Well, a couple of things going on here.

First some of those secondary guys that use clomid long term only use enough to get LH to move T within range, and this is long term use, not weeks.

Second post cycle with either the use of hCG during, or in PCT hCG hammers LH to lowest detectable levels and even at just .1 is common depending on how much hCG.

When LH is so low, 100mg for a week or two is not a bad idea, once GnRH becomes more sensitive at the pituitary, less can be used, and then tapering would be a good idea.

The issue would be that of ocular toxicity with the higher doses of clomid being used.

We know that endo docs use clomid at 100mg per day for 5 to 7 days to get the pituitary to respond to notice an influence to diagnose secondary hypogonadism.

So, I really don't see an issue with this, unless the person is prone to clomids sides, but many will not notice any sides from clomid like myself.

So, 2 weeks with 100mg clomid I don't really have a problem with as guys need those androgens up ASAP.

But the question is whether taking such a high dose like 100mg will really bring LH and FSH output up any faster. Once oestrogen is inhibited, it can't be inhibited any further, so whacking in a massive initial dose doesn't necessarily have any benefits. The MOA doesn't really relate well to the idea of "the more you take, the better/faster it works". Once oestrogen is inhibited, it all comes down to how quickly the hypothalamus and pituitary begin releasing their relevant hormones, and more clomid won't really do anything to speed that up if it's already doing its job.

My point here is mostly regarding the side effects such as ocular toxicity and depression/emotional issues, so if guys don't have any of that, then perhaps it isn't an issue. But either way, it's still not a healthy thing, so guys might be giving themselves much higher doses for no discernible benefit but some potentially negative effects.

I've also been having a look through the web and I'm sure that Crisler and Shippen have both done one week 50mg ED clomid tests. Given that they've said that 25mg ED of clomid is a "whopping" dose for HPTA stimulation, 50mg would still be double that amount and considered a high dose.

 

I personally don't think so, but it wouldn't do any harm providing that it's a sensible front load. Something like 100mg for the first day and then 50mg thereafter with a gradual taper.

The studies mentioned in my original post achieved huge boosts in test on low doses without any front-loading. Hackskii also did a small clomid run with a starting dose of 50mg and achieved a large increase in T levels.

People say that clomid should be front-loaded to build up the half-lives, but they're perhaps erroneously applying the concept of AAS half-lives to clomifene. Steroids have an ester attached where the hormone only becomes active when it's gradually cleaved away by enzymes. Clomid doesn't have any of that. You take 50mg and 50mg is in your blood and working within a few hours. It then gradually takes time to leave the system.

It's more clear now that not a lot of clomid is required to inhibit the effect of oestrogen on the hypothalamus, and once it's working, it can't really work any more effectively, so I don't think there's any merit in the idea of trying to get half-life peaks to overlap like you would with AAS.

But as I said, I suppose a 100mg single day front load won't hurt. That's still quadruple what has been proven to work in HPTA stimulation.

Makes sense.

I guess the question is, we have no proof that a higher dose of 100mg ED does NOT have a more significant impact on levels. What we know is the increase in side effects (or risks thereof).

So theoretically, someone who appears to have no negative side effects at 100mg ED could continue with that protocol on the chance there is further benefits to a higher dose, with no detriment (to this individual).

 

Makes sense.

I guess the question is, we have no proof that a higher dose of 100mg ED does NOT have a more significant impact on levels. What we know is the increase in side effects (or risks thereof).

So theoretically, someone who appears to have no negative side effects at 100mg ED could continue with that protocol on the chance there is further benefits to a higher dose, with no detriment (to this individual).

They could, yes. But I'd be cautious of doing so.

These side effects aren't just mild annoyances. Ocular toxicity is a serious thing, which is likely to be present even if no symptoms are apparent during these initial stages. We just don't know for sure what's really going on inside the body.

Given that doctors and numerous studies have suggested that 25mg to 50mg works very well, and they've advocated 50mg in clomid tests and PCT therapies, I would be weary of doubling the dose of clomid. That's one hell of a big jump which may well have hidden issues we don't know about.

Perhaps it's required if someone needs a seriously heavy PCT after exhausting all other options, but I don't think anywhere near that much is required for a normal 10-12 week cycle. Bear in mind that clomid is often partnered with another SERM with similar mechanisms, so you have to factor that in as well. 100mg of clomid and 20mg of nolva or 60mg or torem may be massive overkill which causes more harm than good for many normal AAS users.

Anyway, I'll be doing 50mg of clomid ED and 60mg of torem ED in my PCT (there's a log ready and waiting in the PCT section of this thread), so I suppose I'll find out. If I get hit hard by the clomid sides, I'll drop to 25mg clomid ed and keep the 60mg of torem.

 

They could, yes. But I'd be cautious of doing so.

These side effects aren't just mild annoyances. Ocular toxicity is a serious thing, which is likely to be present even if no symptoms are apparent during these initial stages. We just don't know for sure what's really going on inside the body.

Given that doctors and numerous studies have suggested that 25mg to 50mg works very well, and they've advocated 50mg in clomid tests and PCT therapies, I would be weary of doubling the dose of clomid. That's one hell of a big jump which may well have hidden issues we don't know about.

Perhaps it's required if someone needs a seriously heavy PCT after exhausting all other options, but I don't think anywhere near that much is required for a normal 10-12 week cycle. Bear in mind that clomid is often partnered with another SERM with similar mechanisms, so you have to factor that in as well. 100mg of clomid and 20mg of nolva or 60mg or torem may be massive overkill which causes more harm than good for many normal AAS users.

Anyway, I'll be doing 50mg of clomid ED and 60mg of torem ED in my PCT (there's a log ready and waiting in the PCT section of this thread), so I suppose I'll find out. If I get hit hard by the clomid sides, I'll drop to 25mg clomid ed and keep the 60mg of torem.

Indeed indeed.

Yes, following your pct thread closely as you are also incorporating aromasin correct?

Need to work out what protocol I'm going to use for my pct in a few weeks.

 

Well if endo docs use 100mg per day, I doubt 50mg would have the same results.

Again I have no issue with 100mg for a couple of weeks, occular issues won't be an issue.

 

Indeed indeed.

Yes, following your pct thread closely as you are also incorporating aromasin correct?

Need to work out what protocol I'm going to use for my pct in a few weeks.

Yep. I'll see how the aromasin goes and adjust my dose if necessary. 12.5mg EOD is my starting point followed by a taper.

 

Well if endo docs use 100mg per day, I doubt 50mg would have the same results.

Again I have no issue with 100mg for a couple of weeks, occular issues won't be an issue.

Dr Shippen and Dr Crisler, who are more specialised in HPTA recovering from AAS use, both seem to be using 50mg of clomid for their clomid tests and on-going therapy:

The clomid was just a brief test-it was a low dose-- 1/2 a 50mg (??)) tablet for only 7 days, with blood work on the 8th. Per Dr. Shippen it was only intended to "rev the engine" (his words) to help determine where the problem lies. It was a limited test only and never intended as a solution. I was encouraged that I could see any results after only a week at a low dose.

This guy was even advised by Shippen to only use 25mg ED for 7 days.

I've never seen endos use 100mg per day personally, but even if they do, I'm not going to take their word as gospel, especially when there's mounting scientific evidence, anecdotal reports and comments from AAS-recovery specialist doctors that even 25mg is a whopping dose, and 50mg is double that.

And why do you think that 100mg of clomid every day won't make ocular toxicity an issue? Scally himself said this:

Regarding side effects, visual disturbances require immediate and prompt attention. In some cases, a migraine (headaches) equivalent may be diagnosed. In the more than 1000 patients I saw prescribed the SERMs tamoxifen and/or clomiphene, very few complained of visual disturbances or migraines/headaches. Tamoxifen was prescribed at 20-40 mg/day for no more than 45 days, while the clomiphene dose was 50-100 mg/day. In those that did, there was an immediate decrease in dose or discontinuation with almost daily follow up. None suffered any consequences.

So even at doses of 50mg-100mg per day, if any patients had eye problems (which he suggests some did), he immediately decreased or stopped the dose.

Given the nature of ocular toxicity, there doesn't need to necessarily be any symptoms for it to still be unhealthy for your eyes. It's a bit like saying that people are fine to drink as much alcohol as they want as long as they don't get cirrhosis of the liver. It's still detrimental to health below the point in which symptoms start to become noticeable.

But you're entitled to your opinion anyway. Personally, after everything I've read, I'll be advocating a lower dose to restore HPTA function for normal, sensible cycles. This board also seems to only be one of the few where 100mg of clomid is still commonplace. Most forums in the US and elsewhere are all suggesting 25mg/50mg clomid doses for their PCTs and recovering very well it seems.

