Kisspeptin-10 as a replacement for compounded HCG?

My Dr told me that their pharmacy can no longer compound HCG, but that he is going to start using Kisspeptin-10 as the alternative without increasing my monthly fee.

He told me that Kisspeptin acts like GnRH and stimulates the Pituitary to release both LH and FSH. I've done some reading online and it seems like a pretty legit alternative (and possibly better, as I would be getting FSH as well, which is why I take HMG once a month).

Has anyone tried Kisspeptin along with TRT? If so, what did you find...did it work well, sides, etc?
Does it even work if you have Secondary HypoG (meaning, with the pituitary gland process it correctly)? I would imagine it wouldn't work if the problem is GnRH reception on the PG.
 

Cataceous

Well-Known Member
The explanation of its function doesn't match what Wiki says:

Kisspeptin's ability to stimulate the release of GnRH and gonadotropins is the result of its effect on GnRH release at the hypothalamus.
What I was wondering is whether or not you need pulsatile delivery of kisspeptin to get normal pulsatile release of GnRH. This research says it's not necessary.

The ability of continuous kisspeptin infusion to induce pulsatile gonadotropin secretion further indicates that GnRH neurons are able to set up pulsatile secretion in the absence of pulsatile exogenous kisspeptin.

Because most men with non-primary hypogonadism respond to clomiphene to some degree it seems as though pituitary reception is not the issue and kisspeptin is an interesting avenue of treatment. However, there is definitely negative feedback from estrogens at the pituitary, and possibly also some from androgens, so the use of kisspeptin with TRT is problematic, and may at a minimum require the use of a SERM.

Another potential issue is half-life. Assuming oral delivery isn't possible, the iv infusion half-life is four minutes, so even if the half-life for subcutaneous administration is ten times as long then you are still looking at a pretty short duration of action. Is the doctor proposing an infusion pump or multiple daily injections?
 
The explanation of its function doesn't match what Wiki says:

Kisspeptin's ability to stimulate the release of GnRH and gonadotropins is the result of its effect on GnRH release at the hypothalamus.
What I was wondering is whether or not you need pulsatile delivery of kisspeptin to get normal pulsatile release of GnRH. This research says it's not necessary.

The ability of continuous kisspeptin infusion to induce pulsatile gonadotropin secretion further indicates that GnRH neurons are able to set up pulsatile secretion in the absence of pulsatile exogenous kisspeptin.

Because most men with non-primary hypogonadism respond to clomiphene to some degree it seems as though pituitary reception is not the issue and kisspeptin is an interesting avenue of treatment. However, there is definitely negative feedback from estrogens at the pituitary, and possibly also some from androgens, so the use of kisspeptin with TRT is problematic, and may at a minimum require the use of a SERM.

Another potential issue is half-life. Assuming oral delivery isn't possible, the iv infusion half-life is four minutes, so even if the half-life for subcutaneous administration is ten times as long then you are still looking at a pretty short duration of action. Is the doctor proposing an infusion pump or multiple daily injections?
I have no idea...it was a very cursory conversation. They haven't finalized the treatment plan yet.
 

Cataceous

Well-Known Member
I have no idea...it was a very cursory conversation. They haven't finalized the treatment plan yet.
I'd be very interested in seeing what you learn about it, if you're willing to share. I see that Tailor Made Pharmacy offers kisspeptin-10. They are suggesting 100 mcg daily. One article I came across suggested that natural men can get a boost in LH for many hours after an injection. Assuming it even works with TRT, I'd want to know what dosing schedule would be needed for various benefits, such as preventing testicular atrophy and improving libido.
 

Nelson Vergel

Founder, ExcelMale.com
Evaluation of serum kisspeptin in infertile men with severe oligospermia

Menoufia Medical Journal, 2019, Vol.32(3), p.1009-1012

Objective
The aim of this study was to determine whether an abnormality in the serum levels of kisspeptin is associated with oligospermia and male infertility.

Background The study of kisspeptin has yielded a new concept on the physiology of the hypothalamic–pituitary–testicular axis and thus the sexual and reproductive functions of men. Patients and methods Our case–control study included 44 male participants aged 20–45 years divided into two groups: a case group composed of 22 infertile men with severe oligospermia and with normal serum levels of testosterone, luteinizing hormone, follicle-stimulating hormone, and prolactin and an age-matched control group composed of 22 fertile men. Serum kisspeptin levels were evaluated by an enzyme-linked immunosorbent assay in both groups.

Results The results of our study showed that the serum levels of kisspeptin in the infertile oligospermic group were significantly lower than those of the fertile group. Conclusion Deficiency of serum kisspeptin might be associated with oligospermia and fertility problems.
 

