Nolvadex vs Clomid - Open Debate

[TwisT]

"Nolvadex vs Clomid"

by William Llewellyn

I have received a lot of heat lately about my preference for Nolvadex over Clomid, which I hold for all purposes of use (in the bodybuilding world anyway); as an anti-estrogen, an HDL (good) cholesterol-supporting drug, and as a testosterone-stimulating compound. Most people use Nolvadex to combat gynecomastia over Clomid anyway, so that is an easy sell. And for cholesterol, well, most bodybuilders unfortunately pay little attention to this important issue, so by way of disinterest, another easy opinion to discuss. But when it comes to using Nolvadex for increasing endogenous testosterone release, bodybuilders just do not want to hear it. They only seem to want Clomid. I can only guess that this is based on a long rooted misunderstanding of the actions of the two drugs. In this article I would therefore like to discuss the specifics for these two agents, and explain clearly the usefulness of Nolvadex for the specific purpose of increasing testosterone production.

Clomid and Nolvadex

I am not sure how Clomid and Nolvadex became so separated in the minds of bodybuilders. They certainly should not be. Clomid and Nolvadex are both anti-estrogens belonging to the same group of triphenylethylene compounds. They are structurally related and specifically classified as selective estrogen receptor modulators (SERMs) with mixed agonistic and antagonistic properties. This means that in certain tissues they can block the effects of estrogen, by altering the binding capacity of the receptor, while in others they can act as actual estrogens, activating the receptor. In men, both of these drugs act as anti-estrogens in their capacity to oppose the negative feedback of estrogens on the hypothalamus and stimulate the heightened release of GnRH (Gonadotropin Releasing Hormone). lh - leutenizing hormone - output by the pituitary will be increased as a result, which in turn can increase the level of testosterone by the testes. Both drugs do this, but for some reason bodybuilders persist in thinking that Clomid is the only drug good at stimulating testosterone. What you will find with a little investigation however is that not only is Nolvadex useful for the same purpose, it should actually be the preferred agent of the two.

Pituitary Sensitivity to GnRH

Studies conducted in the late 1970's at the University of Ghent in Belgium make clear the advantages of using Nolvadex instead of Clomid for increasing testosterone levels (1). Here, researchers looked the effects of Nolvadex and Clomid on the endocrine profiles of normal men, as well as those suffering from low sperm counts (oligospermia). For our purposes, the results of these drugs on hormonally normal men are obviously the most relevant. What was found, just in the early parts of the study, was quite enlightening. Nolvadex, used for 10 days at a dosage of 20mg daily, increased serum testosterone levels to 142% of baseline, which was on par with the effect of 150mg of Clomid daily for the same duration (the testosterone increase was slightly, but not significantly, better for Clomid). We must remember though that this is the effect of three 50mg tablets of Clomid. With the price of both a 50mg Clomid and 20mg Nolvadex typically very similar, we are already seeing a cost vs. results discrepancy forming that strongly favors the Nolvadex side.

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 - leutenizing hormone - 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 - leutenizing hormone - 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 - leutenizing hormone - 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 - leutenizing hormone - 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 [sex hormone binding globulin ] 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," ?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 - leutenizing hormone - 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 - leutenizing hormone - response. Furthermore it mildly blocked the effects of estrogen when both were incubated in the same culture.

Conclusion

To summarize the above research succinctly, Nolvadex is the more purely anti-estrogenic of the two drugs, at least where the hpta - hypothalamic-pituitary-testicular axis - (Hypothalamic-Pituitary-Testicular Axis) is concerned. This fact enables Nolvadex to offer the male bodybuilder certain advantages over Clomid. This is especially true at times when we are looking to restore a balanced hpta - hypothalamic-pituitary-testicular axis - , and would not want to desensitize the pituitary to GnRH. This could perhaps slow recovery to some extent, as the pituitary would require higher amounts of hypothalamic GnRH in the presence of Clomid in order to get the same level of lh - leutenizing hormone - stimulation.

Nolvadex also seems preferred from long-term use, for those who find anti-estrogens effective enough at raising testosterone levels to warrant using as anabolics. Here Nolvadex would seem to provide a better and more stable increase in testosterone levels, and likely will offer a similar or greater effect than Clomid for considerably less money. The potential rise in sex hormone binding globulin levels with Clomid, supported by other research (3), is also cause for concern, as this might work to allow for comparably less free active testosterone compared to Nolvadex as well. Ultimately both drugs are effective anti-estrogens for the prevention of gynecomastia and elevation of endogenous testosterone.

 

[MDR]

Kinda dated info. Nolva has been out for years. Clomid works better for recovery for many reasons. Nobody I know still uses Nolva for PCT. Sources for this article are from 1978 and 1981.

 

[TGB1987]

I have to agree with MDR it seems to me that Clomid is the better option for PCT. Nolva lowers IGF-1 which is not something you want during PCT when your anabolic hormones are already low. Clomid and Aromasin is the route I prefer. William Llewellyn also suggests the use of Clomid, Nolva, and Hcg for PCT together. I never see him recommend an AI in his books. He says AIs are hard on the lipids. Aromasin is not as harsh on the lipids though. Without an AI you are risking estrogen rebound post PCT. Needless to say I really like William Llewellyn's work but I don't agree with PCT and believe Heavyiron's PCT protocol is much more modern and effective.

 

[Vibrant]

Why is this a sticky right away? Everybody on this board prefers clomid/aromasin over nolva for pct, with TwisT being the only exception that I know of.

