Change in Erectile Function after Stopping Clomid and Pramipexole

[SacToSD]

I wanted to post this and seek advice/input from all of you on my current situation.

I attempted a clomiphene restart lasting 10 weeks at 50 mg/day, and during that time, I was treating my erectile dysfunction with pramipexole and cialis.

I got off of clomiphene and pramipexole 1 month ago.

During the 1st week off of clomiphene and pramipexole, I was having good erections taking 5 mg of cialis, per day.

Now, 1 month later, I am having consistent difficulties achieving erections with 20 mg cialis, per day.

However, I have started having morning erections these last 2 weeks, after not having them for over 1 year.

My lab work on August 1st, immediately after stopping clomiphene and pramipexole, was:

Total Testosterone: 875
Estrogen 48.9 (10-50, 20-30 recommended)
Prolactin 14.8 (4-15)
LH 6.5 (~5-15)
FSH 2.4 (~5-15)

I would like to order a new panel of labs, and want to include SHBG and DHT, in addition to an ultra-sensitive estradiol, free and total testosterone, prolactin, LH, and FSH.

I would like to not become dependent on TRT if at all possible.

Thanks

 

[zkt]

I wanted to post this and seek advice/input from all of you on my current situation.

I attempted a clomiphene restart lasting 10 weeks at 50 mg/day, and during that time, I was treating my erectile dysfunction with pramipexole and cialis.

I got off of clomiphene and pramipexole 1 month ago.

During the 1st week off of clomiphene and pramipexole, I was having good erections taking 5 mg of cialis, per day.

Now, 1 month later, I am having consistent difficulties achieving erections with 20 mg cialis, per day.

However, I have started having morning erections these last 2 weeks, after not having them for over 1 year.

My lab work on August 1st, immediately after stopping clomiphene and pramipexole, was:

Total Testosterone: 875
Estrogen 48.9 (10-50, 20-30 recommended)
Prolactin 14.8 (4-15)
LH 6.5 (~5-15)
FSH 2.4 (~5-15)

I would like to order a new panel of labs, and want to include SHBG and DHT, in addition to an ultra-sensitive estradiol, free and total testosterone, prolactin, LH, and FSH.

I would like to not become dependent on TRT if at all possible.

Thanks

Not sure what I could advise. How do you feel the prami effected you? The effect of the parasympathetic nervous system on wood is greatly under-sestimated around here.

 

[SacToSD]

Not sure what I could advise. How do you feel the prami effected you? The effect of the parasympathetic nervous system on wood is greatly under-sestimated around here.

The pramipexole didn't seem to have a noticeable effect in terms of libido or erectile function. I used it for 4 months at 0.5 mg/day, in one dose, in the morning, after titrating up for 2 weeks.

I tried intermittent doses of pramipexole during the second week of august when I noticed the beginnings of increased erectile dysfunction, and to my dismay, my normal dose made me a zombie. This would seem to indicate that my dopaminergic neurons had upregulated, as evidenced by my reduced tolerance.

Since August 6th I have been on Wellbutrin, aka burpopion, a norepinephrine/dopamine reuptake inhibitor. I started this at the request of my primary care physician to combat the extreme depression I was experiencing after getting off of clomiphene and pramipexole.

If what I'm thinking is correct, my norepinephrine is high, my dopamine is low, and my estrogen is high or low.

Here's my research.

Premise: High norephinephrine can cause ED
Support:
"High norepinephrine levels (or relatively high norepinephrine levels compared to the other neurotransmitters) can cause erectile dysfunction (chronic or otherwise).

Norepinephrine is the primary signal in the brain for stress. It is a excitatory neurotransmitter. It keeps a person awake. It can help improve attention. It causes an increase in ACTH production, which then drives adrenal hormone production. A spike of norepinephrine triggers orgasm/ejaculation in men. Norepinephrine is the primary chemical messenger of the sympathetic nervous system (the system that responds to fight-or-flight, stressful situations).

When a person has chronically high norepinephrine, it can cause anxiety or irritability. It can eventually cause adrenal depletion, fatigue, or frank adrenal insufficiency. This can then lead to erectile dysfunction, loss of libido, sexual dysfunction.

To keep norepinephrine levels high, the brain may have to lower the production of dopamine, which can lead to loss of libido and erectile dysfunction. Lowered dopamine production, itself, can reduce testosterone production (though high norepinephrine can raise it - causing a wash if the balance is maintained). Lower testosterone can lead to erectile dysfunction. Lowered testosterone production can lead to insulin resistance and further metabolic cascades that can cause erectilve dysfunction and lack of libido.

Chronically high norepinephrine production in the absence of other neurotransmitter, hormone, cytokine problems, can lead to premature ejaculation - since it doesn't take much to get a higher norepinephrine spike to trigger ejaculation.

Chronically high norepinephrine can raise blood pressure. This leads to long-term consequences, including renal dysfunction and erectile dysfunction.

What can be done is to either directly address the high norepinephrine production (e.g. with a serotonergic, anxiolytic, mood stabilizing, beta-blocking medication or others), or treat the consequences - such as adrenal fatigue (where the higher cortisol levels from treatment can help reduce via a feedback loop in the brain to lower CRH production, to lower norepinephrine levels), or treat the underlying cause of higher norepinephrine levels (which can include psychological stress, trauma, mental illness, thyroid dysfunction, hypogonadism, insulin resistance, infection or other chronic physical illness, etc.). In a way, a global treatment once assessment occurs, needs to be done. I usually don't see a single substance (drug, hormone, or nutrient, or even herb) working. There are many entrypoints to dysfunction when a single hormone/neurotransmitter is out of whack in function. What I usually see are multiple hormone/neurotransmitter/cytokine problems as a consequence.

https://thinksteroids.com/community/threads/134249500

_____________________________________________________________________

Premise: Impaired Nervous System Function re: norepinephrine
Support:
"OBJECTIVES:
To examine and compare the courses of norepinephrine (NE) and epinephrine (E) plasma levels in the systemic and cavernous blood taken during different penile conditions from healthy men and a group of patients with erectile dysfunction (ED). Knowledge concerning the neurophysiology of penile erection has improved tremendously during the past two decades. However, only few in vivo studies on human peripheral neurotransmission have been carried out to date.

METHODS:
Fifty-three healthy adult male subjects and 47 patients with ED of different etiologies were exposed to erotic stimuli to elicit penile tumescence and, in the group of healthy subjects, rigidity. Whole blood was simultaneously aspirated from the corpus cavernosum and the cubital vein during different penile conditions. Plasma levels of NE and E were determined by means of a radioimmunoassay.

