Positive Outcome Of Clomiphene Citrate Treatment In Young Hypogonadal Men

[chp5]

So the conclusion of this study is: "Long-term follow-up of CC treatment for HG shows that it appears to be an effective and safe alternative to testosterone supplementation in men wishing to preserve their fertility."

Dr. Scally and Dr. Jim - do agreement with this conclusion?

One reason I ask is because of the following info quoted below, which I found here: http://www.musclechatroom.com/forum/content.php?119-testosterone-boost-101:

"WHY SERMS (CLOMID / TAMOXIFEN) SHOULD BE AVOIDED FOR LONG TERM USE
Clomid and Tamoxifen are used in male hormone modulation therapy only as part of a "restart" protocol, as described earlier in this primer.
Any SERM (Clomid, tamoxifen) definitely causes two main problems after long term use:
1) You can't use any commercially available labs to quantify how your E2 (estadiol) is working in your body. This is because:
...a) SERMS (ie: clomid and tamoxifen) block E2 receptors, so very few of the E2 molecules present in your body will ever be lucky enough to trigger an unblocked receptor. So most of the E2 molecules will simply be "floating junk".
...b) Measurements of total E2 only measure E2 molecules (which are mostly "floating junk") but what is actually needed is to measure the number of moecules which get lucky enough to trigger an unblocked receptor.
...c) There are no labs which can measure the "number of trigger events of unblocked E2 receptors". If we could measure this we would have a direct measurement of E2 metabolism. No such test exists.

2) Long term use of SERMs (ie: clomid and tamoxifen) cause eye issues - especially eye floaters. Google "clomid + floaters", and "tamoxifen and floaters",
Eye floaters are damaged structures within your eye fluid which appear as visual obstructions to your vision. A floater is identified as a vision obstruction which lags behind a rapid movement of your eye. Ie: if you look up quickly, and the obstruction initially stays where it was and then catches up to where you are looking, then that's a floater.
The fundamental link between E2 and eye floaters is not well understood, but they occur because E2 levels are too low for too long.
Nor is it well understood why SERMs trigger eye floaters more frequently than aromatase inhibitors such as Arimidex, but that is indeed the case."

On point #2 from the above, the current study didn't seem to indicate that the patients experienced any floaters. Thoughts?

On point #1 from the above (You can't use any commercially available labs to quantify how your E2 (estadiol) is working in your body), - is there any relevance separate from floaters?

Thanks.

 

[Dr JIM]

Thanks to Dr. Scally for the applicable articles!

 

[Michael Scally MD]

So the conclusion of this study is: "Long-term follow-up of CC treatment for HG shows that it appears to be an effective and safe alternative to testosterone supplementation in men wishing to preserve their fertility."

Dr. Scally and Dr. Jim - do agreement with this conclusion?

One reason I ask is because of the following info quoted below, which I found here: http://www.musclechatroom.com/forum/content.php?119-testosterone-boost-101:

"WHY SERMS (CLOMID / TAMOXIFEN) SHOULD BE AVOIDED FOR LONG TERM USE
Clomid and Tamoxifen are used in male hormone modulation therapy only as part of a "restart" protocol, as described earlier in this primer.
Any SERM (Clomid, tamoxifen) definitely causes two main problems after long term use:
1) You can't use any commercially available labs to quantify how your E2 (estadiol) is working in your body. This is because:
...a) SERMS (ie: clomid and tamoxifen) block E2 receptors, so very few of the E2 molecules present in your body will ever be lucky enough to trigger an unblocked receptor. So most of the E2 molecules will simply be "floating junk".
...b) Measurements of total E2 only measure E2 molecules (which are mostly "floating junk") but what is actually needed is to measure the number of moecules which get lucky enough to trigger an unblocked receptor.
...c) There are no labs which can measure the "number of trigger events of unblocked E2 receptors". If we could measure this we would have a direct measurement of E2 metabolism. No such test exists.

2) Long term use of SERMs (ie: clomid and tamoxifen) cause eye issues - especially eye floaters. Google "clomid + floaters", and "tamoxifen and floaters",
Eye floaters are damaged structures within your eye fluid which appear as visual obstructions to your vision. A floater is identified as a vision obstruction which lags behind a rapid movement of your eye. Ie: if you look up quickly, and the obstruction initially stays where it was and then catches up to where you are looking, then that's a floater.
The fundamental link between E2 and eye floaters is not well understood, but they occur because E2 levels are too low for too long.
Nor is it well understood why SERMs trigger eye floaters more frequently than aromatase inhibitors such as Arimidex, but that is indeed the case."

On point #2 from the above, the current study didn't seem to indicate that the patients experienced any floaters. Thoughts?

On point #1 from the above (You can't use any commercially available labs to quantify how your E2 (estadiol) is working in your body), - is there any relevance separate from floaters?

