HCG Efficacy: Should We Measure 17-OH-progesterone to Titrate HCG Dose?

[Vince Carter]

With an increase to 500iu E3.5D for ~5 weeks I did not see an effect in downstream hormones, DHEA (174-165) or DHT (40-34), the two values actually went down as shown.

 

[Nelson Vergel]

So far, three studies agree on the 500 IU every other day (not twice per week as most of us use) as a good dose to use with TRT if you want optimum fertility. We have no data on that dose used every 3.5 days.


Here is a description of the method used in the reference I posted in the first post on this thread:


"All subjects were treated with testosterone enanthate (TE) 200 mg IM on day 0, 7 and 14 to suppress endogenous gonadotropin secretion from the pituitary. After enrollment, the hospital pharmacist, randomly assigned subjects to one of four hCG treatment groups: hCG 0 (saline placebo), 125, 250 or 500 IU, which was administered subcutaneously every other day for 3 weeks (11 total doses). "

"At end-of-treatment, serum 17-hydroxyprogesterone was significantly reduced in the 0 IU hCG group [median (25%, 75%): 5.1 (3.8, 6.2) nmol/L at baseline vs. 2.1 (1.5, 2.5) nmol/L at end-of-treatment; p = 0.02). In contrast, serum 17-hydroxyprogesterone was significantly increased in the 500 IU hCG group [median (25%, 75%): 4.6 (4.1, 5.4) nmol/L at baseline vs. 7.8 (5.5, 9.4) nmol/L at end-of-treatment; (p = 0.02)]. "


Full paper: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2674872/

You guys may remember that 500 IU every other day was also the dose used in the Lipshultz study.

I am trying to get Dr Lipshultz and his fellows to look at our dose of 500 IU twice per week. We will see if that dose is good enough for fertility. In my opinion, it is good enough for testicular atrophy and libido but I have doubts that it can help a man to maximize his sperm count and quality on TRT. I remember one of our members posting sperm sample results that support my opinion.


I agree that some men gain too much water on HCG. This is due to its inhibiting effect on 17 beta hydroxysteroid dehydrogenase. This enzyme "clears out" cortisol from the blood. When it is inhibited, more cortisol accumulates which can cause water retention (note: this is the main reason for edema in TRT, NOT high estradiol as most of you believe).

Water Retention Caused by Testosterone May Have Nothing to Do with Estradiol

 

[Dr Justin Saya MD]

I agree that some men gain too much water on HCG. This is due to its inhibiting effect on 17 beta hydroxysteroid dehydrogenase. This enzyme "clears out" cortisol from the blood. When it is inhibited, more cortisol accumulates which can cause water retention (note: this is the main reason for edema in TRT, NOT high estradiol as most of you believe).

Treating both males AND females gives me a much deeper understanding of sex hormones than I would have if I only treated males.

Estradiol (or perhaps more importantly estrogen dominance) is well known to cause fluid retention in females during various parts of the menstrual cycle. The same can occur for males with increases in estradiol (especially if progesterone is near undetectable levels).

Below is one description of a mechanism.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3984489/#!po=54.6296

"Estradiol stimulates the liver to synthesize angiotensinogen, a substrate to the kidney hormone renin. Renin is necessary to form angiotensin I that is subsequently converted to angiotensin II (ANG II) by angiotensin-converting enzyme. Angiotensin II, one of the most powerful vasoconstrictors in the body, can increase blood pressure and also stimulate the adrenal gland to release aldosterone. Aldosterone is a primary hormone involved in tubular-regulated sodium retention by the kidney, and this greater sodium retention usually results in water retention. In our studies during hypertonic saline infusions in older women, we found that the primary cause of the estrogen-related water retention was a reduction in sodium and total osmol excretion, consistent with other studies in PM women during long-term estrogen therapy."

 

[johndoesmith]

Treating both males AND females gives me a much deeper understanding of sex hormones than I would have if I only treated males.

Estradiol (or perhaps more importantly estrogen dominance) is well known to cause fluid retention in females during various parts of the menstrual cycle. The same can occur for males with increases in estradiol (especially if progesterone is near undetectable levels).

Below is one description of a mechanism.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3984489/#!po=54.6296

"Estradiol stimulates the liver to synthesize angiotensinogen, a substrate to the kidney hormone renin. Renin is necessary to form angiotensin I that is subsequently converted to angiotensin II (ANG II) by angiotensin-converting enzyme. Angiotensin II, one of the most powerful vasoconstrictors in the body, can increase blood pressure and also stimulate the adrenal gland to release aldosterone. Aldosterone is a primary hormone involved in tubular-regulated sodium retention by the kidney, and this greater sodium retention usually results in water retention. In our studies during hypertonic saline infusions in older women, we found that the primary cause of the estrogen-related water retention was a reduction in sodium and total osmol excretion, consistent with other studies in PM women during long-term estrogen therapy."

I'm glad you said this, I've never looked into progesterone before, thinking it was a "female hormone" like an idiot.

