Is “Enclomiphene Citrate” going to replace hCG in the USA?

[jacb]

Forgive my ignorance, but if I understand you correctly, you are saying that both enclomiphene and clomid cancel the negative feedback system. A feedback system that (ultimately) reduces LH (in Clomid‘s case) and LH & FSH (in the case of enclomiphene) that enables the body to maintain its own set point values (Production).

Looking at it a different way, Clomid may increase LH (by canceling the negative feedback) and enclomiphene may increases LH & FSH (For the same reason). If the negative feedback system is cancelled and the throttle removed, dosnt the body produce its maximum LH and in turn its maximum Testosterone?

If the above hypothesis is correct, why can‘t the bodies production of Testosterone not then be supplemented with extra external testosterone Even when clomid or enclomiphene are used?

With the negative feedback effectively removed wouldn’t the naturally produced testosterone value, simply be sumated with the external testosterone to provide the Total Testosterone?

The effect of SHBG (in the main) will then attempt to adjust the Free Testosterone to the bodies desired value. One of the downside things about Clomid is that it raises SHBG and that it also has considerable unpleasant side effects. Is this true with enclomiphen?

I must have got something backwards?

 

[captain]

The feedback sees the testosterone as well from what I have read. The feedback is not totally removed. I don't know just what I got from some post about it.

 

[jacb]

 

[jacb]

I beleive enclomiphene and clomid are both SERM’s?

Maybe the main problem here is that the E2 might “go through the roof”?

 

[Cataceous]

Clomid aka clomiphene consists of about 60% enclomiphene and 40% zuclomiphene. Enclomiphene is the isomer that selectively antagonizes estrogen receptors—and in particular those in the hypothalamus and pituitary. Zuclomiphene is estrogenic, selectively agonizing some estrogen receptors. Clearly enclomiphene is more potent than zuclomiphene with respect to the HPTA, as overall clomiphene stimulates rather than suppresses. However zuclomiphene is still potent; taking it by itself can effectively castrate a natural male, the same way taking estrogen does. In general it doesn't make sense for men to take zuclomiphene at all unless they really needed added estrogenic activity.

There is some degree of negative feedback at the hypothalamus from both estrogens and androgens. Enclomiphene reduces or eliminates the negative feedback from estrogens by blocking those receptors. At the pituitary, however, it appears there is minimal, if any negative feedback from androgens; the negative feedback is from estrogens. Therefore, in principle enclomiphene allows the pituitary to respond fully to whatever GnRH is delivered by the hypothalamus.

There are some lingering questions about the effects of androgens on the hypothalamus. Why is it possible for some men to have quite high endogenous testosterone with clomiphene monotherapy, when in contrast it seems few can sustain HPTA activity with concurrent TRT? Is it related to absolute levels of the hormones, or does it also involve how the levels change? Testosterone is naturally delivered in pulses. Natesto imitates this to an extent and Natesto is the only form of exogenous testosterone proven to allow continued HPTA activity. A further question: how much natural variability between men is there in the strength of negative androgen feedback at the hypothalamus? If there's wide variability then it could explain some of the unusual anecdotes.

 

[jacb]

SERM …. Selective Estrogen Receptor Modulators, also known as estrogen receptor agonist/antagonists, are a class of drugs that act on the estrogen receptors.

 

[jacb]

There are some lingering questions about the effects of androgens on the hypothalamus. Why is it possible for some men to have quite high endogenous testosterone with clomiphene monotherapy, when in contrast it seems few can sustain HPTA activity with concurrent TRT? Is it related to absolute levels of the hormones, or does it also involve how the levels change? Testosterone is naturally delivered in pulses. Natesto imitates this to an extent and Natesto is the only form of exogenous testosterone proven to allow continued HPTA activity. A further question: how much natural variability between men is there in the strength of negative androgen feedback at the hypothalamus? If there's wide variability then it could explain some of the unusual anecdotes.

Thanks Cataceous

Interesting what you say … It seems that the changes the FDA have made re HCG may indirectly lead to some further “Study“ regarding the issues above.

But where does that leave hCG users now?