 

Dr Shippen and Dr Crisler, who are more specialised in HPTA recovering from AAS use, both seem to be using 50mg of clomid for their clomid tests and on-going therapy:

This guy was even advised by Shippen to only use 25mg ED for 7 days.

I've never seen endos use 100mg per day personally, but even if they do, I'm not going to take their word as gospel, especially when there's mounting scientific evidence, anecdotal reports and comments from AAS-recovery specialist doctors that even 25mg is a whopping dose, and 50mg is double that.

And why do you think that 100mg of clomid every day won't make ocular toxicity an issue? Scally himself said this:

So even at doses of 50mg-100mg per day, if any patients had eye problems (which he suggests some did), he immediately decreased or stopped the dose.

Given the nature of ocular toxicity, there doesn't need to necessarily be any symptoms for it to still be unhealthy for your eyes. It's a bit like saying that people are fine to drink as much alcohol as they want as long as they don't get cirrhosis of the liver. It's still detrimental to health below the point in which symptoms start to become noticeable.

But you're entitled to your opinion anyway. Personally, after everything I've read, I'll be advocating a lower dose to restore HPTA function for normal, sensible cycles. This board also seems to only be one of the few where 100mg of clomid is still commonplace. Most forums in the US and elsewhere are all suggesting 25mg/50mg clomid doses for their PCTs and recovering very well it seems.

I forone get really bad clomid sides, as ive mentioned on here before and that was 50mg ed for 10 days, thats all I could take, im going to try 25mg and see difference this pct and run for a longer period

 

I forone get really bad clomid sides, as ive mentioned on here before and that was 50mg ed for 10 days, thats all I could take, im going to try 25mg and see difference this pct and run for a longer period

Crisler, a doctor and AAS HPTA restoration specialist, said this:

As Dr. Shippen and I have each discovered independently, and discussed in a private conversation at an A4M conference in Las Vegas over two years ago, just 25mg of clomid is indeed a whalloping dose with respect to HPTA-stimulation. I therefore would want to see dosage decreases in 5 day increments, with the last step at 12.5mg QD.

So I think you'll be fine with 25mg ED along with another SERM like 20mg of nolva or 60mg of torem if 50mg ED provides too many bad side effects.

I'll personally be dropping from 50mg to 25mg ED if the side effects are too bad for me in my PCT next week.

 

Dr Shippen and Dr Crisler, who are more specialised in HPTA recovering from AAS use, both seem to be using 50mg of clomid for their clomid tests and on-going therapy:

This guy was even advised by Shippen to only use 25mg ED for 7 days.

I've never seen endos use 100mg per day personally, but even if they do, I'm not going to take their word as gospel, especially when there's mounting scientific evidence, anecdotal reports and comments from AAS-recovery specialist doctors that even 25mg is a whopping dose, and 50mg is double that.

And why do you think that 100mg of clomid every day won't make ocular toxicity an issue? Scally himself said this:

So even at doses of 50mg-100mg per day, if any patients had eye problems (which he suggests some did), he immediately decreased or stopped the dose.

Given the nature of ocular toxicity, there doesn't need to necessarily be any symptoms for it to still be unhealthy for your eyes. It's a bit like saying that people are fine to drink as much alcohol as they want as long as they don't get cirrhosis of the liver. It's still detrimental to health below the point in which symptoms start to become noticeable.

But you're entitled to your opinion anyway. Personally, after everything I've read, I'll be advocating a lower dose to restore HPTA function for normal, sensible cycles. This board also seems to only be one of the few where 100mg of clomid is still commonplace. Most forums in the US and elsewhere are all suggesting 25mg/50mg clomid doses for their PCTs and recovering very well it seems.

For the record Scally does use 100mg per day, and thus suggested that out of the thousands that have been treated very few complained of visual disturbances.

I myself at 100mg see some things going on after 21 days being on.

I really do not think that 50 or 25mg will give the same response as 100mg.

Here are some studies suggesting both side of things.

Here's a study showing low-dose Clomid therapy (25mg ED) boosts testosterone by 250% in 4-6 weeks:



Clomiphene citrate effects on testosterone/estrogen ratio in male hypogonadism
,
Shabsigh A, Kang Y, Shabsign R, Gonzalez M, Liberson G, Fisch H, Goluboff E.
Department of Urology, NY Presbyterian Medical Center, New York, NY, USA. J Sex Med. 2005 Sep;2(5):716-21.

AIM: Symptomatic late-onset hypogonadism is associated not only with a decline in serum testosterone, but also with a rise in serum estradiol. These endocrine changes negatively affect libido, sexual function, mood, behavior, lean body mass, and bone density. Currently, the most common treatment is exogenous testosterone therapy. This treatment can be associated with skin irritation, gynecomastia, nipple tenderness, testicular atrophy, and decline in sperm counts. In this study we investigated the efficacy of clomiphene citrate in the treatment of hypogonadism with the objectives of raising endogenous serum testosterone (T) and improving the testosterone/estrogen (T/E) ratio. METHODS: Our cohort consisted of 36 Caucasian men with hypogonadism defined as serum testosterone level less than 300 ng/dL. Each patient was treated with a daily dose of 25 mg clomiphene citrate and followed prospectively. Analysis of baseline and follow-up serum levels of testosterone and estradiol levels were performed.

RESULTS: The mean age was 39 years, and the mean
pretreatment testosterone
and estrogen levels were
247.6 +/- 39.8 ng/dL
and 32.3 +/- 10.9, respectively.
By the first follow-up visit (4-6 weeks), the mean testosterone level rose to 610.0 +/- 178.6 ng/dL
(P < 0.00001). Moreover, the T/E ratio improved from 8.7 to 14.2 (P < 0.001). There were no side effects reported by the patients.

CONCLUSIONS: Low dose clomiphene citrate is effective in elevating serum testosterone levels and improving the testosterone/estradiol ratio in men with hypogonadism.This therapy represents an alternative to testosterone therapy by stimulating the endogenous androgen production pathway.

Study showing a hypogonadic 30-year old male, suffering permanent shutdown from steroid abuse, fully recovered natural hormone levels and HPTA function from 2 months of 100mg Clomid therapy:

Use of clomiphene citrate to reverse premature andropause secondary to steroid abuse
,
Tan RS, Vasudevan D.

Department of Family and Community Medicine, University of Texas Health Sciences Center, Houston, Texas 77030, USA.

OBJECTIVE: To report a case of symptomatic hypogonadism induced by the abuse of multiple steroid preparations that was subsequently reversed by clomiphene. DESIGN: Case report. SETTING: University-affiliated andrology practice within family practice clinic. PATIENT(S): A 30-year-old male.

INTERVENTION(S): Clomiphene citrate, 100-mg challenge for 5 days, followed by treatment at same dose for 2 months.

MAIN OUTCOME MEASURE(S): Clinical symptoms, androgen decline in aging male questionnaire, total T, FSH, LH.

RESULT(S):
Reversal of symptoms, normalization of T levels with LH surge, restoration of pituitary-gonadal axis.


CONCLUSION(S): Clomiphene citrate is used typically in helping to restore fertility in females. This represents the
first case report of the successful use of clomiphene to restore T levels and the pituitary-gonadal axis in a male patient. The axis was previously shut off with multiple anabolic steroid abuse.


Here's another study showing only 7 days of Clomid therapy increased total testosterone by 100% and, more importantly, free testosterone by over 300% in young men:



The effects of aging in normal men on bioavailable testosterone and luteinizing hormone secretion: response to clomiphene citrate
, J Clin Endocrinol Metab. 1987 Dec;65(6):1118-26.

Geriatric Research, Education, and Clinical Center, Veterans Administration Medical Center, Seattle, Washington.

Serum testosterone (T) levels in men decline with age while serum LH levels, as measured by RIA, increase. To assess if the decline in serum T levels in healthy aging men is paralleled by an age-related decline in the bioavailable non-sex hormone-binding globulin (SHBG)-bound fraction of T and to determine whether there are age-related changes in LH secretion or LH control of T production, we studied 29 young (aged 22-35 yr) and 26 elderly (aged 65-84 yr) healthy men. All men had single random blood samples drawn, and 14 men in each age group underwent frequent blood sampling for 24 h, both before and after
7 days of clomiphene citrate (CC) administration.
Both mean 24-h serum total T levels and non-SHBG-bound T were reduced in elderly men compared to those in young men (P less than 0.05), while estradiol and SHBG levels were similar in the 2 age groups. Serum FSH determined by RIA and LH by RIA and bioassay were higher in the elderly men compared to those in young men (P less than 0.05), but the ratios of LH bioactivity to immunoreactivity and the LH pulse frequency and amplitude were similar.
After CC administration, mean serum total T and non-SHBG-bound levels in young men increased by 100% and 304%
, respectively, while in older men these values increased by only 32% and 8%, respectively. However, CC-stimulated LH pulse characteristics and serum levels of estradiol, SHBG, FSH, and bioactive and immunoreactive LH were similar in the 2 groups. Thus, both at baseline and after CC stimulation, elderly men had significantly lower serum total T and non-SHBG-bound (bioavailable) T levels than did young men, despite similar or increased levels of bioactive LH and similar bioactive to immunoreactive LH ratios and LH pulse characteristics. These results suggest that major age-related changes in the hypothalamic-pituitary-testicular axis occur at the level of the testes and are manifested by decreased responsiveness to bioactive LH. Administration of CC to young and elderly men resulted in similar changes in LH pulse characteristics and LH bioactivity and immunoreactivity, suggesting preserved hypothalamic-pituitary responsiveness in the elderly.

