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

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Gene Devine

Super Moderator
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 (HTPA). I like to analogize the HPTA regulation of androgen's and estrogen's to a room thermostat.


Thermostat clicks ON = When the hypothalamus (H) senses that estrogen (E) is too low, it releases Gonadotropin-releasing hormone (GnRH), which tells the pituitary (P) to release luteinizing hormone (LH), which in turn tells the testes to make Testosterone. Some of this Testosterone will be aroamatased into estrogen and dihydrotestosterone (DHT).


Thermostat clicks OFF = When Estrogen levels are adequate, the Hypothalamus stops releasing GnRH. This means that nothing is telling the pituitary to release LH. That in turn, means nothing is telling the testes to make Testosterone.


How does Clomid raise T levels? It tricks the Hypothalamus such that it doesn’t see as much Estrogen as is there. So relative to my thermostat analogy, Clomid causes the thermostat to GET STUCK IN THE ON POSITION for longer than it would normally. Thus, more GnRH--->more LH--->more--->T production.


What happens when you take Clomid while on an APPROPRIATE AMOUNT of testosterone? Well, I left something very important out in my thermostat analogy. You see, the Hypothalamus senses androgen's as well as estrogen. So when you are on TRT, the exogenous testosterone shut the HTPA. So, properly-dosed TRT causes the thermostat to be stuck in the OFF position.

Take all the Clomid you want, the HTPA will not respond because it is suppressed by the exogenous testosterone. Sure Clomid will still blind the hypothalamus to your estrogen. However, in this case It won’t matter; HTPA is shutdown.
 
Defy Medical TRT clinic doctor
Comparing the gonadotropin responses to selective E2 inhibitionvs. complete castration demonstrates that T has bothdirect negative feedback effects on LH presumably mediatedby the androgen receptor as well as indirect effects mediatedby aromatization to E2

So essentially, this study shows that Test and E2 BOTH have a role in the negative feedback loop. So, this shows that clomid should work while on TRT, but we know that it does not.

It also shows that testosterone existing with estrogen receptor blockade does not sufficiently cause full shutdown, but DOES cause SOME. Essentially, you need both testosterone and estradiol levels to produce full shut down.

At the end of the day, it does not matter, as we know clomid does not work with TRT. It certainly highlights some interesting interesting complex mechanisms involved in HPTA regulation.


lhfshe2regulation.jpg
 

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Gamnc

New Member
This is interesting, I have been on TRT for several years, and on Clomid for a year now. What I did see within a month or two was the return of normal size testes. I also noted when my Testosterone cycle is at it end I still have some remaining T. Pre Clomid I did not and would be less than 100 (I was on shots first one per two weeks, than Testopel 12 pellets every 3 months, now I am taking shots every 3 days, but when on Testopel I saw the levels hold in the 300 range. not good, but better than sub 100. I saw this as a sign my Testes were also working again. Again I am not a medical person, but I recognize the changes in my own body.
 

MikeXL

Member
What do you mean when you say "when my Testosterone cycle is at it end"? Cycle always seem to refer to more of a BBer type use than TRT.

You that you have remaining testosterone at the end of your cycle. I would imagine you mean after your cycle. Testing testosterone "at the end of" would imply that you are still on T when testing. And if that was the case, there would be testosterone in the serum from the TRT. If after the cycle, there is more T with clomid because that is when clomid works - while not on.

The real test for you would be to get total and free testosterone, and FSH and LH
1 - Test TT, FT, LH and FSH after 6 weeks of testosterone ONLY
2 - Then add clomid with your testosterone for six weeks - run the same labs at the same laboratory
3 - Then remove the clomid and go with testosterone ONLY for six weeks - run the same labs at the same laboratory

I am willing to bet that there would be no significant differences in any of the labs. Just my thoughts


This is interesting, I have been on TRT for several years, and on Clomid for a year now. What I did see within a month or two was the return of normal size testes. I also noted when my Testosterone cycle is at it end I still have some remaining T. Pre Clomid I did not and would be less than 100 (I was on shots first one per two weeks, than Testopel 12 pellets every 3 months, now I am taking shots every 3 days, but when on Testopel I saw the levels hold in the 300 range. not good, but better than sub 100. I saw this as a sign my Testes were also working again. Again I am not a medical person, but I recognize the changes in my own body.
 