Are Low T Nation trying to answer the question about what percentage of men can sustain HPTA activity with concurrent TRT? I do find it interesting to contrast two of the company’s own videos … clearly their thinking is dramatically changing as times change. But what about the Clomid side effects and raised SHBG they talk about in the older video? Wont that become a factor for Enclomiphene Citrate users as well?

Their latest video: Why we are replacing hcg with Enclomiphene Citrate

Their older video: HCG or Clomid while on Testosterone and fertility

I personally think the use of a testosterone nasal gel like Natesto would quickly become irksom.

It will be interesting to see how the Enclomiphene Citrate protocol develops in time.

 

[Cataceous]

I'd like my skepticism of the Low T Nation protocol to be wrong. It would mean that in general it's a lot easier to keep the HPTA alive under TRT than I'd been thinking—and experiencing. Time will tell, but for now I remain doubtful.

It's likely that Clomid raises SHBG via the estrogenic action of the zuclomiphene isomer. The clinical trials on enclomiphene show virtually no change in SHBG.

 

[jacb]

It's likely that Clomid raises SHBG via the estrogenic action of the zuclomiphene isomer.
The clinical trials on enclomiphene show virtually no change in SHBG.

Well that is something that is very definitely in enclomiphene‘s favour When it come to Free T.

What about the other side effects of long term Covid use? What are they and would they not also be a factor with Enclomiphene‘s use?

 

[Cataceous]

Well that is something that is very definitely in enclomiphene‘s favour When it come to Free T.
...

Probably not. HPTA regulation is primarily through free testosterone, both directly, and indirectly via free estradiol. What this means is that high SHBG doesn't have much influence over free testosterone. Instead it pushes up total testosterone.

...
What about the other side effects of long term [Clomid] use? What are they and would they not also be a factor with Enclomiphene‘s use?

Estrogenic side effects should be attenuated with enclomiphene compared to Clomid. I speculate that visual disturbances are possible with both drugs, but remain uncommon at normal doses. Further speculation is that some men will have trouble with both drugs due to too much reduction in estrogenic activity in some parts of the brain—affecting libido, etc.

 

[jacb]

Hi Cataceous

Have I got this right?

If a guy takes Clomid (Clomiphene, 60% enclomiphene & 40% zuclomiphene) their Total Testosterone will increase, but so will their SHBG, resulting (at best) in only a small change of Free Testosterone. Supplementing with IM/SubQ Testosterone will probably still not change the Free Testosterone values because the "HPTA regulation is primarily through free testosterone", the body would automatically adjust its SHBG values and negate any Free Testosterone change?

You say that the clinical trials on Enclomiphene show virtually no change in SHBG. So Enclomiphene will increase Total and Free Testosterone. Now what will the effect Supplementing with IM/SubQ Testosterone be? Is this what Low T Nation are trying to work out?

 

[Cataceous]

...
If a guy takes Clomid (Clomiphene, 60% enclomiphene & 40% zuclomiphene) their Total Testosterone will increase, but so will their SHBG, resulting (at best) in only a small change of Free Testosterone. Supplementing with IM/SubQ Testosterone will probably still not change the Free Testosterone values because the "HPTA regulation is primarily through free testosterone", the body would automatically adjust its SHBG values and negate any Free Testosterone change?

You say that the clinical trials on Enclomiphene show virtually no change in SHBG. So Enclomiphene will increase Total and Free Testosterone. Now what will the effect Supplementing with IM/SubQ Testosterone be? Is this what Low T Nation are trying to work out?

Starting from a natural state, a guy taking clomiphene usually sees an increase in the rate of testosterone production. Even if SHBG doesn't change, we expect the increased production rate to raise free testosterone, which in turn pushes up total testosterone. It's common for the added estrogenic action of zuclomiphene to raise SHBG. This shouldn't affect the increase in free testosterone, but it means total testosterone is increased more than if SHBG hadn't changed. Conventional wisdom has been that increases in SHBG limit gains in free testosterone, but this is probably incorrect—because free testosterone should be pretty independent of SHBG as long as total testosterone is unconstrained.

