Excess DHT and P.E.

[PeakT]

I spent a couple of years trying to figure out the MTHRF test results and spent a couple of thousand dollars with 3 different doctors and finally came to the conclusion that although they have some answers such as why something is wrong, they are yet to find solutions that fixes them without causing other side effects... so I let it go for now

Here is what you don't want to ignore:  high homocysteine from MTHFR or any other reason.  This will likely lower nitric oxide and lead to heart disease:

http://www.peaktestosterone.com/Erectile_Dysfunction_High_Homocysteine

MTHFR can cause a host of issues and, like you said, they are just getting their arms around treatment for methylation issues.  But I do know you don't want high homocysteine.  So pull that.  Imo every man should do that fairly regularly.  It's a pretty cheap test anyway.

This is great info, but honestly I don't have ED my problem is PE so I think it may be different mechanism.

You want to pull homocysteine anyway.  Getting an erection is not proof that you are not building up plaque.  In addition, there is considerable evidence that homocysteine causes/accelerates some cancers. 

And here is the thing that I think you may be missing:  if you are high with homocysteine, you probably are not taking enough of your methylfolate or some other B vitamin.

Kudos for having good erectile strength, but it's just a matter of time if you are slowly builidng up plaque.  And reversing plaque, while doable, is non-trivial and takes a lot of work. 

Hey a q for you:  do you have the dual homozygous MTHFR?  Sorry if you answered that already.

[Kierkegaard]

PE is often driven by excess norepinephrine.  How's your thyroid?

My thyroid is okay as far as tests but you are right on as far as excess norepinephrine,
I have the COMT+ gene and it causes excess norepinephrine,
Any suggestions on how I can lower it?
I use magnesium at night which has been great to promote sleep but has not done anything for PE

Oh wow, I didn't even think of that connection!  I'll be looking into genetic testing. 

As for lowering norepinephrine, it's hard to find good substances, but from what I can tell l-theanine and rhodiola are known to lower norepinephrine.  I'm taking an adrenal supplement called "Adrenal Health" by Gaia, and it's been the only supplement that has made my erections and libido better, indicating lowered NE (it has rhodiola and ashwagandha). 

http://www.lifeextension.com/magazine/2011/3/the-chemistry-of-calm/Page-01

The above link has inositol, omega-3s, and n-acecyl-cysteine (NAC) as other supplements.  I'm currently thinking my problems are caused by excess norepinephrine (though I don't have PE, except every now and then).  Theoretically, if you have lower than optimal cortisol, this would mean higher norepinephrine, given that cortisol is what lowers the stress response (including NE, which is what starts it via the locus coeruleus in the brain stem).

The reason I mentioned thyroid is that hypothyroidism involves elevated levels of norepinphrine (lots of people, including doctors, don't know this).  Do you have your thyroid numbers?  I think shooting for the upper fourth of the range for free T3 is the way to go, so there's usually room for improvement in most people.  Gaia makes another supplement for thyroid that I'll be asking my doc about in a few days, so that might be enough to give it a bump. 

ETA: how's your sleep and stress level, btw?  Any chance you get brain fog?

Wow, I had no idea there is a correlation between Cortisol and Norepenephrine.... I have high Cortisol too, no wonder
when I take P.S. to lower Cortisol I get really bad headaches and anger..... It's probably jacking up my Norepenephrine...
This is been a real problem for me... I wish there was a supplement that would lower each one without effecting the other.

Out of the supplements that you mentioned I have pretty much tried all (Ashwaghanda, Rohdiola, Omega-3 and NAC) and the first 3 cure my P.E. but give me anger and headaches...

As far as Thyroid, here are my numbers:
TSH 2.58 (Range 0.45-4.5)
Pregnenolone  97
T4 = 1.39 (range 0.82-1.77)
Reverse T3 14.3 (range 9.2- 24.1)

So my thyroid is in check.

Those numbers look good, but have you had a free T3 number pulled?  It's probably fine, but it's also the most important thyroid number you can get.

I don't have Free T3 on Blood Plasma but I do have it from my 24 hour urine test:
649 (300-1100)

Your post has really made me think though, if lowering Cortisol increases Norepenephrine then that's exactly my problem... I try to lower Cortisol and my Norepenephrine shoots up! That's pretty abnormal.

I don't have experience with urinary free T3, but if that translates smoothly to serum levels, that's just barely below the middle.  I think it would be worth it to get a blood level pulled, and if it's below 3.3 pg/ml or so you should try and find a doc to put you on a trial of Armour or T3/T4, or give a good thyroid glandular or supplement a shot.