Gamnc

New Member
I was on Testopel till this week, and what I call a cycle was three months. The pellets drop off fast toward the end of the 3 months. Prior to the pellets I was getting shots once per two weeks. The end of that 2 week cycle always tested low. Testicle size was small. I switched to Testopel to try and get a steady feed of Testosterone. The doctor suggested the Clomid when I asked about the small testicles. That was a year ago, and my testicles are back to normal size now. I will have to get my labs from the doctor, but those test have been run. When I get them I will post them. I will be getting new test next month after going on shots every three days. Hope to see a stable pattern.
 

Weasel

Member
I saw someone's labs awhile back that showed on a TRT dosage of say 100mg per week and I believe it was 25mg daily clomid they did regain some lh/fsh activity. It was a small amount mind you but they did have like 0.8 lh levels vs 0.0 levels with Testosterone only.

I achieved roughly the same using Anastrozole while on 100mg per week. The question in my case should be was this achieved by suppressing e2 levels beyond a healthy level? Possibly.
 

seppuku

Active Member
I saw someone's labs awhile back that showed on a TRT dosage of say 100mg per week and I believe it was 25mg daily clomid they did regain some lh/fsh activity. It was a small amount mind you but they did have like 0.8 lh levels vs 0.0 levels with Testosterone only.

I achieved roughly the same using Anastrozole while on 100mg per week. The question in my case should be was this achieved by suppressing e2 levels beyond a healthy level? Possibly.


Hmm. I wonder what result would happen if someone on clomid therapy (say 12.5mg three times a week), that achieves a testosterone level of approximately 600ng/dl were to add SMALL amounts of injectable testosterone (say, 10mg twice a week)? Surely, as long as the amount of exogenous testosterone didn't push total testosterone levels too high (lets say from the 600ng/dl on just clomid, to 900ng/dl with the added exogenous), then that person could enjoy a higher level of total testosterone, but without having to be shut down/lose testicle size. Any thoughts?
 

ratbag

Member
Dr Crisler also prescribes taking clomid with Testosterone injections, him and Dr. Shippen work pretty close together so I'd assume shippen does the same.
 

seppuku

Active Member
Dr Crisler also prescribes taking clomid with Testosterone injections, him and Dr. Shippen work pretty close together so I'd assume shippen does the same.

Really? I didn't know that, and i often look at his forum. Is that something you've got from his book?
 

seppuku

Active Member
Hmm. I wonder what result would happen if someone on clomid therapy (say 12.5mg three times a week), that achieves a testosterone level of approximately 600ng/dl were to add SMALL amounts of injectable testosterone (say, 10mg twice a week)? Surely, as long as the amount of exogenous testosterone didn't push total testosterone levels too high (lets say from the 600ng/dl on just clomid, to 900ng/dl with the added exogenous), then that person could enjoy a higher level of total testosterone, but without having to be shut down/lose testicle size. Any thoughts?

Sorry, i meant chip in with regards to the above!
 

Gamnc

New Member
Sorry, i meant chip in with regards to the above!

I can ad my 2 cents worth of non medical advice. I am on Clomid, have been for 14 months now. Prior to Clomid at the end of the two week span between shots I would be in the 200 range. Without TRT I was below 100. I went on Testopel and 12.5 mg of clomid every day. Within two months my testicles were back to their normal size. At the end of the 3 month Testopel insertions I had T levels in the low 300. I think without the Clomid it would have been in the 100-200 range. My feelings is it gives me a buffer. That said after reading as much as I could find I see no harm in it, than just the normal size testicles are worth the $20 dollars a month.
 

