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Kisspeptin-10 Peptide Benefits: Testosterone, Fertility & Hormones

Hormonal health has always been an extremely difficult niche of medicine to tackle.

See, it’s difficult enough to help men feel like men and women feel like women.

Thousands of hormones and biomolecules all interact with one another simultaneously… changing just one part of the equation can wildly throw the entire human body off balance.

It’s why you hear horror stories of men who use testosterone therapy — either they didn’t know what they were doing, their doctor didn’t know what they were doing, or a combination or both.

But there’s one therapeutic peptide which I can believe can make optimizing testosterone levels much easier for men (and women).

It goes by the name of Kisspeptin, and this article will dish out everything we know on this compound highly sought after by hormone optimization physicians.

What Is Kisspeptin?

Kisspeptin is a 10-amino-acid neuropeptide that is encoded by the KISS1 gene within the human body, known for its cancer suppression effects:

(Source)

Its discovery dates all the way back to 1996, and it comes from a much larger protein that gets broken down in the human body:

“…where it was discovered— in Hershey, Pennsylvania, of course, the home of the famous Hershey Kisses! The KISS1 gene encodes for a hydrophobic 145 amino acid protein, which can be cleaved into a 54 amino acid protein, originally called metastin for its ability to inhibit cancer metastasis.

Both the 145 and 54 amino acid proteins contain a sequence that predisposes the proteins for ubiquitination and proteosome degradation, suggesting that they may have a short half-life. The 54 amino acid metastin and the shorter peptides (10, 13 and 14 amino acids long) were collectively named kisspeptins, because they are the proteolytic bi-products of a common precursor protein encoded by the KISS1 gene”

We’re going to be mainly focusing on Kisspeptin-10, as that is the most well-studied by-product of the original 145-amino-acid protein.

Kisspeptin is not only produced in the hypothalamus but also stimulates neurons in the same brain region to release gonadotropin-releasing hormone (GnRH)… but more on that later.

(Other areas of production include the pancreas, testes, ovaries, and placenta)

Kisspeptin is also critical for puberty and fertility, as evidenced by its interactions with its receptor GPR54:

“Kisspeptin is unable to stimulate LH [leuteinizing hormone] secretion in GPR54 knockout mice, and kisspeptin knockout mice are infertile. Thus, kisspeptin and GPR54 are essential for puberty and subsequent fertility in mammals.

The majority of research on kisspeptin to date has focused on mammals that maintain relatively continuous reproductive function (e.g., laboratory mice and rats, monkeys and humans)”

But what does all of this have to do with hormone optimization?

How Does Kisspeptin Work?

Before I tell you exactly how Kisspeptin works in the human body, we have to review the basic mechanism of action for testosterone.

For this, I’ll quote The TOT Bible:

“The testosterone production process begins when your brain sends a chemical signal to the hypothalamus (the part of your brain that connects the endocrine system with the nervous system) and tells it to make some testosterone.

In turn, the hypothalamus releases a chemical messenger called gonadotropin (GnRH) that gets picked up by the pituitary gland (the part of your brain that controls other hormone glands in your body).

This causes the pituitary gland to release two hormones: luteinizing hormone (LH) and follicle-stimulating hormone (FSH). These hormones signal the Leydig cells in the testes to produce testosterone”

The testosterone production process never goes overboard, largely thanks to the body’s natural process of restoring hormonal balance:

“When there is enough testosterone in the human body, a negative feedback loop known as the HypothalamicPituitary-Testicular-Axis (HPTA) [a.k.a. the hypothalamic–pituitary–gonadal axis (HPGA)] sends messages to the pituitary saying that there is enough testosterone freely circulating around.

The pituitary then slows production of LH, and eventually FSH. Testosterone will be reduced (i.e. broken down) into a number of other metabolites that serve important functions”

Kisspeptin comes into this cycle by stimulating GnRH release and continuing the subsequent release of FSH and LH:

“Evidence suggests that kisspeptin acts directly on the GnRH neurons and stimulates the release of GnRH after interaction with its receptor. GnRH further stimulates gonadotrophs in the pituitary gland to secrete FSH and LH into the peripheral circulation.

