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.

 

[Tom79bmth]

This appears to state that K10 is potentially ineffective due to a short half life and a molecular size that may not cross the BBB. Then this statement:

In healthy men, both an intravenous bolus and a continuous infusion of KP-10 produced significant LH responses with the latter maintaining LH secretion for at least 22.5 h [17,25]. Acute and chronic administration of intravenous KP-10-induced LH increases in obese hypogonadal diabetic men [27] and healthy older men [28], thereby highlighting promising therapeutic avenues for the use of kisspeptin in male functional hypogonadism related to diabetes, obesity, or age.

They reference only IV administration however.

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...

There are some interesting animal studies, which I won't post here, that have the same mixed reviews. Good results were seen with constant IV administration.

Out of curiosity and a glimmer of hope, I ordered some and will post my personal findings.

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...

It’s been a while, just seeing how you’re getting on with kisspeptin and if you’re still taking it?

 

[ehrise]

It's an incredibly complex system with wide individual differences, it would be hard to know for sure, I'd think. I would love to try kisspeptin in conjunction with PT-141 to test the effects on libido.

Don't test both together. Test Kisspeptin seperate from PT-141.
PT-141 used as-and-when required is going to surprise you... a lot. I love it and am never low on stock of PT-141.

 

[DorianGray]

Don't test both together. Test Kisspeptin seperate from PT-141.
PT-141 used as-and-when required is going to surprise you... a lot. I love it and am never low on stock of PT-141.

Actually, I’ve tried PT-141 several times and like it too. But, last batches gave me more nausea. I just ordered some PT-141 nasal spray, hoping that will be better.

 

[madman]

Bet those run-of-the-mill clinics will go ape shit pushing injectable KP-10 as the next best thing!

Everyone needs to keep this in mind!


*KP-10, KP-54, and kisspeptin receptor agonists such as TAK-683 [11] and MVT-602 (formerly known as TAK448) [12] are the kisspeptin peptides that have been studied in humans to date. KP-10 is potent against KISS1R in vitro but is not believed to cross the blood-brain barrier and has a shorter half-life than KP-54 (t1/2 3 vs. 28 min) due to significant enzymatic degradation, making it less suitable for bolus administration [2]. Native KP-54 has a longer half-life and induces greater LH rises in vivo after bolus administration but is more expensive to manufacture than KP-10 due to its longer peptide length [13]. KISS1R-analogs, such as TAK-683 and MVT-602, which have been recently developed by modification of KP-10, possess increased stability and potency, hence enabling more cost-effective peptide manufacture [11,12].


*different kisspeptin peptide forms (KP-54, KP-10, KP-analogue), durations, frequencies (bolus or continuous infusion), and administration routes (central, subcutaneous, intranasal, or intravenous)

Novel therapeutic avenues for kisspeptin - ExcelMale Forum. TRT, Hormones, Peptides, Men’s Health

Novel therapeutic avenues for kisspeptin (2022) Jovanna Tsoutsoukia, Ali Abbarab, and Waljit Dhillo Abstract Kisspeptin is a hypothalamic neuropeptide that acts via the hypothalamus to stimulate hypothalamic gonadotrophin-releasing hormone secretion and downstream gonadotrophin release. In...

www.excelmale.com

Background

The kisspeptins are a family of peptides encoded by the KISS1 gene in humans (KISS1 in non-human primates and Kiss1 in other mammals) [1]. The prepropeptide consists of 145 amino acids that are subsequently proteolyzed into shorter peptides of lengths denoted by their suffixes, such as kisspeptin-54 (KP-54), -14, -13, and -10 (KP-10) [2]. All forms share a common C-terminal decapeptide sequence, equivalent to KP-10, which is important for their binding to the G-protein-coupled kisspeptin receptor, KISS1R (formerly known as the orphan receptor GRP54) [2]. Kisspeptin primarily stimulates the hypothalamus to regulate the hypothalamic-pituitary-gonadal axis [3]. Indeed, the decreased KISS1R signaling in humans results in absent puberty and hypogonadotropic hypogonadism [4,5], whereas increased KISS1R signaling results in precocious puberty [6]

Outside the human hypothalamus [7], kisspeptin and its receptor are expressed in the brain in key limbic and paralimbic regions [7], and in peripheral tissues such as the gonads, placenta, liver, adipose tissue, and bone [7]. Consequently, beyond its central role in stimulating hypothalamic gonadotrophin-releasing hormone (GnRH) secretion, kisspeptin has been studied in sexual and emotional brain processing [7], bone turnover [8], metabolism [9], and as a biomarker of pregnancy complications [10]. Herein, we summarise data on the pharmacological use of kisspeptin in reproductive disorders and fertility treatment, as well as its putative utility in hypoactive sexual desire disorder (HSDD), osteoporosis, and non-alcoholic fatty liver disease, now known as metabolic dysfunction-associated fatty liver disease (MAFLD) (Figure 1).




