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SERMs as an alternative to testosterone replacement therapy

By Patrick Arnold

SERM stands for selective estrogen receptor modulator.  Also known as estrogen receptor agonist/ antagonists (or anti-estrogens), these drugs are used by bodybuilders to block the estrogenic effects of anabolic steroids and/or to help stimulate the production of natural testosterone after a steroid cycle.  Examples of SERMs are tamoxifen (Nolvadex), clomiphene (Clomid), and raloxifene (Evista).

These drugs work at the estrogen receptor  to block the effects of estrogen in certain areas of the body (such as the central nervous system and breast)  while in other parts of the body (bone, liver) they act as active estrogens.  Their antagonist properties at the breast make them useful in avoiding or treating anabolic steroid induced gynecomastia, while at the hypothalamus/pituitary the anti-estrogen action helps to block the suppressive effect of estrogens upon luteinizing hormone production (and hence testosterone production).

Lately, some people have explored using SERMs as an alternative to testosterone replacement therapy.  Indeed they do work to stimulate testosterone production in most males and they can restore healthy levels to guys who have lower than normal testosterone blood readings.  The question is however, are you getting the full biological effect of testosterone when you are taking a SERM?

This is an interesting question since it has been observed by many SERM users that the subjective physical response one gets from a SERM often does not correlate with the measured substantial increase in circulating testosterone.  In other words, you don’t feel the same when your blood testosterone is doubled by taking a SERM as compared to when it is doubled by a testosterone injection or testosterone gel.  Why is that?

There are some theories.  Number one, SERMs may act as estrogen antagonists in the brain and it is well known that many of the effects of testosterone upon libido and mood are due to its local conversion to DHT as well as estrogen (estradiol) in the CNS.  Therefore blocking the effects of estrogen upon key levels of the brain may blunt the psychological response one would expect from testosterone.

SERMs also are known to act as estrogen agonists (active estrogens) in the liver.  This can have a couple of relevant effects.  First of all, estrogens strongly promote the production of sex hormone binding globulin (SHBG).  This protein circulates in your blood and irreversibly binds to sex hormones such as testosterone, rendering them inactive.  So with a SERM you may have high total testosterone levels but actual bioactive testosterone may not be so high.

Another consequence of SERM estrogen agonist action in the liver is suppression of IGF-1 production.  IGF-1 is a systemic hormone responsible for whole body anabolism and it is produced in the liver under the positive influence of growth hormone, as well as other hormones such as insulin, thyroid hormone, and androgens.  Estrogens on the other hand suppress IGF-1 production in the liver.  In a recent study* it was directly demonstrated that administration of either tamoxifen or raloxifene to males increased LH and testosterone levels (as expected).  However they also significantly reduced circulating IGF-1 production.  Given the fact that it is well demonstrated that exogenous administration of testosterone increases IGF-1 levels in the blood you begin to see that this may be a big part of the SERM testosterone mystery.  Systemic IGF-1 levels may not do much for contractile muscle tissue growth but they can lead to overall body composition changes and increases in bodyweight.  The difference between the suppressed  IGF-1 state (compared to control) of the SERM user to the heightened IGF-1 state (compared to control) of the exogenous testosterone user may indeed be quite profound.

In conclusion, I suspect that once all this information is considered and digested by people then the use of SERMs may go out of favor as an alternative to testosterone replacement therapy.  It is my personal opinion that carefully titrated estrogen control via use of an aromatase inhibitor (perhaps combined with a proven natural testosterone elevator such as D-Aspartic Acid)  may be a smarter way to achieve the end goal of natural testosterone elevation.


4 Responses so far

Hi PA, I’m wondering if you think an AI + test booster would be sufficient for cycle recovery.

SERM + DAA + SHBG binder + L-Dopa (at night)

still a no go?

my pct consist of above 2
+last two added in after 2 weeks


Great topic, and insight. Goes to support it’s a much more complex system than some would like to think.

I don’t think the depressed IGF-1 sounds good at all. Phew…

As for aromatase inhibitor, what do you like there?


A little anecdotal bit on Clomid. I picked up some RC Clomid and took about 17 mg per day for 2 months. I’m 48 and on a testosterone compounded cream for low T therapy. I did *not* get any blood work done while on the trial of Clomid – it was just a self experiment. I discontinued my cream during this period. I noted no difference in libido, erectile function/ejaculation, energy or weight. I weight trained as normal (powerlifting) during this period without any adverse effects. I noted a marked decrease in acne, which had been a big problem for me. I noticed a “loosening?” or the testes – they seemed to hang lower and a bit fuller. Anyhow, just thought I’d mention this.

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