Pituitary restart while on TRT: promising initial results with GnRH plus enclomiphene

[DaytonaJonah]

Your first measure of progress should be in increasing LH/FSH. At least for me it took a couple months to see significant effects.

That is exactly what I want to accomplish. Both of my numbers are at zero or near zero currently and it is due to this fact that I suspect why most guys are with crushed libido, flat emotions, along with mild exhaustion.

I can source Gonadorelin with Kisspeptin-10 and will probably add that at some point in the near future. But, I'd like to see what happens to my numbers AND my overall wellbeing on a simple Kisspeptin-10 daily/twice daily dose + Enclomiphene. I'm planning to start with a small daily dose of Kisspeptin-10 and then see what effect it is having on LH & FSH. I'll likely stick with this basic plan for at least 2 months and then adjust up or down depending on where things are by then.

Looking forward to this new journey and want to thank you for your blazing this trail for those of us to follow. I appreciate greatly your very measured approach and fine details. Will try to post when I have something worthwhile to share.

DJ

 

[Willyt]

Cat - After reading your summary post on potential of RF9, I started wondering how would introduction of RF9 change your protocol? All theoretical of course.

RF9: May it be a new therapeutic option for hypogonadotropic hypogonadism?

Intriguing stuff, possibly highlighting another distinct cause of hypogonadism, along with a new treatment option. There's been little discussion of gonadotropin-inhibitory hormone or GnIH. This hormone counters kisspeptin and suppresses the HPTA. An excess of GnIH may lead to hypogonadism. RF9...

www.excelmale.com

 

[Cataceous]

Cat - After reading your summary post on potential of RF9, I started wondering how would introduction of RF9 change your protocol? All theoretical of course.
...

From the sound of it RF9 could act as a more potent replacement for kisspeptin, particularly if it does have both kisspeptin agonism and GnIH antagonism. RF9 has a much longer half-life than kisspeptin. It's not clear if that's good or bad, because they're saying that constant infusion of kisspeptin may lead to desensitization, as with GnRH. But it also doesn't seem to be true for females, at least in an experiment on ewes. It's definitely a case where more research is needed, and I'd want to see some human safety trials before even thinking about trying it.

 

[DaytonaJonah]

Where I live, I'm not too sure I can source Enclomiphine. Clomid can be easily obtained here. Similar but not the same...but, can Clomid still accomplish the same objective? If so, what dosage would be useful?

 

[Cataceous]

Where I live, I'm not too sure I can source Enclomiphine. Clomid can be easily obtained here. Similar but not the same...but, can Clomid still accomplish the same objective? If so, what dosage would be useful?

Clomid can be thought of as enclomiphene plus estrogen (zuclomiphene). The enclomiphene is strong enough at the hypothalamus and pituitary to overcome both the endogenous and exogenous estrogens. So Clomid can help with the HPTA activation described in this thread, but with a higher risk of side effects than enclomiphene alone. I'd expect somebody who naturally has higher estradiol relative to testosterone would be at greater risk of side effects than someone who has lower estradiol.

On the flip side, somebody who naturally has lower estradiol might do worse with enclomiphene alone, though there's no guarantee that Clomid would compensate for excessive antagonism of estrogen receptors by the enclomiphene component. I mention this because one individual tried this protocol and successfully restarted his pituitary, but his subjective results were poor, and we speculate that the enclomiphene may be to blame.

Clomid is a little more than half enclomiphene, so to get the same dose of enclomiphene you would use about twice as much Clomid. However, I wouldn't take more than 25 mg per day, and I would start lower, with 12.5 mg EOD or daily.

A significant problem with Clomid is that the zuclomiphene component has a very long half-life, on the order of weeks. This means the build-up of zuclomiphene may take months, and the onset of side effects can be delayed. When Clomid is discontinued it takes a long time for the zuclomiphene to clear, which implies that side effects can linger.

 

[DaytonaJonah]

Clomid can be thought of as enclomiphene plus estrogen (zuclomiphene). The enclomiphene is strong enough at the hypothalamus and pituitary to overcome both the endogenous and exogenous estrogens. So Clomid can help with the HPTA activation described in this thread, but with a higher risk of side effects than enclomiphene alone. I'd expect somebody who naturally has higher estradiol relative to testosterone would be at greater risk of side effects than someone who has lower estradiol.