"Supplementing" with exogenous testosterone can be rather complicated, but let's assume the most likely scenario, in which the usual negative HPTA feedback is saturated with excess testosterone. Normally estradiol is the larger contributor to this suppression, but it has been blocked by enclomiphene. In this case natural testosterone production still ceases and free testosterone is now a function of the dosing of the exogenous testosterone. If free testosterone is higher than pre-TRT then this may somewhat counteract the effect of zuclomiphene on SHBG. If SHBG goes down as a result then total testosterone also falls, but free testosterone is unaffected; free testosterone is the independent variable.

I don't see any reason why replacing clomiphene with enclomiphene in the above situation should produce different results, except for the possible variations in SHBG. It will be interesting and puzzling if enclomiphene is shown to be a viable replacement for hCG. I'm still betting against it at this point.

 

[technomentor]

FWIW....
Thru Defy, last summer I opted to test enclomiphene treatment vs. shots. My T has been low (250-300) for the past few years. Primary symptoms I wanted to improve:

• Lack of energy
• Muscle loss
• Loss of libido
• Lack of focus/drive

Results
2021-07-08 - Initial labs, before consultation and starting treatment
Total T: 227 ng/dL
Free T: 6.6
DHEA-S: 353
LH: 3.4
PSA: 0.9
IGF-1: 132
Estradiol: 11.6
SHBG: 38.7

2021-09-01 - started enclomiphene 25mg by mouth daily

2021-10-01
Total T: 872 ng/dL <-- major jump in just one month
I chose to test more frequently than Defy recommended. Since my target was 600-800 I shared results with Dr. Saya. We decided to titrate back to 25 mg three times per week.

2021-11-09
Total T: 750 ng/dL <-- now w/i my desired range
Free T: 19.4
LH: 9.6
PSA: 1.5
FSH: 10.9
DHEA-S: 289
IGF-1: 109
Estradiol: 24.1 <-- more than doubled
SHBG: 48.3

My Results
Although all T levels improved, none of my symptoms did. I discussed this with Dr. Saya during a Dec appointment. He explained the difference between how enclomiphene works vs. exogenous testosterone.

Conclusion
I chose to stop enclomiphene treatment becasue I experienced no change in my symptoms. Dr. Saya said I needed to wait 90 days for it to clear my system, then complete a new male hormone baseline before deciding on the protocol using shots. I have a lab order for my new tests.

Personal Stats
I'm 57, 175 lbs, 5'-11" with a BMI of just under 25. I exercise regularly (4-5 times/wk) and have changed my eating habits (significantly lower carbs) since I have confirmed CVD, as determined by recent CAC and CIMT testing. My thyroid levels are all in ideal ranges. That said, I recently completed a diurnal saliva test and determined that I'm at Stage 3 of adrenal dysfunction. Several of the symptoms I want to improve are also affected by cortisol levels. I am reading Adrenal Fatigue by D. James L Wilson to determine a treatment protocol for this -- since most endocrinologists don't believe in adrenal insufficiency/fatigue. Hell, they won't even order diurnal saliva tests - I did that on my own. I am also planning on getting a sleep study to check for sleep apnea since I don't sleep well/experience unrestful sleep -- and we all know that sleep is a key factor in overall health.

 

[jacb]

2021-09-01 - started enclomiphene 25mg by mouth daily

2021-10-01
Total T: 872 ng/dL <-- major jump in just one month
I chose to test more frequently than Defy recommended. Since my target was 600-800 I shared results with Dr. Saya. We decided to titrate back to 25 mg three times per week.

2021-11-09
Total T: 750 ng/dL <-- now w/i my desired range
Free T: 19.4
LH: 9.6
PSA: 1.5
FSH: 10.9
DHEA-S: 289
IGF-1: 109
Estradiol: 24.1 <-- more than doubled
SHBG: 48.3

Thank you technomentor for your feedback and practical experience of enclomiphene.

Re your test 2021-10-1 did you get a full panel of tests, as per 2021-11-09?

If you did, could we see the other results please. (SHBG etc)

 

[technomentor]

Thank you technomentor for your feedback and practical experience of enclomiphene.

