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

[Cataceous]

I think you’d need to know its binding affinity to SHBG to be able to guess at that. E.g. if it had very high SHBG affinity (much more than estradiol), then it’s less likely to have more free molecules. I wasn’t able to figure it out with a quick search.

Good point. The Wiki article on SHBG says 3β-androstanediol has the same binding affinity as DHT. So free levels may be relatively low.

 

[AdamYoung]

I hate to chime in on this, given that I respect many of the posters and knowledge they provide, but there is a great deal of misinformation presented here.



This is misleading. If the thermostat clicks on when estrogen (E) is too low, then men with an androgen deficiency would, from concomitant low estradiol, experience an elevated LH pulse. The mistake here is that the "thermostat clicks on" in eugonadal men only. With secondary hypogonadism, where clomiphene citrate is normally indicated, the level of E deficiency required to "click on the thermostat" is substantially reduced and irregular. The thermostat is NOT operating properly. If it were working properly, there wouldn't be secondary hypogonadism in the first place.



Except, with secondary hypogonadism, T and E2 levels are already inadequate and yet the thermostat is already "off." Again, the thermostat is broken. We have to virtually starve it of E2 to get it to work properly.



The action of testosterone on the hypothalamus is mostly indirect, versus direct AR stimulation, and vastly, vastly less than the inhibitory effect of E2. In fact, T mostly affects the pulse frequency of LH and does not significantly attenuate the pulse amplitude. E2, however, affects amplitude. Regardless, per studies, it requires BOTH E2 and T to be sufficient to cause feedback. E2 insufficiency will still amplify the LH pulse even when T is normalized. In fact, that's why men on Clomid can have normal LH along with normal T and E.



This is false. Normal testosterone levels alone will not suppress the HPTA when E2 is blocked from inhibiting the LH pulse hypothalamus. Clomid will succeed in convincing the hypothalamus of an imbalance and LH will increase.

It will only increase marginally, however, because the LH will cause T/E2 to increase to the point of actual hypothalamic suppression. You'll hit a wall.

So, what actually interrupts the MoA of of Clomid? Extremely elevated androgens (steroids/supraphysiological FT) or significantly elevated free estradiol.

Normal T will NOT suppress LH without E2 also being normal, and in such a case — Clomid will always falsify E2 to the hypothalamus and cause it to panic.

I have the labs to prove it, because I have used this combination myself. Apparently, so have other people in this thread. LH does return, but not fully.

I don't know why this myth persists. It requires a severely fundamental misunderstanding of the HPTA.

What about FSH? Does it increases too when you take clomid and while having normal T levels.

 

[AdamYoung]

There is a study which shows the use of TRT+HCG+Clomid to restore fertility but for severe cases, TRT+HCG+FSH is ideal.
Indications for the use of human chorionic gonadotropic hormone for the management of infertility in hypogonadal men

I am primary hypogonadism which means i already have high LH/FSH (above normal range) and i have low sperm count. I was planning to take HMG or FSH but its too costly. I am thinking to use it when i try for kids but meanwhile if i can manage to restore fertility with TRT+HCG+Clomid then it would be awesome. I will give a try and let you guys know. Starting the protocol from tomorrow.

 

[Cataceous]

There is a study which shows the use of TRT+HCG+Clomid to restore fertility but for severe cases, TRT+HCG+FSH is ideal. (Read the last paragraph)
Indications for the use of human chorionic gonadotropic hormone for the management of infertility in hypogonadal men

I am primary hypogonadism which means i already have high LH/FSH (above normal range) and i have low sperm count. I was planning to take HMG or FSH but its too costly. I am thinking to use it when i try for kids but meanwhile if i can manage to restore fertility with TRT+HCG+Clomid then it would be awesome. I will give a try and let you guys know. Starting the protocol from tomorrow.

Unless I missed it, the article is suggesting hCG plus Clomid after stopping TRT. The underlying reference for the combination says:

HCG therapy was supplemented with clomiphene citrate, tamoxifen, anastrozole, or recombinant FSH (or a combination) according to physician preference and clinical situation. The supplemental therapies were added to raise native FSH levels, as HCG does not raise FSH levels and has no activity on FSH receptors.​

I'm not sure what good it would do you to take HMG or FSH when you already have high levels. If you do have primary hypogonadism then isn't low instratesticular testosterone the main problem with respect to fertility, and one that none of these treatments can address?

