Kisspeptin vs. HCG | A Comprehensive Comparison

Researcher looking for an expert comparison of kisspeptin vs. hCG are in the right place.

This comprehensive guide aims to outline and compare the evidence-based benefits of both compounds, including how the two may be applied in research settings to:

• Improve testosterone synthesis
• Restore fertility in men and women
• Potentially enhance mood and sexual stimuli

Further, we will explain what should be known about their safety, dosing, and administration. In the end, we will also share our most trusted vendor of research peptides, including kisspeptin-10.

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What is Kisspeptin?

Kisspeptin-10 is an endogenous peptide and the shortest kisspeptin out of several peptide fragments produced from the main kisspeptin protein.

Kisspeptins are a family of proteins produced in the hypothalamus. In 1996, they were discovered to play a crucial role in regulating the reproductive system [1].

Here's a brief overview of what researchers should know about kisspeptin-10, the most potent member of the family:

• Structure: The name “kisspeptin” comes from the “KISS1” gene that encodes a 145 amino acid peptide, which is then cleaved into four shorter peptides, named according to their length: kisspeptin-54, kisspeptin-14, kisspeptin-13, and kisspeptin-10. Thus, kisspeptin-10 is a decapeptide [1, 2].
• Function: Like the other kisspeptins, Kisspeptin-10 regulates the hypothalamic-pituitary-gonadal (HPG) axis. It stimulates the release of gonadotropin-releasing hormone (GnRH) from the hypothalamus, which triggers the pituitary to release luteinizing hormone (LH) and follicle-stimulating hormone (FSH). These hormones are essential for the function of the ovaries in females and testes in males [3, 4].
• Research applications: Kisspeptin-10 is under research as a potential tool for stimulating the HPG axis in various conditions. Clinical studies report that the peptide can successfully stimulate the production of GnRH and LH within 30-40 minutes of application, and the effect quickly diminishes due to its short half-life of 4 minutes [5].

Kisspeptin-10 is not approved by the United States Food and Drug Administration (FDA) for any use and it is currently only legally available for research.

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What is HCG?

hCG is an endogenous hormone first identified in 1920. It plays a vital role in pregnancy and intrauterine development. The hormone is primarily produced by the placenta during pregnancy, but it is also found in minor quantities in the gonads of non-pregnant women and adult men [6, 7].

The hormone was initially isolated from the urine of pregnant women and eventually purified for therapeutic use. Currently, the hCG is manufactured via recombinant DNA technology, which helps create a molecule identical to the native hormone. The first recombinant hCG (trade name Ovidrel) was approved by the FDA for human use in September 2000 [8].

Here is what researchers should know about hCG:

• Structure: hCG is a complex glycoprotein comprising the two polypeptide chains alpha (92 amino acids) and beta (145 amino acids), which are linked to different carbohydrate units [9].
• Function: In pregnancy, hCG sustains the uterine lining and stimulates fetal growth. It also plays a pivotal role in fetal reproductive system development by mimicking luteinizing hormone (LH) until maturation of the pituitary gland [10].
• Therapeutic Applications: hCG's ability to emulate LH and activate reproductive organs has led to its therapeutic use via exogenous injections. The FDA has approved hCG for treating prepubertal cryptorchidism (unrelated to anatomical issues), hypogonadotropic hypogonadism in men, and inducing ovulation in assisted reproduction [11, 12, 13].

In the United States, hCG is a prescription-only medication and is marketed under various names, including Novarel, Ovidrel, and Pregnyl [14].

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HCG vs. Kisspeptin | Comprehensive Comparison

Kisspeptin-10 and hCG both work to stimulate the HPG axis at different levels, ultimately modulating testicular function in men and ovarian function in women.

In men, this can help faster recovery of testicular function, fertility, and testosterone synthesis after exogenous hormone use, including testosterone replacement therapy (TRT) and anabolic androgenic steroid (AAS) use.

Here are the most notable aspects of hCG therapy, including the mechanisms behind its potential to increase serum testosterone (T) levels:

• hCG mimics the function of LH, directly stimulating the testes in men and ovaries in women. However, hCG cannot mimic the function of FSH. Therefore, FSH is sometimes added to hCG therapy to improve its effectiveness [15].
• Once applied, hCG can stimulate the function of the ovaries in women and testes in men regardless of the condition of the pituitary gland or the hypothalamus. Thus, it can be used in subjects with pituitary problems and infertility. Yet, it will be ineffective in individuals with testicular or ovarian damage.
• A study in men with an average total testosterone of 361.8ng/dl reported that an average of six months of 2000IU/weekly hCG led to a mean T level rise to 519.8ng/dl [16].

While kisspeptin-10 differs in its mechanisms, it may lead to a similar increase in T levels after a single administration:

• Studies suggest that kisspeptin-10 can kickstart the HPG axis, stimulating the release of GnRH and triggering both LH and FSH release. As mentioned, these are the main hormones stimulating the testes in men and ovaries in women. Moreover, researchers also report that it can “reset” the hypothalamic GnRH pulse generator in men [17].
• Kisspeptin-10 is effective only in individuals who retain the capacity for hormonal production in the hypothalamus, pituitary, and reproductive glands. Injecting the peptide is believed to trigger peripheral dendritic terminals of GnRH neurons and stimulate the HPG axis without crossing the blood-brain barrier (BBB) [18].
• A study in healthy male volunteers reports that a single continuous infusion of kisspeptin-10 can boost mean serum testosterone levels from a baseline of 479ng/dl to 692ng/dl [19].

