Are guys that do well on low dose clomid unicorns...or do they really exist?

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Dr Justin Saya MD

Dr Justin Saya MD

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They actually EXIST!!!

There are certainly some challenges in treating with low dose clomid, specifically in dealing with the varying effect (estrogen antagonist/agonist) of the two isomers enclomiphene and zuclomiphene. However, as I (and Dr Crisler) have said many times...I DO ACHIEVE SUCCESS in a fair number of guys with both a good objective AND subjective (symptomatic) response. This is one of my patients. Now there are certainly many guys that do NOT respond well to clomid for various reasons (wrong dosing, mismanagement, poor estrogen control, high SHBG, lack of response from HPTA, or just simply not tolerating the medication), but there are also many that have a good and even great response.

Admittedly, the online and forum tone is overwhelmingly negative regarding clomid...as for some reason the guys that actually do well on clomid (you know who you are...LOL) are not as vocal as the guys who've had a negative experience. I've seen the quote many times in one form or another as a matter of fact statement: "clomid will get your T levels up, but you won't feel it...or you won't feel better". Indeed, there are guys that feel good and even great on clomid, from my estimation anywhere from 30-50% of the guys (especially under 40yo) that I treat. It does, however, take PATIENCE and I think this is where some guys give up too quicky, possibly partly due to the negative bias that they had already formed from their "expectations" of clomid not working for anyone. For a younger guy (or even older...my oldest guy on clomid is 58yo and has had a GREAT response...he doesn't want to come off!) that can or wants to stimulate his endogenous testosterone production, maintain OPTIMAL fertility, and buy himself precious years of natural production before having to rely on TRT - clomid can be a perfect treatment for these guys!

After all, if it fails then the TRT option is always there as a backup plan.
 
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I think the reason that Clomid gets a lot of negative feedback is because its side effect profile. Anxiety, depression, panic attacks, psychosis and then throw in the possible ocular toxicity. I am quite spooked of clomid and I'm not sure I would ever use it for a restart. I would almost opt to restart naturally just because the drug freaks me out a bit. On Dr. Crisler's forums, there was a guy only taking 12.5mg TIW and he was having visual problems. That drug just scares me.
 
You should have a healthy amount of "fear" of ANY drug...as every drug carries a profile of side effects and possible adverse events. In fact, IMO too many patients begin taking new meds from their physician (BP meds, statins, antidepressants, etc) WITHOUT a healthy amount of trepidation to the point that they often aren't even cognizant of the possible adverse outcomes (in part due to lack of counseling by their prescribing doc).

Having said that, Clomid carries a side effect profile...for sure, but the side effects are often overstated and are overwhelmingly temporary (if a patient experiences them, they stop the drug and the side effects go away...unlike, say, finasteride). The visual side effects are fairly rare (at low doses) and typically occur very early in treatment (within first few weeks). If a patient is unfortunate enough to experience the ocular side effects (typically mild), they stop taking the medication and (in cases I have been involved in) the ocular symptoms go away within a few days to a week or so. Once again, fairly uncommon, mild, and temporary.

Many other "common" side effects of the Clomid that you mentioned - anxiety, depression, panic attacks, psychosis (I've never seen this one in clinical practice BTW) - are often due to higher doses of Clomid, pre-existing psychological morbidity (I'm slightly more cautious with Clomid in folks with pre-existing psychological diagnoses or symptoms), and often the estrogen issues mentioned previously (increase in endogenous E from increase in endogenous T - without management when appropriate, and also some of the E agonist affect - again more pronounced at higher doses).

Have a healthy fear/skepticism of all drugs, it will serve you well and prevent "polypharmacy", a significant cause of morbidity in our geriatric population, but don't completely write off clomid...it is a GOOD drug when used appropriately and in the right context by an experienced clinician.
 
Dr. Saya, what results have you seen when trying to manage estrogenic difficulties of zuclomiphene with low-dose Clomid (example: 12.5mg 2x/wk) via the use of DIM and Calcium D-Glucarate? What doses of each have proven useful in the process?
 
Dr. Saya, thank you for the great topic. What would be the starting dose of clomid (12.5mg twice a week maybe) ? What parameters to check on it ? T, free T, LH, E2, SHBG ?

I'm low SHBG guy and had nagative experience on TRT (was very hard for me to manage corect dose of AI) and I will try with clomid 12.5mg twice a week to see my levels on that dose. My natural T was always around 3.5ng/ml from the age of 20. I'm now 25.
 
