Swale, Is Secondary Hypo Caused By Nitric Oxide Deficiency?

[DavidZ]

Medline articles (11444107, 12324658 and others) indicate that nitric oxide deficiency suppresses LH and FSH production. In other words, nitric oxide deficiency may explain, or partially explain, “idiopathic” hypogonadotrophic hypogonadism (i.e., secondary hypogonadism).

Nitric oxide is a gas the body manufactures that serves many vital functions. In 1998, The Nobel Prize for Medicine was awarded to three medical researchers for their pioneering discoveries about how our bodies manufacturer and use nitric oxide.

L-Arginine is an amino acid (i.e., protein component) that, among other things, stimulates nitric oxide production. L-Arginine is in many of the foods we eat and is also available as a supplement. For more information about L-Arginine and nitric oxide read The Arginine Solution by Robert Fried, PhD and Woodson Merrell, MD.

In 1999, I was diagnosed with secondary hypogonadism (T of about 200; no history of steroid use). In February 2000, I started on HCG. In 2001, I started using DIM to control E2. My dosages are very low (dosages shown below).

About 2 years ago, I did a trial of a very small dosage (about 1500 mg per week) of L-Arginine that had powerful, but mixed, results. My T went up about 40% (from 800 or 900 to 1200), but my E2 went up about 100% (from 30 or 40 to 70). Based on these results, I lowered my HCG dosage in half, but my overall hormone profile deteriorated because my T/E2 ratio went way down. More importantly, Free T went down to the bottom of the normal range (see blood test results below). I backed off of L-Arginine at that point.

My results indicate that, while nitric oxide boosts T production significantly, it boosts E2 production even more. Why would nitric oxide increase aromatization?

I’m beginning a new experiment with L-Arginine, this time at a lower dose.

Below are the results of my L- Arginine trial two years ago.

July 27, 2002 (before L-Arginine)
HCG 310 IU 2x/wk
Indolplex/DIM 34 mg/day (about one quarter of a 120 mg tablet)
Selegiline 2.5 mg/night
L-Arginine none
T 889 (260-1000)
Free T 23.9 (10-27)
E2 30 (<50)

August 24, 2002 (after 4 weeks of L-Arginine)
HCG 310 IU 2x/week
Indolplex/DIM 32 mg/day
Selegiline 2.5 mg/night
L-Arginine 1500 mg/week
T 1202 (260-1000)
Free T 35.7 (10-27)
E2 71 (<50)

October 5, 2002 (after 10 weeks of L-Arginine)
HCG 140 IU 2x/week
Indolplex/DIM 32 mg/day
Selegiline 2.5 mg/night
L-Arginine 1500 mg/week
T 534 (260-1000)
Free T 10.6 (10-27)
E2 38 (<50)

November 2, 2002 (after 14 weeks of L-Arginine)
HCG 140 IU 2x/week
Indolplex/DIM 39 mg/day
Selegiline 2.5 mg/night
L-Arginine 1500 mg/week
T 570 (260-1000)
Free T 12.3 (10-27)
E2 59 (<50)

[maxzax]

That's a very interesting study!!!

[DavidZ]

Originally Posted by maxzax

That's a very interesting study!!!

Yes, it is. And puzzling, too!

I wonder if anyone else has experienced a spike in E2 (or T) from L-Arginine? The effects may have been quite different if I was on TRT instead of HCG, but who knows?

[SWALE]

I do not know anything about this.

IMPO, adding in the Selegiline negated your results, as it is a true confounder.

Total Testosterone assays are notoriously unreliable.

Using HCG in the way you did meant you put yourself on such a hormonal roller coaster that no single t assay is of any value whatsoever.

This does not mean you have not asked good questions, however, and you have definitely sparked some interesting thought. Please continue.

I did get to shake hands with Dr. Ignaro (I hope I am spelling his name correctly), though, who won that Nobel Prize.

[DavidZ]

Originally Posted by SWALE

I do not know anything about this.

You're not alone. No one else I've talked to, including Dr. Shippen, does either.

Originally Posted by SWALE

IMPO, adding in the Selegiline negated your results, as it is a true confounder.

The Selegiline dosage was held constant throughout the trial. Doesn't that effectively eliminate it from the analysis?

BTW, I was taking Selegiline for two years before and two years after the above trial. And the first blood test represents a good baseline because I got similar and consistent blood test results prior to that test.

Originally Posted by SWALE

Total Testosterone assays are notoriously unreliable.

I definitely felt things going on in my body at the time and was very curiously awaiting the 2nd blood test results cited above. I have no reason to doubt the blood test results. In fact, I'm pretty confident they are correct based on my clinical response.