 

So, as you can see, for some it may work, for others perhaps not, we all are different.

Notice the guy that was diagnosis permanent shutdown and the 100mg dosing.

Remember Scally still uses 100mg, Dr. John Crisler will not say how much he gives his guys, what he dose kind of for recovery he will not say, and if his guys talk openly he drops them as patients.

I have followed Scally from 2006, Shippen since 2002, and same with Crisler.

I am fully aware of their doses, what they say, and in contrast they all say similar things, not same.

Scally uses more hCG, and more SERM's.

Another thing, tamox and clomid are both SERM's but are used together for synergy, they do not act the same way, clomid is acts as an estrogen at the pituitary, nolva does not.

I feel they work best together.

Some suggest some estrogen priming with clomid, but all based on speculation and the debate on meso board never got rolling.

I do feel there are times that 100mg may be appropriate, and others not.

It would be like saying just take an aspirin for that broken arm, it kills the pain, yet was the wrong med being used.

 

For the record Scally does use 100mg per day, and thus suggested that out of the thousands that have been treated very few complained of visual disturbances.

I myself at 100mg see some things going on after 21 days being on.

Scally may have used 100mg consistently in the past, but I've seen more recent comments directly from him suggesting that he uses 50mg-100mg depending on the situation. I've even quoted it up there.

I know he has his PoWeR protocol, but it seems that this wasn't just created by Scally. Scally was part of the team at the Program for Wellness Restoration, which created the PCT. Considering that this was mentioned in William Llewellyn's 9th edition book which was released in 2009, the protocol may now be anywhere from 6-10+ years old. Things can come a long way in that time period. Scally, Shippen and Crisler have both mentioned in more recent times the effectiveness and use of 25mg-50mg doses.

I really do not think that 50 or 25mg will give the same response as 100mg.

But why? As I've said before, many studies, anecdotal reports and comments from Shippen and Crisler suggest that 50mg is more than enough and even 25mg is a "whopping" dose for HPTA simulation. I'm basing this point on all of this evidence, and unless you have some evidence add weight to your theory, it just seems to be speculation.

Clomiphene citrate effects on testosterone/estrogen ratio in male hypogonadism
,
Shabsigh A, Kang Y, Shabsign R, Gonzalez M, Liberson G, Fisch H, Goluboff E.
Department of Urology, NY Presbyterian Medical Center, New York, NY, USA. J Sex Med. 2005 Sep;2(5):716-21.

AIM: Symptomatic late-onset hypogonadism is associated not only with a decline in serum testosterone, but also with a rise in serum estradiol. These endocrine changes negatively affect libido, sexual function, mood, behavior, lean body mass, and bone density. Currently, the most common treatment is exogenous testosterone therapy. This treatment can be associated with skin irritation, gynecomastia, nipple tenderness, testicular atrophy, and decline in sperm counts. In this study we investigated the efficacy of clomiphene citrate in the treatment of hypogonadism with the objectives of raising endogenous serum testosterone (T) and improving the testosterone/estrogen (T/E) ratio. METHODS: Our cohort consisted of 36 Caucasian men with hypogonadism defined as serum testosterone level less than 300 ng/dL. Each patient was treated with a daily dose of 25 mg clomiphene citrate and followed prospectively. Analysis of baseline and follow-up serum levels of testosterone and estradiol levels were performed.

RESULTS: The mean age was 39 years, and the mean
pretreatment testosterone
and estrogen levels were
247.6 +/- 39.8 ng/dL
and 32.3 +/- 10.9, respectively.
By the first follow-up visit (4-6 weeks), the mean testosterone level rose to 610.0 +/- 178.6 ng/dL
(P < 0.00001). Moreover, the T/E ratio improved from 8.7 to 14.2 (P < 0.001). There were no side effects reported by the patients.

CONCLUSIONS: Low dose clomiphene citrate is effective in elevating serum testosterone levels and improving the testosterone/estradiol ratio in men with hypogonadism.This therapy represents an alternative to testosterone therapy by stimulating the endogenous androgen production pathway.

It's a useful study, but as you will already know, they used 25mg of clomid ED for powerful results in hypogonadal men. 50mg is still DOUBLE that dose, so it's still on the more excessive end of the scale.

Study showing a hypogonadic 30-year old male, suffering permanent shutdown from steroid abuse, fully recovered natural hormone levels and HPTA function from 2 months of 100mg Clomid therapy:

Use of clomiphene citrate to reverse premature andropause secondary to steroid abuse
,
Tan RS, Vasudevan D.

Department of Family and Community Medicine, University of Texas Health Sciences Center, Houston, Texas 77030, USA.

OBJECTIVE: To report a case of symptomatic hypogonadism induced by the abuse of multiple steroid preparations that was subsequently reversed by clomiphene. DESIGN: Case report. SETTING: University-affiliated andrology practice within family practice clinic. PATIENT(S): A 30-year-old male.

INTERVENTION(S): Clomiphene citrate, 100-mg challenge for 5 days, followed by treatment at same dose for 2 months.

MAIN OUTCOME MEASURE(S): Clinical symptoms, androgen decline in aging male questionnaire, total T, FSH, LH.

RESULT(S):
Reversal of symptoms, normalization of T levels with LH surge, restoration of pituitary-gonadal axis.


CONCLUSION(S): Clomiphene citrate is used typically in helping to restore fertility in females. This represents the
first case report of the successful use of clomiphene to restore T levels and the pituitary-gonadal axis in a male patient. The axis was previously shut off with multiple anabolic steroid abuse.

I have no doubt it works, but this was the "first case report" from 2003, which was 12 years ago. Considering it's the first case report, there would not have been much, if any, past information to go on regarding clomid therapy for this sort of thing, so they can be forgiven for going straight in at 100mg. But things have came along way since then.

It would also be interesting to see the more specific details of that (i.e. pre and post blood work) as it's difficult to really tell if his results were any more successful or faster than the other lower doses which have been proven to work. He was on the 100mg clomid dose for 2 months, so it muddies the ability to tell how quickly it did actually work and whether a lower dose would have worked just as quickly.

Here's another study showing only 7 days of Clomid therapy increased total testosterone by 100% and, more importantly, free testosterone by over 300% in young men:



The effects of aging in normal men on bioavailable testosterone and luteinizing hormone secretion: response to clomiphene citrate
, J Clin Endocrinol Metab. 1987 Dec;65(6):1118-26.

Geriatric Research, Education, and Clinical Center, Veterans Administration Medical Center, Seattle, Washington.

Serum testosterone (T) levels in men decline with age while serum LH levels, as measured by RIA, increase. To assess if the decline in serum T levels in healthy aging men is paralleled by an age-related decline in the bioavailable non-sex hormone-binding globulin (SHBG)-bound fraction of T and to determine whether there are age-related changes in LH secretion or LH control of T production, we studied 29 young (aged 22-35 yr) and 26 elderly (aged 65-84 yr) healthy men. All men had single random blood samples drawn, and 14 men in each age group underwent frequent blood sampling for 24 h, both before and after
7 days of clomiphene citrate (CC) administration.
Both mean 24-h serum total T levels and non-SHBG-bound T were reduced in elderly men compared to those in young men (P less than 0.05), while estradiol and SHBG levels were similar in the 2 age groups. Serum FSH determined by RIA and LH by RIA and bioassay were higher in the elderly men compared to those in young men (P less than 0.05), but the ratios of LH bioactivity to immunoreactivity and the LH pulse frequency and amplitude were similar.
After CC administration, mean serum total T and non-SHBG-bound levels in young men increased by 100% and 304%
, respectively, while in older men these values increased by only 32% and 8%, respectively. However, CC-stimulated LH pulse characteristics and serum levels of estradiol, SHBG, FSH, and bioactive and immunoreactive LH were similar in the 2 groups. Thus, both at baseline and after CC stimulation, elderly men had significantly lower serum total T and non-SHBG-bound (bioavailable) T levels than did young men, despite similar or increased levels of bioactive LH and similar bioactive to immunoreactive LH ratios and LH pulse characteristics. These results suggest that major age-related changes in the hypothalamic-pituitary-testicular axis occur at the level of the testes and are manifested by decreased responsiveness to bioactive LH. Administration of CC to young and elderly men resulted in similar changes in LH pulse characteristics and LH bioactivity and immunoreactivity, suggesting preserved hypothalamic-pituitary responsiveness in the elderly.