Dr. Saya, great post - for those experiencing minimal effect with Clomid or side effects, do you ever find satisfactory or better results moving the patient to tamoxifen?
 
txmx said:
Dr. Saya, what results have you seen when trying to manage estrogenic difficulties of zuclomiphene with low-dose Clomid (example: 12.5mg 2x/wk) via the use of DIM and Calcium D-Glucarate? What doses of each have proven useful in the process?
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The MAIN benefit of low dose Clomid (which is really anything 25mg or less) is exactly that - to minimize the estrogenic impact of the zuclomiphene. Also less SHBG stimulation at lower doses (although that SHBG stimulation can actually be a GOOD thing for low SHBG guys).

I like DIM at 100mg daily or 200mg BIW-TIW (I often add this to compounded low dose anastrozole WHEN the AI is needed). Calcium D-Glucarate can help typically at doses of 1000-1500mg daily. However, for guys that have true E2 sensitivity/symptoms, neither of these will have the efficacy of a LOW dose of anastrozole.
 
JPB said:
Dr. Saya, great post - for those experiencing minimal effect with Clomid or side effects, do you ever find satisfactory or better results moving the patient to tamoxifen?
Click to expand...

Short answer - yes. For VISUAL side effects of Clomid, it's simple, we STOP the Clomid. Tamoxifen can be an alternative in these cases, although I find it to be slightly less effective clinically and can sometimes lower IGF-1 levels. As mentioned previously, for other side effects of Clomid - these can usually be mitigated in other ways (dosage changes, estrogen control, etc).

An interesting use of tamoxifen for those that have a less than optimal response to even adequate Clomid dosages, is actually adding tamoxifen CONCURRENTLY with Clomid. Now this is only if they haven't already decided to "give up" on the Clomid, partly due to a potential preconceived negative bias (as mentioned earlier...I'll get off the soapbox lol). I've found in some of these folks that the cumulative effect of Clomid/tamoxifen (typically on alternating days when I prescribe together) appears to be synergistic (though not for all). Hope that answers your question.
 
Speed said:
Dr. Saya, thank you for the great topic. What would be the starting dose of clomid (12.5mg twice a week maybe) ? What parameters to check on it ? T, free T, LH, E2, SHBG ?

I'm low SHBG guy and had nagative experience on TRT (was very hard for me to manage corect dose of AI) and I will try with clomid 12.5mg twice a week to see my levels on that dose. My natural T was always around 3.5ng/ml from the age of 20. I'm now 25.
Click to expand...

Younger, low SHBG guys may actually have a higher success rate with Clomid than the "typical" guy with normal or higher SHBG, as the SHBG increase can sometimes come as a benefit for these low SHBG guys (assuming the HPTA is very responsive/healthy and has a robust enough response).

Yes, monitor Total/free T, E2, LH, SHBG, check prolactin if LH/FSH suppressed for unknown reasons (elevated prolactin may be that "unknown" reason).

Starting dose can vary greatly depending on many individual factors, but as noted previously, anywhere from 25mg on down typically. I will often start a little more aggressive early (so I know right away if the HPTA is going to respond adequately), and then simply titrate down GRADUALLY over time to either:

A. Get the patient off of Clomid completely and see if levels maintain after a prolonged "kick start" so to speak (better chance of this by SLOWLY titrating down on the Clomid).

or

B. Get he patient down to the MINIMUM amount of Clomid that they need to keep their system stimulated (this is determined during the titration process via monitoring labs/symptoms).

Hope that helps!
 
Dr Justin Saya said:
The MAIN benefit of low dose Clomid (which is really anything 25mg or less) is exactly that - to minimize the estrogenic impact of the zuclomiphene. Also less SHBG stimulation at lower doses (although that SHBG stimulation can actually be a GOOD thing for low SHBG guys).

I like DIM at 100mg daily or 200mg BIW-TIW (I often add this to compounded low dose anastrozole WHEN the AI is needed). Calcium D-Glucarate can help typically at doses of 1000-1500mg daily. However, for guys that have true E2 sensitivity/symptoms, neither of these will have the efficacy of a LOW dose of anastrozole.
Click to expand...