 

[TwisT]

I have to agree with MDR it seems to me that Clomid is the better option for PCT. Nolva lowers IGF-1 which is not something you want during PCT when your anabolic hormones are already low. Clomid and Aromasin is the route I prefer. William Llewellyn also suggests the use of Clomid, Nolva, and Hcg for PCT together. I never see him recommend an AI in his books. He says AIs are hard on the lipids. Aromasin is not as harsh on the lipids though. Without an AI you are risking estrogen rebound post PCT. Needless to say I really like William Llewellyn's work but I don't agree with PCT and believe Heavyiron's PCT protocol is much more modern and effective.

Im kind of shocked that you dont understand lol. What is the point of PCT? Now when you answer that, what would you rather have, lower IGF-1 levels or a lowered pituitary sensitivity to gnrh? Especially when you can supplement IGF-1 in PCT.

Really a no-brainer.

 

[TwisT]

Kinda dated info. Nolva has been out for years. Clomid works better for recovery for many reasons. Nobody I know still uses Nolva for PCT. Sources for this article are from 1978 and 1981.

State those reasons?

 

[TwisT]

Heres BigCat's article as to why he also agrees on Nolvadex.

Nolvadex vs. Clomid for PCT

It seems like everyday questions concerning PCT pop up, and weather one should use either Clomid or nolva or a combo of both. I hope that this article written by BigCat may help to clear up some misconceptions.

While practically similar compounds in structure, few people ever really consider Clomid and nolva to be similar. Its not just a common myth in steroid circles, but even in the medical community. This misconception originates from their completely different uses. Nolvadex is most commonly used for the treatment of breast cancer in women, while Clomid is generally considered a fertility aid. In bodybuilding circles, from day one, Clomid has generally been used as post-cycle therapy and Nolvadex as an anti-estrogen.

But as I intend to demonstrate this is in essence the same. I believe the myth to have originated because nolva is clearly a more powerful anti-estrogen, and the people selling Clomid needed another angle to sell the stuff, so it was mostly used as a post-cycle aid. But few users really understand how Clomid (and also Nolvadex, logically) works to bring back natural testosterone in the body after the conclusion of a cycle of androgenic anabolic steroids. After a cycle is over, the level of androgens in the body drop drastically. The body compensates with an overproduction of estrogen to keep steroid levels up. Estrogen as well inhibits the production of natural testosterone, and in the period between the return of natural testosterone and the end of a cycle, a lot of mass is lost. So its in everybody's best interest to bring back natural test as soon as humanly possible. Clomid and Nolvadex will reduce the post-cycle estrogen, so that a steroid deficiency is constated and the hypothalamus is stimulated to regenerate natural testosterone production in the body. That's basically how the mechanism works, nothing more, nothing less.

Both compounds are structurally alike, classified as triphenylethylenes. Nolvadex is clearly the stronger component of the two as it can achieve better results in decreasing overall estrogen with 20-40 mg a day, than Clomid can in doses of 100-150 mg a day. A noteworthy difference. Triphenylethylenes are very mild estrogens that do not exert a lot, if any activity at the estrogen receptor, but are still highly attracted to it. As such they will occupy the receptor and keep it from binding estrogens. This means they do not actively work to reduce estrogen in the body like Proviron, Viratase or arimidex would (by competing for the aromatase enzyme), but that it blocks the receptor so that any estrogen in the body is basically inert, because it has no receptor to bind to.

This has advantages and disadvantages. The disadvantage is that when use is discontinued, the estrogen level is still the same and new problems will develop much sooner. The advantage is that it works much faster and has results sooner than with an aromatase blocker like Proviron or arimidex. Therefor, when problems such as gynocomastia occur during a cycle of steroids one will usually start 20 mg/day of nolva or 100 mg/day of Clomid straight away, in conjunction with some Proviron or arimidex. The proviron or arimidex will actively reduce estrogen while the Clomid or Nolvadex will solve your ongoing problem straight away. This way, when use is discontinued there is no immediate rebound.

So which one should you use? Well personally, I'd have to say Nolvadex. Both as an on-cycle anti-estrogen and a post-cycle therapy. As an anti-estrogen its simply much stronger, demonstrated by the fact that better results are obtained with 20-40 mg than with 100-150 mg of Clomid. For post-cycle, this plays a key role as well. It deactivates rebound estrogen much faster and more effective. But most importantly, Nolvadex has a direct influence on bringing back natural testosterone, where as Clomid may actually have a slight negative influence. The reason being that tamoxifen (as in Nolvadex) seems to increase the responsiveness of LH (luteinizing hormone) to GnRH (gonadtropin releasing hormone), whereas Clomid seems to decrease the responsiveness a bit1.

Another noteworthy fact about Nolvadex is that it acts more potently as an estrogen in the liver. As you remember, I mentioned that clomiphene and tamoxifen are basically weak estrogens. Well, tamoxifen is apparently still quite potent in the liver. This offers us the positive benefits of this hormone in the liver, while avoiding its negative effects elsewhere in the body. As such Nolvadex can have a very positive impact on negative cholesterol levels2 in the body, and therefore too should be considered a better choice than Clomid. It will not solve the problem of bad cholesterol levels during Steroid use, but will help to contain the problem to a larger degree.

Another reason why I promote the use of Nolvadex over Clomid post-cycle (as if being 3-4 times stronger and having more of a direct effect on restoring natural test wasn't enough) is because it's a lot safer. Not just because it improves lipid profiles, but also because it simply doesn't have the intrinsic side-effects that Clomid has. Clomid causes more acne for sure, but that's mainly because you need to use a 3-4 times higher dose. But Clomid seems to also affect the eyesight. Long-term Clomid therapy causes irreversible changes in eyesight3 in users. Irreversible. For me that alone is reason enough to prefer Nolvadex.