On the flip side, somebody who naturally has lower estradiol might do worse with enclomiphene alone, though there's no guarantee that Clomid would compensate for excessive antagonism of estrogen receptors by the enclomiphene component. I mention this because one individual tried this protocol and successfully restarted his pituitary, but his subjective results were poor, and we speculate that the enclomiphene may be to blame.

Clomid is a little more than half enclomiphene, so to get the same dose of enclomiphene you would use about twice as much Clomid. However, I wouldn't take more than 25 mg per day, and I would start lower, with 12.5 mg EOD or daily.

A significant problem with Clomid is that the zuclomiphene component has a very long half-life, on the order of weeks. This means the build-up of zuclomiphene may take months, and the onset of side effects can be delayed. When Clomid is discontinued it takes a long time for the zuclomiphene to clear, which implies that side effects can linger.

As it is, my E2 stands right around 25 pg/ml with a total T of 850 ng/dL+/- sustained peak(pellets), so I have some room to play with...just a little. I imagine with the use of microdosing an AI, one could mitigate somewhat of the longer effects of the zuclomiphene as they slowly fade if my protocol fails.

A lot of moving parts. Hmmmm, may have to re-consider the risks and hassle. May have to have someone bring down some Enclomiphine for me to begin this all with. Clomid to me, sounds like trouble to be avoided.

 

[DaytonaJonah]

Waiting to hear back from Tailor Made Pharmacy if they have enclomiphine tablets, and will accept a script from a foreign doc.

In the meantime, I've found enclomiphine citrate liquid from a reputable(as per message boards & limited reviews) peptide company. Injecting sub-q would be fine...just wanting to get nudged in the right direction on how to properly calculate injection dosage equivalence to 12.5mg tablets?

 

[Cataceous]

Waiting to hear back from Tailor Made Pharmacy if they have enclomiphine tablets, and will accept a script from a foreign doc.

In the meantime, I've found enclomiphine citrate liquid from a reputable(as per message boards & limited reviews) peptide company. Injecting sub-q would be fine...just wanting to get nudged in the right direction on how to properly calculate injection dosage equivalence to 12.5mg tablets?

Surely it's intended for oral use. I haven't heard of any injectable products. A quick search for "enclomiphine citrate liquid" shows that a lot of the products are 25 mg per milliliter. In these cases half an mL in your oral syringe gives you 12.5 mg enclomiphene, assuming the product is legitimate. I think some guys order tablets from India, maybe the Enclofert brand? I can't vouch for any of these. I've obtained mine from Tailor Made Pharmacy and now Empower Pharmacy.

 

[DaytonaJonah]

Surely it's intended for oral use. I haven't heard of any injectable products. A quick search for "enclomiphine citrate liquid" shows that a lot of the products are 25 mg per milliliter. In these cases half an mL in your oral syringe gives you 12.5 mg enclomiphene, assuming the product is legitimate. I think some guys order tablets from India, maybe the Enclofert brand? I can't vouch for any of these. I've obtained mine from Tailor Made Pharmacy and now Empower Pharmacy.

I've got messages now into both TMP and EP about their enclomiphine oral tablets. I checked the product list on EP's website and they aren't yet showing enclomiphine listed as an available product. So, it must be rather new for them and haven't yet updated their site.

One way or another, I'll get it here in Mex where I'm at. Thanks for your advice, Cat.

 

[gusamaso]

Any follow up, guys?

 

[Cataceous]

I did try another experiment with reduced enclomiphene and minimal TRT dosing. Unfortunately the results are inconclusive. This was a three month period in which I injected 4.5 mg testosterone propionate daily, with no other ester. I reduced the enclomiphene dosing to 12.5 mg every four days. The GnRH regimen was unchanged. There were no problems with testicular discomfort this time. The subjective results were adequate, but lacking when compared to the standard protocol that uses an ester blend and EOD enclomiphene. With the standard protocol I've had libido, cognition, mood and sexual function be consistently good for months. In this experiment there was some unevenness in libido, mood and sexual function, and I felt that cognition was somewhat degraded.