Thanks.

Without going into the details, the above is a LOAD of CRAP. Wherever you found this POS, I would be very very wary for ANY & ALL information they provide. Did they provide supportive literature? The whole "receptor" theory comes from places unknown (i.e., from their ass). And, while SERMs are known to have visual disturbances, they are not due to E2 changes. Further, as you state, apparently they are not a problem in low-dose long-term use.


FWIW: Clomiphene is a racemic mix of trans (enclomiphene ) and cis (zuclomiphene ) isomers. The trans (enclomiphene) is the active isomer.

Szutu M, Morgan DJ, McLeish M, et al. Pharmacokinetics of intravenous clomiphene isomers. Br J Clin Pharmacol 1989;27(5):639-40. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1379933/pdf/brjclinpharm00087-0114.pdf

In conclusion, not only is clomiphene a mixture of two isomers with different pharmacodynamics, but relative plasma concentrations of the two isomers change with time after dosage and with route of administration.

Hill S, Arutchelvam V, Quinton R. Enclomiphene, an estrogen receptor antagonist for the treatment of testosterone deficiency in men. IDrugs 2009;12(2):109-19. Enclomiphene, an estrogen receptor antagonist for the... [IDrugs. 2009] - PubMed - NCBI

Enclomiphene (Androxal), in development by Repros Therapeutics Inc, is a non-steroidal estrogen receptor antagonist that promotes gonadotropin-dependent testosterone secretion by the testes. Enclomiphene constitutes the trans-stereoisomer of clomiphene citrate, a drug that has been widely prescribed for several decades for the treatment of female ovulatory dysfunction. Because of the antagonistic effects of enclomiphene, the drug has the potential to increase serum testosterone levels in men with secondary hypogonadism by restoring physiological endogenous testosterone secretion while maintaining testicular volume and, potentially, spermatogenesis. In clinical trials conducted to date, enclomiphene demonstrated significant efficacy in the physiological restoration of testosterone levels in males with secondary hypogonadism. The compound also exhibited an unanticipated favorable effect on fasting plasma glucose; this result has been accompanied by rapidly accumulating evidence from other researchers for a bidirectional relationship between low serum testosterone and obesity/metabolic syndrome (syndrome X) in men. Short-term clinical safety data for enclomiphene have been satisfactory and equivalent to safety data for testosterone gels and placebo. Enclomiphene demonstrates promise in the management of secondary hypogonadism associated with obesity, metabolic syndrome and, possibly, infertility, and should undergo placebo-controlled, randomized clinical trials for these indications.

 

[Michael Scally MD]

FYI: https://thinksteroids.com/community/posts/761057

 

[Dr JIM]

I couldn't have said it better Dr. Scally! Don't believe everything you read especially from a
non-referenced self help "medical" blog with outlandish assertions. I checked their references at the end of their commentary and none of them corroborated their presumptive "fact based" claims of causation and or treatment. As Dr Scally mentioned to locate peer reviewed journals log on to;
NCBI.NLM.NIH.GOV/PUBMED

 

[Michael Scally MD]

One reason I ask is because of the following info quoted below, which I found here: http://www.musclechatroom.com/forum/content.php?119-testosterone-boost-101:

2) Long term use of SERMs (ie: clomid and tamoxifen) cause eye issues - especially eye floaters. Google "clomid + floaters", and "tamoxifen and floaters",
Eye floaters are damaged structures within your eye fluid which appear as visual obstructions to your vision. A floater is identified as a vision obstruction which lags behind a rapid movement of your eye. Ie: if you look up quickly, and the obstruction initially stays where it was and then catches up to where you are looking, then that's a floater.
The fundamental link between E2 and eye floaters is not well understood, but they occur because E2 levels are too low for too long.
Nor is it well understood why SERMs trigger eye floaters more frequently than aromatase inhibitors such as Arimidex, but that is indeed the case."[/I]

Thanks.

Where is the evidence, ANY evidence, between AIs and "floaters" or ocular/visual disturbances?

Their whole idea that it is the E2 level is contrary to the action of AI vs SERM. And, their receptor theory.

 

[Michael Scally MD]

FWIW: https://thinksteroids.com/community/posts/812345

IMO, RPRX is NOT an investable company.

 

[Dr JIM]

I discussed the issue of "visual disturbances" with THREE of my opthalmology colleagues. All
concurred that "floaters" while relatively common in patients with underlying retinal disease (diabetics, glaucoma, HTN patients etc)
NONE believed the literature or their experience, of fifty years combined, supports such an "absurd estrogen relationship" excluding patients with a predilection for vascular headaches.