Thanks for your insight, Dr. Saya. One follow up question: Is there any difference in the estrogenic effects themselves being addressed that would lean toward DIM and/or Cal D-G vs. going the anastrozole route? For example, does DIM and/or Cal D-G work better with zuclomiphene-specific issues vs. anastrozole working better with simply high E2?
 
txmx said:
Thanks for your insight, Dr. Saya. One follow up question: Is there any difference in the estrogenic effects themselves being addressed that would lean toward DIM and/or Cal D-G vs. going the anastrozole route? For example, does DIM and/or Cal D-G work better with zuclomiphene-specific issues vs. anastrozole working better with simply high E2?
Click to expand...

You caught me just before going offline ;-) I'll take a quick stab at your question. I love educating if you haven't suspected already!

So...there really isn't a better way to manage the estrogenic effects of the zuclomiphene other than simply LIMITING the burden of zuclomiphene (via dosage adjustment of Clomid) based on the patient's sensitivity. This is superior to DIM, CDG, or AI. Now some patients tolerate the zuclomiphene fine even at higher Clomid dosages, some need much lower due to sensitivity...this is where working with an experienced practitioner is IMPERATIVE!

Also keep in mind that with the increase in testosterone with SUCCESSFUL Clomid treatment -> there will be a concurrent increase in E2. Now this is cumulative to the estrogenic zuclomiphene effect (thus an E2 level of 30pg/mL in a TRT guy isn't apples to apples comparable to an E2 level of 30pg/mL in a Clomid guy).. Hope that makes sense as that is a difficult concept for even most physicians that treat with Clomid (and not coincidentally a common reason for the failure of their Clomid treatment for their patients). Now that increase in endogenous E2 (again concurrent with the estrogenic zuclomiphene), IF CAUSING ISSUES - will respond to DIM, CDG, and if needed LOW dose anastrozole (with AI > DIM/CDG).

Hope this makes sense, even many physicians I try to educate on this cannot grasp it!
 
Speed said:
Thank you very much Dr. for quick response. Can you please clarify, is this weekly or daily dosing you're talking? Tnx
Click to expand...

As mentioned, many factors at play for dosing, but can vary from 12.5mg-25mg DAILY, on down to even 12.5mg twice weekly (often towards the end of a downward titration).

Alright, going offline for a while guys. My "off" day from clinical duties, but family duties call. Have a great weekend!
 
Dr Justin Saya said:
Younger, low SHBG guys may actually have a higher success rate with Clomid than the "typical" guy with normal or higher SHBG, as the SHBG increase can sometimes come as a benefit for these low SHBG guys (assuming the HPTA is very responsive/healthy and has a robust enough response).

Yes, monitor Total/free T, E2, LH, SHBG, check prolactin if LH/FSH suppressed for unknown reasons (elevated prolactin may be that "unknown" reason).

Starting dose can vary greatly depending on many individual factors, but as noted previously, anywhere from 25mg on down typically. I will often start a little more aggressive early (so I know right away if the HPTA is going to respond adequately), and then simply titrate down GRADUALLY over time to either:

A. Get the patient off of Clomid completely and see if levels maintain after a prolonged "kick start" so to speak (better chance of this by SLOWLY titrating down on the Clomid).

or

B. Get he patient down to the MINIMUM amount of Clomid that they need to keep their system stimulated (this is determined during the titration process via monitoring labs/symptoms).

Hope that helps!
Click to expand...


Dr. Saya, what is the minimum amount of Clomid you have seen that can keep the proper effective stimulation, considering the half-lives of the zuclomiphene and enclomiphene isomers? I have had success at 12.5mg E3D and am now trying 12.5mg 2x/week.
 
txmx said:
Dr. Saya, what is the minimum amount of Clomid you have seen that can keep the proper effective stimulation, considering the half-lives of the zuclomiphene and enclomiphene isomers? I have had success at 12.5mg E3D and am now trying 12.5mg 2x/week.
Click to expand...

12.5mg BIW is about the lowest. Once you're down to that amount, the next step would be a trial of stopping it altogether to see if your production maintains itself (assuming whatever factors may have been suppressing in the first place - stress, poor sleep, pain meds/antidepressants/benzos, prolactin, etc etc - have been remedied).
 
Dr Justin Saya said:
You caught me just before going offline ;-) I'll take a quick stab at your question. I love educating if you haven't suspected already!