Unless I'm missing something, that study doesn't even state what clomid dose was used.

But anyway, you have your opinions and I have mine. Based on everything I've seen and read, it seems more plausible now that a 50mg clomid dose ED will work very well on a normal 10-12 week cycle. Scally, Shippen and Crisler (who said 25mg is a big dose) have and still do use those doses (even when these men have seeked out these specialists because their own personal PCT has failed), studies support these doses, and anecdotal reports from other BB forums support this dose and its effectiveness as well.

Each to their own!

 

You know, on Meso board, both Scally, and Cristler did not agree with the dosing of each others protocol, in fact they were mortal enemies.

So, do you see any issue with 100mg ED for a week, or two, then tapering the dose down?

If so state your concerns, end explain why?

 

You know, on Meso board, both Scally, and Cristler did not agree with the dosing of each others protocol, in fact they were mortal enemies.

So, do you see any issue with 100mg ED for a week, or two, then tapering the dose down?

If so state your concerns, end explain why?

For the record I'm not suggesting that I know any of this for a fact. I'm simply applying some thinking to various sources of information which may perhaps help people with their future PCTs. Especially those who have serious emotional/depression problems or eye issues.

My reasoning is the following:

1). The majority of studies, anecdotal reports and comments from HPTA restoration specialist doctors like Crisler and Shippen all point to doses of around 50mg (and sometimes less) being extremely effective at restoring HPTA, and this isn't even factoring in the uses of other serms like torem or nolva which will add to that effect, so 100mg (which is double to quadruple the dose used effectively in many men) may increase the risk of side effects and emotional problems (thus hampering diet and training during the critical PCT phase) along with potentially dangerous occular toxicity for no discernible benefit.

2). Scally's post suggests that he has given guys 50-100mg per day clomid therapy to treat hypogonadism and has had some patients start experiencing eye problems, with which he's immediately reduced or dropped the dose, so there's evidence that occular toxicity can occur at those doses, and can also occur even if symptoms are not readily apparent.

3). There's plenty of evidence that 50mg of clomid works very well, and sometimes even 25mg, but there's zero evidence that 100mg of clomid works any faster or more effectively, so there's solid ground for suggesting 50mg ED, but it's just speculation to suggest anything higher when many guys have used 50mg PCTs and recovered well.

4). Higher doses of clomid like 100mg ED may be useful in extreme circumstances when someone has exhausted all other options, but this dose is being suggested for guys running normal 10-12 week cycles, which I think is completely unnecessary.

5). I don't see how the MOA would make double or quadruple what's an effective dose more effective or faster. Once oestrogen is inhibited at the hypothalamus, it can't be any more inhibited. The speed of LH and FSH production is related directly to the speed of the hypothalmus and pituitary production, and clomid dosages have no bearing on that. They just simulate the environment which the hypothalamus uses as an indicator to start producing LH and FSH.

Crisler and Shippen have both agreed that 25mg is a "whopping" dose, so even if we were to be very over generous with the dosage, 50mg is still double that and has been shown to work. Perhaps someone can frontload clomid for a few days if they wish (even though it increases the risk of occular toxicity and emotional problems), but I think 50mg every day with a taper in the last week or two is more than enough for normal guys on sensible cycles which avoids the bad side effects.

I've also been doing some reading on GnRH sensitivity at the pituitary, and it seems that high clomid doses may even DECREASE the GnRH sensitivity at the pituitary and therefore cause a reduction in LH and FSH output. This is by William Lewellyn:

Researchers were also conducting GnRH stimulation test before and after various points of treatment with Nolvadex and Clomid, and the two drugs had markedly different results. These test involved infusing patients with 100mcg of GnRH and measuring the output of pituitary LH in response. The focus of this test is to see how sensitive the pituitary is to Gonadotropin Releasing Hormone. The more sensitive the pituitary, the more LH will be released. The test showed that after ten days of treatment with Nolvadex, pituitary sensitivity to GnRH increased slightly compared to pre-treated values. This is contrast to 10 days of treatment with 150mg Clomid, which was shown to consistently DECREASE pituitary sensitivity to GnRH (more LH was released before treatment). As the study with Nolvadex progresses to 6 weeks, pituitary sensitivity to GnRH significantly higher than pre-treated 10 day levels. At this point the same 20mg dosage was also raising testosterone and LH levels to an average of 183% and 172% of base values, respectively, which again is measurably higher that what was noted 10 days into therapy. Within 10 days of treatment Clomid is already exerting an effect that is causing the pituitary to become slightly desensitized to GnRH

Given this, I would suggest that the "more is better" mantra may actually be harming recovery, and that it's important to just settle on the right sort of mid-lower range dose which has been proven to be highly effective without the unnecessary risk of going higher and causing bad side effects, occular toxicity and potential hypothalamus desensitising issues.

 

Lurking this thread, nice studies and references btw, going to take a look at both chrisler and shippen and there work later

 

For the record I'm not suggesting that I know any of this for a fact. I'm simply applying some thinking to various sources of information which may perhaps help people with their future PCTs. Especially those who have serious emotional/depression problems or eye issues.

My reasoning is the following:

1). The majority of studies, anecdotal reports and comments from HPTA restoration specialist doctors like Crisler and Shippen all point to doses of around 50mg (and sometimes less) being extremely effective at restoring HPTA, and this isn't even factoring in the uses of other serms like torem or nolva which will add to that effect, so 100mg (which is double to quadruple the dose used effectively in many men) may increase the risk of side effects and emotional problems (thus hampering diet and training during the critical PCT phase) along with potentially dangerous occular toxicity for no discernible benefit.

2). Scally's post suggests that he has given guys 50-100mg per day clomid therapy to treat hypogonadism and has had some patients start experiencing eye problems, with which he's immediately reduced or dropped the dose, so there's evidence that occular toxicity can occur at those doses, and can also occur even if symptoms are not readily apparent.

3). There's plenty of evidence that 50mg of clomid works very well, and sometimes even 25mg, but there's zero evidence that 100mg of clomid works any faster or more effectively, so there's solid ground for suggesting 50mg ED, but it's just speculation to suggest anything higher when many guys have used 50mg PCTs and recovered well.

4). Higher doses of clomid like 100mg ED may be useful in extreme circumstances when someone has exhausted all other options, but this dose is being suggested for guys running normal 10-12 week cycles, which I think is completely unnecessary.

5). I don't see how the MOA would make double or quadruple what's an effective dose more effective or faster. Once oestrogen is inhibited at the hypothalamus, it can't be any more inhibited. The speed of LH and FSH production is related directly to the speed of the hypothalmus and pituitary production, and clomid dosages have no bearing on that. They just simulate the environment which the hypothalamus uses as an indicator to start producing LH and FSH.

Crisler and Shippen have both agreed that 25mg is a "whopping" dose, so even if we were to be very over generous with the dosage, 50mg is still double that and has been shown to work. Perhaps someone can frontload clomid for a few days if they wish (even though it increases the risk of occular toxicity and emotional problems), but I think 50mg every day with a taper in the last week or two is more than enough for normal guys on sensible cycles which avoids the bad side effects.

I've also been doing some reading on GnRH sensitivity at the pituitary, and it seems that high clomid doses may even DECREASE the GnRH sensitivity at the pituitary and therefore cause a reduction in LH and FSH output. This is by William Lewellyn:

Given this, I would suggest that the "more is better" mantra may actually be harming recovery, and that it's important to just settle on the right sort of mid-lower range dose which has been proven to be highly effective without the unnecessary risk of going higher and causing bad side effects, occular toxicity and potential hypothalamus desensitising issues.

A few things, clomid comes in 50mg tabs, not 25, so they split the tabs but it comes in 50mg per tab.

Women for ovulation purposes, start out with 50mg, when this does not work, they up that to 100mg per day.

Less than 1% of women have sides associated with clomid, and read that again, less than 1%.

You suggest that 50mg works the same as 100mg and zero evidence to support its use at 100mg per day.

But, the clomiphene test is 100mg per day for 5 to 7 days, not 50, if they are trying to illicit a response they use 100mg, not 50.

So, there is more evidence that 100mg has a bigger response than 50, otherwise endo docs would be using 50mg.

SERM's especailly clomid works by making GnRH more sensitive at the pituitary, otherwise guys would just use an AI.

Its not inhibiting estrogen that is making it work, read your study about GnRH sensitivity, your posts states it right there in writing.

So, it is not inhibiting estrogen, it is making GnRH more sensitive so there is a bigger spike in LH.