 

[bax]

All well and good except I tried low dose clomid for three months and felt positively horrid even tho it did increase t. My shbg also went way up to. And I know plenty of others who experienced this too. I was only taking 12.5 mg 3x per week. I'll never touch that shit again.

 

[foreveryoung]

my eyes have gone very bad, with extremely bad night vision and halos around high contrast lights at night

could be a coincidence but I often wonder if it has something to do with the various protocals I've done over the years, did some higher dose runs of clomid before, and many "hormonal alterations" over the decades

my eyesight is worse than my parents and they are much older, obviously, so that really makes me wonder, and hope that things don't get worse

 

[Dr JIM]

Anecdotes are meaningless unless corroborated by supportive evidence. My suspicion, based on well established evidence, is your vision has become more myopic over time, irrespective of prior Clomid ise, which is VERY common.
Should you believe otherwise have your visual acuity checked by an ophthalmologist even though most assuredly your diagnosis won't be "estrogen mediated floaters".

 

[LW64]

The optic nerve comes close to the pituitary gland. That might cause visual issues when on a SERM, but it wouldnt be floaters, IIUC. E2 is not in that mix at all, and neither are AIs...they have other issues and should be avoided.

I also dont believe the assertion that E2 measurements are useless when on a SERM. Hey, you take a SERM and if your pituitary can still do it, your LH goes up and if your Leydigs can still do it so does your T level, followed by the subsequent conversion to E2. Your bloodwork measures the E2 serum level. The agonist/antagonist effect of clomid mixes things up as far as your reaction to it all goes, but your serum level is still your serum level.

 

[chp5]

Very interesting thread. Thanks for all the info!

 

[Dr JIM]

Actually the "optic nerve" is reasonably well removed from the pituitary, the majority being encased by the bony orbits. What is "IUO"? What are you suggesting should be "avoided" and why?

 

[LW64]

Actually the "optic nerve" is reasonably well removed from the pituitary, the majority being encased by the bony orbits. What is "IUO"? What are you suggesting should be "avoided" and why?

IIUC - If I understand correctly.

"...comes close to..."
"...is reasonably well removed from..."

I had looked at this picture:

http://www.mayoclinic.com/health/medical/IM02722

I'm suggesting AIs be avoided. Why take them when simple adjustments in protocol might be all that's needed to reduce E2?

 

[idmd]

The optic nerve comes close to the pituitary gland. That might cause visual issues when on a SERM, but it wouldnt be floaters, IIUC. E2 is not in that mix at all, and neither are AIs...they have other issues and should be avoided.

I also dont believe the assertion that E2 measurements are useless when on a SERM. Hey, you take a SERM and if your pituitary can still do it, your LH goes up and if your Leydigs can still do it so does your T level, followed by the subsequent conversion to E2. Your bloodwork measures the E2 serum level. The agonist/antagonist effect of clomid mixes things up as far as your reaction to it all goes, but your serum level is still your serum level.

It's my understanding that the SERM-related vision loss is based on it's effects on the retina...the optic nerve does run "near" the pituitary but it's enclosed in the bony sella turcia in the sphenoid bone. Not saying a neoplasm like a pituitary adenoma can't affect vision by putting pressure on the optic nerves but that's because the pituitary is bulging out of sella turcica.

 

[Dr JIM]

I may be wasting my time here but once again the optic NERVE IS primarily encased within the ORBITS while the optic chasm lies posterior to the pitutitary ON TOP of the sphenoid bone. Thus pituitary adenomas compress the OPTIC CHIASM and only RARELY exttend so far laterally to involve the OPTIC NERVE at its juncture with the ocular globe.
What are you talking about?
What protocol?
Incidentally while peripherally acting SERMs have NOT been associated with visual DISTURBANCES, Clomid (a central mediated SERM) has.
However changes in visual ACUITY consequent to its use has only VERY RARELY been reported. (I am aware of TWO case reports and both reverted to normal upon discontinuation)

 

[idmd]

Dr. Jim,

I didn't feel the need to distinguish between the optic nerve and optic chasm for the purpose of this discussion since one is contiguous with the other and most people here wouldn't necessarily care.....FWIW I was supporting your previous point that there is little data out there supporting SERMs affecting vision.

 

[idmd]

(sorry continuation of last post due to distraction) ....and if it did I can not see how the pituitary's relationship to the optic chiasm/nerve has anything to do with it.

 

[idmd]

It's my understanding that the SERM-related vision loss is based on it's effects on the retina...the optic nerve does run "near" the pituitary but it's enclosed in the bony sella turcia in the sphenoid bone. Not saying a neoplasm like a pituitary adenoma can't affect vision by putting pressure on the optic nerves but that's because the pituitary is bulging out of sella turcica.

and by "it's" I'm referring to the pituitary and not the optic chiasm/nerve. Sorry that wasn't made clear.