Re your test 2021-10-1 did you get a full panel of tests, as per 2021-11-09?

If you did, could we see the other results please. (SHBG etc)

jacb,

On 10-1-2021, I only tested for Total T. I added that to a blood draw I was doing for other, non-hormone related, biomarkers. Since I direct order and pay out of pocket, I did want to do the full panel.

 

[aneuman]

FWIW....
Thru Defy, last summer I opted to test enclomiphene treatment vs. shots. My T has been low (250-300) for the past few years. Primary symptoms I wanted to improve:

• Lack of energy
• Muscle loss
• Loss of libido
• Lack of focus/drive

Results
2021-07-08 - Initial labs, before consultation and starting treatment
Total T: 227 ng/dL
Free T: 6.6
DHEA-S: 353
LH: 3.4
PSA: 0.9
IGF-1: 132
Estradiol: 11.6
SHBG: 38.7

2021-09-01 - started enclomiphene 25mg by mouth daily

2021-10-01
Total T: 872 ng/dL <-- major jump in just one month
I chose to test more frequently than Defy recommended. Since my target was 600-800 I shared results with Dr. Saya. We decided to titrate back to 25 mg three times per week.

2021-11-09
Total T: 750 ng/dL <-- now w/i my desired range
Free T: 19.4
LH: 9.6
PSA: 1.5
FSH: 10.9
DHEA-S: 289
IGF-1: 109
Estradiol: 24.1 <-- more than doubled
SHBG: 48.3

My Results
Although all T levels improved, none of my symptoms did. I discussed this with Dr. Saya during a Dec appointment. He explained the difference between how enclomiphene works vs. exogenous testosterone.

Conclusion
I chose to stop enclomiphene treatment becasue I experienced no change in my symptoms. Dr. Saya said I needed to wait 90 days for it to clear my system, then complete a new male hormone baseline before deciding on the protocol using shots. I have a lab order for my new tests.

Personal Stats
I'm 57, 175 lbs, 5'-11" with a BMI of just under 25. I exercise regularly (4-5 times/wk) and have changed my eating habits (significantly lower carbs) since I have confirmed CVD, as determined by recent CAC and CIMT testing. My thyroid levels are all in ideal ranges. That said, I recently completed a diurnal saliva test and determined that I'm at Stage 3 of adrenal dysfunction. Several of the symptoms I want to improve are also affected by cortisol levels. I am reading Adrenal Fatigue by D. James L Wilson to determine a treatment protocol for this -- since most endocrinologists don't believe in adrenal insufficiency/fatigue. Hell, they won't even order diurnal saliva tests - I did that on my own. I am also planning on getting a sleep study to check for sleep apnea since I don't sleep well/experience unrestful sleep -- and we all know that sleep is a key factor in overall health.

Are you me?

About the same age, same height, same issues (except CVD, instead add BPH). I'm also on enclomiphene 12.5 mg ED and my T shot up from 390 to 780 in a month. E2 went only from 27 to 31.All symptoms remain the same, except perhaps, a bit more willing to do things around the house.

What a difference with HCG (while it worked, only 3 weeks). All my symptoms were resolved, then everything tanked and I'm still at the bottom.

I wonder if the problem may not really be T but E. These are my current hypothesis:
1.- My E2 is too low. According to some research, libido only returns after E2 hits 50
2.- My E2 is too high, According to some research, healthy men have E2 around the low 20s
3.- My E2 is fine, but somehow enclomiphene blocks E2 receptors in some area important for libido, in which case, enclomiphene will not work despite the beautiful numbers and ease of use.

 

[Cataceous]

...
I wonder if the problem may not really be T but E. These are my current hypothesis:
1.- My E2 is too low. According to some research, libido only returns after E2 hits 50
2.- My E2 is too high, According to some research, healthy men have E2 around the low 20s
3.- My E2 is fine, but somehow enclomiphene blocks E2 receptors in some area important for libido, in which case, enclomiphene will not work despite the beautiful numbers and ease of use.