Lastly, one should be aware that use of these compounds can reduce the gains made on steroids. Nolvadex more so than Clomid, simply because it is stronger. Estrogen is responsible for a number of anabolic factors such as increasing growth hormone output, upgrading the androgen receptor and improving glucose utilization. This is why aromatizing steroids like testosterone are still best suited for maximum muscle gain. When reducing the estrogen levels, we therefore reduce the potential gains being made. For this reason one may opt to try Clomid during a cycle instead of Nolvadex. Although I would imagine that the problem that needed solved would be of more concern, in which case nolva remains the weapon of choice. It's a plain fact that there is a high correlation between gains and side-effects. Either you go for maximum gains and tolerate the side-effects, or you reduce the side-effects, and with it the gains. That's life, nothing is free.

 

[exphys88]

Why not use both like dr scally suggests?

 

[TwisT]

Why not use both like dr scally suggests?

There is no real "need", one or the other normally does the trick bro. But they do some some synergetic properties together, its not really needed.

-T

 

[MDR]

State those reasons?

The reasons for this have been discussed over and over on this forum. Here is the applicable section of Heavyiron's sticky that TGB1987 refers to that addresses the issue very clearly. Mr. Llewellyn is quoting thirty year old studies in his article, as I already stated, and that, by definition, is dated information. Many of "Big Cat's" articles from Bodybuilding.com are also from quite some time ago. I do not know anyone who still bases their PCT around Nolva alone as a SERM of choice. There are just better and more effective ways of reestablishing natural Testosterone production.

I strongly believe that an AI should be used as long as there is an aromatizing compound being administered. In this case Testosterone and HCG aromatize therefore using an AI until these meds clear and a few weeks longer is what I am recommending. There is some evidence that adding Nolva to an AI does not increase the effectiveness of estro control therefore Nolva has no real advantage alongside an AI unless one is experiencing gyno. Additionally Nolva has been shown to reduce IGF-1 and GH levels when used alone. This is not a big deal on cycle as testosterone increases IGF-1 in a dose dependant relationship. However off cycle this is a problem. PCT is a fragile time and lower IGF-1 and GH levels is not desirable. I am recommending an AI that is specific to men that can be used on cycle and during PCT. It is my conclusion that Aromasin is the obvious choice.

Mr. Llewelyn is quoting 30 year old sources of information in the article you quoted. That, by definition, is dated information.

 

[MDR]

Heres BigCat's article as to why he also agrees on Nolvadex.

Nolvadex vs. Clomid for PCT

It seems like everyday questions concerning PCT pop up, and weather one should use either Clomid or nolva or a combo of both. I hope that this article written by BigCat may help to clear up some misconceptions.

While practically similar compounds in structure, few people ever really consider Clomid and nolva to be similar. Its not just a common myth in steroid circles, but even in the medical community. This misconception originates from their completely different uses. Nolvadex is most commonly used for the treatment of breast cancer in women, while Clomid is generally considered a fertility aid. In bodybuilding circles, from day one, Clomid has generally been used as post-cycle therapy and Nolvadex as an anti-estrogen.

But as I intend to demonstrate this is in essence the same. I believe the myth to have originated because nolva is clearly a more powerful anti-estrogen, and the people selling Clomid needed another angle to sell the stuff, so it was mostly used as a post-cycle aid. But few users really understand how Clomid (and also Nolvadex, logically) works to bring back natural testosterone in the body after the conclusion of a cycle of androgenic anabolic steroids. After a cycle is over, the level of androgens in the body drop drastically. The body compensates with an overproduction of estrogen to keep steroid levels up. Estrogen as well inhibits the production of natural testosterone, and in the period between the return of natural testosterone and the end of a cycle, a lot of mass is lost. So its in everybody's best interest to bring back natural test as soon as humanly possible. Clomid and Nolvadex will reduce the post-cycle estrogen, so that a steroid deficiency is constated and the hypothalamus is stimulated to regenerate natural testosterone production in the body. That's basically how the mechanism works, nothing more, nothing less.

Both compounds are structurally alike, classified as triphenylethylenes. Nolvadex is clearly the stronger component of the two as it can achieve better results in decreasing overall estrogen with 20-40 mg a day, than Clomid can in doses of 100-150 mg a day. A noteworthy difference. Triphenylethylenes are very mild estrogens that do not exert a lot, if any activity at the estrogen receptor, but are still highly attracted to it. As such they will occupy the receptor and keep it from binding estrogens. This means they do not actively work to reduce estrogen in the body like Proviron, Viratase or arimidex would (by competing for the aromatase enzyme), but that it blocks the receptor so that any estrogen in the body is basically inert, because it has no receptor to bind to.

This has advantages and disadvantages. The disadvantage is that when use is discontinued, the estrogen level is still the same and new problems will develop much sooner. The advantage is that it works much faster and has results sooner than with an aromatase blocker like Proviron or arimidex. Therefor, when problems such as gynocomastia occur during a cycle of steroids one will usually start 20 mg/day of nolva or 100 mg/day of Clomid straight away, in conjunction with some Proviron or arimidex. The proviron or arimidex will actively reduce estrogen while the Clomid or Nolvadex will solve your ongoing problem straight away. This way, when use is discontinued there is no immediate rebound.

So which one should you use? Well personally, I'd have to say Nolvadex. Both as an on-cycle anti-estrogen and a post-cycle therapy. As an anti-estrogen its simply much stronger, demonstrated by the fact that better results are obtained with 20-40 mg than with 100-150 mg of Clomid. For post-cycle, this plays a key role as well. It deactivates rebound estrogen much faster and more effective. But most importantly, Nolvadex has a direct influence on bringing back natural testosterone, where as Clomid may actually have a slight negative influence. The reason being that tamoxifen (as in Nolvadex) seems to increase the responsiveness of LH (luteinizing hormone) to GnRH (gonadtropin releasing hormone), whereas Clomid seems to decrease the responsiveness a bit1.