Although no studies have confirmed this for kisspeptin-10, research on kisspeptin-54 shows that repeated administration in women (twice daily) may decrease the effectiveness of both the peptide and endogenous kisspeptins, thereby shutting down the HPG axis. The effect on desensitization was less pronounced but still present with twice-weekly application [20].

Researchers should also note that kisspeptin-54 may lead to stronger receptor desensitization compared to kisspeptin-10 due to its longer half-life as reported by preclinical trials [21].

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Benefits of HCG

The benefits of hCG stem from its capacity to mimic LH, which is the hormone that directly stimulates the testes in men and ovaries in women.

• Post cycle therapy (PCT): In subjects coming off TRT or AAS use, hCG can speed up the restoration of testosterone synthesis and fertility, which might otherwise span up to 24 months [22]. For example, a study involving 49 males with infertility due to TRT revealed that administering 3,000U hCG q.a.d., with or without supplementary medication, reinstated testosterone synthesis and sperm production in 4-5 months [23].
• Ovulation induction: Successful in vitro fertilization (IVF) requires ovulation induction via pharmacological agents such as hCG. For example, one study showed that hCG facilitated successful ovulation in 91.4% of women undergoing assisted reproductive technology (ART) therapy, with a subsequent clinical pregnancy rate of 24.7% [24].
• Infertility due to pituitary dysfunction (hypogonadotropic hypogonadism): Issues like pituitary tumors can result in diminished LH production, reduced testosterone in men, decreased estrogen in women, and infertility in both. Research in men with this condition suggests that hCG offers benefits akin to TRT while maintaining fertility and testicular function [25].

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Benefits of Kisspeptin

The potential benefits of kisspeptin-10 are still under research. Nevertheless, the peptide has been actively investigated for a variety of effects. Below, we will outline some of the most notable clinical studies on kisspeptin-10 and related kisspeptins:

• Post cycle therapy and T boosting: Clinical trials report a significant increase in gonadotropins and testosterone following kisspeptin-10 application. For example, Chan et al. examined its effects on LH secretion in healthy males. A single bolus of 0.3mcg/kg induced an immediate LH pulse with greater amplitude than physiological pulses, and serum T rose from 430ng/dl to 480ng/dl [17]. As previously noted, continuous kisspeptin-10 infusion also increased serum T by over 40% [19].
• Improving mood and enhancing sexual stimuli: A study in 29 healthy heterosexual young men reported that kisspeptins enhanced brain activity in response to sexual and couple-bonding stimuli. In addition, kisspeptin administration attenuated negative mood among the participants [26]. Another trial also suggests kisspeptin enhances brain activity in response to olfactory and visual cues of attraction in men [27]. In these studies, the authors did not clarify whether they used kisspeptin-10 or another kisspeptin peptide such as kisspeptin-54.
• Potential benefits based on kisspeptin-54 research: Kisspeptin-54 has been reported to trigger egg maturation in women undergoing in vitro fertilization [28]. It has also been reported to stimulate ovarian function in women with hypothalamic amenorrhea [20].

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HCG Side Effects

Injectable hCG has been FDA-approved since 2000 as safe for human use based on extensive trials [8]. Nevertheless, exogenous hCG therapy is not free of side effects.

Research into hCG in men indicates that injecting the medication may result in side effects such as [29]:

• reactions at the site of injection
• allergic responses
• restlessness
• headaches
• mood swings

Additionally, at elevated hCG dosages, there's potential for acne, gynecomastia, and thromboembolic incidents, as noted by some experts [30].

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Kisspeptin Side Effects

Studies have shown that kisspeptin-10 may be administered safely in the short-term without serious adverse effects. Clinical trials involving a single dose reported no adverse events [17, 19].

Some potential side effects suggested by preclinical studies are:

• Based on murine studies, kisspeptin-10 may have metabolic effects related to reduced food intake, likely due to potential appetite-suppressant effects [31].
• Animal research also suggests that kisspeptin-10 may have a negative effect on prepubertal testes, although human research is lacking [32].

As noted, frequent kisspeptin-10 application may result in receptor desensitization and suppress the HPG axis, leading to reduced testosterone and fertility.

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HCG vs. Kisspeptin | Dosage Calculator

Below, we outline the latest data on the dosing of hCG and kisspeptin-10, either of which can be used to speed up recovery of testicular function, testosterone levels, and fertility in men with TRT/AAS history.

HCG Dosage for PCT

Research indicates that hCG can be administered either intramuscularly or subcutaneously due to its consistent bioavailability [33].

For the restoration of spermatogenesis and testosterone production, studies recommend initiating hCG at doses ranging from 1,500 to 5,000IU, administered 2–3 times weekly for a duration of three to six months immediately after discontinuing AAS or TRT [34].

