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Lifting the aetiological clouds over brain fog

No-one seems to know who first coined the term ‘brain fog’ as a symptom – or syndrome – of the menopause. Was it Davina McCall in her 2021 TV series on ‘sex, myths and the menopause’, with her own mid-life story of hot flushes, depression and mental fog? Whenever and wherever, it was not long ago, but long enough for a whole industry of self-help to spring up and for the term to enter the scientific literature of the menopause – and even now with its own defining review.(1)

This new-age publication, whose first author also brought brain fog to the recent World Congress on Menopause, is in fact an IMS-commissioned annual white paper timed to coincide with the Society’s own theme for World Menopause Day, cognition and mood. However, brain fog, notes the paper, is not a single symptom amenable to precise definition and scientific evidence (hence the plethora of self-help lifestyle advice) but is more a ‘constellation of cognitive changes’ evident in memory and attention disorders, concentration and forgetfulness. Thus, any everyday task which usually requires no more than instinctive concentration, multitasking or even simple planning becomes bogged down in a lack of clarity and focus. The syndrome has gathered further attention in the past year or so in its association with COVID-19 infection and the more durable long-COVID.

Because brain fog at the menopause comes at a time when cycles become irregular and when difficulties in learning and verbal memory seem increasingly common, the IMS white paper reports that the timing of these changes ‘suggests an aetiology linked to hormones and menopause symptoms’ rather than to an imminent risk of Alzheimer’s, which is anyway rare at this time, or other cognitive decline. Thus, adds the paper, the majority of symptoms seem to resolve over time.

It may also be that, because of this apparent link with endocrine status, hormone therapy may be the most appropriate way to lift the brain fog. However, the paper makes it clear that HRT should not be used to prevent cognitive decline or dementia, but more to treat symptoms in line with current recommendations. Thus, HRT ‘in early postmenopause appears safe for cognitive function’, while use of estrogen therapy in women with early menopause ‘may be helpful in maintaining cognitive function and lowering risk of dementia’. Similarly, the review offers the usual recommendations to reduce modifiable risk factors in obesity, hypertension, diabetes, physical activity, smoking and cognitive activity.

* Brain fog also figured in the British Menopause Society’s own contribution to World Menopause Day in a TV programme produced to follow the stories behind the menopause headlines.(2) BMS speakers included recently appointed BMS Chair Paula Briggs, consultant at Liverpool Women’s Hospital, and former Chairs Heather Currie (joint editor of this journal) and Haitham Hamoda. The experts reaffirmed BMS advice on HRT (for symptom relief and in specific circumstances such as breast cancer) and, as another hot topic of headline interest, also attributed the burgeoning prevalence of brain fog to hormonal changes associated with the menopause.

1. Maki PM, Jaff NG. Brain fog in menopause: a healthcare professional’s guide for decision-making and counselling on cognition. Climacteric 2022; doi.org/10.1080/13697137.2022.2122792

Preventing secondary fractures

World Menopause Day, this year on 18 October, was marked just two days before World Osteoporosis Day, whose theme for 2022 was the tenth anniversary of the International Osteoporosis Foundation’s ‘Capture the Fracture’ initiative, a fracture liaison programme designed to prevent secondary fracture in those suffering an initial fragility fracture.(1) The IOF estimates that some 543,000 patients have received post-fracture care from the many Capture the Fracture prorammes around the world, and has ambitions to extend its programmes to more target countries. Presently there are said to be 785 fracture liaison services in 51 countries, with many in the UK.

The IOF reports that anyone who suffers a fragility fracture has a five times greater risk of having a further fracture – and that almost half of those presenting with hip fractures have previously broken another bone. ‘That first fracture was a red flag that should have prompted post-fracture care’, says the IOF, ‘including osteoporosis and falls prevention management that would reduce the likelihood of recurring fractures. Sadly, some 80% of fracture patients around the world are simply ‘repaired’ and sent home without the post-fracture care needed to prevent potentially devastating secondary fractures.’

Fracture liaison services are usually built around a multi-disciplinary team to identify those over 50 who have broken a bone, assess their risk of further fractures and ensure they receive anti-osteoporosis treatment and falls assessment. ‘All fragility fracture patients should be screened and treated through a post-fracture care model, said IOF president Cyrus Cooper. ‘This has been shown to reduce re-fracture rates and mortality, and ultimately reduces the burden of fractures on healthcare systems.’ A cost-effectiveness study of a fracture liaison programme from more than decade ago in Glasgow found that, from a cohort of 1000 fragility-fracture patients, 18 fractures, including 11 hip, would have been prevented.