250mg test cycles work well, 500mg works better, but then again more may just be better.

Not saying every situation would require a higher dose.

Remember, Shippen, and Crisler both are TRT docs, Crisler works with bodybuilders with AAS use, trust me I am very aware of both of these guys, read their stuff for more than 10 years longer actually.

I know what they say, all of them.

Your statement of more is better may actually be harming recovery has no validity, I only help guys with what they need, I don't go in both barrels and give them a shopping list of stuff to cram down their neck.

Nobody on this board has helped as many guys as myself, not all together.

Every single day, here with PM, and via email I help guys all over the world.

I was the first person on this board to suggest the use of vitamin D with hCG as in Shippens book, he said that deficiencies in vitamin D make hCG not work well.

Fact is 3/4 of the population is low in D, hence my suggestion to add anyway.

The study on the desensitization, that was originally written by Big Cat out of the Netherlands, and it is a myth, asked Scally that myself, he has never seen that.

What I have noticed, once the pituitary becomes more sensitive, you need less clomid.

Pretty funny guys will do grams of gear, but oh man, stay away from that nasty clomid.

I never recommend 100mg per day for a month like my original post, never.

Both clomid and nolva are SERM's, period, they are similar not same.

Here is one for you, 20mg of nolva works the same as 150mg of clmid for its strength of blocking the receptors.

Using your math, you may want to cut the nolva down to 10mg then eh? :lol:

I do feel that 100mg for some may be needed to move things when 50mg does not, if you are prone to feeling not your self, and lets be clear, low androgen will cause a man to have similar sides to Clomid, so a lot of blame clomid gets is really just low androgens.

So, at the doses I suggest for clomid to be run shorter at a higher dose, then longer as it is tapering, ocular issues will be zero, and the hypo desensitization issue is also a myth.

Oh, and you will not find any studies on dosing and T response in men, they are not there.

I don't get any sides from clomid, other than monster loads, a bit watery, but 3 times or more volume.

 

A few things, clomid comes in 50mg tabs, not 25, so they split the tabs but it comes in 50mg per tab.

Women for ovulation purposes, start out with 50mg, when this does not work, they up that to 100mg per day.

Less than 1% of women have sides associated with clomid, and read that again, less than 1%.

It's originally a female fertility drug so obviously the dosages and pills will be different, as will the side effects.

You suggest that 50mg works the same as 100mg and zero evidence to support its use at 100mg per day.

But, the clomiphene test is 100mg per day for 5 to 7 days, not 50, if they are trying to illicit a response they use 100mg, not 50.

So, there is more evidence that 100mg has a bigger response than 50, otherwise endo docs would be using 50mg.

But there's no evidence that 100mg works better than 50mg, whilst there's a lot of evidence that 50mg and even less works very well, and Crisler and Shippen have both said that 25mg is a "whopping" dose for HPTA stimulation, which is half of 50mg. What's your response to that?

And Dr Shippen has actually used 25mg for his clomid test:

The clomid was just a brief test-it was a low dose-- 1/2 a 50mg (??)) tablet for only 7 days, with blood work on the 8th. Per Dr. Shippen it was only intended to "rev the engine" (his words) to help determine where the problem lies. It was a limited test only and never intended as a solution. I was encouraged that I could see any results after only a week at a low dose.

I've never personally seen endos dose clomid at 100mg, but considering that some endos outright refuse to use things like HCG and clomid and prefer to just put some users straight on TRT, I wouldn't take their word as gospel.

Also, do you have any recent examples of the doses endos are suggesting? Anything I've seen regarding 100mg doses has been from 10-20 years ago when the use of clomid was still in its infancy.

SERM's especailly clomid works by making GnRH more sensitive at the pituitary, otherwise guys would just use an AI.

Its not inhibiting estrogen that is making it work, read your study about GnRH sensitivity, your posts states it right there in writing.

So, it is not inhibiting estrogen, it is making GnRH more sensitive so there is a bigger spike in LH.

250mg test cycles work well, 500mg works better, but then again more may just be better.

Not saying every situation would require a higher dose.

Remember, Shippen, and Crisler both are TRT docs, Crisler works with bodybuilders with AAS use, trust me I am very aware of both of these guys, read their stuff for more than 10 years longer actually.

I know what they say, all of them.

I didn't want to say it but I strongly believe that this is incorrect. Clomid may help with GnRh sensitivity, but it's medically well established that the primary mechanism of a SERM inhibits the effect of oestrogen on the hypothalamus. It does both of these things. You even said it yourself in a sticky on this forum:

Now next we want to block the hypothalamus and pituitary gland from that excess estrogen as that in itself is suppressive.

How is this done? With a drug called Clomiphene citrate (clomid). This is really a drug to help women ovulate but it acts as a Selective Estrogen Receptor Modulator (SERM).

It occupy's the estrogen receptors in the hypothalamus and pituitary and blocks estrogens exertion on those glands. It's like putting a key in a lock but not turning the key. It is just occupying that space without really doing anything.

I can give you heaps upon heaps of material from doctors and other sources which state that SERMS work primarily by blocking oestrogen. It also makes a lot of sense from a MOA perspective too. In fact, due to the feedback loop, it makes perfect sense. If you can show me an example of where the serms don't block oestrogen and instead work only by increasing GnRH sensitivity, then I'll believe you, but I've never seen that mentioned anywhere before in my life. Also, if it only increases GnRH sensitivity, then how will that even work when the oestrogen will still be having an inhibiting effect on the hypothalamus and therefore be preventing GnRH release in the first place?

What is Clomid and how does it work? * Why has my doctor recommended Clomid? * How is Clomid prescribed? What can I expect to feel? * Associates In Women's Health Care

Fertility drug: clomifene citrate (clomifene, clomid) - BabyCentre

DrugBank: Clomifene (DB00882)

Clomifene - Wikipedia, the free encyclopedia

Clomiphene Citrate (Clomid) in Men - A Testosterone Alternative

http://www.maledoc.com/blog/2010/04/28/how-clomid-works-in-men/

http://jeffreydachmd.com/clomid-for-low-testosterone-part-one/

You're claiming clomid works in a way which contradicts pretty much every description of it on the internet, including those from qualified doctors. How do you explain that?

I've also just noticed that Scally seems to have said this (the only one), but it has been debunked already: https://thinksteroids.com/community/threads/ask-michael-scally-why-use-both-clomid-and-nolvadex-together-for-pct.134289740/#post-687502

I strongly disagree with Dr. Scally's reasoning behind the use of clomid. What he is describing here is "estrogen priming," the concept that estrogen makes the pituitary more sensitive to GnRH from the hyp[othalamus, so that more LH is released for a given GnRH stimulus. This is well known to occur in females leading up to ovulation. Unlike females, however, men don't have a preovulatory period or spikes in LH. The research is fairly clear that estrogen priming does not occur in males. For starters, take a look at an authoritative reference work like Grossman's http://www.amazon.com/Clinical-Endocrinology-Ashley-Grossman/dp/0865426295]Clinical Endocrinology[/URL], which states (pg. 99):

Progesterone, acting synergistically with oestrogens, exerts negative feedback on the hypothalamus during the luteal phase, thus limiting GnRH pulsatility and slowing LH pulse frequency. The mechanism of positive oestrogen feedback at the time of the LH surge has been much debated. There is now evidence that enhancement of both hypothalamic GnRH pulse generator activity and pituitary responsiveness to GnRH are involved. All species so far studied have shown an increased 'self-priming' effect of GnRH on the pituitary during the preovulatory period... In males, the situation is more straightforward. Since LH surges do not occur, only negative feedback effects are relevant. testosterone (and its active metabolite dihydrotestosterone, DHT) exerts major suppressive effects on both LH and FSH secretion, largely by inhibiting the GnRH pulse frequency generator, but possibly also by direct pituitary actions. Oestrogens in the male reduce pituitary responsiveness to GnRH.

It seems he's got the idea from the fact that this happens in females. However, this does not occur in females. Scally also seems to sidestep the question in that thread.

Your statement of more is better may actually be harming recovery has no validity, I only help guys with what they need, I don't go in both barrels and give them a shopping list of stuff to cram down their neck.

Nobody on this board has helped as many guys as myself, not all together.

Every single day, here with PM, and via email I help guys all over the world.

I was the first person on this board to suggest the use of vitamin D with hCG as in Shippens book, he said that deficiencies in vitamin D make hCG not work well.

Fact is 3/4 of the population is low in D, hence my suggestion to add anyway.

The study on the desensitization, that was originally written by Big Cat out of the Netherlands, and it is a myth, asked Scally that myself, he has never seen that.

What I have noticed, once the pituitary becomes more sensitive, you need less clomid.

Pretty funny guys will do grams of gear, but oh man, stay away from that nasty clomid.

