Low dose enclomiphene combined with Low dose TRT

[UCFguy01]

History.... never had great libido on injections. I've tried high doses, low doses. I've tried with and without an AI. I've tried one a week, twice a week, every day injections, etc. Nothing ever worked that great for libido to be honest. Everything else is amazing on TRT...just not the libido. I have libido but it's just never what it was pre TRT injections. My theory is that it's shut down my natural system and with that comes a lot of other things getting shut down.

So, my doctor prescribed me enclomiphene to try out so I'm going to do an experiment. I want to try low dose enclomiphene to help restart my natural production a bit....while also adding in some low dose testosterone injections. My natural production wasn't that great (450 total T) but I'm hoping my natural levels with a little additional T might be the thing I've been needing. I love the way I feel when my T is high....energy, great sleep, can handle stress, etc... but I just also want that great libido I used to have.

I'd love to hear some thoughts on this experiement.....

 

[Guided_by_Voices]

Several things...there's more to libido than just T. For me for example, DHEA is a big factor, but there are others as well. For your plan, I would expect that using the shortest possible version of T, such as T with no ester is the most likely to succeed, but you are in fairly uncharted waters. A LOW dose of PT-141 might also be something to add in, low being around 100-300 mcg every other day. If your estrogen is low for some reason, that could be a factor as well.

 

[UCFguy01]

Several things...there's more to libido than just T. For me for example, DHEA is a big factor, but there are others as well. For your plan, I would expect that using the shortest possible version of T, such as T with no ester is the most likely to succeed, but you are in fairly uncharted waters. A LOW dose of PT-141 might also be something to add in, low being around 100-300 mcg every other day. If your estrogen is low for some reason, that could be a factor as well.

I've tried PT-141. It caused some anxiety for me for some reason. Not sure why a peptide would do that.

I've never tried DHEA. Maybe that will be something I look into in the future as well.

 

[Cataceous]

In line with what @Guided_by_Voices says, if you want this experiment to work as intended then you need a short-acting form of testosterone, which implies troches or nasal gels. Most other forms are likely to be too suppressive; you won't get much of an additive effect with endogenous testosterone production, and upstream hormone production may also be too low to see benefits. An alternative is to include direct supplementation of GnRH. The results of this trial lead me to believe that secondary effects of HPTA shutdown can harm libido for some of us.

 

[FunkOdyssey]

An alternative is to include direct supplementation of GnRH. The results of this trial lead me to believe that secondary effects of HPTA shutdown can harm libido for some of us.

I think TRT actually works better and more consistently for libido in women than in men for this reason: they are able to supplement reasonable doses of testosterone without shutting down the female HPGA.

 

[Guided_by_Voices]

Thinking about this some more, some men are very dependent on DHT for libido and there are other threads here about ways to raise DHT such as T creams or DHT-like compounds (e.g. proviron). That is by no means the case for all men however. Nandrolone raises libido in some, and you can find threads about that as well.

 

[UCFguy01]

Thinking about this some more, some men are very dependent on DHT for libido and there are other threads here about ways to raise DHT such as T creams or DHT-like compounds (e.g. proviron). That is by no means the case for all men however. Nandrolone raises libido in some, and you can find threads about that as well.

My DHT is usually pretty high on my blood work (Out of range or high end of range).

I'm still stuck on my thesis that enclomiphene could raise libido by restarting the whole reproductive system. There is a lot to the system that gets shut down and I think restarting it all would have some benefit...... Then adding a small amount of TRT to get the energy benefits of higher testosterone could be the best of both worlds.

 

[aneuman]

I'm still stuck on my thesis that enclomiphene could raise libido by restarting the whole reproductive system.

This hypothesis appears to make sense at first, and that's the reasoning my taking Enclomiphene Citrate for more than a year, however, just as Donald Rumsfeld said, there are unknown unknowns.

EC is a SERM that "selectively" block certain estrogen receptors. Which one, I don't know. There are ER in many organs. We know for a fact that it blocks ER in the hypothalamus and the pituitary, and thus the effect in raising LH/FSH, but we don't know what other receptors could be blocking and what there effects could be.