Seems like progesterone does a lot of things, 2 of which I think apply to me. One being fluid retention, I had a lot of issues with excessive urination and thirst before TRT due to my low E2. I also had a lot of anxiety. Seems like progesterone has a large role in fluid regulation, and acts as a positive allosteric modulator of GABAa.

I really enjoy not urinating all the time, do you think it's worth looking into my progesterone levels, or leave it alone?

 

[Dr Justin Saya MD]

I'm glad you said this, I've never looked into progesterone before, thinking it was a "female hormone" like an idiot.

Seems like progesterone does a lot of things, 2 of which I think apply to me. One being fluid retention, I had a lot of issues with excessive urination and thirst before TRT due to my low E2. I also had a lot of anxiety. Seems like progesterone has a large role in fluid regulation, and acts as a positive allosteric modulator of GABAa.

I really enjoy not urinating all the time, do you think it's worth looking into my progesterone levels, or leave it alone?

Never hurts to check. In fact, I now include progesterone for all new patient initial labs. Not sure if this was in effect when you came on board, but we can certainly add it to follow-up.

 

[Nelson Vergel]

Treating both males AND females gives me a much deeper understanding of sex hormones than I would have if I only treated males.

Estradiol (or perhaps more importantly estrogen dominance) is well known to cause fluid retention in females during various parts of the menstrual cycle. The same can occur for males with increases in estradiol (especially if progesterone is near undetectable levels).

Below is one description of a mechanism.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3984489/#!po=54.6296

"Estradiol stimulates the liver to synthesize angiotensinogen, a substrate to the kidney hormone renin. Renin is necessary to form angiotensin I that is subsequently converted to angiotensin II (ANG II) by angiotensin-converting enzyme. Angiotensin II, one of the most powerful vasoconstrictors in the body, can increase blood pressure and also stimulate the adrenal gland to release aldosterone. Aldosterone is a primary hormone involved in tubular-regulated sodium retention by the kidney, and this greater sodium retention usually results in water retention. In our studies during hypertonic saline infusions in older women, we found that the primary cause of the estrogen-related water retention was a reduction in sodium and total osmol excretion, consistent with other studies in PM women during long-term estrogen therapy."

I am not disputing this. What I am disputing is assuming that high estradiol is the cause of edema and giving a patient anastrozole based on that assumption without testing their sensitive E2. I have seen a lot of blood work in the past 5 years from men who complain of water retention and whose E2 is under 30 pg/ml. All I am asking is for everyone to open their minds to another possibility.

I am also yet to see any data on water retention before and after anastrozole treatment in men. I have looked and found nothing.

 

[johndoesmith]

Never hurts to check. In fact, I now include progesterone for all new patient initial labs. Not sure if this was in effect when you came on board, but we can certainly add it to follow-up.

That definitely wasn't a thing when I had initial labs done, I imagine with labcorp's new and intelligently revised lab ranges, it causes a lot of problems.

What do you think of what I had said earlier?

Seems like progesterone does a lot of things, 2 of which I think apply to me. One being fluid retention, I had a lot of issues with excessive urination and thirst before TRT due to my low E2. I also had a lot of anxiety. Seems like progesterone has a large role in fluid regulation, and acts as a positive allosteric modulator of GABAa.

 

[Dr Justin Saya MD]

I am not disputing this. What I am disputing is assuming that high estradiol is the cause of edema and giving a patient anastrozole based on that assumption without testing their sensitive E2. I have seen a lot of blood work in the past 5 years from men who complain of water retention and whose E2 is under 30 pg/ml. All I am asking is for everyone to open their minds to another possibility.

I am also yet to see any data on water retention before and after anastrozole treatment in men. I have looked and found nothing.

We certainly agree on that. Not often that I see fluid retention with sensitive estradiol <30pg/mL UNLESS there is another contributing factor.

 

[Dr Justin Saya MD]

That definitely wasn't a thing when I had initial labs done, I imagine with labcorp's new and intelligently revised lab ranges, it causes a lot of problems.

What do you think of what I had said earlier?

Indeed, a lot of time/productivity wasted having to explain LabCorp's new bogus reference range for progesterone.

You're statements regarding progesterone are valid. It is involved with fluid regulation (as somewhat of a "counter-balance" to estradiol) and has CNS calming effect (good for sleep and anxiety).

 

[johndoesmith]

Indeed, a lot of time/productivity wasted having to explain LabCorp's new bogus reference range for progesterone.

You're statements regarding progesterone are valid. It is involved with fluid regulation (as somewhat of a "counter-balance" to estradiol) and has CNS calming effect (good for sleep and anxiety).

I can't understand how they suddenly made such a huge change in their range. It's one thing to adjust slightly, but that's literally making their range so there's almost nothing! How do they justify this?

 

[Gianluca Bonetti]

why not testing Pregnelonone to see if HCG is working?

