My dear GFPs, it’s been a longer break than intended. While I was in the US visiting family I had some medical issues which put me out of action for a while. I am now back in the UK, on the mend, and more or less ready to dive back into the questionable world of women and data. Hold my hand!

Gender data gap of the week

This week we’re revisiting the data gap in Alzheimer’s research, and unlike last time I covered this topic, this week I have something actually positive to report!

But first, a quick recap:

Back in December 2022 I wrote about a study that had been heralded across the news media as representing a “historic breakthrough” and “new dawn” in Alzheimer’s treatment. The top-line results of a new study on a drug called lecanemab found that the drug reduced the rate of cognitive decline in Alzheimer’s patients by 27%. This might not sound like much, but as we explored back in December, this was the first time a drug had been shown to have any impact at all on the progression of the disease. So it was seen by the research community as something to celebrate.

As ever though, the top-line results hid a female-shaped problem: the paper itself provided no sex disaggregated analysis (as I wrote in the same edition, this is standard for Alzheimer’s research which, despite being a highly female dominated disease, is notoriously bad at sex analysis, sex disaggregation, and even at adequately representing females). But a table tucked away in a supplementary appendix did reveal that there was a potentially (the confidence intervals were overlapping) large sex difference when it came to the efficacy of this drug. The average rate of decline for female patients taking lecanemab was a measly 12%, while for men it was a whopping 43%.

More grist for the law I shall be passing as soon as I am anointed supreme ruler of the world that all results must be reported by sex on pain of death.

Anyway.

The other point of interest in the supplementary data was the impact of the drug on carriers of the ApoE-4 gene variant. As I noted back in December, ApoE-4 itself has a sex-dependent effect:

women who carry this gene variant are twice as likely to go on to develop Alzheimer’s disease as women without the gene. But men who carry this variant are hardly more at risk than men who don’t.

Given the potentially large sex difference revealed in the data for this drug, it should perhaps not be surprising that the data revealed a similar discrepancy when it came to carriers versus non-carriers of the gene variant. Essentially, lecanemab worked pretty well for non-carriers of the gene, coming in at an average of 41% slowing of decline — careful readers may note that this is not far off the percentage efficacy in male patients. But when it came to carriers of the homozygote variant, the average percentage slowing of decline came in at -22% — that is, the cognitive decline was on average WORSE, not better.

As I also noted at the time, the ApoE-4 data was not sex disaggregated, which is annoying, but, in the context of what we already know about sex differences in ApoE-4 and also in the potential sex differences in the impact of lecanemab as indicated by the data, it is certainly suggestive.

OK, but why have I been revisiting this study in such detail? Because, my dear GFPs, another study has just come out that may, rather unusually, have good news for female carriers of the ApoE-4 gene variant.

This new study, which analysed the data of 1178 female participants of the European Prevention of Alzheimer’s Dementia EPAD initiative, has found that HRT could be a really important tool when it comes to preventing Alzheimer’s in women — and specifically, women who carry the ApoE-4 gene variant. That is, the patient population at highest risk of developing Alzheimer’s. For these women, the use of HRT was associated with improved memory and larger brain volumes.

Importantly, this impact was only seen when women had started HRT during the perimenopause or very soon after the menopause; this suggests, the researchers say, that there is a “critical window” for starting HRT when it comes to protecting your brain. Something to think about for all those medics who are still curiously resistant to the evidence on HRT and reluctant to prescribe it.

I’d just like to take a bit of a detour here to share a screengrab I took when I was doing a some research into the ongoing issue of certain GPs still refusing to prescribe HRT to women who need it. As GFPs will I’m sure know, this forces those women who can afford it to go private, and those who can’t to go without, with all the attendant issues for their mental and physical health.

The screengrab is of some comments that appeared on the website PULSE, which calls itself “the leading publication for GPs in the UK.” They appeared below this article reporting on the finding of the House of Commons Women and Equalities Committee that GPs need training in menopause & HRT prescribing.

GFPs, I can’t be sure that Doc Solo is a man, but I feel that the withering tone about women who need to “learn” makes this a fairly safe bet. And yes, Andrew, that is what we want.

Anyway, these comments are, depending on your perspective, hilarious or disheartening, but they are certainly enlightening, especially given the majority of GPs in the UK are female.

To return to the study on Alzheimer’s and HRT, it was observational, so it can’t prove causation, but this is still really exciting, especially given the massive data gap for women in this female-dominated disease. Lecanemab may not do it — but your HRT just might. That is, assuming you can ever get hold of your prescription….

Default male of the week

Thanks this week to the Brits, for providing a really useful example of how “gender neutral” really all too often means….men.

The shortlist for artist of the year is all male and four out of five nominees for album of the year are men. (Source)

For more on why gender neutral doesn’t usually work for women, my own very unbiased opinion is that you can’t do better than read the Introduction to Invisible Women. Here’s an extract:

In 2012, a World Economic Forum analysis found that countries with gender-inflected languages, which have strong ideas of masculine and feminine present in almost every utterance, are the most unequal in terms of gender. But here’s an interesting quirk: countries with genderless languages (such as Hungarian and Finnish) are not the most equal. Instead, that honour belongs to a third group, countries with ‘natural gender languages’ such as English. These languages allow gender to be marked (female teacher, male nurse) but largely don’t encode it into the words themselves. The study authors suggested that if you can’t mark gender in any way you can’t ‘correct’ the hidden bias in a language by emphasising ‘women’s presence in the world’. In short: because men go without saying, it matters when women literally can’t get said at all. (IW, p.7)

Obv my emphasis added. And there’s plenty more where that came from…. 😘

Poppy pic of the week

God I’ve missed her so much

That’s it! Until next time, my dear GFPs…xoxoxo