RESULTS:
In the healthy subjects, a significant reduction of NE in cavernous plasma was detected from flaccidity (362 +/- 173 pg/mL) to rigidity (248 +/- 122 pg/mL), followed by an increase in the detumescence phase (336 +/- 199 pg/mL). Changes in NE levels in the peripheral plasma were less pronounced. Cavernous E levels significantly increased from flaccidity (47 +/- 41 pg/mL) to tumescence (130 +/- 106 pg/mL) and dropped from rigidity (113 +/- 67 pg/mL) to detumescence (76 +/- 57 pg/mL). The course of systemic E plasma levels was similar to that in the cavernous blood. In contrast, median NE levels in the systemic and cavernous blood of the ED group slightly increased from flaccidity to tumescence (from 199 +/- 88 pg/mL to 210 +/- 99 pg/mL and from 273 +/- 140 pg/mL to 278 +/- 118 pg/mL, respectively).

CONCLUSIONS:
In healthy men, penile erection is accompanied by a reduction of NE in the cavernous blood and a rise in E levels in the peripheral and cavernous blood. That NE levels in the cavernous and systemic blood increase during sexual arousal in patients with ED might be an indication of a somatic dysregulation in sympathetic transmission or alterations of NE reuptake mechanisms as a cause of impaired erectile function.

Cavernous and systemic plasma levels of norepinephri... [Urology. 2002] - PubMed - NCBI

Urology. 2002 Feb;59(2):281-6.
Becker AJ, Uckert S, Stief CG, Scheller F, Knapp WH, Hartmann U, Jonas U.

_______________________________________________________________

Conclusions:

If my morning erections serve to indicate a proper testosterone:estrogen ratio, and I'm getting morning erections consistently, then my testosterone:estrogen ratio is good.

If I'm failing to achieve good erections when desired, then that is a function of the nervous system, since we've eliminated the testosterone:estrogen ratio as a culprit.

My use of Wellbutrin, a norepinephrine reuptake inhibitor, may be contributing to my erectile dysfunction, since "alterations of NE reuptake mechanisms [can be]... a cause of impaired erectile function," (Becker, et all).


Planned course of action:
1. Stop taking Wellbutrin/bupropion
2. Monitor morning erections
3. Get blood test in 1 week for: total and free testosterone, ultra-sensitive estradiol (E2), prolactin, DHT, SHBG, LH, FSH, norepinephrine, dopamine.

 

[SacToSD]

More support for increased norepinephrine hypothesis:

"In the flaccid state of the penis, frequent release of norepinephrine from sympathetic nerves contracts the arteries in the penis and also contracts the smooth muscles of the corpora cavernosum. Therefore, in the normal state, norepinephrine keeps the penis soft. A relative predominance of norepinephrine-induced contraction over nitric oxide-mediated relaxation may contribute to erectile dysfunction. Two amino acids phenylalanine and tyrosine, sold as supplements, are converted into dopamine. Dopamine, in turn, is converted into norepinephrine, and then epinephrine. The ingestion of these amino acids elevates dopamine and norepinephrine levels, and hence will lead to alertness and mood elevation and increased sexual interest. However, excess amounts of norepinephrine and epinephrine may make it difficult to have erections. In addition, high amounts raise blood pressure, increase heart rate, and cause anxiety, irritability, and insomnia. Yohimbe, the natural sex booster from Africa, facilitates erections by blocking the inhibitory action of norepinephrine on the penis."

Subjective support for norepinephrine hypothesis:
Over the last few weeks, since this whole problem has started, I've noticed that I've had increased shrinkage of the penis, as in, it's smaller than normal in the flaccid state, feels like I just got out of the pool. This would be symptomatic of high norepinephrine levels.

Plan: try using yohimbe.

 

[zkt]

Damn! Youve been doing your homework !
One problem is that serum levels dont reflect local brain levels of neurotransmitters, NE DA,etc.
To further complicate the matter, certain neurons in the brain secrete certain neurotransmitters and whose effect is only local. So you cant alter brain chemistry by changing systemic levels.
Abd the neurotransmiters do different things in different areas of the brain. Not th mention the many subsets of the basic receptors, The opiate receptors alone have 12 subclasses each having a bit different effect.
Bupropion is well known to not cause sexual side effects. To the contrary it often increases libido.
I totally agree that T and E must be in the proper ratio for the wood to work. For an erection to happen nitric oxide must increase to cause vasodialation in the cavernous vessels. NE is a vasoconstrictor via action on the Alpha2 receptors in the vascular endothelium. Its a very complicated mess and I fear that you are oversimplifing the system. But I hope you are in the right track.

The pramipexole didn't seem to have a noticeable effect in terms of libido or erectile function. I used it for 4 months at 0.5 mg/day, in one dose, in the morning, after titrating up for 2 weeks.

I tried intermittent doses of pramipexole during the second week of august when I noticed the beginnings of increased erectile dysfunction, and to my dismay, my normal dose made me a zombie. This would seem to indicate that my dopaminergic neurons had upregulated, as evidenced by my reduced tolerance.

Since August 6th I have been on Wellbutrin, aka burpopion, a norepinephrine/dopamine reuptake inhibitor. I started this at the request of my primary care physician to combat the extreme depression I was experiencing after getting off of clomiphene and pramipexole.

If what I'm thinking is correct, my norepinephrine is high, my dopamine is low, and my estrogen is high or low.

Here's my research.

Premise: High norephinephrine can cause ED
Support:
"High norepinephrine levels (or relatively high norepinephrine levels compared to the other neurotransmitters) can cause erectile dysfunction (chronic or otherwise).

Norepinephrine is the primary signal in the brain for stress. It is a excitatory neurotransmitter. It keeps a person awake. It can help improve attention. It causes an increase in ACTH production, which then drives adrenal hormone production. A spike of norepinephrine triggers orgasm/ejaculation in men. Norepinephrine is the primary chemical messenger of the sympathetic nervous system (the system that responds to fight-or-flight, stressful situations).

When a person has chronically high norepinephrine, it can cause anxiety or irritability. It can eventually cause adrenal depletion, fatigue, or frank adrenal insufficiency. This can then lead to erectile dysfunction, loss of libido, sexual dysfunction.

To keep norepinephrine levels high, the brain may have to lower the production of dopamine, which can lead to loss of libido and erectile dysfunction. Lowered dopamine production, itself, can reduce testosterone production (though high norepinephrine can raise it - causing a wash if the balance is maintained). Lower testosterone can lead to erectile dysfunction. Lowered testosterone production can lead to insulin resistance and further metabolic cascades that can cause erectilve dysfunction and lack of libido.

Chronically high norepinephrine production in the absence of other neurotransmitter, hormone, cytokine problems, can lead to premature ejaculation - since it doesn't take much to get a higher norepinephrine spike to trigger ejaculation.

Chronically high norepinephrine can raise blood pressure. This leads to long-term consequences, including renal dysfunction and erectile dysfunction.

