My blood tests (PSSD)

[Shadow]

My blood tests(fasting). Things to keep in mind: Im a PSSD sufferer, my diet is very bad and I was taking Inositol.

High progesterone is common in pssd, if Im remember well some people reported high DHEA too.

[mention]gbolduev[/mention] [mention]mattyb[/mention] anything interesting?

My symptoms: https://www.hackstasis.com/viewtopic.php?f=28&t=139&p=2117#p2117

Glucose_______________95 mg/dl_____________60 - 99mg/dl
ACTH_________________36.0 pg/mL___________< 46.0 pg/mL
Aldosterone___________37 ng/mL_____________2 - 31 ng/mL
Androstenedione_______2.3 ng/mL____________0.6 - 3.1 ng/mL
Cortisol_______________18.52 µg/dL__________6.70 - 22.60 µg/dL
DHEA_________________7.6 ng/mL___________1.7 - 6.1 ng/mL
S-DHEA_______________385 µg/dL____________85 - 690 µg/dL
Estradiol______________29 pg/ml_____________< 44 pg/ml
Insulin________________25.6 µUI/mL__________1.9 - 23 µUI/mL
FSH__________________2.43 mUI/mL__________0.95 - 11.95 mUI/mL
LH___________________1.73 mUI/mL__________0.57 - 12.07 mUI/mL
Free Testosterone______307.71 ng/dL__________175 - 781 ng/dL
Progesterone__________0.36 ng/mL___________< 0.20 ng/mL
Prolactin______________9.5 ng/mL____________2.1 - 17.7 ng/mL
SHGB_________________11.5 nmol/L__________13.2 - 89.5 nmol/L
TSH__________________1.53 µUI/mL__________0.34 - 5.60 µUI/mL
Free T4_______________1.25 ng/dL___________0.54 - 1.48 ng/dL
Ferritin_______________328.8 ng/mL__________23.9 - 336.2 ng/mL
Zinc__________________88 µg/dL_____________70 - 115 µg/dL
Potassium_____________3.70 mEq/L___________3.5 - 5.1 mEq/L
Sodium_______________135.0 mEq/L__________135 - 148 mEq/L

 

[Shadow]

[mention]namaste[/mention] [mention]barbaar[/mention] [mention]expendable[/mention] did you guys tested progesterone and dhea?

 

[namaste]

@namaste @barbaar @expendable did you guys tested progesterone and dhea?

Unfortunately I've never had DHEA or prog tested. I know blood tests are viewed as being super important but honestly I've been considering a mineral test in the near future, as it seems that is the direction things are trending in.

 

[mattyb]

Isn't this all pretty standard PFS/PSSD?

High prog creates low level insulin resistance, so insulin goes up to compensate, and glucose remains borderline high? And DHEA is high because SSRIs lower activity of 3a/b HSD?

I am not an expert on PSSD/PFS and sex hormones, but it sounds pretty typical to many of the cases around here, doesn't it?

 

[Shadow]

First thank you [mention]mattyb[/mention], like PFS, PSSD sufferers have high progesterone too, and I saw some people reported high DHEA too. SSRIs and tetracyclics affects 3a-HSD directly, they boost the 5aDHP -> Allo process.

Something is bugging me, my Potassium and Sodium are borderline low, and I think that my intake of both is pretty good.

 

[Jaxx]

Only other thing ive seen is that many, but definately not everybody with PSSD has elevated TSH. Not sure how that link works

 

[mattyb]

First thank you @mattyb, like PFS, PSSD sufferers have high progesterone too, and I saw some people reported high DHEA too. SSRIs and tetracyclics affects 3a-HSD directly, they boost the 5aDHP -> Allo process.

Something is bugging me, my Potassium and Sodium are borderline low, and I think that my intake of both is pretty good.

If you are like PFS people, and gbold's theory is right, you would be in metabolic alkalosis. This would lower serum potassium and sodium. In alkalosis minerals don't go into their ionized forms easily, they are more likely to be trapped inside cells, bound to proteins, or excreted in urine.