Another noteworthy fact about Nolvadex is that it acts more potently as an estrogen in the liver. As you remember, I mentioned that clomiphene and tamoxifen are basically weak estrogens. Well, tamoxifen is apparently still quite potent in the liver. This offers us the positive benefits of this hormone in the liver, while avoiding its negative effects elsewhere in the body. As such Nolvadex can have a very positive impact on negative cholesterol levels2 in the body, and therefore too should be considered a better choice than Clomid. It will not solve the problem of bad cholesterol levels during Steroid use, but will help to contain the problem to a larger degree.

Another reason why I promote the use of Nolvadex over Clomid post-cycle (as if being 3-4 times stronger and having more of a direct effect on restoring natural test wasn't enough) is because it's a lot safer. Not just because it improves lipid profiles, but also because it simply doesn't have the intrinsic side-effects that Clomid has. Clomid causes more acne for sure, but that's mainly because you need to use a 3-4 times higher dose. But Clomid seems to also affect the eyesight. Long-term Clomid therapy causes irreversible changes in eyesight3 in users. Irreversible. For me that alone is reason enough to prefer Nolvadex.

Lastly, one should be aware that use of these compounds can reduce the gains made on steroids. Nolvadex more so than Clomid, simply because it is stronger. Estrogen is responsible for a number of anabolic factors such as increasing growth hormone output, upgrading the androgen receptor and improving glucose utilization. This is why aromatizing steroids like testosterone are still best suited for maximum muscle gain. When reducing the estrogen levels, we therefore reduce the potential gains being made. For this reason one may opt to try Clomid during a cycle instead of Nolvadex. Although I would imagine that the problem that needed solved would be of more concern, in which case nolva remains the weapon of choice. It's a plain fact that there is a high correlation between gains and side-effects. Either you go for maximum gains and tolerate the side-effects, or you reduce the side-effects, and with it the gains. That's life, nothing is free.

Same thing. Big Cat is using sources from 1978 and 1988 for this article. If I used a 30+ year old source in an academic article in school, the validity of the source would be questioned, and I would be asked why I could not find another, more recent source of information. The article was clearly written some time ago.

 

[TwisT]

Just as a side note, I'm not trying to be a dick...I honestly love being proven wrong and I love a good educated discussion

So on that note, where is this "evidence"? You need to bring me a study, from a medical journal...not just bro-science as there is way too much of that around here. Prove me wrong buddy, honestly I would really love to learn something new...I'm not always right and I understand that, but I need to see hard facts and evidence before I consider alternative philosophies.... I hope you understand dude.

The lowering of IGF levels, still, is sub-par to a lowered sensitivity to GnRH, as the whole point behind PCT is to restore natural function. Especially with the ability to supplement IGF-1.

-T

The reasons for this have been discussed over and over on this forum. Here is the applicable section of Heavyiron's sticky that TGB1987 refers to that addresses the issue very clearly. Mr. Llewellyn is quoting thirty year old studies in his article, as I already stated, and that, by definition, is dated information. Many of "Big Cat's" articles from Bodybuilding.com are also from quite some time ago. I do not know anyone who still bases their PCT around Nolva alone as a SERM of choice. There are just better and more effective ways of reestablishing natural Testosterone production.

I strongly believe that an AI should be used as long as there is an aromatizing compound being administered. In this case Testosterone and HCG aromatize therefore using an AI until these meds clear and a few weeks longer is what I am recommending. There is some evidence that adding Nolva to an AI does not increase the effectiveness of estro control therefore Nolva has no real advantage alongside an AI unless one is experiencing gyno. Additionally Nolva has been shown to reduce IGF-1 and GH levels when used alone. This is not a big deal on cycle as testosterone increases IGF-1 in a dose dependant relationship. However off cycle this is a problem. PCT is a fragile time and lower IGF-1 and GH levels is not desirable. I am recommending an AI that is specific to men that can be used on cycle and during PCT. It is my conclusion that Aromasin is the obvious choice.

Mr. Llewelyn is quoting 30 year old sources of information in the article you quoted. That, by definition, is dated information.

 

[TwisT]

And if you're are able to support your claims with credible sources and citations ill ship you a clomid for your effort lol.

-T

 

[MDR]

Just as a side note, I'm not trying to be a dick...I honestly love being proven wrong and I love a good educated discussion

So on that note, where is this "evidence"? You need to bring me a study, from a medical journal...not just bro-science as there is way too much of that around here. Prove me wrong buddy, honestly I would really love to learn something new...I'm not always right and I understand that, but I need to see hard facts and evidence before I consider alternative philosophies.... I hope you understand dude.

The lowering of IGF levels, still, is sub-par to a lowered sensitivity to GnRH, as the whole point behind PCT is to restore natural function. Especially with the ability to supplement IGF-1.

-T

Here is one of many to start. It is from 2003.