 

[AdamYoung]

If Semen parameters fail to improve and FSH remains low, Gonal-f (recombinant FSH) 75 IU every other day can be added. In men who desire pregnancy within 6–12 months TRT can be continued with co-administration of 500 IU of HCG every other day ± clomiphene citrate can be used. When planning for pregnancy in greater than 12 months TRT should be cycled off every six months replaced by a four-week cycle of 3,000 IU of hCG every other day. For men who do not desire to preserve fertility testicular size can me maintained while undergoing TRT with 1,500 IU of HCG given weekly. Which is enough to maintain pre-TRT levels of intratesticular Testosterone (11)

My aim is to maintain the sperm count while on TRT so that it will not reach to zero either my TRT+HCG+HMG or TRT+HCG+Clomid.
I know i already have high LH n FSH n low T n sperm count. I left with no option but to take TRT+HCG+ HMG, but since HMG is expensive, i am trying to achieve this my clomid. Even if clomid can able to maintain my FSH sub optimal level i am fine. I dont know it will but just trying out

 

[Cataceous]

It's actually very interesting that in the underlying reference they did manage to obtain large increases in LH and FSH with hCG and a SERM. But the average (probably peak) testosterone level during this treatment was 476 ng/dL. The question is, with TRT are you willing to keep your levels this low? If not it will reduce the likelihood of success.

 

[Vvs1]

Can estrogen cream or pills be added to enclomiphene?

I have low e2, and while Clomid(zu+en) raises my e2, I’m not sure about enclomiphene’s effects on e2.

 

[Cataceous]

Can estrogen cream or pills be added to enclomiphene?

I have low e2, and while Clomid(zu+en) raises my e2, I’m not sure about enclomiphene’s effects on e2.

Taking exogenous estradiol isn't recommended because it works directly against the effectiveness of enclomiphene. But if Clomid raised your estradiol then you should see similar results with enclomiphene. The extra endogenous estradiol is coming from the higher testosterone and luteinizing hormone, which are probably not increased by zuclomiphene.

 

[AdamYoung]

It's actually very interesting that in the underlying reference they did manage to obtain large increases in LH and FSH with hCG and a SERM. But the average (probably peak) testosterone level during this treatment was 476 ng/dL. The question is, with TRT are you willing to keep your levels this low? If not it will reduce the likelihood of success.

Hi Cataceous,
What do u recommend for me? Do u think my approach is good? Or should i just take chance by going into TRT+HCG and Off TRT when i am about to have kids. Since i already have low sperm count i doubt my sperm count will return to normal after it become zero bcas of TRT. I know usually this doesnt not happen to people whos testicles are working 100% but in my case, i believe only 10% is working. So thats y i thought of adding HMG or FSH to my protocol but since its expensive considering i have to pay for TRT+HCG+Cialis, i am thinking to deal with clomid n see if i can maintain my FSH level while keeping my testosterone level around 450-500 US metrics. I am from canada and attaching my blood report

 

[Cataceous]

Hi Cataceous,
What do u recommend for me? Do u think my approach is good? Or should i just take chance by going into TRT+HCG and Off TRT when i am about to have kids. Since i already have low sperm count i doubt my sperm count will return to normal after it become zero bcas of TRT. I know usually this doesnt not happen to people whos testicles are working 100% but in my case, i believe only 10% is working. So thats y i thought of adding HMG or FSH to my protocol but since its expensive considering i have to pay for TRT+HCG+Cialis, i am thinking to deal with clomid n see if i can maintain my FSH level while keeping my testosterone level around 450-500 US metrics. I am from canada and attaching my blood report

In a similar situation I would freeze some sperm if I could afford it as insurance against loss of fertility. Then I would be on TRT+hCG, only temporarily switching to TRT+hCG+FSH/HMG when I wanted to maximize fertility.

 

[AdamYoung]

Ya i am freezing my sperm but this is extra precaution. Ya i am thinking to go to HMG or FSH if i dont see any improvement with clomid. Atleast i know that it wont work rather than just assuming. Thanks.

