Highlights from the European Congress of Endocrinology, Sweden, 2024

Link between premature menopause and mortality risk

Women who experience premature ovarian insufficiency (POI) before the age of 40 are more likely to die early, but hormone therapy may lower this risk, according to research presented at the 2024 European Congress of Endocrinology (ECE), 11-14 May, 2024, Stockholm, Sweden. The long-term Finnish study is the largest to date on the links between premature menopause and mortality, and highlights the importance of evidence-based, appropriate hormone therapy for these patients. Around 1 per cent of women go through menopause before the age of 40 and are subsequently at a higher risk of long-term health problems such as cardiovascular disease. The cause is largely unknown, but can be brought on spontaneously or by some treatments such as chemotherapy or bilateral oophorectomy.

In this study, researchers from the University of Oulu and Oulu University Hospital, Finland, investigated 5,817 women who were diagnosed with spontaneous or surgical POI in Finland between 1988 and 2017. They compared these women with 22,859 women without POI and found that those who had experienced early menopause were more than twice as likely to die of any cause or of heart disease, and more than four times as likely to die of cancer. However, the risk of all-cause and cancer mortality was approximately halved in women who used hormone replacement therapy (HRT) for more than six months.

Previous studies have also shown that women with premature menopause have a higher risk of early death. However, this association has never been studied in women on such a large scale before, or for such a lengthy follow-up period (up to 30 years). “To our knowledge, this is the largest study performed on the linkage between POI and mortality risk,” said Ms Hilla Haapakoski, a PhD student at the University of Oulu, who led the study.

She added: “Our study is one of the first to explore both surgical and spontaneous POI in women’s all-cause, cardiovascular, and cancer-related mortality, and examine whether HRT for over six months may reduce mortality risk. Our findings suggest specific attention should be paid to the health of women with spontaneous POI to decrease excess mortality.”

The team will now assess whether women with premature menopause are more likely to have other illnesses or conditions, such as cancer or heart disease, and whether long-term use of HRT affects these conditions. “Various health risks of women with POI have not been well recognised and the use of HRT is often neglected. We hope to improve the health of these women by increasing awareness of the risks among healthcare professionals and the women themselves,” added Ms Haapakoski.

Fezolinetant safely reduces hot flushes in menopause for almost six months

Attendees at the ECE Congress 2024 heard that fezolinetant reduces the frequency and severity of hot flushes during menopause for 24 weeks without serious side-effects. Vasomotor symptoms (VMS) affect up to 80 per cent of women going through menopause and can severely impact many aspects of wellbeing.

Hormone replacement therapy (HRT) is not suitable for, or desired by, all women, and fezolinetant – which was recently approved in Ireland for VMS – acts directly on the thermo-regulatory pathway to alleviate these issues, and is a non-hormonal alternative for symptom management.

Previous late-stage clinical trials (SKYLIGHT 1 and SKYLIGHT 2) have shown that fezolinetant reduces both the frequency and severity of hot flushes in women with moderate or severe symptoms compared to placebo over 12 weeks. This phase 3b study, known as DAYLIGHT, investigated the effect of fezolinetant use over 24 weeks.

A total of 453 menopausal women aged 40-65 with moderate or severe hot flushes, who were unsuitable for HRT, were randomised to receive either fezolinetant or placebo. The primary endpoint was mean change in daily VMS frequency of moderate to severe episodes from baseline to week 24, while secondary endpoints included mean change in VMS severity and safety.

Women who took fezolinetant reported less frequent and severe hot flushes throughout the 24 weeks. They had consistently fewer hot flushes in the first week, with the strongest decrease during the first three days. The severity of their hot flushes was also reduced significantly by the drug in the first week from the second day. No safety issues were found for the 45mg fezolinetant dose over the 24 weeks.

“DAYLIGHT is the first study of fezolinetant to investigate placebo-controlled efficacy over 24 weeks,” said Prof Antonio Cano, INCLIVA Research Institute in Valencia, Spain, and senior author of the study. “Fezolinetant was effective and well tolerated for 24 weeks and the effect was observed as early as day one of treatment. While there are other NK (neurokinin-3) antagonists, none have shown a similar concurrence of efficacy and safety in clinical studies with a sufficiently high number of participants.