Use of clomiphene citrate to reverse
premature andropause secondary to
steroid abuse
Robert S. Tan, M.D., and Deepa Vasudevan, M.D.
Programs in Geriatrics and Andrology, Department of Family and Community Medicine, University of Texas
Health Sciences Center, Houston, Texas​

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. (Fertil Steril​

​

2003;79:

203–5. ©2003 by American Society for Reproductive Medicine.)
​

Key Words: ​

​

Andropause, clomiphene, testosterone

​

Andropause can be defined as a biochemical
state of low T or hypogonadism (1). It is frequently
associated with the aging process. This
hypogonadal state can be symptomatic or
asymptomatic and symptoms can include loss
of libido, energy, concentration, and memory.
Long-term effects of hypogonadism include
bone and muscle loss and possible effects on
the brain and cardiovascular system. Premature
andropause can result from excessive use of
anabolic steroids, which lead to a shutdown of
the pituitary– gonadal axis through interfering
with LH and FSH. Other causes of premature
andropause can include obesity, diabetes, and
testicular infections.
CASE REPORT
A 30-year-old patient presented with severe
depression and loss of libido and energy. He
admitted to the use of steroids for bodybuilding
purposes for several months. He had obtained
nandrolone decanoate, deca Durabolin, primobolan
depot, and Winstrol from a foreign
country without a prescription. He is on an
antidepressant, bupropion (Wellbutrin, Glaxo
Smith Kline, Philadelphia, PA). While showering,
he noticed that his testicles were gradually
shrinking, despite a more muscular body.
He does not report anosmia or any childhood
orchitis. There was no history of galactorrhea
or gynecomastia. There was no family history
of hypogonadism.
Physical examination of the genitalia revealed
fully descended testicular size of 4 ​

​

​

2.5 ​

​

1.5 cm on the right and 3.3 2.5 1.5

com on the left. He had no hypospadias nor
abnormalities in the epididymis. There was no
goiter, gynecomastia, or visual field defects.
Muscle strength in all four limbs was grade 5 in
both flexor and extensor groups. The androgen
decline in aging male (A.D.A.M.) question-
​

Received February 19,
2002; revised and
accepted May 15, 2002.
Reprint requests: Robert S.
Tan, M.D., Geriatrics and
Andrology Program,
Department of Family and
Community Medicine, 6431
Fannin Street JJL Suite
308, Houston, Texas 77030
(FAX: 713-500-0750;
E-mail: robert.s.tan@
uth.tmc.edu).
CASE REPORTS ​

​

FERTILITY AND STERILITY

​

​

VOL. 79, NO. 1, JANUARY 2003
Copyright ©2003 American Society for Reproductive Medicine
Published by Elsevier Science Inc.
Printed on acid-free paper in U.S.A.
0015-0282/03/$30.00
PII S0015-0282(02)04550-8
203
naire was applied, and he scored 8/10. For standardization
purposes, blood work was done at 9 ​

​

AM. Just before clomiphene

citrate administration, laboratory examination revealed
a total T of 71 ng/dL (reference range, 260​

​

–1000

ng/dL), free T of 29 pg/dL (reference range, 34​

​

–194 pg/dL),

bioavailable T of 61 ng/dL (reference range, 84​

​

–402 ng/dL),

LH of 3.7 miu/mL (reference range, 1.5​

​

–9.3 miu/mL), FSH

of 2.4 miu/mL (reverence range 1.4​

​

–18.1 miu/mL), prolactin

of 5 ng/mL (reference range, 2​

​

–18 ng/mL), and TSH of 1.36

miu/mL (reference range, 0.40​

​

–5.50 miu/mL). Free and total

Ts were measured by radioimmunoassay methods. Magnetic
resonance imaging did not show any abnormality in the
pituitary area. Cortisol and thyroxine were also in the normal
ranges. Sperm samples were not collected as the patient
declined. Total T levels rather than free or bioavailable T
were used for follow-up.
He was challenged with 100 mg of clomiphene citrate for
5 days. Two weeks later, his total T was 828 ng/dL. The
patient reported better moods and return of libido and energy,
but still continued on his antidepressant. The patient
was followed up, and 2 months after clomiphene citrate
challenge, he had a relapse of symptoms including tiredness
and loss of libido. At this time, his total T dropped again to
301 ng/dL. A decision was made to continue treatment with
clomiphene citrate for 2 months. At the end of 2 months, his
total T was 705 ng/dL, and LH was 26.3 miu/L (Fig. 1). The
magnetic resonance imaging of the pituitary was repeated
and remained normal. Symptoms resolved and the patient
continues to be followed up.
Institutional review board approval was obtained for writing
this case report.
​

​

DISCUSSION
Clomiphene citrate is an orally administered, nonsteroidal
ovulatory drug typically used in female infertility management.
It has both estrogenic and antiestrogenic properties.
Clomiphene citrate initiates a series of endocrinologic events
that cause a gonadotropin surge, which in turn causes an
increase in steroidogenesis. Clomiphene citrate is thought
not to have any inherent androgenic or anti-androgenic effect.
In this case, we were challenging the pituitary gland to
produce a surge of gonadotropins to help restore function to
the Leydig cells to produce T.
Clomiphene citrate has been shown to increase T levels in
both normal and impotent hypogonadal men probably re​

​

flecting

the primacy of estrogen over T in the feedback
regulation of male gonadal function. In a small, doubleblind,
placebo-controlled, crossover study of clomiphene
against placebo in impotent men with secondary hypogonadism,
there was a signi​

​

ficant rise of LH, FSH, and T with

clomiphene (2). However, the study in these 17 men did not
​

​

F I G U R E 1
The effect of clomiphene citrate on T with time. ​

​

Filled square total T (ng/dL).

​

​

Tan. Premature andropause reversed with CC. Fertil Steril 2003.
204 ​

​

Tan et al. ​

Premature andropause reversed with CC Vol. 79, No. 1, January 2003

​

​

reveal any improvement of sexual function as measured with
questionnaires and penile tumescence and rigidity testing.
Another study investigated the hormonal response to clomiphene
in alcoholics with hypogonadism (3) and found that
clomiphene can increase androgens and estrogens. The rise
in estrogens was thought to be due to peripheral conversion
of androgens to estrogens. Paradoxically, one study failed to
show that clomiphene could restore pituitary testicular responsiveness
in hypogonadotrophic hypogonadism but succeeded
with human chorionic gonadotropin (4).
Clomiphene citrate has been used successfully in the
treatment of idiopathic hypogonadotrophic hypogonadism
induced by excessive exercise such as marathon running (5).
In that case report, reestablishment of the physiologic hypothalamic​

​

–

​

​

pituitary​

​

–gonadal axis with the return of normal T

and gonadal function was achieved with clomiphene citrate
(50 mg, 2 times per day) over 5 months. In our case, the
reestablishment of eugonadal status was achieved with just a
short challenge of clomiphene citrate 100 mg over 2 weeks,
but the patient relapsed. He needed a longer course of 2
months of clomiphene citrate to maintain eugonadal status.
Both cases, including ours, suggest that early intervention
with clomiphene can restore the hypothalamic​

​

–pituitary–

​

​

gonadal axis. We are still continuing to follow up our patient
to establish long-term effects. The patient did not suffer from
any hot ​

​

flashes or other side effects from clomiphene citrate.