Kisspeptin trials in healthy men and women

KP-10, KP-54, and kisspeptin receptor agonists such as TAK-683 [11] and MVT-602 (formerly known as TAK448) [12] are the kisspeptin peptides that have been studied in humans to date. KP-10 is potent against KISS1R in vitro but is not believed to cross the blood-brain barrier and has a shorter half-life than KP-54 (t1/2 3 vs. 28 min) due to significant enzymatic degradation, making it less suitable for bolus administration [2]. Native KP-54 has a longer half-life and induces greater LH rises in vivo after bolus administration but is more expensive to manufacture than KP-10 due to its longer peptide length [13]. KISS1R-analogs, such as TAK-683 and MVT-602, which have been recently developed by modification of KP-10, possess increased stability and potency, hence enabling more cost-effective peptide manufacture [11,12].

Exogenous kisspeptin has been reported to potently stimulate GnRH and in turn luteinizing hormone (LH), in healthy men and women, and in patients with the reproductive disease, using different kisspeptin peptide forms (KP-54, KP-10, KP-analogue), durations, frequencies (bolus or continuous infusion) and administration routes (central, subcutaneous, intranasal or intravenous) [2,14-19]. Subcutaneous KP-54 stimulated gonadotrophin secretion in healthy females throughout all phases of their menstrual cycle [18,20,21], but with the greatest LH rises during the preovulatory phase [18,22e24]. Intravenous KP-10 was the least effective during the follicular phase of the menstrual cycle and evoked no gonadotrophin response when administered subcutaneously [25,26].

In healthy men, both an intravenous bolus and a continuous infusion of KP-10 produced significant LH responses with the latter maintaining LH secretion for at least 22.5 h [17,25]. Acute and chronic administration of intravenous KP-10-induced LH increases in obese hypogonadal diabetic men [27] and healthy older men [28], thereby highlighting promising therapeutic avenues for the use of kisspeptin in male functional hypogonadism related to diabetes, obesity, or age.

Recently, kisspeptin receptor agonists, including MVT-602 and TAK-683, were shown to potently increase LH secretion in men and women [12,29-31]. MVT-602 administered during the follicular phase of the menstrual cycle of healthy women triggered a similar LH amplitude to KP-54 yet produced a more sustained LH rise, with a correspondingly increased area under the curve of LH rise [12]. However, pharmacokinetic properties were similar between MVT-602 and KP-54, suggesting that the longer duration of effect was centered on differential activation of the kisspeptin receptor [12]. When studied in vitro on mouse GnRH neurons, MVT-602 was more potent and induced a more sustained duration of GnRH-neuronal firing than KP-54 (115 vs. 55 min) [12]. Importantly, kisspeptins have been administered to a few hundred patients by different research groups and to different populations but have not been associated with any adverse effects [11,15-17,32-34]. Indeed, kisspeptin levels increase dramatically during pregnancy from non-pregnant levels (8 pmol/L) to 1230 pmol/L during the first trimester and 9590 pmol/L during the third trimester [35e37], consistent with the reported wide therapeutic safety window [10].

* As previous studies have varied in the isoform of kisspeptin used and their pharmacokinetics[50, 51], it is important to remember that kisspeptin-10 and − 54 may differ with respect to thresholds for receptor saturation and desensitization.


* In summary, while our study reinforces previous observations that kisspeptin-10 infusion initially stimulates the hypothalamic-pituitary-gonadal axis, it remains unclear whether prolonged exposure duration will attenuate kisspeptin receptor signaling in eugonadal male. Modulation of kisspeptin receptor signaling in humans is likely to be both time- and dose-dependent.

Thread 'Dynamic Modulation of LH Secretion by Continuous Kisspeptin Infusion in Healthy Men'

Yesterday at 6:33 PM

* Within the arcuate nucleus, a specialized subset of kisspeptin neurons, known as KNDy (Kisspeptin/Neurokinin B/Dynorphin) cells, functions as a “pulse generator,” coordinating rhythmic bursts of activity that drive the pulsatile release of GnRH [3, 4].


* Three healthy adult men received a continuous intravenous infusion of kisspeptin-10 at a dose of 12.5 mcg/kg/h for 24 hours


* Continuous administration of kisspeptin resulted in an immediate increase in LH levels, 5 to 10-fold above baseline, which were sustained for several hours...

• madman
• hypogonadism kisspeptin; lh/fsh; testosterone
• Replies: 2
• Forum: Testosterone and Men's Health Articles

 

[Willyt]

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...

Also interested in your experience. What amount were you dosing? (I only see units).
I just received some KP 10 and am going to experiment.