What can be done is to either directly address the high norepinephrine production (e.g. with a serotonergic, anxiolytic, mood stabilizing, beta-blocking medication or others), or treat the consequences - such as adrenal fatigue (where the higher cortisol levels from treatment can help reduce via a feedback loop in the brain to lower CRH production, to lower norepinephrine levels), or treat the underlying cause of higher norepinephrine levels (which can include psychological stress, trauma, mental illness, thyroid dysfunction, hypogonadism, insulin resistance, infection or other chronic physical illness, etc.). In a way, a global treatment once assessment occurs, needs to be done. I usually don't see a single substance (drug, hormone, or nutrient, or even herb) working. There are many entrypoints to dysfunction when a single hormone/neurotransmitter is out of whack in function. What I usually see are multiple hormone/neurotransmitter/cytokine problems as a consequence.

https://thinksteroids.com/community/threads/134249500

_____________________________________________________________________

Premise: Impaired Nervous System Function re: norepinephrine
Support:
"OBJECTIVES:
To examine and compare the courses of norepinephrine (NE) and epinephrine (E) plasma levels in the systemic and cavernous blood taken during different penile conditions from healthy men and a group of patients with erectile dysfunction (ED). Knowledge concerning the neurophysiology of penile erection has improved tremendously during the past two decades. However, only few in vivo studies on human peripheral neurotransmission have been carried out to date.

METHODS:
Fifty-three healthy adult male subjects and 47 patients with ED of different etiologies were exposed to erotic stimuli to elicit penile tumescence and, in the group of healthy subjects, rigidity. Whole blood was simultaneously aspirated from the corpus cavernosum and the cubital vein during different penile conditions. Plasma levels of NE and E were determined by means of a radioimmunoassay.

RESULTS:
In the healthy subjects, a significant reduction of NE in cavernous plasma was detected from flaccidity (362 +/- 173 pg/mL) to rigidity (248 +/- 122 pg/mL), followed by an increase in the detumescence phase (336 +/- 199 pg/mL). Changes in NE levels in the peripheral plasma were less pronounced. Cavernous E levels significantly increased from flaccidity (47 +/- 41 pg/mL) to tumescence (130 +/- 106 pg/mL) and dropped from rigidity (113 +/- 67 pg/mL) to detumescence (76 +/- 57 pg/mL). The course of systemic E plasma levels was similar to that in the cavernous blood. In contrast, median NE levels in the systemic and cavernous blood of the ED group slightly increased from flaccidity to tumescence (from 199 +/- 88 pg/mL to 210 +/- 99 pg/mL and from 273 +/- 140 pg/mL to 278 +/- 118 pg/mL, respectively).

CONCLUSIONS:
In healthy men, penile erection is accompanied by a reduction of NE in the cavernous blood and a rise in E levels in the peripheral and cavernous blood. That NE levels in the cavernous and systemic blood increase during sexual arousal in patients with ED might be an indication of a somatic dysregulation in sympathetic transmission or alterations of NE reuptake mechanisms as a cause of impaired erectile function.

Cavernous and systemic plasma levels of norepinephri... [Urology. 2002] - PubMed - NCBI

Urology. 2002 Feb;59(2):281-6.
Becker AJ, Uckert S, Stief CG, Scheller F, Knapp WH, Hartmann U, Jonas U.

_______________________________________________________________

Conclusions:

If my morning erections serve to indicate a proper testosterone:estrogen ratio, and I'm getting morning erections consistently, then my testosterone:estrogen ratio is good.

If I'm failing to achieve good erections when desired, then that is a function of the nervous system, since we've eliminated the testosterone:estrogen ratio as a culprit.

My use of Wellbutrin, a norepinephrine reuptake inhibitor, may be contributing to my erectile dysfunction, since "alterations of NE reuptake mechanisms [can be]... a cause of impaired erectile function," (Becker, et all).


Planned course of action:
1. Stop taking Wellbutrin/bupropion
2. Monitor morning erections
3. Get blood test in 1 week for: total and free testosterone, ultra-sensitive estradiol (E2), prolactin, DHT, SHBG, LH, FSH, norepinephrine, dopamine.

 

[SacToSD]

Damn! Youve been doing your homework !

Bupropion is well known to not cause sexual side effects. To the contrary it often increases libido.
I totally agree that T and E must be in the proper ratio for the wood to work. For an erection to happen nitric oxide must increase to cause vasodialation in the cavernous vessels. NE is a vasoconstrictor via action on the Alpha2 receptors in the vascular endothelium. Its a very complicated mess and I fear that you are oversimplifing the system. But I hope you are in the right track.

It does seem oversimplified, yes. The reason I presumed that norepinephrine is high is due to the conversion of dopamine to norepinephrine, and the potential effects of using a dopamine agonist like pramipexole and the type of effects it might cause. In other words, using pramipexole may have downregulated my dopaminergic neurons, and now that I'm off of pramipexole, more dopamine is being produced since there is less dopaminergic activity at the neurons since there are fewer receptors. That creates an excess of dopamine, and therefore an increase in norepinephrine, atypical of the results people using Wellbutrin experience re: sexual side effects, or lack thereof.

I may be on the wrong track, but I'm on a track, regardless. I'm going to try some yohimbe, since that seems to negate the effects of norepinephrine in regard to erectile function. This should either support or refute my hypothesis.

Thanks for the feedback, so far.

 

[zkt]

What you say does sound reasonable. Keep us appraised of your experiments.

 

[4-chloro]

Receptor down regulation from only 500mcg of pramipexole is highly unlikely, and usually occurs from acute floods of neurotransmitters such as those caused by pyschotropic drugs like methamphetamine and MDMA. MDMA for example can cause serotonin receptor downregulation for 7 years after a single dose, as it releases the equivalent of 6 years of serotonin at once.

Pramipexole might cause your brain to produce less dopamine or upregulate it's oxidative proteins as it is essentially acquiring it exogenously from the mirapex.

Your elevated prolactin level could be a sign of this. It is also important to keep in mind that wellbutrin does not lower prolactin as it doesn't target the reuptake of a large enough percentage of dopamine receptors in the brain, it also however does not raise it. NE's effect on the dopamine transporter pump is statistically insignificant in most cases.

As stated before, this is all a summary of a largely complex process. It is not likely that NE alone can cause ED, but more in the ratio of NT's. Methamphetamine for example will cause a ~1200% increase in dopamine, and a ~500% increase in NE (thus raising TSH, LH, FSH and cortisol) but produces a wildly increased libido and sexual performance.

I would put money down that a low dose of Dextroamphetamine (Dexedrine) would significantly improve your case, and would help with Mirapex "withdrawal".

It would also be wise to address the prolactin and estradiol issue.

 

[SacToSD]

What you say does sound reasonable. Keep us appraised of your experiments.

Thanks, I will.

I don't like clutching at straws, but if I clutch at enough of them, maybe something will pan out.

I'm going in for a full blood panel on Monday or Tuesday.

Receptor down regulation from only 500mcg of pramipexole is highly unlikely, and usually occurs from acute floods of neurotransmitters such as those caused by pyschotropic drugs like methamphetamine and MDMA. MDMA for example can cause serotonin receptor downregulation for 7 years after a single dose, as it releases the equivalent of 6 years of serotonin at once.

Pramipexole might cause your brain to produce less dopamine or upregulate it's oxidative proteins as it is essentially acquiring it exogenously from the mirapex.