There have been no previously documented cases of
clomiphene citrate improving exogenous steroid​

​

–induced

testicular failure. The mechanism of initial testicular failure
could be due to the suppression of LH due to the use of
exogenous steroids, which in turn leads to decreased T
levels. We postulate that clomiphene citrate can reestablish
the axis even after steroid abuse has initially shut down the
axis. It can induce the gonadotropin surge, initiate T levels to
increase, and improve gonadal function and reverse symptoms.
This was possible in this case as the patient was
relatively young and presumably had a more elastic axis.
​

​

Acknowledgments: ​

​

The authors are grateful to Shahla Nader, M.D., Division

of Reproductive Endocrinology, Department of Obstetrics and Gynecology,
for her kind input in managing this case.
​

​

References
1. Tan RS, Philip P. Perceptions of and risk factors for andropause. Arch
Androl 1999;43:227​

​

–33.

2. Guay AT, Bansal S, Heatley GJ. Effect of raising endogenous testosterone
levels in impotent men with secondary hypogonadism. J Clin Endocrinol
Metab 1995;80:3546​

​

–52.

3. Martinez-Riera A, Sanolaria-Fernandez F, Gonzalez Reimers E, Milena
A. Alcoholic hypogonadism: hormonal response to clomiphene. Alcohol
1995;12:581​

​

–7.

4. Weinstein RL, Reitz RE. Pituitary-testicular responsiveness in male
hypogonadotrophic hypogonadism. J Clin Invest 1974;53:408​

​

–15.

5. Burge MR, Lanzi RA, Skarda ST, Eaton RP. Idiopathic hypogonatrophic
hypogonadism in a male runner is reversed by clomiphene citrate. Fertil​

Steril 1997;67:783–5.

​

 

[TwisT]

No, I know clomid is very very effective as a PCT drug. I need you to prove your statements that nolvadex is "counter productive" to PCT in regards to restoration of HTPA function, as that is what PCT is for right? And show me why, you believe, that in PCT having a lower GnRH sensitivity is okay, and why you believe clomid is superior. Write me a nice article or something, no rush! Prove bigcat, llewellyn, and anthony roberts wrong! They are among the many that are supporters of nolvadex over clomid for PCT. I myself have a degree in a related field and am also a strong supporter (obviously). But there are a few highly educated out there who believe the oposite . One guy who's a doctor, just forget him name.... Ill look it up for you later.

-T

 

[MDR]

I'm glad we can agree that Clomid is a highly effective PCT drug. How about you show me some (recent) studies now that prove that Nolva is more effective than Clomid and that Nolva does not lower IGF-1 and GH levels. I have read evidence that Nolva does lower IGF-1 and GH levels. I look forward to checking back and reading the recent research evidence you can provide.

 

[TwisT]

I'm glad we can agree that Clomid is a highly effective PCT drug. How about you show me some (recent) studies now that prove that Nolva is more effective than Clomid and that Nolva does not lower IGF-1 and GH levels. I have read evidence that Nolva does lower IGF-1 and GH levels. I look forward to checking back and reading the recent research evidence you can provide.

I dont believe one is nessisarily "more effective" than the other, I didn't ever state that. I do believe however, that the side effects of Clomid, the major one being the reduction in pituitary sensitivity and simply being a much "weaker" drug, make it not the best option for PCT compared to Nolva, as a lowered sensitivity will obviously be "not as good" or "counter productive" (not sure how I should word that but I'm sure you understand) in HPTA restoration. You are correct, Nolvadex does lower IGF-1 and GH serum levels (note that the studies that show this usually are done with use from 3-36 months). But neither of those hormones have a pronounced effect on HPTA, in which the goal of PCT is to recover natural function.

What research evidence would you like me to provide on any of this?

-T

 

[MDR]

The article you posted stated a clear preference for Nolva over Clomid. Any recent references backing up this assertion will do.

 

[TwisT]

The highlighted in bold should alone put your argument to rest.


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
American Journal of Physiology: Endocrinology and Metabolism
Abstract

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.


So, we see that clomid acts more ESTROGENIC then ANTIESTROGENIC in pituitary cells... And as you hopefully know the ANTIESTROGENIC actions are what cause an INCREASE in LH and FSH, which in turn increases testosterone. How much tamoxifen is needed for that effect? 20mgs/day to increase testosterone 150% as per this study. How much clomid would be needed to have the same effect? 150mg.