I never recommend 100mg per day for a month like my original post, never.

Both clomid and nolva are SERM's, period, they are similar not same.

Here is one for you, 20mg of nolva works the same as 150mg of clmid for its strength of blocking the receptors.

Using your math, you may want to cut the nolva down to 10mg then eh? :lol:

I do feel that 100mg for some may be needed to move things when 50mg does not, if you are prone to feeling not your self, and lets be clear, low androgen will cause a man to have similar sides to Clomid, so a lot of blame clomid gets is really just low androgens.

So, at the doses I suggest for clomid to be run shorter at a higher dose, then longer as it is tapering, ocular issues will be zero, and the hypo desensitization issue is also a myth.

And I certainly appreciate that you do help lots of people. However, there's no harm in a debate, is there? We're all still learning here.

Your concept of nolva doses doesn't really work because, as I've posted previously multiple times, 50mg has been proven to work very well, and Crisler and others have suggested that even 25mg is a significant dose.

50mg-100mg of clomid has also been stated by Scally to induce occular toxicity in some of his patients, so it's irresponsible to suggest that there will be "zero" issues when there may well be. There's also plenty of guys (including Ollie in this thread) who have had serious emotional and depression problems on higher doses.

All I'm saying is that, for normal guys doing sensible cycles, 50mg should really be ample. I see no evidence anywhere which shows a direct improvement in GnRH response or the speed of LH or FSH production by taking 100mg, which is double to quadruple what has been proven to work well and has been mentioned by Crisler and Shippen as a highly effective dose. 50mg or less has a lot of evidence behind it, but increasing the dose in an attempt to induce a faster or more effective response is speculation.

 

Ok, first off, all those cut and past came from the very boards I am a member of, between 5 and 10 years ago, look it up, don't take my word for it, just see for your self my post counts there.

I joined probably 30 boards, many are gone, but was very active during those times on Meso, among many others, all the information you are giving, I already read, and dropped it into my knowledge pool.

I appreciate your passion, and love a good debate, realize this is the student, trying to challenge the teacher, and although I post to enlighten, you have an emotional stance, and your ego will not allow you to see through your emotional stance.

Another thing, Shippen, as well as Crisler in the context given, they are solely referring to secondary hypogonadal men, and their treatment was clomid mono therapy for TRT, these men are on for years, not weeks, modifying and adjusting their protocol through blood test both LH, and testosterone to move the meds up, or down.

Now, probably did not see it that way, and that is cool, but in contact diagnosing secondary hypogonadism uses much higher doses.

Follow my logic here.

If 100mg clomid over 5 to 7 days doubles LH, and a guy has been using hCG, LH will be very low, if testicular function has been achieved, you want the fastest response possible to move the HPTA into homeostasis.

Not mono therapy, but direct stimulation to push LH up as fast as possible, if LH is very low, doubling that still is under reference range and this is a compromise.

Now to the meat.

My article I wrote years ago about what you are saying was put on 20 different boards, and in 2 magazines, one was The Beef.

So, like rumors, that is how that started, most of those actually are quoting me.

I got called on my article by another member and said "I did not know what I was talking about making reference to blocking estrogen to move LH."

He linked me to that, and after confirmation, I put a post somewhere after the sticky moving my position.

Unlike you, I don't have to be right, I move my position when I find the information is not entirely true.

Here is something to chew on:clomid and E2 "priming" in rat pituitary cells...

Disparate effect of clomiphene and tamoxifen on pituitary gonadotropin release in vitro

E. Y. Adashi, A. J. Hsueh, T. H. Bambino and S. S. Yen

The direct effects of clomiphene citrate (Clomid), tamoxifen, and estradiol (E2) on the gonadotropin-releasing hormone (GnRH)-stimulated release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were studied in cultured anterior pituitary cells obtained from adult ovariectomized rats. Treatment of pituitary cells with Clomid or enclomid (10(-8) M) in vitro for 2 days resulted in a marked sensitization of the gonadotroph to GnRH as reflected by a 6.5-fold decrease in the ED50 of GnRH in terms of LH release from 2.2 x 10(-9) M in untreated cells to 3.6 x 10(-10) M. Treatment with E2 or Clomid also increased the sensitivity of the gonadotroph to GnRH in terms of FSH release by 4.3- and 3.3-fold respectively. Tamoxifen, a related antiestrogen, comparable to Clomid in terms of its ability to compete with E2 for pituitary estrogen receptors, was without effect on the GnRH-stimulated LH release at a concentration of 10(-7) M. Furthermore, tamoxifen, unlike Clomid, caused an apparent but not statistically significant inhibition of the sensitizing effect of E2 on the GnRH-stimulated release of LH. Our findings suggest that Clomid and its Enclomid isomer, unlike tamoxifen, exert a direct estrogenic rather than an antiestrogenic effect on cultured pituitary cells by enhancing the GnRH-stimulated release of gonadotropin. "

I remember you saying that on American boards nobody uses 100mg per day.

Funny, they all front load with 100mg per day.

Now we know now that both doctors use the lowest amount of clomid mono therapy for TRT replacement therapy, and are on that for ever,

Remember I said but can't prove, that clomid over times seems to keep working better?

Id suggest that same for the start of the drug, that lower doses do not quite work as well to prime the pituitary, if it did, then the endo docs would be using less clomid, not 100mg, and they do not use nolva, they use clomid at 100mg per day.

I wish I could find that link to that information the other member sent me, it has been years.

If SERM's moved LH by the body not seeing estrogen, then AI's would show the same results in both LH, and T production, they do work, just not as well, and to be honest, that is not why clomid works so well, it is because GnRH becomes more sensitive at the pituitary.

In context, I have shown evidence you refuse to accept, using things out of context to come to some reaching conclusion is a nice try.

Again, in women, the use from 50 to 200mg to get the desired benefit from clomid for fertility, this is short term use to induce ovulation, not long term mono therapy like you suggest.

1% of women have sides with clomid, the drug is pretty well tolerable.

Are people taking too much clomid?

Perhaps, and I have moved my position on the dose, and duration of clomid after looking at guys bloods over time.

Id break that one down too, but it would start another debate:lol:

You did mention sensible doses.

My first cycle was 23 years ago, 200mg deca a week, 5mg anavar, and 2.5mg winny.

Guys now take that in a day....lol

Guys take grams now, and have an issue with 100mg clomid?

 

Can we break this thread down into bullet point cliffs pls? [emoji23]

 

Can we break this thread down into bullet point cliffs pls? [emoji23]

Wont happen, opinions are hard to bullet point:lol:

 

Now for a spanner in the mix:lol:

Insulin augments GnRH-stimulated LHbeta gene expression by Egr-1, Buggs C, Weinberg F, Kim E, Wolfe A, Radovick S, Wondisford F., Mol Cell Endocrinol. 2006 Apr 25;249(1-2):99-106

Previous studies have shown that insulin augments GnRH-stimulated LH synthesis and release from primary gonadotrophs. In this study, regulation of LHbeta gene expression by GnRH and insulin was examined in LbetaT2 cells. Endogenous LHbeta mRNA is stimulated 2.4-fold by insulin alone, 2.6-fold by GnRH alone, and 4.7-fold by insulin together with GnRH.

This effect of insulin, like GnRH, mapped to sequences -140 to +1 in the mouse LHbeta gene. Insulin together with GnRH stimulates activity of an LHbeta-reporter gene 7.1-fold; whereas, GnRH alone or insulin alone stimulates the reporter activity 2.8- and 3.1-fold, respectively. Blocking the binding of Egr-1 to sequences -51 to -42 in the LHbeta gene inhibits effects of insulin and GnRH. Insulin together with GnRH increases Egr-1 mRNA levels and total Egr-1 binding to LHbeta DNA. These findings indicate that insulin may impact regulation of the reproductive axis at the level of the pituitary.

Another

I guess I am amazed that bodybuilders never seem to discuss or know about insulin use in PCT. I have used it for years because it helped recovery. Anyway what catches my eye here is that insulin acts to decrease the amount of GnRH needed to effect an equivalent amount of LH & FSH.

The additional lesson seems to be that exogenous insulin need not be administered if you just eat in a fun carby way abundantly. Insulin is needed to help restart a broken HPTA either exogenous or endogenous, however glucose is not needed. It is insulin.

Insulin Enhancement of Luteinizing Hormone and Follicle-Stimulating Hormone Release by Cultured Pituitary Cells, ELI Y. ADASHI, AARON J. W. HSUEH and SAMUEL S. C. YEN, Endocrinology Vol. 108, No. 4 1441-1449 1981

The role of insulin in the regulation of basal and gonadotropin-releasing hormone (GnRH) -stimulated release of LH and FSH was investigated in vitro using primary cultures of rat anterior pituitary cells from adult ovariectomized rats. Anterior pituitary cells were incubated for 2 days in the presence or absence of insulin in a serum-free medium. At the end of the insulin treatment, the cells were washed and reincubated in the presence or absence of GnRH, and the LH and FSH released into the medium were measured by RIA.