 

[_CTI_]

I know this is an old thread but I wanted to update it in case anyone was looking for information. I recently came across the study that nelson mentioned and had 17-ohp tested along with a few other things. My protocol when I tested was 12mg T IM / 150ui HCG DAILY. I was on this protocol for 5 weeks prior to testing. My 17-ohp came back today @ 15 ng/DL ref 27 - 199. if you convert that to nmol/L as in the referenced study you'll see that I came in @ 0.5201nmol/L. EXTREMELY LOW. It looks like in my case daily dose HCG does not produce the desired effect. These labs are a confirmation of symptoms that I've been experiencing, to include low (almost 0) libido, cognitive impairment, sleep disturbances, mild depression, low energy, and a few others. The kicker is that HCG does raise my E2 quite a bit but I have anastrozole on hand if necessary. I'm going to increase my HCG to 500iu EOD as the study suggests and retest in 3 weeks. I'll report back.

 

[Nelson Vergel]

Like I said before, HCG doses of 500 IU three times per week (plus TRT) increased intratesticular T (ITT) which is activated by 17-OH progesterone. Any dose below that is a waste of time if you really want to activate upstream hormones and ITT. However, 30 percent of men (older and/or on long term TRT) may not respond even at that dose.

 

[Nelson Vergel]

How can we predict efficacy of HCG plus testosterone in sperm production?

 

[_CTI_]

Like I said before, HCG doses of 500 IU three times per week (plus TRT) increased intratesticular T (ITT) which is activated by 17-OH progesterone. Any dose below that is a waste of time if you really want to activate upstream hormones and ITT.

I really feel like this should be common knowledge among HCG users.

 

[Nelson Vergel]

It isn't. They do not read published literature. They are busy and they just copy other doctor's protocols. A layperson like me should not be needed to educate them, but here I am sounding like a broken record. I have been to several conferences and training sessions for physicians and it horrifies me how dogma is repeated there all the time without any regard to data available.

 

[bfoley]

However, 30 percent of men (older and/or on long term TRT) may not respond even at that dose.

Why is that Nelson ? I only ask because I may be one of those men. I've been on TRT for 18 months. I was using two doses of HCG per week, 500 iu each time. Libido was strong, erections firm. I expected my testicles to fill out, at least a little, but nothing happened. I am now back down to two doses of 250 iu per week. Libido/erection strength still very good. I'm 58.

 

[_CTI_]

Why is that Nelson ? I only ask because I may be one of those men. I've been on TRT for 18 months. I was using two doses of HCG per week, 500 iu each time. Libido was strong, erections firm. I expected my testicles to fill out, at least a little, but nothing happened. I am now back down to two doses of 250 iu per week. Libido/erection strength still very good. I'm 58.

What does the rest of your protocol look like? I've found that erection quality has more to do with T/E2 ratio than anything else. Libido is another issue and if you can figure that out let me know!

 

[Nelson Vergel]

I am really not talking about libido or erections. I am talking about ITT needed for fertility. We really don't know if using HCG to activate upstream hormones that were shut down by the lack of LH means anything clinically beyond decreased fertility. No one has looked into what happens to men with long term HPTA shut down. Does shutting down pregnenolone, progesterone, etc affect mood?

Anabolic steroids and TRT decrease SHBG, DHEA, pregnenolone and progesterone in men.

Pregnenolone 101: What You Need to Know About this Precursor Hormone - ExcelMale

Taking DHEA and Pregnenolone with surprising result

 

[Nelson Vergel]

Association of aging and obesity with decreased 17-hydroxyprogesterone, a serum biomarker of intratesticular testosterone.

Thiago Fernandes Negris Lima, Fabio Stefano Frech, Ruben Blachman-Braun, Evgeniya Rakitina, Premal Patel & Ranjith Ramasamy
International Journal of Impotence Research (2020)



Metricsdetails

Abstract
Obesity’s negative association with serum testosterone can be explained by either decreasing luteinizing hormone (LH) production from the pituitary gland and/or directly impacting intratesticular testosterone production. We hypothesize that obesity will negatively impact intratesticular testosterone levels when compared to those of non-obese men. We performed a cross-sectional analysis of men with symptoms of testosterone deficiency and male infertility between July 2018 and April 2020 to evaluate the association between body mass index (BMI) and age with intratesticular testosterone (using serum 17-hydroxyprogesterone (17-OHP) as a biomarker), and between BMI with LH. Univariable and multiple linear regression analysis were performed using confounding variables to predict 17-OHP and testosterone. A total of 340 men were selected. Median age was 38 [33–44] years, BMI 27.8 [25.4–31.1] kg/m2, serum testosterone 363 [256.3–469.6] ng/dl, 17-OHP 60.5 [39.3–85.8] ng/dl, and LH 4.2 [2.8–5.7] mIU/ml. Older and obese men had lower testosterone compared to younger and non-obese men. Interestingly, increasing age and higher BMI were associated with lower 17-OHP (p < 0.001). Contrarily, age and BMI were not associated with LH levels (p = 0.478). In conclusion, obesity and aging negatively affected 17-OHP independent of LH, suggesting a possible direct effect on testicular function, rather than a secondary effect from a decline in pituitary signaling.