“A safe and effective non-hormonal molecule may be available for the very high number of menopausal women who suffer from VMS and improve their overall health, quality of life, and work performance. However, these symptoms vary in prevalence or intensity depending on ethnicity – for example, VMS are more frequent and severe in black women – so more clinical data are needed in different populations or geographical areas in the world.”

Arm fat may indicate risk of spinal fracture

Measuring the total fat mass of the arms could potentially predict those over 50 who are at increased risk of spinal fracture, according to research presented at the ECE Congress 2024. Osteoporosis is a common disease among older people, but is also one of the most underdiagnosed and untreated medical conditions in the world. The findings may help identify high-risk individuals with a very simple and inexpensive method.

To date, the relationship between body composition and bone health is still unclear. Therefore, to further understanding in the area, researchers from the National and Kapodistrian University of Athens, Greece, analysed 14 men and 101 women without osteoporosis.

The sample had an average age of 62 and demonstrated that total fat mass is negatively associated with trabecular bone score (TBS). Moreover, total lean mass was positively associated with TBS. Visceral fat, in particular, was associated with lower quality trabecular bone.

The researchers then looked at the distribution of subcutaneous body fat and discovered that individuals with higher fat mass in the arms were more likely to have lower bone quality and strength in the spine.

“Surprisingly, we identified, for the first time, that the body composition of the arms – in particular, the fat mass of the arms – is negatively associated with the bone quality and strength of the vertebrae,” said senior author Prof Eva Kassi, Professor of Endocrinology/Biochemistry, National and Kapodistrian University of Athens, Medical School, Athens, Greece.

“This could mean that the arm’s subcutaneous fat, which can be easily estimated even by the simple and inexpensive skin-fold calliper method, may emerge as a useful index of bone quality of the spine, possibly predicting the vertebrae fracture risk.

“It should be noted that visceral fat, which we found to be strongly correlated with low bone quality, is the hormonally more active component of the total body fat. It produces molecules called adipocytokines that provoke a low-grade inflammation, so the increased inflammatory status plausibly poses a negative impact on bone quality.” 

Prof Kassi also acknowledged that larger studies are needed to confirm the link between arm fat and spinal fracture risk, and that research is still ongoing. “Although our results remain robust after controlling for age and weight, we will now increase the number of participants and expand the age range by including younger adults between the ages of 30 and 50 years old, as well as more men.

“Moreover, using the loss of arm fat mass as a marker, we will try to determine the most effective physical exercise routine that not only targets the visceral fat, but also focuses on the upper part of the body so that these higher-risk adults lose arm fat and achieve a favourable effect on vertebrae bone quality.”

Blood sugar levels at gestational diabetes diagnosis correlate with level of risk

The level of glucose above diagnostic threshold at the time of gestational diabetes (GD) diagnosis is associated with worse neonatal outcomes and abnormal maternal glucose homeostasis, but not with obstetric outcomes, according to data presented at the ECE 2024 Congress.

GD affects around 20 million pregnancies worldwide and poses a range of health risks for both mothers and their babies. The higher the blood sugar level in pregnant women when first diagnosed, the higher the risk of complications, attendees heard.

Researchers from the Tâmega e Sousa Hospital Centre, Portugal, conducted a retrospective study based on the national register of GD. A total of 6,927 women aged between 30-37 with live-born singleton pregnancies were included and analysed between 2012 and 2017.

The researchers found that for every 5mg/L increase in their blood sugar levels, there was a 9 per cent higher risk of hypoglycaemia and a 6 per cent higher risk of large birth weight in newborns, as well as a 31 per cent higher risk of post-partum maternal hyperglycaemia. The findings suggest that high-risk women with GD should be classified further to limit these complications for both mothers and newborns.

“While it is not surprising that high glucose levels are associated with these adverse outcomes in mothers and newborns, our study shows for the first time how much increase in risk there is with 5mg/dL of increase in the mother’s blood glucose levels when first diagnosed with GD,” said study co-lead Dr Catarina Cidade-Rodrigues.

“The magnitude of elevated risk can be calculated with our measurements and, in practice, could be used to identify and stratify women at higher risk of developing these complications. We now want to evaluate if there is a benefit in further stratifying these high-risk women with GD, who will need to be more closely monitored and to whom pharmacological interventions can be carried out appropriately. This may help reduce complications during labour and in newborns and prevent future diabetes in these women.”