The evidence related to the stimulatory effects of kisspeptins on GnRH neurons has been provided mainly from animal studies. They have shown increased expression of GnRH mRNA by GnRH neurons after kisspeptin exposure.

Likewise, it has been shown that kisspeptins can evoke an increased firing rate of GnRH neurons as measured by voltage recordings in hypothalamic slices from mice, stimulate the release of GnRH in hypothalamus explants, and cause a dramatic increase in GnRH in the CSF of sheep”

Notably, a few additional things are happening here:

  • There are Kisspeptin antagonists that stop the GnRH neurons from firing non-stop, thus showing Kisspeptin production and release are also regulated
  • Kisspeptin does not directly stimulate the pituitary gland to release LH and FSH, but rather indirectly as a result of its actions on GnRH. 

Let’s now see how this applies to fully optimizing human health!

Kisspeptin-10 Benefits

Kisspeptin’s health benefits should be numerous, given the +2,900 studies available in Pubmed.

But is testosterone-boosting all there is to this peptide, or can it do more for other chronic health problems?

It turns out Kisspeptin’s roles in the human body are far more important than we once believed…

May Be a Viable Replacement for Testosterone Therapy

Kisspeptin has become popular among hormone therapy physicians as a possible way to boost the body’s endogenous production of testosterone.

In other words, unlike exogenous testosterone, you won’t have the normal ‘doctor created side effects’ and you won’t shut down the body’s ability to produce testosterone.

While this is an extremely bold claim, there is some evidence suggesting it could be a useful monotherapy for some men (or as part of an overall hormonal optimization regimen).

First, Kisspeptin can generate a pulse of LH that matches what the human body already does:

“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. 

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.”

Second, we also see Kisspeptin leading to increases in serum testosterone within men:

“Intravenous bolus kisspeptin-10 resulted in a rapid and dose-dependent rise in serum LH concentration, with maximal stimulation at 1 μg/kg (4.1 ± 0.4 to 12.4 ± 1.7 IU/liter at 30 min, P < 0.001, n = 6). Administration of 3 μg/kg elicited a reduced response vs. 1 μg/kg (P < 0.05).

Infusion of kisspeptin-10 at 4 μg/kg · h for 22.5 h elicited an increase in LH from a mean of 5.4 ± 0.7 to 20.8 ± 4.9 IU/liter (n = 4; P < 0.05) and serum testosterone increased from 16.6 ± 2.4 to 24.0 ± 2.5 nmol/liter (P < 0.001).”

This is also observed in other animals such as goats and donkeys.

Finally, we also see an increase in FSH levels within men:

“Intravenous bolus kisspeptin-10 was administered to men and women (n = 4–5 per group). Subcutaneous bolus and iv infusion of kisspeptin-10 was also administered to female women (n = 4–5 per group). Circulating reproductive hormones were measured.

In healthy men, serum LH and FSH were elevated after iv bolus kisspeptin-10, at doses as low as 0.3 and 1.0 nmol/kg, respectively.”

Kisspeptin therapy will definitely be something I worth watching in the future especially for younger Men desiring to retain their fertility.

Enhances Sexual Arousal

Given Kisspeptin’s ability to increase testosterone levels, it should naturally follow that sexual drive also rises.

Yet what’s interesting is how Kisspeptin may regulate sexual motivation independently of testosterone.

Headlines were made in 2020 when a randomized study done in 33 healthy straight men involved exposing them to certain “triggers” associated with sexual arousal after Kisspeptin administration:

“Previous work has shown that this perfume (Chanel No. 5) is associated with sexual arousal.  The participants also viewed female faces. During these tasks researchers scanned their brains to see how kisspeptin affected the brain’s responses to the perfume and faces.

The team found that kisspeptin enhanced attraction pathways in the brain, when smelling the female perfume as well as when viewing female faces,compared to the placebo. They also found that on viewing female faces, kisspeptin had a greater effecton attraction pathways in men who had lower sexual quality of life.”