Your elevated prolactin level could be a sign of this. It is also important to keep in mind that wellbutrin does not lower prolactin as it doesn't target the reuptake of a large enough percentage of dopamine receptors in the brain, it also however does not raise it. NE's effect on the dopamine transporter pump is statistically insignificant in most cases.

As stated before, this is all a summary of a largely complex process. It is not likely that NE alone can cause ED, but more in the ratio of NT's. Methamphetamine for example will cause a ~1200% increase in dopamine, and a ~500% increase in NE (thus raising TSH, LH, FSH and cortisol) but produces a wildly increased libido and sexual performance.

I would put money down that a low dose of Dextroamphetamine (Dexedrine) would significantly improve your case, and would help with Mirapex "withdrawal".

It would also be wise to address the prolactin and estradiol issue.

Great post, 4-chloro. What compound are you referring to in your name that has chlorine on c4?

You're probably right. I did some digging into Wellbutrin research, and found this study:

Effects of Bupropion Sustained-Release on Sexual Functioning and Nocturnal Erections in Healthy Men
Labbate, Lawrence A. MD*‡; Brodrick, Peter S. MD*‡; Nelson, Robert P. MD†‡; Lydiard, R. Bruce MD, PhD*; Arana, George W. MD*‡

"Many antidepressants are known to cause adverse sexual effects. Bupropion is an antidepressant with fewer reported adverse sexual effects. Studies of sexual side effects are often confounded by psychiatric and medical conditions affecting sexual function. In this study, the effects of bupropion on subjective and objective sexual functioning were measured in healthy men. Thirteen men without psychiatric or medical illness completed a 2-week, placebo-controlled, double-blind, crossover trial of bupropion sustained-release 300 mg/day. Subjects had a 1-week washout period between trials. Sexual function was measured using a validated, self-administered questionnaire and the RigiScan, an instrument measuring nocturnal penile tumescence and rigidity. No differences were found in self-reported sexual function, number of erections, total erection time, or penile rigidity in subjects taking bupropion compared with those taking placebo or baseline. These findings support that bupropion does not have subjective adverse sexual side effects and does not affect nocturnal erections in healthy men."

So, if Wellbutrin doesn't help anything but the desire component, then I'm getting off, to find a better starting point for this puzzle of ED/libido that I'm trying to solve.

You're probably right about the estradiol and prolactin, too.

On that topic, I strongly suspect that my estradiol is causing problems. When I was treating with clomiphene, it may have caused an estrogen rebound when my labs showing high estradiol were taken. When I treated it with Arimidex for ~10 days, my estrogen went too low and I was having all of the classic signs and symptoms of low estrogen (joint pain, complete ED that wouldn't correct with PDE5 inhibitors [Cialis]). I stopped taking the Arimidex 2 weeks ago. Therefore, there might be lingering effects of low (or high) estradiol contributing to my altered erectile capacity.

If my labs on Monday show high or low estradiol, I'll know what is going on in that regard.

Hopefully, with getting my DHT, SHBG, free and total testosterone, ultra sensitive estradiol, prolactin, we can find out more.

I wish that I could order my own labs. That would make this so much easier.

 

[4-chloro]

Thanks, I will.

I don't like clutching at straws, but if I clutch at enough of them, maybe something will pan out.

I'm going in for a full blood panel on Monday or Tuesday.



Great post, 4-chloro. What compound are you referring to in your name that has chlorine on c4?

You're probably right. I did some digging into Wellbutrin research, and found this study:

Effects of Bupropion Sustained-Release on Sexual Functioning and Nocturnal Erections in Healthy Men
Labbate, Lawrence A. MD*‡; Brodrick, Peter S. MD*‡; Nelson, Robert P. MD†‡; Lydiard, R. Bruce MD, PhD*; Arana, George W. MD*‡

"Many antidepressants are known to cause adverse sexual effects. Bupropion is an antidepressant with fewer reported adverse sexual effects. Studies of sexual side effects are often confounded by psychiatric and medical conditions affecting sexual function. In this study, the effects of bupropion on subjective and objective sexual functioning were measured in healthy men. Thirteen men without psychiatric or medical illness completed a 2-week, placebo-controlled, double-blind, crossover trial of bupropion sustained-release 300 mg/day. Subjects had a 1-week washout period between trials. Sexual function was measured using a validated, self-administered questionnaire and the RigiScan, an instrument measuring nocturnal penile tumescence and rigidity. No differences were found in self-reported sexual function, number of erections, total erection time, or penile rigidity in subjects taking bupropion compared with those taking placebo or baseline. These findings support that bupropion does not have subjective adverse sexual side effects and does not affect nocturnal erections in healthy men."

So, if Wellbutrin doesn't help anything but the desire component, then I'm getting off, to find a better starting point for this puzzle of ED/libido that I'm trying to solve.

You're probably right about the estradiol and prolactin, too.

On that topic, I strongly suspect that my estradiol is causing problems. When I was treating with clomiphene, it may have caused an estrogen rebound when my labs showing high estradiol were taken. When I treated it with Arimidex for ~10 days, my estrogen went too low and I was having all of the classic signs and symptoms of low estrogen (joint pain, complete ED that wouldn't correct with PDE5 inhibitors [Cialis]). I stopped taking the Arimidex 2 weeks ago. Therefore, there might be lingering effects of low (or high) estradiol contributing to my altered erectile capacity.

If my labs on Monday show high or low estradiol, I'll know what is going on in that regard.

Hopefully, with getting my DHT, SHBG, free and total testosterone, ultra sensitive estradiol, prolactin, we can find out more.

I wish that I could order my own labs. That would make this so much easier.

I would make a suggestion of Aromasin Vs Arimidex. Although I don't have any studies in bag o' tricks to support it (If people would like me to source more I can), I've heard it stated that Aromasin doesn't effect testosterone's aromatisation to estrogen in the brain, nearly as much as other non-steroidal AI's. Anecdotal evidence supports that it has a lowered negative effect on sex drive, and if you search pub med you can find evidence that it has lowered effects on cholesterol.

