 12-week, novel, self management behavioural intervention for pain (Skills To Manage Pain (STOMP)) was associated with significantly reduced pain immediately after the intervention and sustained improvement compared with enhanced usual care at three months (Brief Pain Inventory total score mean difference −1.25 and −0.62 points respectively).

It’s curious that it worked at all. Most participants attended fewer than half the sessions on offer, and 24% didn’t go to any at all. The strength of STOMP could be that it’s delivered by trained and paid peers who can relate to the participants. Further work is needed to compare different behavioural interventions, the ideal combination of individual and group sessions, and how to ensure sustained benefit.

The effect size associated with STOMP was similar to that achieved by analgesic drugs, but without the potential harms of addiction, criminality, and overdose.

JAMA Intern Med doi:10.1001/jamainternmed.2024.3071

Upselling IVF

One in six people globally are affected by infertility. Assisted reproductive technology has brought hope and opportunity to millions, but successful live birth rates have stalled. Good research is stymied by the fact that most assisted reproduction is provided in the private sector by multiple agencies. But if we want to improve outcomes, we need to know more about how to choose the best embryos for transfer.

This large randomised trial of women undergoing in vitro fertilisation (IVF) at seven IVF centres in the UK and Hong Kong looked at whether time-lapse imaging of embryos incubated in closed systems with a controlled environment (undisturbed culture) could be a useful extra tool in selecting those most likely to survive compared with embryos in undisturbed culture but no time lapse imaging, and a third group in standard culture. They found no difference in live birth rates between the groups (33-36.6%)

Add-on technologies are associated with add-on prices, and results like these are essential to inform women’s choices if they are upsold during the vulnerable, expensive, and often desperate process of IVF.

Lancet doi:10.1016/S0140-6736(24)00816-X

Bleeding triumph

We’ve come a long way in the management of haemophilia A (factor VIII deficiency), but life threatening bleeds and painful bleeding into joints still occur with standard prophylactic treatment. Keeping factor VIII levels in the normal range requires multiple injections every week, which is particularly hard for young children. A once-weekly effective factor VIII injection would be a godsend.

A previous phase 3 study found that once-weekly efanesoctocog alfa (a new class of factor VIII replacement designed to overcome interaction with von Willebrand factor that limits the half-life) provided better bleeding protection than prestudy factor VIII prophylaxis and normal to near-normal factor VIII activity for most of the week in previously treated patients over 12 years old with severe haemophilia. This study found similar results in children under 12 years. Once weekly dosing provided excellent protection against bleeding episodes, and no factor VIII inhibitors developed. Longer term safety and efficacy data are awaited, but it’s looking like a game changer.

N Engl J Med doi:10.1056/NEJMoa2312611

Dying to be thin?

The phenomenal sales of diabetes and weight loss GLP-1 receptor agonist (GLP-1 RAs) drugs Wegovy and Ozempic (semaglutide) mean that the Danish producer Novo Nordisk is currently valued at $600bn—more than the GDP of the whole of Denmark.

But there’s been concern about a possible increase in suicidal ideation and behaviours in people taking these drugs. This US study compared two matched cohorts of older adults (≥66 years old) with diabetes and no history of suicidal ideation or behaviours who were started on either a GLP-1 RA or a different class of medication (SGLT2i or DPP4i) and followed up for three years.

Over 21 000 pairs of patients were treated with a GLP-1 RA or SGLT2i (for example, dapagliflozin) and a similar number of pairs were treated with a GLP-1 RA or DPP4i (such as sitagliptin). There was no clear increased risk of suicidal ideation or attempts with GLP-1 RAs, though estimates were imprecise and several potential confounders weren’t measured. The authors admit that “a modest adverse risk could not be ruled out.”

This study offers some reassurance, but with soaring sales and potentially vulnerable people, we need a clear answer on safety alongside tighter regulation of supply.

Ann Intern Med doi:10.7326/M24-0329