1. https://www.capturethefracture.org

Vegan diet rich in soybeans reduced hot flushes by 88%

A role for diet in the prevention and control of vasomotor symptons has long been proposed and studied. A dietary intervention increasing whole grains, fruits and vegetables and reducing dietary fat proved modestly effective in the Women’s Health Initiative Dietary Modification trial.(1) The effect appeared more dependent on weight loss than on dietary composition alone, but there have been countless studies of plant-based isoflavones suggesting a benefit in reducing the severity of symptoms. Last year, a RCT from a US group known as the Women’s Study for the Alleviation of Vasomotor Symptoms (WAVS) found that subjects with at least two hot flushes a day randomised to a low-fat, vegan diet for 12 weeks (which included a small quantity of soybeans each day) reduced their frequency of hot flushes by 84%; there were no changes in a non-intervention control group.(2)

Now, the same group has published a second trial in two successive groups (with interventions in Spring and Autumn) which thereby eliminated any effect of time and season. Again, results showed that the same plant-based diet rich in soy reduced moderate to severe hot flushes by 88% and helped women lose, on average, 8 pounds in 12 weeks.(3) The authors suggested that this dietary intervention was ‘about as effective as hormone replacement therapy’ and even proposed that ‘a diet change should be considered as a first-line treatment for troublesome vasomotor symptoms’.

The benefits of soy-based isoflavone diets have long been explained by their phyto-estrogenic chemical structure, but it is also recognised that such diets are typically high in fibre and low in fat and favour weight loss. However, in commenting on these latest study results its first author said in a press statement: ‘We do not fully understand yet why this combination works but it seems that these three elements are key – avoiding animal products, reducing fat and adding a serving of soybeans’. He also added that a precedent appears to be found in pre-Westernised Japan, where a low-fat, plant-based diet including soybeans was prevalent and where postmenopausal women seemed to experience fewer symptoms.

1. Kroenke CH, Caan BJ, Stefanick ML, et al. Effects of a dietary intervention and weight change on vasomotor symptoms in the Women’s Health Initiative. Menopause 2012; 19: 980-988. doi: 10.1097/gme.0b013e31824f606e

Core outcome sets to resolve heterogeneity in menopause studies

There are few meta-analyses published today in women’s health whose conclusions do not draw attention to the relatively poor quality of the evidence – and thereby explaining doubts over any firm conclusion. Risk of bias, confounding and heterogeneity in methodology and outcome usually figure prominently. This problem was put into stark profile in a full session at the recently ended International Menopause Congress in Lisbon, and in its concluding hopes that two new core outcome sets for menopause studies might help resolve these deficiencies.

Sarah Lensen, opening the session, described three problems of heterogeneity on menopause studies: different outcomes (e.g. vulvovaginal dryness vs pain with sex); the same outcome but measured in a different way (clinical assessment or self-report); or outcomes of little importance (vaginal pH). Lensen, who is herself associated with Cochrane O&G group, noted that even the assessment of hot flushes might be measured in terms of number per day after treatment, percentage decrease in frequency, severity score or population effect. Similarly, said her fellow speaker Monica Christmas from Chicago, there were no ‘agreed’ measurement tools for clinical trials in the menopause.

In response, a collaboration group was set up in 2016 to measure core outcomes in menopause studies. The work began with systematic literature reviews in two essential subjects: vasomotor and genitourinary symptoms. As expected, said the session’s third speaker Martha Hickey from the University of Melbourne, the literature too threw up huge variations in outcome and method. However, after assembling a huge catalogue of symptomatology, an expert group (of whom many were postmenopausal women) rated each set for validity and after a second review developed a final outcome set for each symptom group. There were six in the vasomotor outcome set: frequency of symptoms; severity; distress, bother or interference caused; impact on sleep; satisfaction with treatment; and side effects of treatment. There were eight core outcomes in the genitourinary set: pain with sex; vulvovaginal dryness; vulvovaginal discomfort or irritation; discomfort or pain when urinating; change in most bothersome symptom; distress, bother or interference of genitourinary symptoms; satisfaction with treatment; and side effects of treatment.

Both these core outcome sets have now been published, but, said Hickey, there is still no consensus – even validation – for measuring the effect of these outcomes, most of which are self-reported.^1,2 ‘But we’re still hoping to deliver a set of simple validated tools’, said Hickey.

* The British Menopause Society is one of several organisations committed to the Core Outcomes in Menopause (COMMA) Initiative and to publication of the consensus statements.