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Male bias in research with animal models prevents women from getting best drugs

Started by xSilverPhinx, June 26, 2017, 09:25:35 PM

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Dave

Re differences betwixt males and females, variety of function of same genes, hormonones etc and sex bias in clinical trials, effects of drugs on gender....

One point of interest, after thalidomide clinical tests on pregnant females was, seemingly, banned in the UK at least.

http://www.bbc.co.uk/programmes/b036f7w2/episodes/downloads

Being broadcast now.

Also, Silver:
http://www.ucl.ac.uk/news/news-articles/0617/260617-Sex-differences-important-for-medical-research

and loads of other stuff on "ucl paper on sex differences and clinical trials" search string!
Tomorrow is precious, don't ruin it by fouling up today.
Passed Monday 10th Dec 2018 age 74

Claireliontamer

Quote from: xSilverPhinx on June 28, 2017, 12:37:33 AM
Quote from: Claireliontamer on June 27, 2017, 10:22:34 AM
I wonder why they just use the males?  It surely can't be that much more difficult to include female animals too.

Females are...complicated. Their estrus cycle (proestrus, estus, metaestrus and diestrus) means that hormones can vary within the same day, estrus typically lasts only about 4 hours in rats, depending on whether there are males near enough for the female to pick up on pheromones. 

Males are less variable and experiments using them are 'cleaner' as well, with smaller standard deviations and variance. Error bars in experiments using females tends to be much larger, which means that histograms aren't as pretty.

There are ethical reasons not to use females as well. If you need a population of about 9 to 10 animals per group in an experiment, ideally you ought to pool together that number of females in each stage of the estrus cycle, which means you end up using a lot more animals. That's one major reason why many opt to use just males. 

I hadn't thought about the increase in numbers of females you'd need to use.

I guess it's one more argument of building more realistic and reliable non-animal models to test on.

xSilverPhinx

Quote from: Gloucester on June 29, 2017, 04:40:05 PM
Re differences betwixt males and females, variety of function of same genes, hormonones etc and sex bias in clinical trials, effects of drugs on gender....

One point of interest, after thalidomide clinical tests on pregnant females was, seemingly, banned in the UK at least.

http://www.bbc.co.uk/programmes/b036f7w2/episodes/downloads

Being broadcast now.

Also, Silver:
http://www.ucl.ac.uk/news/news-articles/0617/260617-Sex-differences-important-for-medical-research

and loads of other stuff on "ucl paper on sex differences and clinical trials" search string!

Cool :grin: I've downloaded the podcast and will listen to it soon.
I am what survives if it's slain - Zack Hemsey


xSilverPhinx

Quote from: Claireliontamer on June 29, 2017, 05:36:49 PM
I guess it's one more argument of building more realistic and reliable non-animal models to test on.

I think that would be great but at the same time I am sceptical that a non-animal model would be better to investigate biological processes as living things are basically complex reagents. 

In neuropharmacology for instance, you can even use living cells in a cell culture or even engineer a brain but as we all know, brain systems and brain cells do not work in isolation from all sorts of hormones and other substances that interact directly or indirectly with the central nervous system. If you want to study memory processes and phases and how certain drugs influence those, you have to have a model with all sorts of biological reactions triggered by experiences, a brain that changes by learning.

How would you test something like learning and recall with a printed brain whose interactions with the outside world are limited? I guess you could quantify biological activity markers but...don't get me started on how I think that sort of reductionsim is detrimental. :P

What I feel people don't understand is cell cultures and tissue and organ engineering have their place and are great models for studying some simple processes, but unfortunately they are not the ideal to study others.
I am what survives if it's slain - Zack Hemsey


Claireliontamer

Quote from: xSilverPhinx on June 29, 2017, 06:14:43 PM
Quote from: Claireliontamer on June 29, 2017, 05:36:49 PM
I guess it's one more argument of building more realistic and reliable non-animal models to test on.

I think that would be great but at the same time I am sceptical that a non-animal model would be better to investigate biological processes as living things are basically complex reagents. 