If this regimen fails to revive spermatogenesis, experts advise the addition of recombinant FSH at doses between 75 to 400IUs, 2–3 times weekly [15].

hCG can also be administered daily alongside TRT to prevent the suppression of natural testosterone synthesis and preserve fertility. Studies report successful outcomes with 500 IU of HCG daily alongside TRT to prevent the suppression of intratesticular testosterone production and preserve fertility during hormone replacement therapy [35].

Kisspeptin-10 Dosage for PCT Research

The available research on kisspeptin-10 in men reports intravenous administration as a continuous infusion [17, 19].

Yet, studies on other kisspeptins report that subcutaneous injections are also a reliable and effective method for administration [20]. Here are the most notable factors to consider when dosing kisspeptin-10:

• The available clinical studies on kisspeptin-10 report that peak stimulation of serum LH is observed 30–40 min after injection, with serum LH gradually returning to baseline 180 min after injection [5].
• Animal studies suggest that kisspeptins induce a better response and LH synthesis when applied in a fasted state [36].
• A single administration of kisspeptin-10 in male study volunteers led to a greater effect in boosting LH levels at 1mcg/kg compared to 3mcg/kg [19].
• Kisspeptin-10 should not be dosed too frequently, as research with other kisspeptins involving twice-daily dosage reports receptor desensitization. This can lead to the opposite effect and reduce testosterone levels [20].

Here is a reference kisspeptin-10 dosing protocol based on the aforementioned studies and evidence-based considerations:

• Dosage: A single subcutaneous injection of kisspeptin-10 at 100-200mcg.
• Frequency: Do not administer daily or more frequently. Administer as a single subcutaneous injection. Repeated use, especially more than twice weekly, carries an unknown risk for desensitization, which may lead to the opposite effect—suppression of LH and testosterone synthesis.
• Notes: To determine the appropriate dosing duration and schedule for a given subject, perform blood work to assess FSH and LH levels.

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Where to Buy Research Peptides Online? | 2024 Edition

Researchers aiming to undertake experiments with kisspeptin-10 are well-advised to source the peptide exclusively from a distinguished vendor that specializes in research chemicals.

Here are our top two picks at Peptides.org.

Limitless Life

Limitless Life stands out as a global frontrunner in peptide sales, renowned for their top-tier kisspeptin-10 and various other research compounds.

Here's why we endorse them:

• Kisspeptin-10 Made in the USA: This vendor sources their kisspeptin-10 from accredited laboratory partners in the United States, ensuring their customers receive genuine and safe peptides. Each peptide batch is tested by a third-party laboratory using HPLC-MS analysis, providing transparent data on the contents and purity of each vial.
• Competitive Pricing & Fast Shipping: Limitless Life offers competitive pricing for kisspeptin-10. Plus, US-based researchers can expect to receive their peptides within 2-3 business days, and orders of $350+ qualify for free shipping.
• Convenient Payments: To support the needs of its diverse client base, the vendor supports a range of convenient payment methods, including Cash App, credit cards, and cryptocurrencies.
• Exceptional Service: Limitless Life provides outstanding support, with experts accessible through email and phone to handle inquiries or issues. Researchers can be assured of timely assistance.

Also, use this coupon code to obtain a 10% discount when buying from Limitless Life:

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Xcel Peptides

Xcel Peptides is another US-based supplier of research-grade kisspeptin-10 that is sure to satisfy the needs of our readers.

Here’s why we endorse this vendor:

• Research-Grade Kisspeptin-10: Xcel Peptides has a strong commitment to product quality and subjects all of its products to thorough testing by Janoshik laboratory. Certificates of Analysis are readily accessible on the vendor’s website.
• Easy Ordering & Payments: Xcel Peptides has a user-friendly website and accepts a variety of online payment methods, including credit cards, e-check, Venmo, and Zelle.
• Responsive Team: The Xcel Peptides team is always quick to respond to our questions by email or phone. They are available during standard business hours and strive to answer every question they receive.

Also, be sure to sign up to Xcel Peptides’ email newsletter for a 10% discount!

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Bacteriostatic Water and Kisspeptin-10

Researchers looking to accurately prepare and store kisspeptin-10 will require specific tools such as bacteriostatic water, sterile vials, and more.

However, sourcing quality supplies from multiple retailers can be a time-consuming and frustrating task for researchers. While an annoyance, sourcing these items is required for research.

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Kisspeptin vs. HCG | Overall

Kisspeptin-10 and hCG have been explored for purposes like triggering ovulation in females and addressing hypogonadotropic hypogonadism in males.

Both compounds have likewise shown potential for boosting testosterone levels in males, which outlines their potential application in post cycle therapy to quicken the recovery of fertility and testosterone production following AAS use or TRT.

Distinctively, even a single dose of kisspeptin-10 can effectively initiate the HPG axis by promoting the secretion of both LH and FSH. Conversely, while hCG emulates LH, some subjects might require supplementary FSH treatment to achieve complete recovery.

Researchers seeking premium kisspeptin-10 for their studies are encouraged to buy from a reputable source, like our top-rated vendor.

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