There was an interesting correlation with pain sensitivity. Earlier this year I started taking some palmitolyethanolamide (PEA) to see if it would help with chronic pain from a damaged joint. Within weeks of starting the pain was substantially lessened, and remained that way until I tried this experiment. During the experiment I realized that the pain had returned to pre-PEA levels. I just assumed the joint had further degraded. But a few weeks after I ended the experiment and returned to the normal protocol the pain abruptly lessened. Is there a causal relationship? I don't know. There's substantial research linking estrogen and pain sensitivity—either as promoter or inhibitor, depending on the study. If the connection is real in this case then it could potentially be linked to enclomiphene's antagonism of estrogen receptors. The skeptic in me notes that it's only E4D versus EOD enclomiphene dosing—should that be enough to make such a pronounced difference? In any case, the hypothesis to test is that PEA and enclomiphene work synergistically to reduce pain sensitivity. This is not a trivial reduction—I'd put it at two to three points on a ten-point scale.

Before resuming my standard protocol I had lab work done at a pre-injection trough. At 430 ng/dL, total testosterone was much higher than expected. This was surprising and disappointing. Based on previous measurements with propionate the trough was expected to be in the 200s ng/dL. It was also the intent of the experiment to see if lower troughs would help to maintain HPTA activity. Given the high trough, it's less surprising that LH was undetectable. Another inexplicable anomaly was having total estradiol in the mid-40s, which yields the highest E2/T ratio I've ever seen.

If the subjective results had been better then I might have continued the experiment and tried to better understand things with additional testing. But I knew that my standard protocol was preferable, and thus I was not motivated to continue this line of research.

 

[docc]

Why inject GnRH? While TRT downregulates its, enclomiphene upregulates it by block estradiol's negative feedback on GnRH production—thus leading to an increase in secretion of GnRH and subsequently LH and FSH. Thus, doesn't enclomiphene make GnRH supplementation redundant?

 

[Cataceous]

Why inject GnRH? While TRT downregulates its, enclomiphene upregulates it by block estradiol's negative feedback on GnRH production—thus leading to an increase in secretion of GnRH and subsequently LH and FSH. Thus, doesn't enclomiphene make GnRH supplementation redundant?

As discussed in the first post, SERMs are generally unable to activate the HPTA during TRT, at least at commonly used testosterone doses. Androgens apply negative feedback directly to the hypothalamus. SERMs do not affect this mechanism; they only block estrogens. Anecdotal reports suggest a few exceptions may exist. However, Dr. Saya has described seeing many patients who were previously on TRT and Clomid, with virtually none showing appreciable HPTA activity.

TRT with clomid

Has anyone tried trt with clomid? 150mg test cyp weekly with __mg clomid?

www.excelmale.com

Clomid & Testosterone: Why they don't work together - By Mike Gaiso

I have seen misinformation on Clomid (Clomiphene) too often - Men on TRT taking Clomid thinking that it will keep their testes producing testosterone (T) while on TRT. WRONG. Let me try to clear up this mess. Testosterone production is controlled by the hypothalamus-pituitary-testicular axis...

www.excelmale.com

 

[Cataceous]

I'm not sure about the significance of this: It appears that sometime in the course of this experiment endogenous progesterone production resumed. Baseline supplementation was 0.6 mg injected per day, and eight months into the experiment serum progesterone was 0.3 ng/mL (0.0-0.5), which was expected with that dose. Earlier this year, around 23 months in, serum progesterone was 0.6 ng/mL, a level considered high by Labcorp. Because it was only one measurement, the conservative response was to reduce the dose slightly to 0.4 mg per day and retest after three months. The serum level was again 0.6 ng/mL, seeming to confirm the previous measurement and suggesting nontrivial endogenous production. The dose has since been reduced to 0.2 mg per day, with the intention being to phase it out entirely. Subjectively it is similar to the initial dose titration with progesterone, when serum levels were also higher. Sleep is improved.

This result doesn't establish causality, but it's interesting to consider the possibility. Previous hCG use had not done something like this: serum progesterone was stuck at 0.1 ng/mL, with or without.

 

[ajax31]

What are your current LH and FSH levels including reference ranges? Also, have your gonadotropin levels changed over this time frame, or have they remained stable?