Fertil Steril. 1978 Mar;29(3):320-7.
Hormonal effects of an antiestrogen, tamoxifen, in normal and oligospermic men.
Vermeulen A, Comhaire F.
Abstract
The administration of tamoxifen, 20 mg/day for 10 days, to normal males produced a moderate increase in luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, and estradiol levels, comparable to the effect of 150 mg of clomiphene citrate (Clomid). However, whereas Clomid produced a decrease in the LH response to LH-releasing hormone (LHRH), no such effect was seen after the administration of tamoxifen. In fact, prolonged treatment (6 weeks) with tamoxifen significantly increased the LH response to LHRL. Treatment of patients with "idiopathic" oligospermia for 6 to 9 months resulted in a significant increase in gonadotropin, testosterone, and estradiol levels. A significant increase in sperm density was observed only in subjects with oligospermia below 20 X 10(6)/ml and normal basal FSH levels. When basal FSH levels were increased or oligospermia was moderate (greater than 20 X 10(6)/ml); no effect on sperm density was seen. As sperm density increased, FSH levels decreased, suggesting an inhibin effect. Sperm motility was not improved by tamoxifen treatment. In five boys with delayed puberty, tamoxifen treatment appeared to activate the pituitary-gonadal axis and pubertal development.

Why would you EVER want a SERM in PCT that has estrogenic effects in the pituitary??!??!?!? Why would you EVER want a decrease in LH response to LHRH in PCT??!?!?!?

Clomid is the true "counter-productive" SERM, I dont know how you can say tamoxifen is


Point made.... I hope

 

[MDR]

Nope, but it does show why a good AI is crucial during PCT.

 

[TwisT]

Nope, but it does show why a good AI is crucial during PCT.

Clearly you didnt understand what I just posted.... try reading it again.

....we are moving on to why we need an AI in PCT now?

Where would you like me to start?

 

[Vibrant]

This thread is heating up now this is what I like to see, two knowledgeable guys making a battle of wills, scientific evidence, and a bit of bro science thrown into the mix. Kudos to both of you.

 

[MDR]

I was always advocating for the use of Aromasin and Clomid together. Perhaps you are the one who need to read my posts a little more carefully. By the way, you might try posting the entire study and looking at it in it's entirety before making an argument, or at least if you expect anyone to listen to your conclusions.

 

[TwisT]

I was always advocating for the use of Aromasin and Clomid together. Perhaps you are the one who need to read my posts a little more carefully. By the way, you might try posting the entire study and looking at it in it's entirety before making an argument, or at least if you expect anyone to listen to your conclusions.

Im glad bro! I never said anything about the use of an AI with Clomid....thats not the topic of the debate? Stay on topic...

I have proven my point, the summary is all thats needed to post, and all that we mods post on this forum. Its accepted, and obviously, you as such a knowledgable person know that the jounrnal info is always posted below the study title, and you can easily go look them up. All journals are very easy to acsess.

You wanted me to prove why tamoxifen is superior to clomid, I did. You havnt come up with any evidence disproving mine, nor have you made any educated statements to back yours up. If you come up with anything new, or want to share a study with me (that is relivant), youre free to PM me.

The case has been proven, so I will close the thread. Thanks for playing

-T

 

[MDR]

Im glad bro! I never said anything about the use of an AI with Clomid....thats not the topic of the debate? Stay on topic...

I have proven my point, the summary is all thats needed to post, and all that we mods post on this forum. Its accepted, and obviously, you as such a knowledgable person know that the jounrnal info is always posted below the study title, and you can easily go look them up. All journals are very easy to acsess.

You wanted me to prove why tamoxifen is superior to clomid, I did. You havnt come up with any evidence disproving mine, nor have you made any educated statements to back yours up. If you come up with anything new, or want to share a study with me (that is relivant), youre free to PM me.

The case has been proven, so I will close the thread. Thanks for playing

-T

You stay on topic. My original post knocked you for relying on old studies and dated conclusions. Then you post ANOTHER 30+ year old study and claim erroneous conclusions again. When you rely on dated studies, you get dated information. As far as I'm concerned, this debate is now over. You already agreed with my assertion that Nolva creates issues with IGF-1 and GH. I think it works ok during a cycle for gyno issues, although I would probably use a suicidal A/I like Letro first. The only difference is that you do not see the IGF-1 and GH issues as a problem. I do. Further, you are an asshole for closing a thread just to get in the last word, and getting nasty and insulting when you are so clearly losing a rational argument. Last resort of a desperate man. I'm done with you. You can't have a battle of wits with an unarmed man. Thank you to Prince for reopening the thread. Someone else can take up the argument from here, and I'm sure they will. Plenty of other people see real problems with Nolva during PCT.

 

[GMO]

Read this article by a male fertility doctor:

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

And here is a study that confirms that Tamox reduces serum levels of IGF-1:

Effect of tamoxifen on GH and IGF-1 serum level in stage I-II breast cancer patients.

Mandalà M, Moro C, Ferretti G, Calabro MG, Nolè F, Rocca A, Munzone E, Castro A, Curigliano G.
Source

Division of Medical Oncology, European Institute of Oncology, Via Ripamonti 435, 20141-Milan, Italy. mario.mandala@ieo.it

Abstract

OBJECTIVE:

Tamoxifen suppresses insulin-like growth factor-1 (IGF-1) plasma levels in early and advanced breast cancer patients. Relationships between tamoxifen (GH) and IGF-1 are complex and not completely described yet. The present investigation was performed to evaluate the effect of acute and chronic tamoxifen administration on GH response to growth hormone-releasing hormone (GHRH), as well as on IGF-1 serum levels.
MATERIALS AND METHODS:

Evaluation of GH after administration of GHRH was performed (a) at baseline, (b) 3 hours after 20 mg oral administration of tamoxifen and (c) after 12 weeks of 20 mg a day oral tamoxifen treatment, in fifteen postmenopausal stage I-II breast cancer patients. IGF-I was measured at baseline and after chronic tamoxifen administration.
RESULTS:

The GH response to GHRH was significantly reduced after 12 weeks of tamoxifen 10 mg administered twice a day orally (mean peak 3.2 +/- 0.2 micrograms/l, mean AUC 261.3 +/- 18.2 micrograms/minute p < 0.01 versus basal AUC). A concomitant significant reduction of IGF-1 was observed after 3 months of tamoxifen treatment. Basal pretreatment levels of 113.2 +/- 15.5 micrograms/l were suppressed to 70 +/- 7.9 micrograms/l (p < 0.01).
CONCLUSION:

Our study confirms the inhibitory effect of tamoxifen on IGF-I and suggested, as shown in previous in vitro data, that its suppression could be directly related to GH reduction in response to GHRH stimulation.