Even more interesting in the study is how Kisspeptin’s effects were specific to select regions in the brain:

“During the olfactory task, areas significantly enhanced by kisspeptin included key limbic regions known to be involved in human olfactory processing and sexual arousal, but crucially, kisspeptin did not affect the motor system, which was used as a control. Similarly, during the facial attractiveness task, kisspeptin selectively amplified the mPFC and SFG (established aesthetic regions)

In contrast, other limbic regions were unaffected by kisspeptin during this facial attractiveness task, unlike in the olfactory task . These data highlight our findings of targeted region-specific effects of kisspeptin, dependent on the nature of the attraction cue (olfactory or visual).”

It’s no wonder why some news outlets referred to Kisspeptin as the “mental Viagra”!

For this reason, it is postulated that Kisspeptin does a lot more than regulate sexual attraction: It also plays a major role in triggering puberty and controlling fertility.

Kisspeptin’s effects on reproductive behavior are seen in nearly every aspect of the mating process: In both males and females, and in partner preferences!

May Address Infertility in Men and Women

Even though Kisspeptin can help those of us who are fully optimized, what about those who don’t have the same privilege?

In 2009, a small study of ten non-menstruating women found Kisspeptin may help restore natural fertility:

“The study at Imperial College included ten women who were not menstruating, five of whom were given kisspeptin, and the other five were given saline solution.

Blood tests of those who received the kisspeptin revealed that there had been a 48-fold increase in the production of lutenising hormone, and a 16-fold increase in follicle stimulating hormone, both key sex hormones for ovulation and fertility. These results were far higher than those previously gathered for fertile women.

…Where most current treatments involve the direct stimulation of a woman’s ovaries which carries a risk of multiple births and side effects, kisspeptin would potentially address the underlying problem and maintain the body’s own protective regulatory mechanisms.”

A year later, a separate study from the same group of researchers was published where twice-weekly injections of Kisspeptin over 56 days yielded similar results.

And in 2020, the experimental drug MVT-602 (designed to target the kisspeptin system) took things one step further and improved upon what natural Kisspeptin could do:

“The researchers behind the study suggest that MVT-602 may be used to effectively treat a range of reproductive conditions that affect fertility such as polycystic ovary syndrome (PCOS) — a common condition that affects how a woman’s ovaries work and hypothalamic amenorrhea (HA) — a condition where a woman’s periods stop [both conditions affecting 10% of women in the UK].

“…because of MVT-602’s much longer duration of action, it can be given less frequently than the naturally occurring form of kisspeptin, whilst still being able to maintain the degree of stimulation of reproductive hormone levels required to restore reproductive health.”

“LH levels peaked at 21-22 hours after MVT-602 and remained elevated for 48 hours. This is in comparison to natural kisspeptin (KP54) whereby LH levels peaked at 4.7 hours after administration and remained elevated for 12-14 hours. Therefore, the duration of LH rise was extended by approximately four times using MVT-602. LH increases following MVT-602 were similar in PCOS and healthy women, but rose more quickly in women in HA”

But fortunately, it may be possible for infertile men to also benefit from Kisspeptin therapy.

Not only are lower kisspeptin levels in the blood associated with lower sperm count, but higher kisspeptin levels are associated with better sperm quality.

Directly Linked To Metabolic Health

Here was the kicker I never expected to find: Kisspeptin also plays a critical role in your overall bodily health!

A comprehensive review released in March 2022 summarizes how Kisspeptin is involved in human metabolism:

“…both Kiss1 and Kiss1r are expressed in many metabolically-relevant peripheral tissues, including both white and brown adipose tissue, the liver, and the pancreas, suggesting possible actions on these tissues or involvement in their physiology.

In addition, there may be central actions of kisspeptin signaling, or factors co-released from kisspeptin neurons, that modulate metabolic, feeding, or thermoregulatory processes.