 

[Cataceous]

I've been intending to review these measurements, so your question can provide the impetus: LH and FSH have bounced around, primarily in response to sub-experiments. Peak values were obtained about 5-6 months in, with LH at 2.2 mIU/mL (1.7-8.6) and FSH at 1.7 mIU/mL (1.5-12.4). These reference ranges apply throughout. The next test yielded 2.1 and 1.4 respectively, so there are three similars sets of measurements representing steady state with 12.5 mg enclomiphene daily along with 5 mg of testosterone in a TP/TE blend.

After that enclomiphene was discontinued for a month, while testosterone intake was reduced to 3.8 mg/day. LH and FSH dropped to 1.5 mIU/mL and 0.8 mIU/mL respectively. As documented previously, this sub-experiment was ended due to unrelenting testicular discomfort.

Next, enclomiphene was resumed at the lower rate of 12.5 mg EOD. Testosterone was increased to 4.4 mg/day. After six months LH and FSH were 1.5 mIU/mL and 0.9 mIU/mL respectively, suggesting a dose-dependent response to enclomiphene.

The next experiment used 3.8 mg of testosterone daily from testosterone propionate, along with 12.5 enclomiphene E4D. After three months of this LH was below the detection threshold. It seems that the lower troughs of pure propionate were not enough to compensate for the reduced enclomiphene.

EOD dosing of enclomiphene was resumed along with 4.4 mg testosterone daily from the TP/TE blend. After three months of this enclomiphene was increased to 12.5 mg daily. Two months later, bringing us almost to the present day, LH had recovered to 1.3 mIU/mL, still below the expected steady state level of about 2 mIU/mL.

 

[Willyt]

I'm not sure about the significance of this: It appears that sometime in the course of this experiment endogenous progesterone production resumed. Baseline supplementation was 0.6 mg injected per day, and eight months into the experiment serum progesterone was 0.3 ng/mL (0.0-0.5), which was expected with that dose. Earlier this year, around 23 months in, serum progesterone was 0.6 ng/mL, a level considered high by Labcorp. Because it was only one measurement, the conservative response was to reduce the dose slightly to 0.4 mg per day and retest after three months. The serum level was again 0.6 ng/mL, seeming to confirm the previous measurement and suggesting nontrivial endogenous production. The dose has since been reduced to 0.2 mg per day, with the intention being to phase it out entirely. Subjectively it is similar to the initial dose titration with progesterone, when serum levels were also higher. Sleep is improved.

This result doesn't establish causality, but it's interesting to consider the possibility. Previous hCG use had not done something like this: serum progesterone was stuck at 0.1 ng/mL, with or without.

Good stuff. What is half life of exogenous progesterone? Does it accumulate over time?

I had to reign in daily dosing (topical oil) because I started to feel side effects after initially experiencing promising results.

 

[Cataceous]

... What is half life of exogenous progesterone? Does it accumulate over time?
...

According to the references cited by Wikipedia, exogenous progesterone's half-life is 20-28 hours for IM injections, 13-18 hours for SC injections, and 30-40 hours for topical applications.

As with testosterone esters, there should be an accumulation of progesterone until steady state is reached. It's generally assumed that after five half-lives you're close enough to say you're there. This means that with SC progesterone you'd expect negligible additional accumulation after four days of use; metabolism and clearance match the dose rate.

...
I had to [rein] in daily dosing (topical oil) because I started to feel side effects after initially experiencing promising results.

What serum levels were you seeing?

 

[Willyt]

What serum levels were you seeing?

I was shooting for 7mg dose as you had mentioned in another thread although that can be challenging with an oil dropper.

Of course, I did not test levels lol. That said, I have learned from this forum to avoid adding more than one variable at a time and found that the side effects diminished as soon as I backed off the daily progesterone.

 

[Willyt]

@Cataceous - As I recall, your daily T dose on the blend is Enan 3.2mg / Prop 2.4mg (= total 5.6mg). Do any of the other elements (GnRH, Enclomiphene, Kisspeptin, etc.) included in your pituitary restart regimen boost endogenous T production?

Stated another way, are your TT/FT test results on the 5.6mg daily T blend affected by these other variables? Or would you expect the same TT/FT results if you were only injecting the T blend and not including GnRH, Enclomiphene, Kisspeptin, etc.?