It can also be noted that daily dosing may not be necessary at all:





Eur J Endocrinol. 2008 May;158(5):741-7.
Letrozole once a week normalizes serum testosterone in obesity-related male hypogonadism.
Loves S, Ruinemans-Koerts J, de Boer H.
Source

Department of Internal Medicine, Ziekenhuis Rijnstate, Wagnerlaan 55, 6800 TA Arnhem, The Netherlands.
Abstract
OBJECTIVE:

Isolated hypogonadotropic hypogonadism (IHH) is frequently observed in severely obese men, probably as a result of increased estradiol (E(2)) production and E(2)-mediated negative feedback on pituitary LH secretion. Aromatase inhibitors can reverse this process. This study evaluates whether letrozole once a week can normalize serum testosterone in severely obese men and maintain its long term effect.
DESIGN:

Open, uncontrolled 6-month pilot study in 12 severely obese men (body mass index>35.0 kg/m(2)) with obesity-related IHH and free testosterone levels <225 pmol/l, treated with 2.5 mg letrozole once a week for 6 months.
RESULTS:

Six weeks of treatment reduced total E(2) from 123+/-11 to 58+/-7 pmol/l (P<0.001, mean+/-s.e.m.), and increased serum LH from 4.4+/-0.6 to 11.1+/-1.5 U/l (P<0.001). Total testosterone rose from 5.9+/-0.5 to 19.6+/-1.4 nmol/l (P<0.001), and free testosterone from 163+/-13 to 604+/-50 pmol/l (P<0.001). Total testosterone rose to within the normal range in all subjects, whereas free testosterone rose to supraphysiological levels in 7 out of 12 men. The testosterone and E(2) levels were stable throughout the week and during the 6-month treatment period.
CONCLUSION:

Letrozole 2.5 mg once a week produced a sustained normalization of serum total testosterone in obese men with IHH. However, free testosterone frequently rose to supraphysiological levels. Therefore, a starting dose <2.5 mg once a week is recommended.





All the AI's have similar half lives, so it would be safe to extrapolate this study to include aromasin and arimidex. 2.5mg of letrozole will reduce estrogen only slightly more than .5mg of letrozole or less. Similar to how 1mg of arimidex will lower estrogen only slightly more than .5mg of arimidex. I'm not sure why this occurs in males, but it could be because a saturation point of aromatase inhibition is reached with each drug as each has differing affinities to the aromatase enzyme.

This could explain why even a low dose of arimidex slaughtered your estradiol. I would (in an unprofessional opinion) suggest 12.5mg of aromasin on Monday and Thursday to start, and the dose can easily be adjusted. 25mg of aromasin will lower estradiol levels a similar amount as 2.5mg of letrozole, so less than 25mg a week will most likely be sufficient, but in order to fine tune it you'll have to get your estradiol retested until the desired dose is found.

Bloodwork is easiest when you ask your physician for a number of standing orders, for example you could ask for 8 standing orders to test:

DHT
Free/TT
Estradiol
Prolactin
LH
FSH
ACTH

That way you can go into the lab whenever you want and get your blood drawn (depending on the length of the order), the results will get sent to your physician and they can then call/email you the results.

To address the issue of prolactin (possibly the most irritating hormone in the male system) I would suggest (if possible) to get back on Mirapex, and take .75mg (half of a 1.5mg tab) 3 times a day. You'll have to work up to it as it can cause nausea and sedation, but it will subside. Your prolactin level will eventually drop, in which case you can stay on the Mirapex, or very very slowly taper off of it, along with 800mg of Vitex taken 1-2x daily. I would say .25mg every two weeks would be a reasonable reduction. It is my belief that most physicians take people off of psychotropic drugs much too quickly, as you've essentially been dependent on them 24/7 for months or even years. Wellbutrin for example inhibits the re-uptake of dopamine at the synapses, guess what drugs also do the same? Cocaine, Amphetamines etc.

I will also note that I never noticed any benefit from mirapex until I was taking it in 3 divided doses, however, my ADHD prescription augments the sedation piece. But even on days I do not take stimulants, I found the sedation to slowly subside after a few weeks.

The 4-chloro refers to Oral Turinabol (4-chlorodehydromethyltestosterone)

 

[DragonRider]

Seems like your estrogen is too high. I don't remember where, but I seem to recall elevated estrogen to be related to elevated seratonin and vice versa. And elevated seratonin from SSRI's is a cause of ED and doesn't elevated seratonin equate to lower levels of dopamine?
I wonder if lowering estradiol wouldn't fix it all.

 

[4-chloro]

Seems like your estrogen is too high. I don't remember where, but I seem to recall elevated estrogen to be related to elevated seratonin and vice versa. And elevated seratonin from SSRI's is a cause of ED and doesn't elevated seratonin equate to lower levels of dopamine?
I wonder if lowering estradiol wouldn't fix it all.

Increased serotonin has the neuroendocrine side effect of elevated levels of prolactin. The rise in prolactin is what causes most of SSRI (which increase serotonin concentrations at the synapse, through inhibition of the serotonin reuptake pump) side effects such as weight gain, and sexual side effects. This is an indirect action of serotonin as it has a regulatory action on dopamine in certain parts of the brain, higher levels of serotonin can reduce/downregulate levels of dopamine and vice versa.

Dopamine regulates the release of prolactin from the pituitary, and a lower concentration of dopamine can cause an increase in prolactin. To put it very simply, because serotonin is high, dopamine is low, because dopamine is low, prolactin is high. If prolactin were injected, it would not raise levels of serotonin or dopamine (in theory, unless there is some regulatory feedback from dopamine).

Estrogen will not cause lactation on its own, rather it is the combined action of Prolactin and Estradiol on breast tissue. Prolactin increases estrogen's proliferation of breast tissue, and I would wager that it would be much more difficult to get gynecomastia with very low prolactin levels.

As a personal anecdote, when I first started SSRI's I begun to experience lactation. I got my bloodwork done (not checking for prolactin, as I was unaware of this SSRI side effect at the time) and my estrogen was low-normal. I then began arimidex, and even when my estradiol came back undectable, I experienced zero reduction in lactation. I later found that my prolactin level was elevated well beyond the normal range, as I appear to be extra sensitive to this side effect.

Estrogen affects serotonin levels in the brain, however it also raises dopamine and other NT's; it also has neuroprotective properties. Considering this, low estrogen is much more likely to cause sexual issues (and depression) than high estrogen as long as testosterone and prolactin levels are in balance. Because prolactin has a much broader scope of negative effects, and little to zero positive benefits to men, dealing with that issue should be the first priority. Prolactin, like estrogen, also inhibits the HPTA. After prolactin is dealt with, estrodial will have less deleterious effects on its own, and you are left to focus on testosterone level. I however believe that compensating low testosterone, by lowering estrogen will likely solve one problem whilst creating another. Having a level of estradial in the normal to low normal range is important for a wide variety of health promoting reasons, and not just neurotransmission.

Estrodial's positive effect on brain chemistry is why I would primarily recommend aromasin over other AI's as it affects aromatisation in the brain very little Vs. other compounds.

Progesterone however can more directly raise prolactin through a number of mechanisms. It has a more direct correlation to serotonin, and because it antagonizes the androgen receptor and the 5-alpha reductase enzyme, androgen action is decreased, thus decreasing dopamine concentrations as well as proliferating estrodial's effects. However, to go along with how the body likes balance, some progesterone is very beneficial, but very low or very high levels can cause problems.

It might also be wise to get DHEA and Pregnenolone levels checked, as they are precursors to many hormones that affect the brain (and thus the body) positively.

It could be said that high levels of estradiol would lower androgen concentrations, increasing the estrogen to androgen ratio, thus reducing dopamine and raising prolactin. That however would be a stretch, and would likely not be nearly a significant enough effect to raise prolactin to the point of lactation.