Originally Posted by SWALE

Using HCG in the way you did meant you put yourself on such a hormonal roller coaster that no single t assay is of any value whatsoever.

Look at the first 2 blood tests. They constitute a before and after, with and without L-Arginine. In other words, all elements of my protocol were held constant EXCEPT adding the L-Arginine.

Further, the Medline articles provide the scientific explanation as to why my T went up. Please note that my reasons for trying L-Arginine were NOT to increase T. My reasons were based on the book I cited above which does not mention anything about increasing T. I found those Medline articles AFTER I did the above 2 blood tests because I was looking for some explanation of the surprising results I got from L-Arginine.

However, I still have no explanation of why E2 went up so much. Do you have any theory as to why nitric oxide would increase aromatization? Even a wild guess of a theory would be appreciated.

[SWALE]

Sorry. I do not have the knowledge base to even hazard a guess.

Something to keep in mind: I regularly get Total T assays, done at two different (reputatble) labs, on the SAME blood sample. They can be off by as much as 50%. SCARY!

[specster]

"Using HCG in the way you did meant you put yourself on such a hormonal roller coaster that no single t assay is of any value whatsoever."

I did n't know that this was such an unusual way to take HCG. I thought once every 3 -4 D @ <500 IU was the way to go.

There must be 50 things that would effect T levels significantly even if these meds were steady - diet, exersize, sleep patterns, stress, seasons, psycho-social events, time of day blood drawn, lab CV, I'm sure you can come up w/ many more.

[DavidZ]

Originally Posted by specster

"Using HCG in the way you did meant you put yourself on such a hormonal roller coaster that no single t assay is of any value whatsoever."

I did n't know that this was such an unusual way to take HCG. I thought once every 3 -4 D @ <500 IU was the way to go.

There must be 50 things that would effect T levels significantly even if these meds were steady - diet, exersize, sleep patterns, stress, seasons, psycho-social events, time of day blood drawn, lab CV, I'm sure you can come up w/ many more.

My HCG shots were taken consistently on Monday and Thursday nights. And my blood tests were all on Saturday morning. So the L-Arginine trial was scientifically sound as far as I can tell. But my E2 went so high that whatever good effect the increase in T had, it was more then offset by the increase in E2.

[SWALE]

HCG must be dosed much more frequently. I recommend every day if you are relying on it.

[1cc]

Originally Posted by DavidZ

Lab1
July 27, 2002 (before L-Arginine)
HCG 310 IU 2x/wk
Indolplex/DIM 34 mg/day (about one quarter of a 120 mg tablet)
Selegiline 2.5 mg/night
L-Arginine none
T 889 (260-1000)
Free T 23.9 (10-27)
E2 30 (<50)

Lab2
August 24, 2002 (after 4 weeks of L-Arginine)
HCG 310 IU 2x/week
Indolplex/DIM 32 mg/day
Selegiline 2.5 mg/night
L-Arginine 1500 mg/week
T 1202 (260-1000)
Free T 35.7 (10-27)
E2 71 (<50)

Lab3
October 5, 2002 (after 10 weeks of L-Arginine)
HCG 140 IU 2x/week
Indolplex/DIM 32 mg/day
Selegiline 2.5 mg/night
L-Arginine 1500 mg/week
T 534 (260-1000)
Free T 10.6 (10-27)
E2 38 (<50)

Lab4
November 2, 2002 (after 14 weeks of L-Arginine)
HCG 140 IU 2x/week
Indolplex/DIM 39 mg/day
Selegiline 2.5 mg/night
L-Arginine 1500 mg/week
T 570 (260-1000)
Free T 12.3 (10-27)
E2 59 (<50)

David,

These labs above are very interesting. Especially Lab2 that shows an increase in Total T.

I'm going to give my guess at why the numbers worked out that way.

Lab2 appears to be accurate because the increase in Total T is confirmed by the corresponding increase in E2. The increase in E2 is quite large because this is "excess" T which is above the range, which will more readily convert to E.

Lab3 and lab4 show a higher proportion of E to T. I wouldn't place too much emphasis on this because when T levels are not optimal, then higher E2 can occur. Higher T levels, within the normal range, actually cause lower E2 levels to occur.

"As testosterone levels sink in the male body, the aromatization of testosterone into estrogen increases, which further lowers testosterone" page. 79 "The Life Extension Revolution" - Dr. Philip Miller and the Life Extension Foundation.

"High levels of testosterone actually depress production of SHBG". page 53 "The Testosterone Syndrome" - by Dr. Eugene Shippen.

So, it is not really the L-Arginine that caused more aromatization, but the level of testosterone at various times - either too high, or not high enough.