 

[namaste]

First thank you @mattyb, like PFS, PSSD sufferers have high progesterone too, and I saw some people reported high DHEA too. SSRIs and tetracyclics affects 3a-HSD directly, they boost the 5aDHP -> Allo process.

Something is bugging me, my Potassium and Sodium are borderline low, and I think that my intake of both is pretty good.

If you are like PFS people, and gbold's theory is right, you would be in metabolic alkalosis. This would lower serum potassium and sodium. In alkalosis minerals don't go into their ionized forms easily, they are more likely to be trapped inside cells, bound to proteins, or excreted in urine.

Can you think of any mechanism by which metabolic alkalosis might cause changes in serotonin receptor (5-HT) density, or any other neurotransmitter receptor density for that matter? I've read studies that point toward this (density) being an issue in people who take SSRI's and the hypothesized cause was epigenetic changes. This was what the PSSD community was focused on for years, similar to how PFS folks were hyper-focused on 5-AR. What has never made sense to me though is how some people come down with these "conditions" within days of starting a medication. I don't think that can be explained by genetic changes.

 

[mattyb]

Can you think of any mechanism by which metabolic alkalosis might cause changes in serotonin receptor (5-HT) density, or any other neurotransmitter receptor density for that matter? I've read studies that point toward this (density) being an issue in people who take SSRI's and the hypothesized cause was epigenetic changes. This was what the PSSD community was focused on for years, similar to how PFS folks were hyper-focused on 5-AR. What has never made sense to me though is how some people come down with these "conditions" within days of starting a medication. I don't think that can be explained by genetic changes.

This is just a guess, as in, I am really pulling this out of my ass and what I'm saying should be taken as a grain of salt.

I think extracellular alkalosis would interfere with electric signalling between neurons, while intracellular alkalosis would interfere with signal transduction pathways that rely on coulomb interactions, interfering with signal transduction from receptor sites to the nucleus. I doubt the effects of alkalization would end at 5-ht receptor, it would probably be much further reaching.

These two papers may be of interest:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3923155/
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0036894

I think focusing on epigenetics is a bit of a waste of time. The whole point of epigenetics is that it introduces plasticity into the genome, meaning any epigenetic change can be changed again. Epigenetic changes are the result of environmental pressures, so it's a waste of time to think about them, they are only responsive agents, not primary actors on their own. My guess is that in the future we will know how to predict some epigenetic changes based on the overall state of the system/individual. So we may as well focus on the state of the system because that is what will more easily translate to figuring out how to alter the environment for the benefit of the individual.

 

[namaste]

Can you think of any mechanism by which metabolic alkalosis might cause changes in serotonin receptor (5-HT) density, or any other neurotransmitter receptor density for that matter? I've read studies that point toward this (density) being an issue in people who take SSRI's and the hypothesized cause was epigenetic changes. This was what the PSSD community was focused on for years, similar to how PFS folks were hyper-focused on 5-AR. What has never made sense to me though is how some people come down with these "conditions" within days of starting a medication. I don't think that can be explained by genetic changes.

This is just a guess, as in, I am really pulling this out of my ass and what I'm saying should be taken as a grain of salt.

I think extracellular alkalosis would interfere with electric signalling between neurons, while intracellular alkalosis would interfere with signal transduction pathways that rely on coulomb interactions, interfering with signal transduction from receptor sites to the nucleus. I doubt the effects of alkalization would end at 5-ht receptor, it would probably be much further reaching.

These two papers may be of interest:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3923155/
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0036894

I think focusing on epigenetics is a bit of a waste of time. The whole point of epigenetics is that it introduces plasticity into the genome, meaning any epigenetic change can be changed again. Epigenetic changes are the result of environmental pressures, so it's a waste of time to think about them, they are only responsive agents, not primary actors on their own. My guess is that in the future we will know how to predict some epigenetic changes based on the overall state of the system/individual. So we may as well focus on the state of the system because that is what will more easily translate to figuring out how to alter the environment for the benefit of the individual.

I appreciate the insight.