In neuropharmacology for instance, you can even use living cells in a cell culture or even engineer a brain but as we all know, brain systems and brain cells do not work in isolation from all sorts of hormones and other substances that interact directly or indirectly with the central nervous system. If you want to study memory processes and phases and how certain drugs influence those, you have to have a model with all sorts of biological reactions triggered by experiences, a brain that changes by learning.

How would you test something like learning and recall with a printed brain whose interactions with the outside world are limited? I guess you could quantify biological activity markers but...don't get me started on how I think that sort of reductionsim is detrimental. :P

What I feel people don't understand is cell cultures and tissue and organ engineering have their place and are great models for studying some simple processes, but unfortunately they are not the ideal to study others.

I'm not for one minute suggesting we're anywhere near the stage where we can do without animals in testing.  However we think about the ethics of it, we have to use them for testing for all the reasons you state.

However, even animal models aren't perfect as this thread emphasises.  At the moment as female animals aren't being used then we can't be clear on how female hormones do interact with medications and like you said originally females are perhaps being denied the ideal treatments for them.  Also like Gloucester said there are groups of people we can't or don't test on like pregnant women and children and their physiology can be very different so again they maybe being denied effective treatments.

I do think therefore there could be a role in the future for alternative testing methods and more research could be done into developing these.

xSilverPhinx

Quote from: Claireliontamer on June 29, 2017, 06:44:31 PM
I'm not for one minute suggesting we're anywhere near the stage where we can do without animals in testing.  However we think about the ethics of it, we have to use them for testing for all the reasons you state.

Well, 'Replacement' is one of the 3R's of ethical considerations. ;) The other two are Reduction and Refinement, and ideally experiments using animal models should be designed taking them into account. 

QuoteHowever, even animal models aren't perfect as this thread emphasises.  At the moment as female animals aren't being used then we can't be clear on how female hormones do interact with medications and like you said originally females are perhaps being denied the ideal treatments for them.  Also like Gloucester said there are groups of people we can't or don't test on like pregnant women and children and their physiology can be very different so again they maybe being denied effective treatments.

Well, a model is exactly that -- a model -- and no model is perfect. Even when testing stages reach clinical trials with humans it could be the case that what works a certain way for a subgroup of humans might not work for another, which is why trails have to highly randomised. Even then it's not perfect as you might be that outlier that doesn't respond to treatment at all or worse, suffers averse side-effects.   

QuoteI do think therefore there could be a role in the future for alternative testing methods and more research could be done into developing these.

I agree, and I guess time will tell, but remain skeptical that animal testing will or should be banned altogether. Unless they basically engineer another life artificially, which would come with a whole different set of ethical concerns. Maybe it's because I lack the imagination, but I just don't see how psychophysical processes could be studied without using living subjects, either humans or non-human animals. They're not something a Petri dish can tell you.
I am what survives if it's slain - Zack Hemsey


No one

I say, instead of testing on mice and they like we use society's dregs, such as the pedophiles, rapists, and murderers.

xSilverPhinx

Quote from: No one on June 30, 2017, 02:00:00 AM
I say, instead of testing on mice and they like we use society's dregs, such as the pedophiles, rapists, and murderers.

:notsure: I don't know...laboratory animals are very well taken care of (they have to be, otherwise they don't do well in tests and are basically lives wasted for nothing), I don't think such scum as you listed should be that well looked after.
I am what survives if it's slain - Zack Hemsey


No one


Davin

And what if some of those convicted, are innocent? Not such an uncommon event that it should be ignored.
Always question all authorities because the authority you don't question is the most dangerous... except me, never question me.

Arturo

A lot of convicted are mentally ill too. Not something you want in a lab.
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No one


Davin

Always question all authorities because the authority you don't question is the most dangerous... except me, never question me.

No one

Look, I get where you're coming from. But, there are those in the stoney lonesome that are truly animals and do not deserve to breath the same air as those that suffer from the inhuman actions. That's all I'm saying.

Davin

Conceptually, I don't have much compassion at all for violent criminals, but I will not trust an imperfect system to enact perfect justice.

Besides, most violent criminals are males, so it doesn't solve the problem presented in this thread.
Always question all authorities because the authority you don't question is the most dangerous... except me, never question me.