 

[Cataceous]

Relevant to this thread, initial evidence suggests that Clomid or enclomiphene can work with exogenous testosterone if GnRH is used to stimulate the pituitary directly:

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

TL;DR: Over a period of seven weeks, treatment with GnRH and enclomiphene raised LH and FSH from around 0.1 mIU/mL to about 1.0 mIU/mL, even though TRT and hCG dosing were continued. Subjective results have been encouraging. I had written previously on the subject of GnRH suppression on TRT...

www.excelmale.com

 

[Ktrt11]

I was notified today that my clinic will be replacing hcg with clomid. My current protocol is 200mg testosterone, hcg. what are your opinions on testoserone and clomid together?

 

[Cataceous]

I was notified today that my clinic will be replacing hcg with clomid. My current protocol is 200mg testosterone, hcg. what are your opinions on testoserone and clomid together?

It's quite likely you will lose all of the benefits you had with hCG. Most guys cannot maintain any significant gonadotropin production on a combination of TRT and Clomid; the relatively high and constant serum testosterone suppresses the hypothalamus, preventing GnRH production. I report in the link above that pituitary activation is possible when GnRH is administered concurrently, but most guys will not find this practical.

 

[Ktrt11]

Funny you mention gondaotropin because they also referred to "gonadorelin" as well. It seems they are unsure of which direction they are going as i was informed of 2 different things....

 

[Cataceous]

Funny you mention gondaotropin because they also referred to "gonadorelin" as well. It seems they are unsure of which direction they are going as i was informed of 2 different things....

Gonadorelin is GnRH. So if they're proposing to give you that along with Clomid then at least they have the right idea. But it probably takes very frequent dosing to get good results. Our bodies normally send out a pulse of GnRH every couple hours or so. In the GnRH trial described above six daily subQ injections were used, and in 12 weeks have taken the gonadotropins (LH and FSH) from 0.1 to around 1 mIU/mL. While it's a good start, it doesn't compare to the activation seen with typical hCG doses; hCG is said to be 6-8 times more potent than LH on a per-IU basis.

 

[Ktrt11]

They did not specify if it would be with clomid as i am currently on testosterone. i think they are looking to do gonadorelin with my test protocol. i do not think there is a real alternative to hcg so they are researching

 

[Cataceous]

They did not specify if it would be with clomid as i am currently on testosterone. i think they are looking to do gonadorelin with my test protocol. i do not think there is a real alternative to hcg so they are researching

Gonadorelin alone with testosterone may not be sufficient. There's negative feedback from estradiol at the pituitary that cuts LH and FSH production. The SERM is used to block this feedback.

Is your clinic stopping hCG due to supply problems? If so can't they just let you buy it from Empower?

 

[Ktrt11]

Yes it seems my clinic is stopping because it is no longer available. I see everyone mentioning Empower but it is even illegal for them to even produce from my understanding and they are breaking the law based on the ruling found here. I know they are not licensed yet so what gives them the ability or right to still produce hCG? How are they not in the same boat as other pharmacies? They have also had issues in the past with the FDA regarding producing hCG.

 

[Cataceous]

Yes it seems my clinic is stopping because it is no longer available. I see everyone mentioning Empower but it is even illegal for them to even produce from my understanding and they are breaking the law based on the ruling found here. I know they are not licensed yet so what gives them the ability or right to still produce hCG? How are they not in the same boat as other pharmacies? They have also had issues in the past with the FDA regarding producing hCG.

The long-term disposition is up in the air. Nelson notes "... many compounding pharmacies (including Empower) will continue to make it while they negotiate other options. No supply issues are foreseen yet."

In the worst case you can follow the lead of a number of guys here on the forum who order hCG from places such as AllDayChemist. I doubt the other options being floated by clinics, such as GnRH or kissspeptin, will be workable for most guys. Kisspeptin is upstream of GnRH, so for it to work it must stimulate GnRH first, which then works on the pituitary. This means the problem of negative feedback from estradiol is the same. In the best case, kisspeptin and a SERM would work without frequent kisspeptin injections. But that seems questionable to me, given its short half-life.