I found this study to be interesting, suggesting that there might be a link between progesterone and the SERT pathway: https://www.ncbi.nlm.nih.gov/pubmed/21481100

The study I was referring to in my post can be found here: https://www.medscape.com/viewarticle/753055

Two separate groups have investigated SSRI-induced changes in 5-HTT density in various regions of the adolescent rat brain following chronic SSRI administration. In contrast to the often-found decrease or null effect on 5-HTT binding density observed in adults, both studies report regional increases in 5-HTT binding in their younger cohort.

Interestingly, Wegerer et al. provide evidence that the regional increases in 5-HTT density endure into adult life,[105] in contrast to the rapid recovery of SSRI-induced 5-HTT downregulation in adults.[119] Lasting changes in 5-HTT may explain the increases in anxiety-like behavior and sexual dysfunction observed in adult rats that have been treated with SSRIs during adolescence

Could this explain why there are so few people over 35 or 40 on the various PSSD forums I've frequented over the years?

Unsurprisingly, there are indications that antidepressant treatment during adolescence may cause lasting perturbations in normal developmental processes, altering dendritic spine development and synaptic outgrowth. For example, chronic treatment of rats with fluoxetine from P21 until P42 prevented the normal age-related increase in dendritic spine density in the CA1 region of the hippocampus.

The question is: are these changes permanent, or persistent? If it is the latter, what is keeping things stuck? For my own sake, I'm hoping the explanation is metabolic in nature.

 

[barbaar]

Can you think of any mechanism by which metabolic alkalosis might cause changes in serotonin receptor (5-HT) density, or any other neurotransmitter receptor density for that matter? I've read studies that point toward this (density) being an issue in people who take SSRI's and the hypothesized cause was epigenetic changes. This was what the PSSD community was focused on for years, similar to how PFS folks were hyper-focused on 5-AR. What has never made sense to me though is how some people come down with these "conditions" within days of starting a medication. I don't think that can be explained by genetic changes.

This is just a guess, as in, I am really pulling this out of my ass and what I'm saying should be taken as a grain of salt.

I think extracellular alkalosis would interfere with electric signalling between neurons, while intracellular alkalosis would interfere with signal transduction pathways that rely on coulomb interactions, interfering with signal transduction from receptor sites to the nucleus. I doubt the effects of alkalization would end at 5-ht receptor, it would probably be much further reaching.

These two papers may be of interest:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3923155/
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0036894

I think focusing on epigenetics is a bit of a waste of time. The whole point of epigenetics is that it introduces plasticity into the genome, meaning any epigenetic change can be changed again. Epigenetic changes are the result of environmental pressures, so it's a waste of time to think about them, they are only responsive agents, not primary actors on their own. My guess is that in the future we will know how to predict some epigenetic changes based on the overall state of the system/individual. So we may as well focus on the state of the system because that is what will more easily translate to figuring out how to alter the environment for the benefit of the individual.

I appreciate the insight.

I found this study to be interesting, suggesting that there might be a link between progesterone and the SERT pathway: https://www.ncbi.nlm.nih.gov/pubmed/21481100

The study I was referring to in my post can be found here: https://www.medscape.com/viewarticle/753055

Two separate groups have investigated SSRI-induced changes in 5-HTT density in various regions of the adolescent rat brain following chronic SSRI administration. In contrast to the often-found decrease or null effect on 5-HTT binding density observed in adults, both studies report regional increases in 5-HTT binding in their younger cohort.

Interestingly, Wegerer et al. provide evidence that the regional increases in 5-HTT density endure into adult life,[105] in contrast to the rapid recovery of SSRI-induced 5-HTT downregulation in adults.[119] Lasting changes in 5-HTT may explain the increases in anxiety-like behavior and sexual dysfunction observed in adult rats that have been treated with SSRIs during adolescence

Could this explain why there are so few people over 35 or 40 on the various PSSD forums I've frequented over the years?