Also, because it raises testosterone, and the aromatization process is unimpeded, the blood work may show normal or even elevated level of estradiol, when you may be feeling symptoms of low estradiol due to the blockage caused by EC, which makes it difficult for doctors to resolve as the evidence (blood work) whose otherwise.

As an anecdote, EC raised by total T to 1183 ng/dL with normal estradiol (33 pg/mL) my I did not feel any different. Perhaps there was a slight mood increase, but nothing really the makes me go back t it or recommend it in any way.

There is a lot to the system that gets shut down and I think restarting it all would have some benefit......

I agree and it seems to make sense...

Then adding a small amount of TRT to get the energy benefits of higher testosterone could be the best of both worlds.

Again, in an ideal world, it makes perfect sense, but going to my first point. For the sake of this thought experiment, let's assume there's an area of the brain responsible for libido and arousal that has an estrogen receptor. Let's assume you go with a small TRT dosage of 7mg of testosterone a day, which will put you close to the top of what most young healthy individuals produce a day. Let's say you add 6.25 mg EC every other day. Everything should be fine and dandy.

What happens if EC blocks that magical hypothetical ER in the brain killing your libido and arousal? Doest matter if your T is at 2000 ng/mL, is going to be all for naught (assuming sexual health is a goal in your experiment)

Additionally, it seems based on information provided by knowledgeable people on this forum including MDs, that if the level of testosterone is too high, such as what happens with TRT, then the androgenic feedback is too strong and cannot be overcome by blocking the ER in the pituitary/hypothalamus and LH production is shutdown anyway.

We don't know what we don't know.

As an experiment, I don't think it would be dangerous, and that would be the only way to test your hypothesis, but without a RCT, it would be difficult to remove confounding variables and declare it a success.

 

[UCFguy01]

As an experiment, I don't think it would be dangerous, and that would be the only way to test your hypothesis, but without a RCT, it would be difficult to remove confounding variables and declare it a success.

Thanks for the detailed reply.

I should get the enclomiphene soon and I'll try out my hypothesis. Your dosage of testosterone and enclomiphene were pretty close to what I was planning on using. I planned on 25mg T twice a week (50mg total per week) & 6.25 Enclomiphene every other day(or maybe M, W, F).

My current protocol is 100mg T per week divided into two shots. This keeps my free T around 25-30(above reference range) and my total T around 800-900. I also take a quarter pill of exemestane once a week which keeps my estrogen in the 30's.

 

[aneuman]

Thanks for the detailed reply.

I should get the enclomiphene soon and I'll try out my hypothesis. Your dosage of testosterone and enclomiphene were pretty close to what I was planning on using. I planned on 25mg T twice a week (50mg total per week) & 6.25 Enclomiphene every other day(or maybe M, W, F).

My current protocol is 100mg T per week divided into two shots. This keeps my free T around 25-30(above reference range) and my total T around 800-900. I also take a quarter pill of exemestane once a week which keeps my estrogen in the 30's.

@UCFguy01

Just so you have a bit more information, some studies show that LH doesn't start to get suppressed with exogenous testosterone until you get to above 5mg testosterone per day. That's exactly what you're planning to use (assuming you are using T.C or T.E). so that means that you should have a functioning H-P which should allow E.C to still produce and effect.

My only concern would be with potentially other estrogen receptors that are blocked by E.C in addition to H-P. If there's none, or if the effect of the blockade is minimal (since E.C has a half life of 7-10 hours), or if the balance produces an overall positive effects, then it might work.

From my standpoint, TC is about $23 a month (for 100 mg a week @ 200mg/ml) and EC is about $162 for 90 pills, that would be about $20/month, so your treatment would cost me less than $50/month which is much cheaper than everything I've tried so far (EC every day, HCG, etc) IF it ended up having the desired benefits you're seeking, which are libido, sensitivity, arousal, and Peter North like shots, etc :-D

From the cost/benefits point of view:

Pros:

1. As close to normal, physiological levels for all (or most) hormones)
2. No Pituitary or testicular atrophy
3. No refrigeration
4. Easy to use IM/SQ, small volume
5. Easy schedule (M-W-F, with potentially Thu for the second T.Cyp injection
6. Relatively cheap compared to alternatives

Cons:

1. More moving parts, more difficult to dial in
2. More dependencies (shortages, supply, etc)
3. More side effects due to changing multiple variables
4. Potentially misleading E2 levels in bloodwork
5. More unknowns, particularly long term (brain, liver, skin, ...?)
6. More expensive than T alone

I'd be interested in following your experiment, so I'd appreciate if you posted back to the group with your results.

