Kisspeptin suppression under TRT: Can it affect mood and libido?

[Aging Disgracefully]

Due to other factors, I did not have the opportunity to have labs done. I still plan to do so at some point, but there are too many other variables at this time for me to focus on this one.

I did receive the product and have several weeks of use. I can give you my personal observations if that helps.

I have been injecting 10 units sub q EOD for 2 weeks. I am on TRT and also HCG, so keep that in mind.

I notice a subtle elevation in mood and wellbeing after injection. Different than HCG, but similar. I never viewed this as any kind of replacement for HCG, my thoughts were that it would be interesting to see if it did indeed cause an elevation in LH, rather than acting as an analog. This can't be proven without labs, but the elevation in mood and an overall feeling of wellbeing indicates it is doing something.

I do notice a nice libido increase, but it's likely due to the elevation of mood. Its similar to oxytocin if you have ever tried that.

Overall, I like it and will continue using it. Once I have the other variables cleared, I'll get labs done.

Hope that helps...

Thanks for the update that is helpful. I might give it a try as I'm trying to regain my libido more than boost hormones.

 

[JRos895]

It’s interesting how people often talk about how we don’t know the long term effects of serm monotherapy, and use this as a reason to justify T monotherapy or T+HCG therapy. But who is to say we know the long term effects of T monotherapy or T+HCG? The kisspeptin research clearly demonstrates that we still dont. @Cataceous

 

[Cataceous]

It’s interesting how people often talk about how we don’t know the long term effects of serm monotherapy, and use this as a reason to justify T monotherapy or T+HCG therapy. But who is to say we know the long term effects of T monotherapy or T+HCG? The kisspeptin research clearly demonstrates that we still dont. @Cataceous

I agree there are unknowns in all of these treatments. I don't have a sense about which carries greater risk. Hopefully all of the risks are small in an absolute sense.

The background for others:
Regarding SERMs, it bothers me that they are—mostly—not endogenous and that there's limited characterization of the effects they have on all the different estrogen receptors in our bodies. We can get the desired effect, with the hypothalamus and pituitary feeling estrogen-deprived. But SERMs are not that purely selective, as we see with enclomiphene's suppression of IGF-1, which implies liver activity. This opens the door to other suppression we're unaware of, which might bite us in the long run.

The testosterone-based treatments use bioidentical molecules, but they can cause HPTA shutdown, reducing or eliminating natural production of kisspeptin, GnRH, LH and FSH. I continue to wonder out loud about the possible negative consequences of this, given that these hormones have effects that are distinct from their roles in the HPTA.

 

[JRos895]

I agree there are unknowns in all of these treatments. I don't have a sense about which carries greater risk. Hopefully all of the risks are small in an absolute sense.

The background for others:
Regarding SERMs, it bothers me that they are—mostly—not endogenous and that there's limited characterization of the effects they have on all the different estrogen receptors in our bodies. We can get the desired effect, with the hypothalamus and pituitary feeling estrogen-deprived. But SERMs are not that purely selective, as we see with enclomiphene's suppression of IGF-1, which implies liver activity. This opens the door to other suppression we're unaware of, which might bite us in the long run.

The testosterone-based treatments use bioidentical molecules, but they can cause HPTA shutdown, reducing or eliminating natural production of kisspeptin, GnRH, LH and FSH. I continue to wonder out loud about the possible negative consequences of this, given that these hormones have effects that are distinct from their roles in the HPTA.

The serm effect on IGF-1 may not imply anti-estrogenic effect on the liver. Rather the reduction in IGF-1 may result from lower growth hormone levels from anti estrogenic effects at the pituitary. Growth hormone stimulates IGF-1 production.

 

[Cataceous]

The serm effect on IGF-1 may not imply anti-estrogenic effect on the liver. Rather the reduction in IGF-1 may result from lower growth hormone levels from anti estrogenic effects at the pituitary. Growth hormone stimulates IGF-1 production.

You're right, I hadn't read far enough into the research. They wrote:

We report here a suppression of IGF-1. This occurs in the absence of any change of SHGB, another liver protein. This indicates a specific suppression rather than a general inhibition of liver function. This suppression of IGF-1 is still within the normal physiologic range which shows an age-related decrease. ...​

But they go on to add:

This observation needs to be confirmed in future studies. If this is due to hGH suppression, we might anticipate a positive effect of serum glucose, given that hGH may be a causative factor for insulin resistance.​

A little more detail in another piece:

In general, enclomiphene citrate had few changes in these hormones and markers, with the exception of IGF-1. IGF-1 is secreted by the liver and is regulated in part by hGH levels; however circulating levels also are dependent on the proteins that bind IGF-1 in the circulation. IGF-1 levels were decreased in the men in the enclomiphene citrate groups, but not in the transdermal testosterone group, but the levels remained within the normal physiological ranges. We are uncertain as to the significance of this observation. Testosterone treatment of men with testosterone deficiency usually increases serum estradiol levels, and may increase hGH and IGF-1 levels. Estrogen is known to potentiate secretion of hGH and IGF-1 levels. Enclomiphene citrate increases serum estradiol levels. We suspect that the anti-estrogen effects of enclomiphene citrate are working at either the hypothalamic-pituitary level or possibly on the liver to reduce IGF-1 levels. Unfortunately, technical issues prevented the measurement of hGH levels in the serum samples from these men. It would also be relevant to know if enclomiphene citrate treatment affects the IGF-binding proteins.​

I tried to dig into the relationship between estrogens and hGH. I found it to be clear as mud. In any case, I think my overall point holds: there's uncertainty about the effects of long-term enclomiphene use. Influence on IGF-1 by whatever route is still demonstrating less-than-ideal selectivity.