Accumulating data from animal models suggests that kisspeptin signaling regulates a wide variety of metabolic parameters, including body weight and energy expenditure, adiposity and adipose tissue function, food intake, glucose metabolism, respiratory rates, locomotor activity, and thermoregulation.

Ironically, Kisspeptin expression is REDUCED by eating a high-fat diet and being obese!

Yet its effects on energy expenditure are mixed:

While some scientists claim Kisspeptin administration reduces it, others claim impaired Kisspeptin signaling is what leads to burning fewer calories.

On the other hand, we have good evidence demonstrating lower food intake from Kisspeptin use via increased time between meals.

And we also see some consistency in Kisspeptin’s ability to increase insulin sensitivity:

“Some, but not all, in vitro work demonstrates positive effects on glucose-stimulated insulin secretion, which is more marked at higher kisspeptin concentrations. Acute and chronic in vivo rodent, non-human primate and human studies reveal enhancement of glucose-stimulated insulin secretion in response to pharmacological doses of kisspeptin.”

But the benefits for male diabetics don’t stop there, considering the high prevalence of hypogonadism (i.e. lowered testosterone production) within this sub-population.

In fact, 2010 was when a group of scientists proposed a connection between Kisspeptin and suboptimal testosterone levels in men with Type 2 diabetes:

“Inactivating mutations of the kisspeptin receptor have been shown to cause hypogonadotropic hypogonadism in man, whilst an activating mutation is associated with precocious puberty.

Data from studies in experimental animals link kisspeptin expression with individual factors known to regulate GnRH secretion, including hyperglycaemia, inflammation, leptin and oestrogen.

We therefore hypothesise that decreased endogenous kisspeptin secretion is the common central pathway that links metabolic and endocrine factors in the pathology of testosterone deficiency seen in men with obesity and T2DM”

And two years later, the same group published a small study of 12 subjects that showed increased serum testosterone, increased LH secretion, and increased LH pulse frequency following Kisspeptin administration in healthy AND diabetic men.

Shows Potent Anti-Cancer Properties

Ironically, one of the earliest discoveries of Kisspeptin’s therapeutic benefits was as a cancer metastasis inhibitor.

But we’ve come a long way since then and Kisspeptin demonstrates anti-cancer activity across numerous cancers:

However, due to Kisspeptin’s small size as a peptide, analogs will have to be developed in order to have longer-lasting effects beyond a single dose.

Unexplored Health Benefits

I sound like a broken record at this point, but Kisspeptin’s effects on testosterone levels should surely lead to the other benefits associated with optimized testosterone use.

And you’re exactly right — here’s just a sample of what Kisspeptin may be used for someday:

Maybe there will be enough intel one day to write a “Kisspeptin Strategies Guide”… who knows?

Kisspeptin Dosage for Hormonal Health

Unfortunately, the best Kisspeptin dosage highly varies because every peptides clinic has a different opinion on the matter.

The dosage to choose, frequency of dosage, method of administration, what to use Kisspeptin with (or not)… all of it is subject to the personal experiences of the individual using it.

That being said, there is some convergence among clinics towards the “right” answer of how to use Kisspeptin:

  • CRE8 Pharmacy — 100 micrograms of Kisspeptin injected subcutaneously every evening for 30 days
  • Wells Pharmacy Network — 100 micrograms of Kisspeptin injected subcutaneously twice a week 

I’ve seen some different dosages mentioned, such as 250 micrograms per day injected nightly on an empty stomach, 50 micrograms every other day, and even some protocols as impractical as 20 micrograms every 2 hours.

So whatever you do is entirely up to you and your physician.

You should also follow best protocols for storing the Kisspeptin peptide: -20°C for long-term storage of the lyophilized form (powder), not thawing and re-freezing it repeatedly, stored in the refrigerator at 2-8°C once reconstituted, not thawing and re-freezing the power

Could Kisspeptin Be a Replacement for TRT?

I was inspired to add this extra intel after reading a Reddit post about how Kisspeptin could replace exogenous testosterone use:

“According to Dr. Seeds of the International Peptide Society 100 mcg. It could replace TRT for the aging male.