Enjoy.

 

[FunkOdyssey]

History.... never had great libido on injections. I've tried high doses, low doses. I've tried with and without an AI. I've tried one a week, twice a week, every day injections, etc. Nothing ever worked that great for libido to be honest. Everything else is amazing on TRT...just not the libido. I have libido but it's just never what it was pre TRT injections. My theory is that it's shut down my natural system and with that comes a lot of other things getting shut down.

So, my doctor prescribed me enclomiphene to try out so I'm going to do an experiment. I want to try low dose enclomiphene to help restart my natural production a bit....while also adding in some low dose testosterone injections. My natural production wasn't that great (450 total T) but I'm hoping my natural levels with a little additional T might be the thing I've been needing. I love the way I feel when my T is high....energy, great sleep, can handle stress, etc... but I just also want that great libido I used to have.

I'd love to hear some thoughts on this experiement.....

Total T is meaningless relative to Free T, but if you were sitting at 450 baseline it is conceivable that you could double that with enclomiphene by itself. Whether you reach 900 total with a combination of TRT and enclomiphene, or just enclomiphene alone, I don't think it will make much difference. Either way, the enclomiphene will be floating around the brain blocking E2 receptors and I predict it will block the perceived benefits of testosterone in its usual manner. I don't want to be discouraging but I wouldn't have high hopes for this experiment.

 

[Cataceous]

...
Just so you have a bit more information, some studies show that LH doesn't start to get suppressed with exogenous testosterone until you get to above 5mg testosterone per day. ...

Would you provide the links? I'm interested in taking a look at the study conditions.

 

[UCFguy01]

Total T is meaningless relative to Free T, but if you were sitting at 450 baseline it is conceivable that you could double that with enclomiphene by itself. Whether you reach 900 total with a combination of TRT and enclomiphene, or just enclomiphene alone, I don't think it will make much difference. Either way, the enclomiphene will be floating around the brain blocking E2 receptors and I predict it will block the perceived benefits of testosterone in its usual manner. I don't want to be discouraging but I wouldn't have high hopes for this experiment.

Interesting....so it seems the blocking E2 aspect of enclomiphene is what raises T but also what depletes the benefits. What a conundrum.

I'll try it out and see. What if it works? What if it's the holy grail a lot of people on TRT have been looking for....?

 

[aneuman]

Would you provide the links? I'm interested in taking a look at the study conditions.

If only I were as organized as you guys... I posted it a while back, and I thought I had saved it, but I promise I'll find it.

 

[FunkOdyssey]

Interesting....so it seems the blocking E2 aspect of enclomiphene is what raises T but also what depletes the benefits. What a conundrum.

I'll try it out and see. What if it works? What if it's the holy grail a lot of people on TRT have been looking for....?

It might work, I've been wrong about plenty of things before. Also, Cataceous here uses enclomiphene as part of a complex regimen to maintain HPTA function on TRT and he seems to do well with it. That puts him in a small minority though that sees net positive results with enclomiphene involved.

 

[aneuman]

Would you provide the links? I'm interested in taking a look at the study conditions.

Unfortunately I still can't find the original article which I thought I had saved in Zotero, but found this in a previous post I made. It's just the abstract though:

Serum LH and FSH levels were measured by radioimmunoassay after exogenous testosterone was administered to four groups of adult males in dosages ranging from 1-25 mg per day. Serum testosterone concentrations, determined by radioimmunoassay, were elevated subsequent to the administration of the higher dosages. Dose-related depression of both LH and FSH was observed subsequent to administration of 5 or more mg of testosterone per day; the smallest dosage (1 mg) was not associated with any consistent changes in LH or FSH. The rate and extent of decline of the two gonadotropins differed. Serum LH values tended to drop and recover more rapidly than FSH following testosterone administration. These results indicate that testosterone suppresses serum levels of both LH and FSH in the human adult male. There was no evidence of stimulation of gonadotropin release at these doses.