If you have less cortisol to reign in norepinephrine, then this means that for each burst of norepinephrine, NE shouldn't be higher than if you had higher cortisol, but it should decrease at a slower rate.  Which means that with multiple stressors (i.e., real life), your NE will pile up faster with lower cortisol than higher cortisol.  Dr. Mariano talks about a positive feedback loop with NE:

"Norepinephrine increases adrenal hormone production by stimulating the release of Corticotropin Releasing Hormone (CRH) from the hypothalamus. CRH then increases Adrenocorticotropic hormone (ACTH) release from the pituitary. ACTH then travels to the adrenal glands to stimulate steroid hormone production - the primary one being Cortisol.

Norepinephrine also triggers a signal that goes through the sympathetic nervous system nerves which travel parallel to the spine. These nerves then trigger the production of Norepinephrine and Epinephrine from the center of the Adrenal Gland. The adrenal gland, itself, is an enlarged ganglion of the sympathetic nervous system.

What is interesting about CRH is that it travels not only to the pituitary to stimulate ACTH production, but it also travels to the rest of the brain, where it stimulates Norepinephrine release.

CRH thus participates in a positive feedback loop - where increased Norepinephrine results in increased CRH - which then increases Norepinephrine release. If this positive feedback loop is not stopped, the stress signal is magnified repeatedly. If not curtailed, this stress signal snowballs and causes panic attacks. If it is stopped, then the stress signal is stopped."

He goes on to say that it's cortisol that stops this positive feedback loop, because cortisol loops back up to the hypothalamus and tells it to put the breaks on CRH.  I wouldn't recommend *increasing* cortisol without a doctor's supervision, but it would be worth considering to get a 4x salivary cortisol test and see where your levels are at.

Funny you should say that, I actually did get a 4x salivary cortisol test
It showed higher than normal in the morning , Very high at noon, then crashed at night and even lower at midnight.
I was just listening to a radio show which was talking about Cortisol and NE, and the Dr. was saying in some patients it may be that the relationship between Cortisol and NE needs to be managed, for example in my case I would think I need to lower my cortisol in the morning but later in the afternoon when it starts to crash I need to up it a little ... I sure wish there was a supplement that could pull the swings in a little and not have high and low crashes (in my case)

Elevated cortisol likely means elevated NE; NE is what starts the stress cascade, and cortisol is what dampens it (when both are elevated this means there's a continued stressor).  So if you want to lower cortisol, look into lowering NE, otherwise lowering cortisol in the presence of elevated NE means less brakes to turn down NE (and epinephrine, etc.), leading to increased accumulation of NE as the stressor(s) continue.  That's why I think getting your thyroid optimized (if it needs to be) could be a great way of lowering NE (and therefore perhaps raising dopamine as well as serotonin), which would also normalize cortisol, and hopefully take care of your symptoms. 

[Boxcar]

SSRI antidepressants are really really good treatments for PE.  Sometimes too good -- with the standard dosage for Zoloft, I can't ejaculate at all -- so you would have to find the exact dose that works best for you.  You can take these meds daily, but you might find that a single pill works for you (although it could take 4-8 hours to begin working), letting you take it based on your evening plans.  There is a short-acting SSRI that can be taken just like viagra, but it is not yet approved by the FDA.

I don't doubt the role of norepinephrine.  The antidepressants that act the most strongly on norepinephrine are the least likely to delay or prevent ejaculation. Of course, SSRI's have no effect on norepinephrine, which probably explains why they are such great treatments for PE.

Most urologists will know about all this.  Here's some reading on the subject:

https://www.auanet.org/education/guidelines/premature-ejaculation.cfm

There are also topical anesthetics that can be used (including condoms impregnated with them), but I would want to know if there is any potential for them to effect my partner.

[Kierkegaard]

SSRI antidepressants are really really good treatments for PE.  Sometimes too good -- with the standard dosage for Zoloft, I can't ejaculate at all -- so you would have to find the exact dose that works best for you.  You can take these meds daily, but you might find that a single pill works for you (although it could take 4-8 hours to begin working), letting you take it based on your evening plans.  There is a short-acting SSRI that can be taken just like viagra, but it is not yet approved by the FDA.

I don't doubt the role of norepinephrine.  The antidepressants that act the most strongly on norepinephrine are the least likely to delay or prevent ejaculation. Of course, SSRI's have no effect on norepinephrine, which probably explains why they are such great treatments for PE.