Unsurprisingly, there are indications that antidepressant treatment during adolescence may cause lasting perturbations in normal developmental processes, altering dendritic spine development and synaptic outgrowth. For example, chronic treatment of rats with fluoxetine from P21 until P42 prevented the normal age-related increase in dendritic spine density in the CA1 region of the hippocampus.

The question is: are these changes permanent, or persistent? If it is the latter, what is keeping things stuck? For my own sake, I'm hoping the explanation is metabolic in nature.

I've seen gbold mention serotonin a few times, in the context of PFS as well so it might be the same mechanism keeping us stuck.
I sure hope it is, and given that there are people who've recovered it's probably not permanent damage or anything. At least that's what I keep telling myself so I don't lose my sanity lol. [mention]gbolduev[/mention] any thoughts on this? I know you've been focussing on PFS mostly, but even an educated guess would be more than appreciated.

 

[namaste]

This is just a guess, as in, I am really pulling this out of my ass and what I'm saying should be taken as a grain of salt.

I think extracellular alkalosis would interfere with electric signalling between neurons, while intracellular alkalosis would interfere with signal transduction pathways that rely on coulomb interactions, interfering with signal transduction from receptor sites to the nucleus. I doubt the effects of alkalization would end at 5-ht receptor, it would probably be much further reaching.

These two papers may be of interest:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3923155/
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0036894

I think focusing on epigenetics is a bit of a waste of time. The whole point of epigenetics is that it introduces plasticity into the genome, meaning any epigenetic change can be changed again. Epigenetic changes are the result of environmental pressures, so it's a waste of time to think about them, they are only responsive agents, not primary actors on their own. My guess is that in the future we will know how to predict some epigenetic changes based on the overall state of the system/individual. So we may as well focus on the state of the system because that is what will more easily translate to figuring out how to alter the environment for the benefit of the individual.

I appreciate the insight.

I found this study to be interesting, suggesting that there might be a link between progesterone and the SERT pathway: https://www.ncbi.nlm.nih.gov/pubmed/21481100

The study I was referring to in my post can be found here: https://www.medscape.com/viewarticle/753055

Two separate groups have investigated SSRI-induced changes in 5-HTT density in various regions of the adolescent rat brain following chronic SSRI administration. In contrast to the often-found decrease or null effect on 5-HTT binding density observed in adults, both studies report regional increases in 5-HTT binding in their younger cohort.

Interestingly, Wegerer et al. provide evidence that the regional increases in 5-HTT density endure into adult life,[105] in contrast to the rapid recovery of SSRI-induced 5-HTT downregulation in adults.[119] Lasting changes in 5-HTT may explain the increases in anxiety-like behavior and sexual dysfunction observed in adult rats that have been treated with SSRIs during adolescence

Could this explain why there are so few people over 35 or 40 on the various PSSD forums I've frequented over the years?

Unsurprisingly, there are indications that antidepressant treatment during adolescence may cause lasting perturbations in normal developmental processes, altering dendritic spine development and synaptic outgrowth. For example, chronic treatment of rats with fluoxetine from P21 until P42 prevented the normal age-related increase in dendritic spine density in the CA1 region of the hippocampus.

The question is: are these changes permanent, or persistent? If it is the latter, what is keeping things stuck? For my own sake, I'm hoping the explanation is metabolic in nature.

I've seen gbold mention serotonin a few times, in the context of PFS as well so it might be the same mechanism keeping us stuck.
I sure hope it is, and given that there are people who've recovered it's probably not permanent damage or anything. At least that's what I keep telling myself so I don't lose my sanity lol. @gbolduev any thoughts on this? I know you've been focussing on PFS mostly, but even an educated guess would be more than appreciated.

I think I keep my sanity by remembering a few things:

1) There is a study showing that estrogen+DHT restored full sexual function in rats treated with antidepressants during adolescence
2) Plenty of people acquire PSSD/PFS within days of taking medication
3) Most adolescents who take these medications, including two of my siblings (granted, they started at a slightly later age than myself), don't ever develop long-term issues
4) Many people acquire PSSD outside of the adolescence window (12-20) I've been discussing

Barbaar, do you mind if I ask how old you were when you took an SSRI?