Here's the link:

Regulation of human gonadotropins. VIII. suppression of serum LH and FSH in adult males following exogenous testosterone administration

I think it makes sense though. You've mentioned in previous occasions that the typical young, healthy male makes between 5-10 mg os testosterone a day. If your provide 5 mg exogenously, you'll be getting close to the natural top, so it means that there's no reason for the HPGA to shut down, as the total level is within its managed range. As exogenous T starts to get cleared from the system, the HPGA takes over and tries to restart natural production.

Once you start going over 5 mg per day, you're getting into persistently elevated levels of T that won't clear soon enough before the next injection for the HPGA to intervene, so it starts to shutdown production until it's atrophies.

I'm obviously oversimplifying a much more complex process that includes aromatization, SHBG, etc and ignores a potential androgenic feedback loop.

Would love to hear your comments in this regard. In the meantime, I'll continue to look for the original article where I saw this, which wasn't this one.

 

[aneuman]

@UCFguy01​

Another thing to consider in your experiment is :

"...that T and/or its metabolites inhibit LH and FSH secretion by a GnRH-independent mechanism, probably directly on the pituitary gland, in man."

This means that under the action of exogenous testosterone, the effect of SERM may be limited in its ability to block negative feedback via estrogen receptor, as there may be another feedback loop that operates on the androgen receptor as well

Testosterone administration inhibits gonadotropin secretion by an effect directly on the human pituitary

I think @Cataceous had previously either cited or speculated on this androgenic feedback reducing the ability of SERMs to work while on exogenous T.

Probably you'd have better results using Natesto and Enclomiphene, as per:

Our findings suggest that short-acting T preparations do not decrease serum FSH or LH to the same extent as longer-acting transdermal gels and injectables.

The Effect of Longer-Acting vs Shorter-Acting Testosterone Therapy on Follicle Stimulating Hormone and Luteinizing Hormone

But that would make the treatment uncomfortable, expensive and inconvenient, as Natesto has to be used at least twice a day, and based on some particular experiences, including a friend of mine, the experience can be "disgusting" although he said the effect was noticeable.

 

[Systemlord]

I want to try low dose enclomiphene to help restart my natural production a bit....

Sorry, but this isn’t going to have the intended outcome you hope for. Exogenous T has a strong suppressive effect.

Nothing ever worked that great for libido to be honest. Everything else is amazing on TRT...just not the libido.

I theorize that the reason why some men don’t have a strong libido on TRT has to due with the hormone levels being almost constantly elevated, no large peaks and valleys in the short term.

The moment I reached steady states on injections, the libido and erections would disappear. On Jatenzo, where levels peak in 2 hours and drop quickly, this is not the case.

The solution, a shorter half-life formulation of TRT, or as someone mentioned, PT-141.

 

[Cataceous]

.... In the meantime, I'll continue to look for the original article where I saw this, which wasn't this one.

I found it—see attached. The more complete story is that the tested doses were 1, 5, 12.5 and 25 mg per day for three days, testosterone in an aqueous solution delivered IM. Suppression was seen in all the subjects except four out of five getting only 1 mg per day. Thus suppression could occur with much less than 5 mg per day. In addition, three days is somewhat short with respect to HPTA shutdown.

...
I think @Cataceous had previously either cited or speculated on this androgenic feedback reducing the ability of SERMs to work while on exogenous T.
...

I'd say this is beyond speculation, having some support in the literature and anecdotally. The interesting part is that androgenic suppression occurs in the hypothalamus but not the pituitary. This is why you can make LH and FSH when using TRT + enclomiphene + GnRH, as I have demonstrated.

 

[UCFguy01]

My enclomiphene arrived but it's in 50mg capsules. WTF? How the heck am I going to split that into a low dose?