There are two negative feedback loops on LH release, estrogen and testosterone.

So having normal or high levels of estrogen will shut down GnRH (gonadotropin releasing hormone) from the hypothalamus and LH (luteinizing hormone) release from the pituitary. SERMs work by selectively antagonizing the estrogen receptors there, making your body think you have low estrogen, thereby tricking it into releasing more LH.

However, as mentioned above, there are ALSO testosterone receptors on the hypothalamus and pituitary as part of the negative feedback loop. So if your testosterone level is normal or high, your body will stop releasing LH.

https://ars.els-cdn.com/content/image/1-s2.0-B9780128000946000029-f02-03-9780128000946.jpg

On TRT, the addition of a SERM only works on one of these negative feedback mechanisms, not the other. So adding a SERM may make your body think you are low on estrogen, but it also recognizes you are high on testosterone (while on TRT). It hits the brakes on one side, and the gas on the other.

This essentially means your body will work harder to produce more estrogen, but not testosterone when you add a SERM to TRT. It is a known fact that men who have tried this combo suffer from high estrogen symptoms (it only blocks the estrogen receptors in the brain, not the rest of the body) and have higher E2 levels.

To date, there have been absolutely zero published studies that have determined the effects of adding a SERM to TRT. All current studies on SERMs are from monotherapy trials alone.

What this means is, for those of you that are using either clomiphene or enclomiphene while on TRT, you should be getting paid considering you are officially being a guinea pig in a study on whether or not TRT/SERM combo therapy works.

Anecdotally, I can say that we at AlphaMD see many patients who transfer to us from other practices who do this untested therapy, and we have never seen it work. Though perhaps we are seeing only the failures.

In general, there is no reason why someone should consider a SERM while on TRT knowing that there is a well studied alternative that provides the same desired outcome. hCG is tried and true, well studied, and effective with fewer side effects.

hCG attaches directly to the testicles, meaning it entirely bypasses the negative feedback mechanisms. As long as you have some remaining testicular function, it always works.

We know that this practice of adding a SERM only developed because clinics have had trouble obtaining hCG from pharmacies due to regulatory changes. We recommend you search for a clinic that has relationships with pharmacies that can supply hCG instead of giving you an alternative inferior therapy.