If you don't want to use Mirapex again, DHT could be a viable option. It would reduce estrodial in a balanced way, through receptor antagonism and aromatase downregulation, as well as reduce prolactin (although to a much lesser extent than a good dose of Mirapex). It is also well known that because DHT is a powerful androgenic agent (although not anabolic) it has largely positive effects on the androgen mediated pathway of sexual arousal. Testosterone however still remains important.

 

[DragonRider]

Thanks 4-chloro. Good post. I'm guessing it would depend on the individual, but I wonder what level prolactin would have to be at before a majority of men would see symptoms?
From what I've read about people being treated with bromcritine or cabergoline for prolactin issues they aren't usually a couple of points over, but hundreds of points over range.

 

[SacToSD]

Increased serotonin has the neuroendocrine side effect of elevated levels of prolactin. The rise in prolactin is what causes most of SSRI (which increase serotonin concentrations at the synapse, through inhibition of the serotonin reuptake pump) side effects such as weight gain, and sexual side effects. This is an indirect action of serotonin as it has a regulatory action on dopamine in certain parts of the brain, higher levels of serotonin can reduce/downregulate levels of dopamine and vice versa.

Dopamine regulates the release of prolactin from the pituitary, and a lower concentration of dopamine can cause an increase in prolactin. To put it very simply, because serotonin is high, dopamine is low, because dopamine is low, prolactin is high. If prolactin were injected, it would not raise levels of serotonin or dopamine (in theory, unless there is some regulatory feedback from dopamine).

Estrogen will not cause lactation on its own, rather it is the combined action of Prolactin and Estradiol on breast tissue. Prolactin increases estrogen's proliferation of breast tissue, and I would wager that it would be much more difficult to get gynecomastia with very low prolactin levels.

As a personal anecdote, when I first started SSRI's I begun to experience lactation. I got my bloodwork done (not checking for prolactin, as I was unaware of this SSRI side effect at the time) and my estrogen was low-normal. I then began arimidex, and even when my estradiol came back undectable, I experienced zero reduction in lactation. I later found that my prolactin level was elevated well beyond the normal range, as I appear to be extra sensitive to this side effect.

Estrogen affects serotonin levels in the brain, however it also raises dopamine and other NT's; it also has neuroprotective properties. Considering this, low estrogen is much more likely to cause sexual issues (and depression) than high estrogen as long as testosterone and prolactin levels are in balance. Because prolactin has a much broader scope of negative effects, and little to zero positive benefits to men, dealing with that issue should be the first priority. Prolactin, like estrogen, also inhibits the HPTA. After prolactin is dealt with, estrodial will have less deleterious effects on its own, and you are left to focus on testosterone level. I however believe that compensating low testosterone, by lowering estrogen will likely solve one problem whilst creating another. Having a level of estradial in the normal to low normal range is important for a wide variety of health promoting reasons, and not just neurotransmission.

Estrodial's positive effect on brain chemistry is why I would primarily recommend aromasin over other AI's as it affects aromatisation in the brain very little Vs. other compounds.

Progesterone however can more directly raise prolactin through a number of mechanisms. It has a more direct correlation to serotonin, and because it antagonizes the androgen receptor and the 5-alpha reductase enzyme, androgen action is decreased, thus decreasing dopamine concentrations as well as proliferating estrodial's effects. However, to go along with how the body likes balance, some progesterone is very beneficial, but very low or very high levels can cause problems.

It might also be wise to get DHEA and Pregnenolone levels checked, as they are precursors to many hormones that affect the brain (and thus the body) positively.

It could be said that high levels of estradiol would lower androgen concentrations, increasing the estrogen to androgen ratio, thus reducing dopamine and raising prolactin. That however would be a stretch, and would likely not be nearly a significant enough effect to raise prolactin to the point of lactation.

If you don't want to use Mirapex again, DHT could be a viable option. It would reduce estrodial in a balanced way, through receptor antagonism and aromatase downregulation, as well as reduce prolactin (although to a much lesser extent than a good dose of Mirapex). It is also well known that because DHT is a powerful androgenic agent (although not anabolic) it has largely positive effects on the androgen mediated pathway of sexual arousal. Testosterone however still remains important.

You're a gold mine, 4-chloro. Thanks for posting in this thread, you have really helped me. You sound like a doctor... I wonder if that's the actual case?

I would write more, but I'm using my mobile and don't have much time. Thanks again, and I'll write a thorough response to your posts when I get home.

 

[4-chloro]

Thanks 4-chloro. Good post. I'm guessing it would depend on the individual, but I wonder what level prolactin would have to be at before a majority of men would see symptoms?
From what I've read about people being treated with bromcritine or cabergoline for prolactin issues they aren't usually a couple of points over, but hundreds of points over range.

Extremely high levels of prolactin such as those you have described are generally an indication of a pituitary tumour or other physiological disruption.

The level of prolactin reached before symptoms would be seen is hard to say, as different people respond so vastly different to hormones. I for example was slightly lactating with a prolactin level of 22.0 ng/ml (range: 0-20.0 ng/ml). It had been higher before when I was on lexapro (I believe about 30 ng/ml) and I was still able to function sexually, however reaching climax was more difficult and sex less pleasurable overall.

Even after I was off of all SSRI's, my prolactin remained elevated for months until I started Mirapex, and even then it wasn't overnight.

 

[SacToSD]

Extremely high levels of prolactin such as those you have described are generally an indication of a pituitary tumour or other physiological disruption.

The level of prolactin reached before symptoms would be seen is hard to say, as different people respond so vastly different to hormones. I for example was slightly lactating with a prolactin level of 22.0 ng/ml (range: 0-20.0 ng/ml). It had been higher before when I was on lexapro (I believe about 30 ng/ml) and I was still able to function sexually, however reaching climax was more difficult and sex less pleasurable overall.

Even after I was off of all SSRI's, my prolactin remained elevated for months until I started Mirapex, and even then it wasn't overnight.

Okay, so I went in yesterday for my blood work, and I should have results within 1 week. I had the following tests done:

ACTH
DHEA
DHT
Estradiol
FSH
LH
Pregnenolone
Prolactin
SHBG
Testosterone Free and Total

**I have the option of adding additional tests and panels on Monday (it's Friday, today). If you look at this hormonal-biosynthesis pathway, you'll see how testosterone, DHT, and everything else is created:

Case in point, I want to test everything in the pathway leading to testosterone, DHT, and estradiol. That would mean adding the following tests:

17a-hydroxyprogesterone
17a-hydroxypregnenolone
Progesterone
Androstenedione

Further, they offer a 5-alpha reductase profile, and I want to get that, too.

Also, I've been looking into other therapies for erectile dysfunction that aren't based on PDE5 inhibitors. Specifically, gene and stem cell therapy. There is a doctor here in LA that performs stem cell therapy for erectile dysfunction. I have an appointment with him on Tuesday of next week.