Discovery41

New Member
I am new to all of this. I have been on HRT for about a year now. I have a bachelors and masters in Biology. So, i am not a Dr, but comfortable with research.I was concerned about my testicular pain and atrophy, but after a sperm test, my Dr. was not (i just became engaged). So i started doing my own research so i could talk to him next month. I see a lot about HPTA "suppression" and it seems to be analogous to "deceased" , for example, Gene Devine "Take all the Clomid you want, the HTPA will not respond because it is suppressed by the exogenous testosterone. Sure Clomid will still blind the hypothalamus to your estrogen. However, in this case It won't matter; HTPA is shutdown." But i've seen research on here by Nelson, and et al on clomid stimulating FSH and LH. So the HPTA is not dead or shutdown, just suppressed. So the E2 blocking Clomid can wake it up and stimulate FSH and LH to get the results of testicular response, as ive read. There are no long term studies about prolonged clomid use that i can find. But long term use of HCG seems to desensitize leydig cells. And anything i find is using Clomid to resensitize leydig cells. So as i read of the success stories on here of Clomid, and compare it to what i can read, I just have to wonder.. Why HCG is deemed the God of testicular atrophy and spermatogenesis. I do not mean to be confrontational, just curious.

 

ERO

Member
I need to see if I can find the studies again, but I *believe* the studies that showed long-term suppression with HCH were using doses much larger than what is normal with TRT. I could be incorrect, but that is what I recall, anyway.

Clomid can cause eyesight issues - floaters, etc...but I believe that is also with larger than usual dosages.
 
Last edited:
Dr Crisler also prescribes taking clomid with Testosterone injections, him and Dr. Shippen work pretty close together so I'd assume shippen does the same.

I worked with Dr Crisler for over 2 years as his medical director when he was collaborating with me/Defy (I only mention medical director as it is relevant - I reviewed all consults/charts). During this time he never prescribed Clomid along WITH TRT, not once. I don't believe this information is accurate.
 
I worked with Dr Crisler for over 2 years as his medical director when he was collaborating with me/Defy (I only mention medical director as it is relevant - I reviewed all consults/charts). During this time he never prescribed Clomid along WITH TRT, not once. I don't believe this information is accurate.

"You know what they say, anyone on the internet can say whatever they want." - Dr Martin Luther King Jr.
 

Vettester Chris

Super Moderator
Lots of interesting talking points!! Here's my angle on it ... The whole purpose of administering HCG or Clomid is for the benefit of LH. Men diagnosed with Secondary Hypogonadism can achieve benefit of testicular well being, and in other areas of the body where LH receptor sites are present. However, most 'secondary' males are lacking adequate GNRH> LH production (for one reason or another), thus TRT is needed (I know this 101 for most, but just recapping).

Clomid is a SERM to stimulate natural LH production in the pituitary, whereas HCG is the LH analog in a bottle, no guesswork, you dial in your dose and it's guaranteed LH each and every time. My point being that we are exploring how to get LH circulating throughout our bodies again, because for whatever reason the brain 'cannot' produce and/or sustain production of it, yet some are taking a medication (Clomid) that will stimulate the pituitary to produce LH?!?! (But wait, we are on TRT because our axis has failed).

It just seems a bit redundant when knowing HCG could easily provide an exact amount of LH every time you take it. Clomid's effectiveness will be different with each person, and it will solely depend on a person's pituitary situation. Additionally, to Gene's point, the HPTA will be in a state of conflict with elevated testosterone serum levels from exogenous medication. This doesn't mean it (Clomid) can't have any upsides, everyone is different, but again it's all guesswork, and you're relying on an area in the brain that was deemed unreliable. This is what warranted TRT to begin with.
 

ratbag

Member
I worked with Dr Crisler for over 2 years as his medical director when he was collaborating with me/Defy (I only mention medical director as it is relevant - I reviewed all consults/charts). During this time he never prescribed Clomid along WITH TRT, not once. I don't believe this information is accurate.

You can read it for yourself on his forum. We are not allowed to post links to other forums. Dr. Crisler posted it himself recently.
 
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