Most urologists will know about all this.  Here's some reading on the subject:

https://www.auanet.org/education/guidelines/premature-ejaculation.cfm

There are also topical anesthetics that can be used (including condoms impregnated with them), but I would want to know if there is any potential for them to effect my partner.

I wonder if SSRIs reduce sensation through reducing dopamine...

[Peyt]

I spent a couple of years trying to figure out the MTHRF test results and spent a couple of thousand dollars with 3 different doctors and finally came to the conclusion that although they have some answers such as why something is wrong, they are yet to find solutions that fixes them without causing other side effects... so I let it go for now

Here is what you don't want to ignore:  high homocysteine from MTHFR or any other reason.  This will likely lower nitric oxide and lead to heart disease:

http://www.peaktestosterone.com/Erectile_Dysfunction_High_Homocysteine

MTHFR can cause a host of issues and, like you said, they are just getting their arms around treatment for methylation issues.  But I do know you don't want high homocysteine.  So pull that.  Imo every man should do that fairly regularly.  It's a pretty cheap test anyway.

This is great info, but honestly I don't have ED my problem is PE so I think it may be different mechanism.

You want to pull homocysteine anyway.  Getting an erection is not proof that you are not building up plaque.  In addition, there is considerable evidence that homocysteine causes/accelerates some cancers. 

And here is the thing that I think you may be missing:  if you are high with homocysteine, you probably are not taking enough of your methylfolate or some other B vitamin.

Kudos for having good erectile strength, but it's just a matter of time if you are slowly builidng up plaque.  And reversing plaque, while doable, is non-trivial and takes a lot of work. 

Hey a q for you:  do you have the dual homozygous MTHFR?  Sorry if you answered that already.

I do not

[Peyt]

SSRI antidepressants are really really good treatments for PE.  Sometimes too good -- with the standard dosage for Zoloft, I can't ejaculate at all -- so you would have to find the exact dose that works best for you.  You can take these meds daily, but you might find that a single pill works for you (although it could take 4-8 hours to begin working), letting you take it based on your evening plans.  There is a short-acting SSRI that can be taken just like viagra, but it is not yet approved by the FDA.

I don't doubt the role of norepinephrine.  The antidepressants that act the most strongly on norepinephrine are the least likely to delay or prevent ejaculation. Of course, SSRI's have no effect on norepinephrine, which probably explains why they are such great treatments for PE.

Most urologists will know about all this.  Here's some reading on the subject:

https://www.auanet.org/education/guidelines/premature-ejaculation.cfm

There are also topical anesthetics that can be used (including condoms impregnated with them), but I would want to know if there is any potential for them to effect my partner.

I wonder if SSRIs reduce sensation through reducing dopamine...

Interesting you mention SSRIs
A few years ago I was going through some emotional problems and a Doctor prescribed Zoloft
It never did anything for my depression but I was a walking hard on! lol It got to the point where my gf at the time could not
take it any more....
But I constantly had to take Tylonal because it was giving me severe headaches.
SSRI's are also vasoconstrictors and so they constrict the blood vessels. Besides that, Zoloft constantly gave me constipation so I stopped it after a couple of months.
Ashwaghanda works the same way but in a milder fashion..

[PeakT]

I do not

Got it.  Well, I think the less severe forms "just" lower enzyme activity by like 7% or something.  Still not a bad idea to pull it tho to play it safe imo...

[Boxcar]

SSRI antidepressants are really really good treatments for PE.  Sometimes too good -- with the standard dosage for Zoloft, I can't ejaculate at all -- so you would have to find the exact dose that works best for you.  You can take these meds daily, but you might find that a single pill works for you (although it could take 4-8 hours to begin working), letting you take it based on your evening plans.  There is a short-acting SSRI that can be taken just like viagra, but it is not yet approved by the FDA.

I don't doubt the role of norepinephrine.  The antidepressants that act the most strongly on norepinephrine are the least likely to delay or prevent ejaculation. Of course, SSRI's have no effect on norepinephrine, which probably explains why they are such great treatments for PE.

Most urologists will know about all this.  Here's some reading on the subject:

https://www.auanet.org/education/guidelines/premature-ejaculation.cfm

There are also topical anesthetics that can be used (including condoms impregnated with them), but I would want to know if there is any potential for them to effect my partner.

I wonder if SSRIs reduce sensation through reducing dopamine...

Could be, although I have also read that there is a specific seratonin receptor that is thought to be involved.  Of course any med that effects dopamine could also reduce libido.