If you're feeling adventurous then you could test these ideas by supplementing estradiol. One minor concern is that the estradiol would oppose your enclomiphene and reduce testosterone. However, I don't think this would be much of an issue at reasonable doses. Normal daily production in men is said to be on the order of 50 mcg. In a test like this I might start at 10 mcg. Estradiol cream would be a convenient option, though you would need to find or make some that has a sufficiently low concentration. If the absorption rate of a topical is about 10% then you'd need to apply 100 mcg of estradiol in cream to absorb 10 mcg. You can get estradiol mixed with estriol on Amazon. But each pump of this product delivers 500 mcg of estradiol, five times more than a prudent starting dose.

 

[tareload]

I'll be a little less nice than @Cataceous. The video you posted is full of half truths and misinformation in the first 3 mins. Insurance won't pay for hCG? ... wow that's news for me. He's just not getting the markup through the compounding pharmacy purchase so you do the math. If you are at this clinic ask why they won't send your Rx to a specialty pharmacy?

Youtube....face palm.

Need hCG, do your homework:

Testosterone versus Clomid (clomiphene citrate) in managing symptoms of hypogonadism in men

I could not see clomid dosages used. This makes a big difference, as we now no too much zuclomiphene causes inverse effects. According to Dr Saya, this does not seem to happen in the low dose patients they see, which appears to be consistent with other doctors now using lower dose clomid...

www.excelmale.com

Adding a recent data point here. Do you homework if you still want hCG:


Solid specialty pharmacy (based on my relevant experience):

Fairview Specialty Pharmacy

Fairview Specialty Pharmacy supplies the same high-quality, FDA-approved medications found at our retail pharmacies.

www.fairview.org

Shipping included and they'll include the syringes (I use 23 g needle with 5 or 10 mL syringe to reconstitute and 30 g insulin pin to inject) and sharps container as part of the hCG price.

Ain't much of a coupon through GoodRx
View attachment 20322


Ok, I went and looked and the price is discounted rate with my insurance. So if you are retail then GoodRx still better than $383. Sad the difference between insurance and retail.
View attachment 20323

 

[aneuman]

If you're feeling adventurous then you could test these ideas by supplementing estradiol. One minor concern is that the estradiol would oppose your enclomiphene and reduce testosterone. However, I don't think this would be much of an issue at reasonable doses. Normal daily production in men is said to be on the order of 50 mcg. In a test like this I might start at 10 mcg. Estradiol cream would be a convenient option, though you would need to find or make some that has a sufficiently low concentration. If the absorption rate of a topical is about 10% then you'd need to apply 100 mcg of estradiol in cream to absorb 10 mcg. You can get estradiol mixed with estriol on Amazon. But each pump of this product delivers 500 mcg of estradiol, five times more than a prudent starting dose.

Thanks @Cataceous! I am feeling adventurous and cautious at the same time. The fact that I have BPH and my PSA shot up from 2.0 to 2.8 in a month gives me pause. I know that there's no strong evidence that testosterone causes PCa, but there's some questions about estrogens.

Here's why I have this interesting hypothesis about low estrogen. When I started taking Cialis 5 mg daily for BPH, everything was great, but as the years went on, I started having delayed orgasm, but libido was still great. I thought it was low testosterone, but I was around 492. Later I learned that Cialis daily decreases estrogen receptors and increases Testosterone to estradiol ratio, which is normally considered to be good.But this coincides with my issues with orgasm and libido. I'm currently off Cialis, but experiencing BPH issues.

I'll be interested in knowing what's the E2 levels of folks around here that do NOT have any problems with libido, orgasm or ejaculation and are on TRT or similar. Is greater or lower than 50? Closer to the low 20? even less?

Anybody else has experienced similar issues with daily Cialis? Delayed orgasm, low libido?

In addition to the issues that @technomentor stated, I also have sleep problems, and mostly in the past, sometimes hot flashes and, night sweats, and extremely cold feet. Everything except the sleep has improved though.

Thanks,

AN

 

[jacb]

Here Dr Andrew McCollough of The Urological Institute of Northeastern New York talks about a ZA-304/305 Study of Enclomiphene for treatment of Secondary Hypergonadism whilst preserving fertility and avoiding testicular atrophy. LINK