So...there really isn't a better way to manage the estrogenic effects of the zuclomiphene other than simply LIMITING the burden of zuclomiphene (via dosage adjustment of Clomid) based on the patient's sensitivity. This is superior to DIM, CDG, or AI. Now some patients tolerate the zuclomiphene fine even at higher Clomid dosages, some need much lower due to sensitivity...this is where working with an experienced practitioner is IMPERATIVE!

Also keep in mind that with the increase in testosterone with SUCCESSFUL Clomid treatment -> there will be a concurrent increase in E2. Now this is cumulative to the estrogenic zuclomiphene effect (thus an E2 level of 30pg/mL in a TRT guy isn't apples to apples comparable to an E2 level of 30pg/mL in a Clomid guy).. Hope that makes sense as that is a difficult concept for even most physicians that treat with Clomid (and not coincidentally a common reason for the failure of their Clomid treatment for their patients). Now that increase in endogenous E2 (again concurrent with the estrogenic zuclomiphene), IF CAUSING ISSUES - will respond to DIM, CDG, and if needed LOW dose anastrozole (with AI > DIM/CDG).

Hope this makes sense, even many physicians I try to educate on this cannot grasp it!
Click to expand...


Beautiful. Thank you for taking the time to educate. These are difficult concepts, but fascinating, and can be grasped if you just take the time to think it through. I really appreciate your willingness to discuss the technical aspects of this. Very, very helpful :)
 
Dr Justin Saya said:
You should have a healthy amount of "fear" of ANY drug...as every drug carries a profile of side effects and possible adverse events. In fact, IMO too many patients begin taking new meds from their physician (BP meds, statins, antidepressants, etc) WITHOUT a healthy amount of trepidation to the point that they often aren't even cognizant of the possible adverse outcomes (in part due to lack of counseling by their prescribing doc).



Having said that, Clomid carries a side effect profile...for sure, but the side effects are often overstated and are overwhelmingly temporary (if a patient experiences them, they stop the drug and the side effects go away...unlike, say, finasteride). The visual side effects are fairly rare (at low doses) and typically occur very early in treatment (within first few weeks). If a patient is unfortunate enough to experience the ocular side effects (typically mild), they stop taking the medication and (in cases I have been involved in) the ocular symptoms go away within a few days to a week or so. Once again, fairly uncommon, mild, and temporary.

Many other "common" side effects of the Clomid that you mentioned - anxiety, depression, panic attacks, psychosis (I've never seen this one in clinical practice BTW) - are often due to higher doses of Clomid, pre-existing psychological morbidity (I'm slightly more cautious with Clomid in folks with pre-existing psychological diagnoses or symptoms), and often the estrogen issues mentioned previously (increase in endogenous E from increase in endogenous T - without management when appropriate, and also some of the E agonist affect - again more pronounced at higher doses).

Have a healthy fear/skepticism of all drugs, it will serve you well and prevent "polypharmacy", a significant cause of morbidity in our geriatric population, but don't completely write off clomid...it is a GOOD drug when used appropriately and in the right context by an experienced clinician.
Click to expand...


Thanks for the response Dr. Saya. I am a new TRT user in my early 30's. I am a RN and I am interested in exploring hormone replacement as a career so I am applying for NP school so I can start doing this as a career. I am also kicking the tires on going with Defy for my care. I am also interested in natural restarts but I have had a history with panic attacks/anxiety but I do not take any pharmaceuticals for this condition and do quite well with it naturally so I don't know if Clomid would be an option for a restart if I decide I want to go down that path. My current doctor pretty much just prescribes me my TRT meds and I tell him what dosages I want to do (testosterone +hcg) and I do it all myself, I have a pretty healthy medical knowledge base, particularly with hormones but I am still learning.

Does Defy have any restart protocols that does not use Clomid if I would like to try a restart in the near future?
 
Last edited:
I read this thread and I think -- "WHY did the FDA drop kick Androxal?" It sounds like just cutting out the harmful (for men) zuclomiphene isomer entirely would simplify everything. Does the FDA hate men or something?
 
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Nocturne said:
I read this thread and I think -- "WHY did the FDA drop kick Androxal?" It sounds like just cutting out the harmful (for men) zuclomiphene isomer entirely would simplify everything. Does the FDA hate men or something?
Click to expand...

You're asking the wrong question. What you should be asking is why didn't Repros do a study comparing Andorxal to Clomid and prove the the FDA that it had some benefit over Clomid?

It is possible that they didn't do this because they may have realized early on that there would not be any benefit over Clomid.

We'll never know.
 
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