Frequency is uncertain but monitoring LH which if you are on TRT should be close to zero. If LH increases then that feedback loop is active again. I think this requires tapering off TRT as Kisspeptin restarts natural testosterone production.”

So if you’re a brave soul who knows what they’re doing, here is an experiment you can try…

If I was completely unrestricted, I would want to take a young 20-something natural man (i.e. NOT on testosterone therapy) and put him on a trial of Kisspeptin.

We take blood work before using Kisspeptin, use it for 6 weeks, and then take another blood test to see what happens.

I would also do two additional blood tests — 6 weeks post-Kisspeptin, and 12 weeks post-Kisspeptin.

This would allow us to see if the body’s endogenous production of testosterone gets shut down.

I theorize that this won’t happen, as the boost in testosterone is meaningful yet small enough to avoid altering natural production.

It may be the case that the boost to LH and testosterone only lasts while using Kisspeptin, but then fades away as soon as you stop using the peptide.

Kisspeptin Side Effects and Safety

Just like the dose of Kisspeptin, the side effects associated with Kisspeptin use are not fully understood.

The majority of the safety studies done with Kisspeptin to date are in animals (such as this one in dogs), and peptide performance in animals is NOT always equal to peptide performance in humans.

And of the few studies done in humans, they are extremely niche and nowhere near the large body of evidence we have for therapeutic testosterone use.

The only positive statement we can make is that nothing has happened so far:

“…administration of single injections of Kisspeptin to healthy male and female subjects temporarily raised plasma Kisspeptin to levels comparable to those seen in pregnancy, and caused no adverse or behavioral effects, such as changes in libido (assessed by questionnaires). No significant changes in heart rate or blood pressure were observed during these studies, which is noteworthy given that vasoconstrictor properties of Kisspeptin have been demonstrated in vitro.”

But there are a few things we can pick up about Kisspeptin’s safety from the available data:

  • For some humans (here and here), there wasn’t a significant difference in overall quality of life or hormonal blood work
  • Degenerative changes in testes have been observed from Kisspeptin use in prepubescent male rats (here and here)
  • Possible formation of plaques within the arteries (here and here) and inhibition of new blood vessel formation, although some people point out the equivalent doses in humans would be several times higher than 100 micrograms
  • Kisspeptin may be most optimal for adults in their 20s-30s, as older men in their 70s see the same boost in LH but not in serum testosterone

Which transitions into one final thing worth knowing BEFORE you use Kisspeptin…

Kisspeptin is NOT going to be a testosterone therapy replacement if your testosterone levels are super-low!

But for younger men, it could potentially be a solid alternative they can use until they reach prime testosterone-using age (usually 35).

And reaching even further, it may be an option for men with low LH levels and fertility issues due to using testosterone optimization therapy.

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Where To Buy Kisspeptin Online

Before you buy Kisspeptin, make sure you are buying Kisspeptin-10 and NOT Kisspeptin-54.

While it is not as well studied, some preliminary evidence suggests Kisspeptin-54 has a longer half-life (32 minutes for Kisspeptin-54 vs. 4 minutes for Kisspeptin-10) and generates a more sustained rise in LH (and FSH).

And some scientists are working on Kisspeptin-10 analogs that do an even better job of increasing testosterone levels.

In the meantime, Kisspeptin-10 is the more popular and better-studied compound, so use that.

As to where to buy it from…

Limitless Life Nootropics  just recently back-ordered Kisspeptin-10 and it’s available for purchase. Give it a spin and see if it works for you.

Use code JAY15 to get 15% off your order! 

Additional Reading Resources For Kisspeptin

Kisspeptin has been extensively studied but rarely used, so there’s not much else I can link to except for the following to gain more intel:

Genemedics has compiled 30 studies on Kisspeptin covering benefits not featured in this article, such as recovery from heart muscle injury and a stronger immune system.

As always…

Raise Your Vibration To Optimize Your Love Creation!

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