Then there's the personal experience that Clomid has always brought me back post cycle.

 

[TwisT]

Have humans evolved in the last 30 years in which our bodies react differently to the chemical Tamoxifen? What does the studys age have to do with the outcome? You clearly have no medical understanding. Yes, every year what we know medically changes, but the outcome of a controlled study does not become "wrong". Again, this is about why Tamoxifen is superior to clomid for PCT purposes, prove me wrong.

I wont reply until you come up with something educated pertaining to your point, which you still havn't.

Read this a few times, before you blow more smoke out your ass, IGF-1 and GH have nothing to do with this argument, we are talking about HPTA restoration in PCT

No need to post anything more about IGF-1, GH, or whatever else you want to divert to. Tell my why you think I'm wrong about my above post proving why Clomid is inferior to restoring HPTA in PCT.

You stay on topic. My original post knocked you for relying on old studies and dated conclusions. Then you post ANOTHER 30+ year old study and claim erroneous conclusions again. When you rely on dated studies, you get dated information. As far as I'm concerned, this debate is now over. You already agreed with my assertion that Nolva creates issues with IGF-1 and GH. I think it works ok during a cycle for gyno issues, although I would probably use a suicidal A/I like Letro first. The only difference is that you do not see the IGF-1 and GH issues as a problem. I do. Further, you are an asshole for closing a thread just to get in the last word, and getting nasty and insulting when you are so clearly losing a rational argument. Last resort of a desperate man. I'm done with you. You can't have a battle of wits with an unarmed man. Thank you to Prince for reopening the thread. Someone else can take up the argument from here, and I'm sure they will. Plenty of other people see real problems with Nolva during PCT.

 

[TwisT]

Has nothing to do with HPTA restoration, in which I have proven above why nolvadex is superior. We aren't talking about IGF-1. I stated above that yes, we all know that Nolvadex reduces IGF-1 levels, but that is unrelated to the point of PCT, to restore HPTA. PS- your study is over a length of 3 months, not really relevant to todays normal PCT duration.

Read this article by a male fertility doctor:

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

And here is a study that confirms that Tamox reduces serum levels of IGF-1:

Effect of tamoxifen on GH and IGF-1 serum level in stage I-II breast cancer patients.

Mandalà M, Moro C, Ferretti G, Calabro MG, Nolè F, Rocca A, Munzone E, Castro A, Curigliano G.
Source

Division of Medical Oncology, European Institute of Oncology, Via Ripamonti 435, 20141-Milan, Italy. mario.mandala@ieo.it

Abstract

OBJECTIVE:

Tamoxifen suppresses insulin-like growth factor-1 (IGF-1) plasma levels in early and advanced breast cancer patients. Relationships between tamoxifen (GH) and IGF-1 are complex and not completely described yet. The present investigation was performed to evaluate the effect of acute and chronic tamoxifen administration on GH response to growth hormone-releasing hormone (GHRH), as well as on IGF-1 serum levels.
MATERIALS AND METHODS:

Evaluation of GH after administration of GHRH was performed (a) at baseline, (b) 3 hours after 20 mg oral administration of tamoxifen and (c) after 12 weeks of 20 mg a day oral tamoxifen treatment, in fifteen postmenopausal stage I-II breast cancer patients. IGF-I was measured at baseline and after chronic tamoxifen administration.
RESULTS:

The GH response to GHRH was significantly reduced after 12 weeks of tamoxifen 10 mg administered twice a day orally (mean peak 3.2 +/- 0.2 micrograms/l, mean AUC 261.3 +/- 18.2 micrograms/minute p < 0.01 versus basal AUC). A concomitant significant reduction of IGF-1 was observed after 3 months of tamoxifen treatment. Basal pretreatment levels of 113.2 +/- 15.5 micrograms/l were suppressed to 70 +/- 7.9 micrograms/l (p < 0.01).
CONCLUSION:

Our study confirms the inhibitory effect of tamoxifen on IGF-I and suggested, as shown in previous in vitro data, that its suppression could be directly related to GH reduction in response to GHRH stimulation.



Then there's the personal experience that Clomid has always brought me back post cycle.

 

[heavyiron]

Good thread TwisT. Thanks for posting this.

Both Clomid and Nolva are SERM's and work well to prevent Gyno and raise T levels. At the end of the day I think it comes down to personal preference. I have always liked Nolva better for emergency Gyno treatment and Clomid better for PCT but either will work.

I think TwisT makes a strong point. You can use IGF-1 with your SERM if you are worried about lower IGF-1 levels. Over the last few years I have felt using IGF-1 is a good idea during PCT so I agree completely with that recommendation.

 

[TwisT]

Why do you prefer clomid in PCT knowing its actions in the pituitary?

Welcome to the fun heavy!!

Good thread TwisT. Thanks for posting this.

Both Clomid and Nolva are SERM's and work well to prevent Gyno and raise T levels. At the end of the day I think it comes down to personal preference. I have always liked Nolva better for emergency Gyno treatment and Clomid better for PCT but either will work.

I think TwisT makes a strong point. You can use IGF-1 with your SERM if you are worried about lower IGF-1 levels. Over the last few years I have felt using IGF-1 is a good idea during PCT so I agree completely with that recommendation.