Here is my current research on the non-PDE5 treatments for ED that I've found:

IGF-1 Treatment
Insulin-like growth factor-1 restores erectile fun... [J Sex Med. 2008] - PubMed - NCBI

"Insulin-like growth factor-1 restores erectile function in aged rats: modulation the integrity of smooth muscle and nitric oxide-cyclic guanosine monophosphate signaling activity.
Pu XY, Wang XH, Gao WC, Yang ZH, Li SL, Wang HP, Wu YL.

INTRODUCTION:
Insulin-like growth factor-1 (IGF-1) is one of the growth factors that have a wide range of biologic effects. We have confirmed that gene transfer of IGF-1 to the penis could improve erectile capacity. However, there are some limitations in gene therapies, such as toxicity or a risk of insertional mutagenesis. Protein treatment may be another choice for decreasing these risks.

AIM:
To investigate whether intracavernosal injection of IGF-1 protein can restore erectile function in the aging rat.

MAIN OUTCOME MEASURES:
Erectile responses, morphological changes, and nitric oxide-cyclic guanosine monophosphate (NO-cGMP) signaling pathways-related marker were determined.

METHODS:
Ten young (4 months) and 30 old (24 months) Sprague-Dawley male rats were enrolled in this study. The old rats were divided into three groups: vehicle-only (N = 10), IGF-1 1 microg/kg (N = 10) and IGF-1 10 microg/kg treatment group (N = 10). After 4 and 8 weeks of single IGF-1 injection treatment, intracavernous pressure (ICP) responses with electrical stimulation to the cavernous nerve were evaluated. The percent of smooth muscle in corpus cavernosum tissue, the expression of mRNA and protein of endothelial nitric oxide synthase (eNOS) were also evaluated. The activity of nitric oxide synthase (NOS) and concentration of guanosine 3',5'-cyclic-monophosphate (cGMP) that act upon the major NO-cGMP signaling pathways in penile tissue were also analyzed.

RESULTS:
After IGF-1 treatment, the ICP responses was significantly increased as the young control group in both the IGF-1 1 microg/kg and the IGF-1 10 microg/kg group compared with the vehicle-only group at 4 and 8 weeks (P < 0.05). Masson's trichrom staining showed the percentage of cavernosal smooth muscle was increased in IGF-1 treatment group. IGF-1 increased e-NOS expression. NOS activities and cGMP concentrations were also significantly increased in IGF-1 treatment rats.

CONCLUSIONS:
IGF-1 improved erectile function in aged rats via restoration the integrity of smooth muscle of corpus cavernosum and modulation of NO-cGMP pathways."




Adipose Derived Stem Cells for Treatment of Erectile Dysfunction
Potential of adipose-derived stem cells for treatm... [J Sex Med. 2009] - PubMed - NCBI

"J Sex Med. 2009 Mar;6 Suppl 3:320-7.

Potential of adipose-derived stem cells for treatment of erectile dysfunction.
Lin G, Banie L, Ning H, Bella AJ, Lin CS, Lue TF.

INTRODUCTION:
Adipose-derived stem cells (ADSCs) are a somatic stem cell population contained in fat tissue that possess the ability for self-renewal, differentiation into one or more phenotypes, and functional regeneration of damaged tissue, which may benefit the recovery of erectile function by using a stem cell-based therapy.

AIM:
To review available evidence concerning ADSCs availability, differentiation into functional cells, and the potential of these cells for the treatment of erectile dysfunction (ED).

METHODS:
We examined the current data (from 1964 to 2008) associated with the definition, characterization, differentiation, and application of ADSCs, as well as other kinds of stem cells for the cell-based therapies of ED.

MAIN OUTCOME MEASURES:
There is strong evidence supporting the concept that ADSCs may be a potential stem cell therapy source in treating ED.

RESULTS:
The ADSCs are paravascularly localized in the adipose tissue. Under specific induction medium conditions, these cells differentiated into neuron-like cells, smooth muscle cells, and endothelium in vitro. The insulin-like growth factor/insulin-like growth factor receptor (IGF/IGFR) pathway participates in neuronal differentiation while the fibroblast growth factor 2 (FGF2) pathway is involved in endothelium differentiation. In a preliminary in vivo experiment, the ADSCs functionally recovered the damaged erectile function. However, the underlying mechanism needs to be further examined.

CONCLUSION:
The ADSCs are a potential source for stem cell-based therapies, which imply the possibility of an effective clinical therapy for ED in the near future."



Muscle Derived Stem Cells for Treatment of Erectile Dysfunction
Effect of muscle-derived stem cells on the restoration of corpora cavernosa smooth muscle and erectile function in the aged rat - Nolazco - 2008 - BJU International - Wiley Online Library

"Effect of muscle-derived stem cells on the restoration of corpora cavernosa smooth muscle and erectile function in the aged rat

DOI: 10.1111/j.1464-410X.2008.07507.x

OBJECTIVE
To determine whether skeletal muscle-derived stem cells (MDSCs) convert into smooth muscle cells (SMCs) both in vitro and in vivo, and in so doing ameliorate the erectile dysfunction (ED) of aged rats, and whether endogenous stem cells are present in the rat corpora cavernosa.

MATERIALS AND METHODS
MDSCs were obtained from mouse muscle, and shown by immunocytochemistry for ?-smooth muscle actin (?SMA) to originate in vitro in myofibroblasts and SMCs, discriminating SMCs by calponin 1 expression. In vivo these MDSCs, labelled with 4?,6-diamidino-2-phenylindole, were implanted into the corpora cavernosa of young adult (5-month old) and aged (20-month old) rats for 2 and 4 weeks. Histological changes were assessed by immunohistochemistry and quantitative Western blot. Functional changes were determined by electrical field stimulation (EFS) of the cavernosal nerve.

RESULTS
The exogenous cells replicated and converted into SMCs, as shown in corporal tissue sections by confocal immunofluorescence microscopy for proliferating cell nuclear antigen (PCNA), ?SMA, and smoothelin, and also by Western blot for ?SMA and PCNA. MDSC differentiation was confirmed by the activation of the ?SMA promoter-linked ?-galactosidase in transfected cells, both in vitro and after implantation in the corpora. Putative endogenous stem cells were shown in corporal tissue sections and Western blots by detecting CD34 and a possible Sca1 variant. EFS showed that implanted MDSCs raised in aged rats the maximal intracavernosal pressure/mean arterial pressure levels above (2 weeks) or up to (4 weeks) those of young adult rats.

CONCLUSIONS
MDSCs implanted into the corpora cavernosa of aged rats converted into SMCs and corrected ED, and endogenous cells expressing stem cell markers were also found in untreated tissue. This suggests that exogenous stem cell implantation and/or endogenous stem cell modulation might be viable therapeutic approaches for ageing-related ED."



_______________________________________________________________________

Response to 4-Chloro:
All of your information is extremely helpful. Unfortunately, I believe the test results that I gave first, taken on August 1st (it's now September 9th), are not reflective of my current hormonal state. Therefore, replying in an itemized way to each of your comments will be futile, at best.