Treatment with insulin (1.0 µg/ml) for 2 days resulted in significant increases in both the basal and the maximal release of LH and FSH, as well as a 3.2- and 6.3-fold decrease in the ED50 values for GnRH in terms of LH and FSH release, respectively. Treatment with increasing concentrations (0.1-10,000 ng/ml) of insulin, led to a dose-dependent increase in the GnRH (3 x 10-10 M)-stimulated release of both LH and FSH. This effect of insulin was significant (P < 0.05) at a physiological concentration of 1 ng/ml (24 µU/ml) with an ED50 value of 4.0 ng/ml. Increasing duration of exposure to insulin resulted in time-dependent increases in the GnRH (3 x 10-10 M)-stimulated release of LH, becoming significant at 24 h with maximal enhancement observed by 48 h.

The effect of insulin was specific; epidermal or fibroblast growth factor did not enhance LH release. The augmenting effect of insulin was not associated with cellular proliferation or an overall change in protein or LH synthesis. Furthermore, the effect of insulin was independent of the ambient glucose concentration. Insulin was, however, without effect on gonadotrophs cultured in a serumsupplemented medium. Our findings suggest that the gonadotroph constitutes a target cell of insulin and that insulin may act directly on the anterior pituitary in the regulation of gonadotropin release.

 

Ok, first off, all those cut and past came from the very boards I am a member of, between 5 and 10 years ago, look it up, don't take my word for it, just see for your self my post counts there.

I joined probably 30 boards, many are gone, but was very active during those times on Meso, among many others, all the information you are giving, I already read, and dropped it into my knowledge pool.

I appreciate your passion, and love a good debate, realize this is the student, trying to challenge the teacher, and although I post to enlighten, you have an emotional stance, and your ego will not allow you to see through your emotional stance.

Not really.

My stance is quite simple. Your concept of how clomid works in males is completely different to literally every piece of literature and comments I've read from every possible source I can find on the internet, including qualified medical doctors.

Basically, either the entire body building community, well-established sites and doctors are wrong, or you are, so I'm sure you can understand why I find it hard to believe, especially when these websites all suggest otherwise:

What is Clomid and how does it work? * Why has my doctor recommended Clomid? * How is Clomid prescribed? What can I expect to feel? * Associates In Women's Health Care

Fertility drug: clomifene citrate (clomifene, clomid) - BabyCentre

DrugBank: Clomifene (DB00882)

Clomifene - Wikipedia, the free encyclopedia

Clomiphene Citrate (Clomid) in Men - A Testosterone Alternative

http://www.maledoc.com/blog/2010/04/28/how-clomid-works-in-men/

http://jeffreydachmd.com/clomid-for-low-testosterone-part-one/

Three doctors, including Craig Niederberger MD, Jeffrey Dach MD And Shira Miller MD, all agree with the general consensus of how clomid primarily works, yet you contradict them completely. I ask what your response is to this. Are they all wrong?

Another thing, Shippen, as well as Crisler in the context given, they are solely referring to secondary hypogonadal men, and their treatment was clomid mono therapy for TRT, these men are on for years, not weeks, modifying and adjusting their protocol through blood test both LH, and testosterone to move the meds up, or down.

Now, probably did not see it that way, and that is cool, but in contact diagnosing secondary hypogonadism uses much higher doses.

Follow my logic here.

If 100mg clomid over 5 to 7 days doubles LH, and a guy has been using hCG, LH will be very low, if testicular function has been achieved, you want the fastest response possible to move the HPTA into homeostasis.

Not mono therapy, but direct stimulation to push LH up as fast as possible, if LH is very low, doubling that still is under reference range and this is a compromise.

I don't disagree with that. My question is whether 100mg of clomid really encourages the fastest response compared to 50mg. I see little evidence of this, but I do see plenty of guys complaining of vision problems, depression and even suicidal thoughts, so I personally wouldn't be so hasty to go with the "more is better" concept, that's all.

Disparate effect of clomiphene and tamoxifen on pituitary gonadotropin release in vitro

E. Y. Adashi, A. J. Hsueh, T. H. Bambino and S. S. Yen

The direct effects of clomiphene citrate (Clomid), tamoxifen, and estradiol (E2) on the gonadotropin-releasing hormone (GnRH)-stimulated release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were studied in cultured anterior pituitary cells obtained from adult ovariectomized rats. Treatment of pituitary cells with Clomid or enclomid (10(-8) M) in vitro for 2 days resulted in a marked sensitization of the gonadotroph to GnRH as reflected by a 6.5-fold decrease in the ED50 of GnRH in terms of LH release from 2.2 x 10(-9) M in untreated cells to 3.6 x 10(-10) M. Treatment with E2 or Clomid also increased the sensitivity of the gonadotroph to GnRH in terms of FSH release by 4.3- and 3.3-fold respectively. Tamoxifen, a related antiestrogen, comparable to Clomid in terms of its ability to compete with E2 for pituitary estrogen receptors, was without effect on the GnRH-stimulated LH release at a concentration of 10(-7) M. Furthermore, tamoxifen, unlike Clomid, caused an apparent but not statistically significant inhibition of the sensitizing effect of E2 on the GnRH-stimulated release of LH. Our findings suggest that Clomid and its Enclomid isomer, unlike tamoxifen, exert a direct estrogenic rather than an antiestrogenic effect on cultured pituitary cells by enhancing the GnRH-stimulated release of gonadotropin. "

Sorry but this really doesn't prove anything.

An ovariectomized rat is a FEMALE rat which its ovaries removed. This brings me right back to the information I posted from a board member who contradicted Scally's interpretation:

I strongly disagree with Dr. Scally's reasoning behind the use of clomid. What he is describing here is "estrogen priming," the concept that estrogen makes the pituitary more sensitive to GnRH from the hyp[othalamus, so that more LH is released for a given GnRH stimulus. This is well known to occur in females leading up to ovulation. Unlike females, however, men don't have a preovulatory period or spikes in LH. The research is fairly clear that estrogen priming does not occur in males. For starters, take a look at an authoritative reference work like Grossman's http://www.amazon.com/Clinical-Endocrinology-Ashley-Grossman/dp/0865426295]Clinical Endocrinology[/URL], which states (pg. 99):

Progesterone, acting synergistically with oestrogens, exerts negative feedback on the hypothalamus during the luteal phase, thus limiting GnRH pulsatility and slowing LH pulse frequency. The mechanism of positive oestrogen feedback at the time of the LH surge has been much debated. There is now evidence that enhancement of both hypothalamic GnRH pulse generator activity and pituitary responsiveness to GnRH are involved. All species so far studied have shown an increased 'self-priming' effect of GnRH on the pituitary during the preovulatory period... In males, the situation is more straightforward. Since LH surges do not occur, only negative feedback effects are relevant. testosterone (and its active metabolite dihydrotestosterone, DHT) exerts major suppressive effects on both LH and FSH secretion, largely by inhibiting the GnRH pulse frequency generator, but possibly also by direct pituitary actions. Oestrogens in the male reduce pituitary responsiveness to GnRH.

Oestrogen priming only happens in females, and your study uses female rats, so it proves nothing about the effect of clomid on males. What is your response to this and the above information I quoted?

I wish I could find that link to that information the other member sent me, it has been years.

If SERM's moved LH by the body not seeing estrogen, then AI's would show the same results in both LH, and T production, they do work, just not as well, and to be honest, that is not why clomid works so well, it is because GnRH becomes more sensitive at the pituitary.

They do. There are a lot of guys out there now doing primarily aromasin PCTs with good results.

The problem with an AI based PCT is whilst SERMS inhibit the effect of oestrogen on the hypothalamus, AIs reduce oestrogen entirely, which causes low E problems. With the SERM MOA, it maintains healthy E levels whilst inhibiting oestrogen at the hypothalamus and therefore triggering the hypothalamus to rapidly start outputting GnRH to bring homeostasis back in the negative feedback loop as it believes that oestrogen levels are near zero.

This makes a lot of sense considering the T/E feedback loop. I ask again, if clomid is only making GnRH more sensitive at the pituitary, then what's actually causing the hypothalamus to release GnRH in the first place when it's been so suppressed by testosterone and oestrogen? If oestrogen levels are normal at the end of the cycle, the negative feedback loop is signalling that homeostatis is normal because the hypothalamus uses oestrogen as an indicator of controlling LH and FSH levels, so the hypothalamus will not put out any GnRH to actually benefit from this supposed sensitisation.

It doesn't make any sense.

 

What does Bill Roberts say?