Nelson Vergel

Founder, ExcelMale.com
Age‐dependent changes in the reproductive axis responsiveness to kisspeptin‐10 administration in healthy men

Andrologia, May 2019, Vol.51(4), pp.n/a-n/a

The present study was designed to assess the responsiveness of hypothalamic–pituitary–gonadal axis to kisspeptin administration with increasing age in men. Human kisspeptin‐10 was administered in single iv bolus dose (1 µg/kg BW) to healthy adult, middle and advanced age men. Serial blood samples were collected for 30 min pre‐ and 120 min post‐kisspeptin injection periods at 30‐min interval. Analysis of plasma LH by ELISA showed a significant ( < 0.05) increase after kisspeptin‐10 administration in all groups, whereas plasma testosterone concentration was significantly elevated ( < 0.05) after kisspeptin‐10 injection only in the adult men group. Present results suggest that in men, central hypothalamic–pituitary axis remains active and shows responsiveness to kisspeptin stimulation across life. However, Leydig cell responsiveness to kisspeptin‐induced LH decreases with age in men.
 

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Nelson Vergel

Founder, ExcelMale.com
Kisspeptin Resets the Hypothalamic GnRH Clock in Men

The Journal of Clinical Endocrinology & Metabolism, June 2011, Vol.96(6), pp.E908-E915


Administration of kisspeptin to healthy men reveals that a single iv dose of kisspeptin induces prolonged GnRH secretion and also resets the GnRH pulse generator.

Context: Reproduction in all mammals is controlled by a hypothalamic clock that produces periodic secretory pulses of GnRH, but how the timing of these pulses is determined is poorly understood. The neuropeptide kisspeptin potently and selectively stimulates the secretion of GnRH. Although this property of kisspeptin is well described, the effects of kisspeptin on endogenous GnRH pulse generation remain largely unexplored.

Objective: The objective of the study was to detail the effects of kisspeptin on GnRH secretion, as reflected by LH secretion, in men.

Participants: Thirteen healthy adult men participated in the study.

Intervention: The intervention was the administration of a single iv bolus of the C-terminal decapeptide of kisspeptin (amino acids 112–121 of the parent protein).

Results: Kisspeptin induced an immediate LH pulse, regardless of the timing of the previous endogenous pulse. The kisspeptin-induced pulses were on average larger than endogenous pulses (amplitude 5.0 ± 1.0 vs. 2.1 ± 0.3 mIU/ml, P = 0.02). Comparison of the morphology of kisspeptin-induced LH pulses in healthy men with that of GnRH-induced LH pulses in men with isolated GnRH deficiency suggests that a single iv bolus of kisspeptin triggered sustained GnRH release lasting approximately 17 min. Furthermore, kisspeptin reset the GnRH pulse generator, as it not only induced an immediate LH pulse but also delayed the next endogenous pulse by an interval approximating the normal interpulse interval.

Conclusions: As the first known agent capable of resetting the hypothalamic GnRH pulse generator, kisspeptin can be used as a physiological tool for studying GnRH pulse generation and opens a door to understanding the mechanisms of biological clocks in general.
 

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Nelson Vergel

Founder, ExcelMale.com
Intratesticular action of kisspeptin in rhesus monkey (Macaca mulatta)
Irfan, S ; Ehmcke, J ; Wahab, F ; Shahab, M ; Schlatt, S
Andrologia (Online), Aug 2014, Vol.46(6), pp.610-617

Kisspeptin-Kiss1R signalling in mammals has been implicated as an integral part of the reproductive cascade. Kisspeptinergic neurons upstream of GnRH neurons are involved in the activation of the hypothalamic GnRH pulse gener- ator during pubertal onset. Thus, the major research focus has been on the central effects of kisspeptin. The demonstration of the presence of KissR expression in human testes suggests additional unknown actions of kisspeptin- KISS1R signalling at the distal component of the male reproductive axis. Here we explored the impact of kisspeptin at the testis in the adult male rhesus monkey. We employed the clamped monkey model to assess the intratesticular actions of kisspeptin. Plasma testosterone and LH levels were monitored in four adult male monkeys. The peripheral administration of human kisspeptin- 10 (50 lg, iv bolus) caused a single LH pulse, which was followed by a robust increase in plasma testosterone levels sustained for at least 180 min. This response was abolished when kisspeptin was administered to GnRH receptor antagonist (acyline) pre-treated animals. However, kisspeptin administration significantly (P < 0.005) elevated hCG-stimulated testosterone levels in acyline pre-treated monkeys when compared with saline+ hCG treatment. These results revealed a novel peripheral facet of kisspeptin signalling.
 

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