All the same, I have been trying to help myself with my ED by getting off of cialis, which I had been taking near-daily for a few weeks, and every three days or so for the last 2 years. I need a break from this medication, to help bring my tolerance to it down, and to give my body a break. I've since been using viagra once daily at 50-75 mg.

Today, and yesterday, I have not had morning erections for the first time in several weeks. I'm not sure if this is due to my estrogen/testosterone ratio, or not, but hopefully, the blood taken yesterday will show some sign of what's going on in this regard.

On a positive note, I had an unassisted, successful erection, yesterday evening. Unfortunately, a reattempt today to have a successful erection failed. I have been off of Cialis for ~4-5 days, now.

I haven't taken any anti-estrogen medications, and have weened down to 150 mg of Wellbutrin per day, and plan on discontinuing it completely in 2 days.

Pending the results of my bloodwork, the appointment I have with the stem cell doctor, and my erectile capacity, we should know more.

What I believe to be the case, at this point, is that the smooth muscle in my penis is atrophied, and that the corpus cavernosum more than likely has fibrosis, all of this due to estradiol's effects on the tissue, as well as my low levels of testosterone.

My options at this point:
get stem cell therapy
inject IGF-1 into my penis
get onto TRT/HRT if required

Here is the stem cell doctor's website:
MetroMD | HGH Human Growth Hormone | Stem Cell Therapy | Regenerative Medicine | Hollywood | Beverly Hills | Los Angeles

I need to be vigilant with this, and not fall behind. The nature of the body is to atrophy what is disused, and the penis is no exception.

 

[SacToSD]

Here is the doctor at UCLA who specializes in stem cell treatment for ED, Nestor Gonzalez-Cadavid:

Physicians and Research Faculty | UCLA Urology

His research foci:
"Dr. Gonzalez-Cadavid has made significant research contributions in several fields of cellular and molecular biology approaches to pathophysiology. He focused initially on alterations of collagen deposition with aging, and later on mitochondrial biogenesis and protein synthesis. These studies evolved into the role of mitochondrial DNA and different oncogenes in tumor progression, and after joining the UCLA Department of Urology he focused on topics of urology relevance, mainly androgen dependence of penile growth and erectile function, and the effect of risk factors for erectile dysfunction, such as aging, diabetes, and smoking, on the nitric oxide/cGMP control of the erectile response. His group reported the first demonstration of the correction of erectile dysfunction in an animal model by gene therapy, and more recently showed that long-term continuous administration of nitric oxide donors and PDE5 inhibitors corrects in animal models the underlying corporal and arterial fibrosis associated with aging, diabetes and radical prostatectomy, as well as the fibrotic plaque of Peyronie’s disease. Lately, he has extended those studies to the modulation of multipotent and stem cell differentiation by nitric oxide, cGMP, and myostatin, and its application to the therapy of erectile dysfunction and other forms of urogenital disease and other conditions associated with tissue fibrosis. He is currently funded for some of these studies by NIH, the Department of Defense, and other agencies.

Dr. Gonzalez-Cadavid has a long-standing teaching experience in biochemistry, and molecular and cellular biology courses. He has been particularly devoted to the training of junior biomedical scientists by supervising numerous PhD and MSc students, as well as postdoctoral researchers and physicians, who are now academic faculty in several countries. He serves as reviewer of many journals and member of several academic and research committees, and has three patents awarded."

Since I'm a biochemistry student at UCLA, I think that I can get some face time with Dr. Gonzalez-Cadavid.

I need to be vigilant with this, and not fall behind. The nature of the body is to atrophy what is disused, and the penis is no exception.

 

[4-chloro]

Before any fancy gene therapy or injecting IGF-1, I would get stabilized on hCG and Testosterone. Both play important physiological and neuropsychological roles in erections and arousal in general.

If you still cannot get an erection on:

500-1000iu's hCG
100mg of testosterone Cypionate
(or otherwise normal LH, FSH, Estrogen and testosterone)

.25mg of Mirapex 3x a day
5-10mg cialis

AND your bloodwork comes back normal (estrogen, DHT etc, I would suspect it to be some sort of enzymatic issue located in the tissues of the genitalia.

There could also be blockage of the blood flow to the penis. Any muscular atrophy should reverse given the Testosterone and Mirapex combination (mirapex raises Growth hormone considerably).

I don't know if you've been on hCG before, but when your own testes are producing testosterone, intratesticular testosterone levels increase, which are important to Nitric Oxide release into the penis. I could drag up some study they did on rabbits if you would like. Supplementing DAA will help with this also in combination with hCG.

Also, Opioid antagonists such as Nalexone will increase libido.

I also assume that you've have your prostate checked and there are no major issues?

Bottom line is that there are still lots of things to try.

 

[SacToSD]

Before any fancy gene therapy or injecting IGF-1, I would get stabilized on hCG and Testosterone. Both play important physiological and neuropsychological roles in erections and arousal in general.

If you still cannot get an erection on:

500-1000iu's hCG
100mg of testosterone Cypionate
(or otherwise normal LH, FSH, Estrogen and testosterone)

.25mg of Mirapex 3x a day
5-10mg cialis

AND your bloodwork comes back normal (estrogen, DHT etc, I would suspect it to be some sort of enzymatic issue located in the tissues of the genitalia.

There could also be blockage of the blood flow to the penis. Any muscular atrophy should reverse given the Testosterone and Mirapex combination (mirapex raises Growth hormone considerably).

I don't know if you've been on hCG before, but when your own testes are producing testosterone, intratesticular testosterone levels increase, which are important to Nitric Oxide release into the penis. I could drag up some study they did on rabbits if you would like. Supplementing DAA will help with this also in combination with hCG.

Also, Opioid antagonists such as Nalexone will increase libido.

I also assume that you've have your prostate checked and there are no major issues?

Bottom line is that there are still lots of things to try.

You've been more helpful to me than you know.

The thing is, I'm not on TRT. I have been trying to correct low testosterone and low LH/FSH for the last year using intermittent bouts of clomiphene (50 mg/day for 1 month, two month break, 50 mg/day for 1 month, two month break, 50 mg/day for 2 months, and I'm now one and a half months off).

If you follow along with these lab results, you'll see the fluctuations in my levels as my treatment with clomiphene cycled.

7/23/10
FSH 1.2
LH 3.7
Testosterone, Total 343

9/22/10
FSH 3.5
LH 4.9
Testosterone, Total 966

11/24/10
FSH 1.8
LH 2.3
Testosterone, Total 429

8/1/11
FSH 2.4
LH 6.5
Testosterone, Total 875

Also on 11/24/10
Cortisol 14
Vitamin D 38
Testosterone, Bioavailable 128 (128 - 430)
Bioavailable Testosterone % 29.8
Sex Hormone Binding Globulin 33

Also on 8/1/11
Estrogen 48.9 (20-30)
Prolactin 14.8 (4-15)
PSA 0.4 (< 5)


So, I'm pretty much on the fence about where to go next, depending on my test results.

 

[zkt]

4-chloro: have you invcestigated the para sympathetic NS NTs as relates to libido?