 

[barbaar]

[mention]namaste[/mention] I was on 10mg of citalopram for around 7 months back in 2015. I quit somewhere in the middle of November iirc, so I've been off them for 2 years now. I was 21 when I started.

 

[Shadow]

I can only give a superficial opinion, because Im not educated in the area, but, as matty said, I think that epigenetic changes are a waste of time in this case.

Problems post SSRIs are often divided in PSSD(sexual focused) and Protracted Withdrawal(all the rest), and they are treated like different things, I dont think that this is good, while it can pinpoint the issue it can mislead and make you run around circles too, and I think that this is what led to overlook at the 5ht receptors. If the serotonergic system plays a major role in this, my bet is that SERT is the problem.

But from all that I read, from anecdotes to researches, I still think that neurosteroids are the ones to blame, mainly the ones from 3a-HSD, Allopregnanolone alone can explain both sexual and non-sexual symptoms. The huge question is, why we are stuck? Alkalosis could be the answer.

I dont know if the things work like what I will say, so [mention]mattyb[/mention] feel free to correct me. [mention]gbolduev[/mention] 2 cents would be appreciated too.

SSRIs affects 3a-HSD, making it produce much more allopregnanolone by reducing 5a-DHP which is synthesized from progesterone. It is correct to say that the synthesis of all the steroids needed for Allo production should go up too, to keep allo production rolling?

Some of these steroids, allo included, are allosteric modulators of GABA-A receptors. So, if what I said holds true, imagine the production of allo returning to normal or even worse, with lower synthesis activity, the body will end up flooded with the other steroids and lacking allo, this should be enough to trigger some nasty cascading crap, doesnt it?

 

[Helen]

@Shadow

As you see you have high progesterone and high aldosterone. Progesterone bind to aldo receptor and blocks it hence low sodium.

Aldosterone increases potassium loss, thus low potassium. This is a fork, that you have here. You can retain sodium and potassium and you are in alkalosis and volume reduction.

This is why licorice root, Ella worked for PSSD I would assume. licorice root retains sodium, this lowers aldosterone, after you quit licorice, your renin axis is suppressed, aldo is low, and you feed potassium. Or the opposite, you block progesterone, this allows the body to retain sodium, aldo falls, then you raise potassium

Usually this is fixed by sodium chloride , potassium chloride IV, since they wont go in from the mouth. Since the retention is blocked.

Just get a ringer solution and do an IV, should fix you .

You see we are trying to fix alkalosis and so forth. But unfortunately alkalosis supports itself , since you get a fork like this. And you cant retain minerals from food.

That is why if no IV, then we have to use something that blocks either aldo, or progesterone.

I bet spiro, or ella is the fix for PSSD and especially your case.



Finasteride people have a different fork. HIGH progesterone, and high cortisol. which is basically the same, since cortisol activates aldosterone receptor. And most Fin people have alkalosis with volume expansion as oppose to yours with volume reduction

 

[Jaxx]

Why would ella stick here? (It didnt seem to with others)

 

[Helen]

it did stick. with many people

But lets say you do spiro. You take spiro , while you are on it. you eat tons of potassium. This will retain potassium from food. Then you stop spiro and right away eat tons of sodium . and this will retain sodium

Another way, is just go and get an IV , potassium chloride sodium chloride, HCL. FIXED in one day.

There is a fork here and body cant retain sodium no potassiu, thus goes into alkalosis with volume depletion.

And those minerals cant be retained from food since hormones are blocking them

 

[Shadow]

[mention]gbolduev[/mention] thanks for the help!

I will see if I can get an IV done! I think that will be easier than buying Ella hehe!

 

[Canari]

What is the hen and what is the egg?!!

And those minerals cant be retained from food since hormones are blocking them

I thought we would act upon hormones with minerals! If minerals cannot be retained form food, same from supps? Or do you mean we have to give the body more than the dose coming from food?

 

[Area-1255]

@Shadow, did you try Cyproheptadine + L-Lysine to bring the Aldosterone down?