Nolvadex doesn't have a proven track record -- largely out of just not having much of a track record -- in 2-week cycles that I have written for others or have done myself. I just don't have the basis to say that it works as well.

For that matter, while I've seen Nolvadex alone much more frequently on longer cycles, I'm not at all convinced that Nolvadex alone is as good as Clomid. I rather suspect that it is not, but I don't have a conclusive basis to say that that is necessarily a fact.

If you hate Clomid, would you be willing to try 50/50 Clomid/Nolvadex? That might suit you better. You would just use half as much of each as would ordinarily be the case.

The main pharmacological difference between Clomid and Nolvadex is that Clomid is estrogenic in the pituitary and perhaps other brain tissues where Nolvadex is antiestrogenic.

Having only antiestrogenic activity perhaps may not give optimum effect, as estrogen can actually result in better responsiveness to LHRH, but having only the estrogenic activity of full dose Clomid can indeed be unsuitable for some. Cutting that in half, and then adding half-antiestrogenic activity, may markedly reduce or eliminate your problems.

I have noticed myself a while ago during a PCT that I dropped the clomid early from 100mg to 50mg and found I lost night time erections.

That guy you seem to quote a lot, has an issue with they way he posts, neither Bill, or Scally agree with him, he takes things out of context to some degree to dress his words.

Look, Scally has a lot of experience with recovery for guys on steroids, id weigh that against any book smart dude suggesting otherwise.

Lets look at AI's and see if they move T up as much as suggested, or at the very least compare to clomid for instance:

At a dose of 20-25mgs/day, Aromasin will raise testosterone levels by about 60%, and also help out your free to bound testosterone ratio by lowering levels of Sex Hormone Binding Globulin (SHBG), by about 20%&#8230;SHBG is that nasty enzyme that binds to testosterone and renders it useless for building muscle. But what about using it along with Nolvadex for PCT?

To understand why Aromasin may be useful in conjunction with Nolvadex while both Letro and A-dex suffer reduced effectiveness, we'll need to first understand the differences between a Type-I and Type-II Aromatase Inhibitor. Type I inhibitors (like Aromasin) are actually steroidal compounds, while type II inhibitors (like Letro and A-dex) are non-steroidal drugs. Hence, androgenic side effects are very possible with Type-I AIs, and they should probably be avoided by women. Of course, there are some similarities between the two types of AIs&#8230;both type I & type II AIs mimic normal substrates (essentially androgens), allowing them to compete with the substrate for access to the binding site on the aromatase enzyme. After this binding, the next step is where things differ greatly for the two different types of AI's. In the case of a type-I AI, the noncompetitive inhibitor will bind, and the enzyme initiates a sequence of hydroxylation; this hydroxylation produces an unbreakable covalent bond between the inhibitor and the enzyme protein. Now, enzyme activity is permanently blocked; even if all unattached inhibitor is removed. Aromatase enzyme activity can only be restored by new enzyme synthesis. Now, on the other hand, competitive inhibitors, called type II AI's, reversibly bind to the active enzyme site, and one of two things can happen: 1.) either no enzyme activity is triggered or 2.) the enzyme is somehow triggered without effect. The type II inhibitor can now actually disassociate from the binding site, eventually allowing renewed competition between the inhibitor and the substrate for binding to the site. This means that the effectiveness of competitive aromatase inhibitors depends on the relative concentrations and affinities of both the inhibitor and the substrate, while this is not so for noncompetitive inhibitors. Aromasin is a type-I inhibitor, meaning that once it has done its job, and deactivated the aromatase enzyme, we don't need it anymore. Letrozole and Arimidex actually need to remain present to continue their effects. This is possibly why Nolvadex does not alter the pharmacokinetics of Aromasin.

Before we close the book on Aromasin, it's worth noting that you can (and should) still use one of the non-steroidal AIs during your cycle to reduce estrogen, if necessary. When you are ready for PCT, you can then switch over to Aromasin and still experience the full effects of an AI, since there is no cross-over tolerance experienced between steroidal and non-steroidal AIs. Since Aromasin is about 65% efficient at suppressing estrogen, it's certainly a very powerful agent, especially considering you won't experience reduced effectiveness because of your concurrent use of Nolvadex or from any sort of tolerance developed by using other AIs on your cycle. There is also a decent amount of preclinical data suggesting that Aromasin has a beneficial effect on bone mineral metabolism that is not seen with non-steroidal agents, and it may also have beneficial effects on lipid metabolism that are not found in the non-steroidal Letro and A-dex.

Ok, so you suppress estrogen by 65% and it only moves testosterone by 60%?

Why does clomid move T levels far higher than an AI?

If clomid blocked estrogen to get a response to LH, and actually is considered a mild estrogen, why do AI's not move T levels as well as clomid?

Sure lower SHBG to allow for less binding and more free T, but if clomids action was the same as an AI, the numbers would move well more.

Mine more than 3 times on low dose clomid, and even 3 days prior to I did nothing.

Both men and women have the very same developmental tissues, like the prostate, and cervix.

Pituitary Sensitivity to GnRH

But something more interesting is happening. Researchers were also conducting GnRH stimulation tests before and after various points of treatment with Nolvadex and Clomid, and the two drugs had markedly different results. These tests involved infusing patients with 100mcg of GnRH and measuring the output of pituitary LH in response. The focus of this test is to see how sensitive the pituitary is to Gonadotropin Releasing Hormone. The more sensitive the pituitary, the more LH will be released. The tests showed that after ten days of treatment with Nolvadex, pituitary sensitivity to GnRH increased slightly compared to pre-treated values. This is contrast to 10 days of treatment with 150mg Clomid, which was shown to consistently DECREASE pituitary sensitivity to GnRH (more LH was released before treatment). As the study with Nolvadex progresses to 6 weeks, pituitary sensitivity to GnRH was significantly higher than pre-treated or 10-day levels. At this point the same 20mg dosage was also raising testosterone and LH levels to an average of 183% and 172% of base values, respectively, which again is measurably higher than what was noted 10 days into therapy. Within 10 days of treatment Clomid is already exerting an effect that is causing the pituitary to become slightly desensitized to GnRH, while prolonged use of Nolvadex serves only to increase pituitary sensitivity to this hormone. That is not to say Clomid won't increase testosterone if taken for the same 6 week time period. Quite the opposite is true. But we are, however, noticing an advantage in Nolvadex.

The Estrogen Clomid

The above discrepancies are likely explained by differences in the estrogenic nature of the two compounds. The researchers' clearly support this theory when commenting in their paper, "The difference in response might be attributable to the weak intrinsic estrogenic effect of Clomid, which in this study manifested itself by an increase in transcortin and testosterone/estradiol-binding globulin [sHBG] levels; this increase was not observed after tamoxifen treatment". In reviewing other theories later in the paper, such as interference by increased androgen or estrogen levels, they persist in noting that increases in these hormones were similar with both drug treatments, and state that," &#8230;a role of the intrinsic estrogenic activity of Clomid which is practically absent in Tamoxifen seems the most probable explanation".

Although these two are related anti-estrogens, they appear to act very differently at different sites of action. Nolvadex seems to be strongly anti-estrogenic at both the hypothalamus and pituitary, which is in contrast to Clomid, which although a strong anti-estrogen at the hypothalamus, seems to exhibit weak estrogenic activity at the pituitary. To find further support for this we can look at an in-vitro animal study published in the American Journal of Physiology in February 1981 (2). This paper looks at the effects of Clomid and Nolvadex on the GnRH stimulated release of LH from cultured rat pituitary cells. In this paper, it was noted that incubating cells with Clomid had a direct estrogenic effect on cultured pituitary cell sensitivity, exerting a weaker but still significant effect compared to estradiol. Nolvadex on the other hand did not have any significant effect on LH response. Furthermore it mildly blocked the effects of estrogen when both were incubated in the same culture.

 

It's posts like this that just put me off juice..

 

What is Clomid and how does it work? * Why has my doctor recommended Clomid? * How is Clomid prescribed? What can I expect to feel? * Associates In Women's Health Care

Fertility drug: clomifene citrate (clomifene, clomid) - BabyCentre

DrugBank: Clomifene (DB00882)

Clomifene - Wikipedia, the free encyclopedia

Clomiphene Citrate (Clomid) in Men - A Testosterone Alternative

http://www.maledoc.com/blog/2010/04/28/how-clomid-works-in-men/

http://jeffreydachmd.com/clomid-for-low-testosterone-part-one/

Three doctors, including Craig Niederberger MD, Jeffrey Dach MD And Shira Miller MD, all agree with the general consensus of how clomid primarily works, yet you contradict them completely. I ask what your response is to this. Are they all wrong?

Actually yes, I do feel they are wrong, and just repeating some doc that originally said that.

Some literature suggests they don't know why it works so well.