See below for an explanation of this image.
Will Powers work on Post-Finasteride Syndromes (PFS) has generated a lot of interest. It would be easy to misread the responses.
This post asks people with PSSD and PAS to get what are often called Dutch tests done. The U in Dutch stands for Urine.
Can send your results to david.healy@rxisk.org – not to Dr. Powers. He was swamped even before the recent Congress and is even more swamped with desperate people getting in touch unaware of the extent to which he is badly over-stretched.
This ask does not apply to Finasteride. Enough material has already been collected by or sent into Dr Powers for Finasteride. His next step involves trying to figure out if the results he already has provide a basis for testing possible remedies – something that will undo the metabolic road-block people with PFS seem to have,
Will and RxISK are on the same page in viewing the enduring sexual dysfunctions as feedback loop disorders – See Enduring Sexual Dysfunction and Love Making Actually. This is not an effort to divert people away from Will – it’s an effort to avoid him burning-out. We will be depending on him to shape any interpretations of the data being asked for here.
Dutch and Double Dutch Science
The response from researchers and mainstream medicine to the idea that Will’s work depends in part on Dutch Tests is that these are barely respectable tests likely to tell us little more about what is going on in people than reading the urinary output of the Kremlin or the Pentagon. I had never heard of Dutch Tests 3 weeks ago.
[It would be great to have an image here but hunting for a not-copyrighted Dutch Test image is like hunting for a not copyright image of Bruce Springsteen].
A skeptical response is normally right but misses the sequence of events here. Will didn’t start with Dutch tests. He began interpreting genomes where he noticed a pattern of gene findings involving the metabolic pathways for steroid and sex hormones that when combined with a drug like Finasteride that targets a key part of these pathways is almost certain to impact on how we metabolize these hormones more generally.
Problems can arise if we have a deletion in the relevant metabolic genes that normally offer a way to bypass a Finsteride obstruction. We can sail by on Finasteride with no problem if those genes are working fine in us.
Based on the deletion profile, Will predicted a set of likely results on Dutch tests. His prediction for PFS Dutch screens was broadly speaking right.
The PFS pattern is probably not going to hold true for PSSD or PAS for a few reasons.
Neither of these drugs directly impact on the metabolic pathways for these hormones the way Finasteride does. An indirect impact, however, is possible, especially with PAS, which does have some metabolic overlap with PFS.
Unlike Finasteride both PSSD and PAS affect women just as much as men and to some extent this is likely to lead to differences.
We can only be sure of what Dutch tests might tell us if we do them. There may be indirect routes to the same final result just as it looks like within the body there appears to be something that is leading PFS, PSSD and PAS folk to end up with a lot of clinical features in common.
It is worth nailing this down as these tests are simple and inexpensive and if the pattern doesn’t hold, it will steer any PSSD or PAS genome investigation in a different direction and perhaps offer hints on the best direction to follow.
There is another reason to move forward like this. In terms of sheer workload, no-one is going to be able to get through all the work single-handedly especially if it involves in the case of PSSD going back to genome scratch.
The great advantage for PSSD sufferers is that PFS and Will Powers have laid down a template for the kind of problem we are dealing with – a feedback loop disorder – even if the details for PSSD and PFS differ.
Confronting a genome without a focus like this is like looking out on the vastness of the universe. Finding something in a genome haystack is harder than finding a needle in a haystack – at least with the needle you have some idea what you are looking for.
It sounds great to hear that Will moved from genetic deletions to predicting Dutch test results. Deletions are a finite number – aren’t they? Not quite. We all have tens of thousands of deletions – so we still need a way to separate the chaff from the wheat and even then the work is likely to be painstaking.
Where Will’s strength and medical input more generally comes in lies in interpreting how we might move from some protein change or change in a metabolic pathway to a final clinical symptom.
The plan also is to apply with Dr Powers and others for a research grant to move this forward and establish that it is not just in his hands alone that promising results materialize. This may mean running higher powered and more expensive genome screens. If need be we will use RxISK Prize money to get this going.
Live With or Die From
Is it worth going ahead to get genome screens at this point using sequencing.com and gene.iobio to read the results the way Will has done?
There are yesses and nos to this.
Yes, because we are rapidly moving into an era where this can be done and more and more people will likely take it up, perhaps reading their own and family genomes to understand more about ourselves.
There is a need to remember here that genomes are likely to be like post-mortems – able to show what people can live with rather than die from.
Finasteride and other drug induced problems are different to the cancers, minor strokes and heart attacks we can live with and perhaps barely notice. They are more like a comet hitting the earth. These one off events offer a better chance of making a link to what has happened.
It’s likely that some people tinkering with genomes the way Will Powers did may come up with reasons why some of us have terrible problems stopping SSRIs or why SSRIs can increase blood alcohol levels for some or why anticonvulsants can weave their way into our nerves and close to become the problem we are trying to treat.
One of many Nos is that there are strict rules on holding genetic material. No one is allowed to hold other people’s genetic material unless it is a doctor or health system and then the holding is governed by strict rules aimed at protecting us from insurance companies finding our results and increasing our premium on the basis of our newly discovered risk profile.
In Will’s case, his work to date has been on his patients. Expanding this to overseas requests for input becomes a lot more complex if it also means he is left holding the gene baby.
If we can get to a point where we have a somewhat clear idea about what we are hunting for, stand a chance of finding it and have ways to return all screens to the individuals they came from rather than hold onto them, this will be a lot safer all round.
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