Peptides For Testosterone | A Comprehensive Overview

Interested in discovering the most potent peptides for testosterone to include in the research?

This comprehensive guide details the latest clinical data on the best peptides for increasing testosterone levels in men. We’ll answer questions like:

• Can peptides directly stimulate testosterone production?
• Which peptides can address causes of low T, like obesity?
• How do peptides stack up against TRT for increasing testosterone?

Keep reading to discover detailed information about the effectiveness, safety, and mechanisms of peptides for testosterone.

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What Are Peptides?

Peptides are a class of organic compounds that can be found in all living organisms. They are made of amino acids joined together by peptide bonds in a specific amino acid chain, similar to proteins.

Unlike proteins, peptide chains are much shorter (usually 2-50 amino acids). Nevertheless, peptides have a variety of functions in the body, including but not limited to the regulation of [1]:

• Metabolism
• Recovery
• Cellular motility
• Appetite
• Endocrine signaling

The unique attributes and roles of a peptide are dictated by the arrangement of amino acids within its chain. Most peptides exhibit a linear formation, while others may feature non-linear or cyclical structures [1, 2].

Due to their wide range of potential functions, peptides have become of significant interest as therapeutic agents. This has led to the development of synthetic peptides that mimic the function of their natural counterparts [3].

Some therapeutic compounds can be bioidentical to endogenous hormones, while others are modified analogs. There are now over 60 peptide-based drugs with regulatory approval for human use in the United States, with a multitude of others being explored for their potential to yield groundbreaking therapeutic outcomes [4].

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Peptides For Testosterone

Certain peptides work to increase testosterone (T) levels and improve testicular function, including by directly stimulating testosterone synthesis or addressing any issues that may impede it.

Two notable peptides that directly interact with the hypothalamic-pituitary-gonadal (HPG) axis and stimulate testosterone synthesis are:

• Kisspeptin-10
• Gonadorelin

These peptides work by stimulating the production of gonadotropin-releasing hormone (GnRH) as well as the release of the gonadotropins luteinizing hormone (LH) and follicle stimulating hormone (FSH), which are the main regulators of testicular function and testosterone production [5, 6].

The bioregulator Testagen may also interact with the pituitary gland to upregulate both testosterone and thyroid hormone production [7].

In addition, peptides that stimulate the production of growth hormone in the pituitary gland may also stimulate LH and FSH. This may consequently lead to increased testosterone synthesis [8].

Some peptides may also help address hormonal imbalance caused by high amounts of body fat and increased aromatization of testosterone into estrogen. High estrogen levels can act as a negative feedback signal to the pituitary gland, which leads to reduced LH, FSH, and testosterone levels [9].

Weight loss peptides that can help shed excess fat include incretin hormone agonists. Incretin mimetics can exert potent appetite-suppressant effects, ultimately leading to weight loss. Notable examples include [10, 11]:

• Tirzepatide
• Semaglutide
• Liraglutide

By suppressing appetite and inducing fat loss, these peptides may reduce the aromatization of testosterone into estrogens and improve testosterone synthesis.

However, it is important to note that peptides for testosterone can increase serum T levels only in test subjects with preserved testicular function. Further, peptides are believed to help increase T levels only to those within a normal reference range of 300ng/dl – 1000ng/dl of total testosterone [12].

Researchers investigating test subjects with testicular damage or aiming to achieve high serum T levels should instead consider direct testosterone replacement therapy (TRT).

TRT is approved to treat male hypogonadism and it can increase testosterone levels (and help manage symptoms of low T) regardless of the subject's medical condition and comorbidities [13].

Depending on the dosage, TRT can also easily achieve supraphysiological serum T levels. Below, we will directly compare the effectiveness of peptide therapy vs. testosterone therapy.

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Peptides Therapy vs. Testosterone Therapy

Testosterone replacement therapy is a potent treatment for increasing androgen levels in men and managing symptoms of low T. It involves administering exogenous testosterone, which raises serum T levels reliably and dose-dependently.

Here are some of the most notable advantages of TRT:

• One study involving high doses of TRT for 10 weeks reported that it can lead to more than 3x the upper limit of the physiological reference range of testosterone (over 3,000ng/dl). The therapy even led to impressive lean muscle gains in those on TRT who did not engage in any exercise during the treatment period [14].
• TRT has also been reported to increase metabolic rate, which may facilitate fat loss and also protect skeletal musculature against muscle loss during restrictive weight loss diets [15, 16].
• Testosterone has also been reported to improve waist circumference, metabolic health, sexual function, and energy levels in men with low T. In addition, the peptide may provide benefits for cardiovascular health and cognitive function in hypogonadal males [17, 18, 19].

A major downside of TRT is the suppression of testicular function and natural T synthesis. As a result, TRT can lead to testicular atrophy and infertility, which may be restored by discontinuing therapy [20].

On the other hand, peptide therapy may increase serum T levels within the physiological range in subjects with preserved testicular function. Nevertheless, a major advantage of peptides over TRT is that peptide therapy does not suppress natural T production or affect fertility.

In fact, peptides have been employed to restore normal T synthesis and fertility, or initiate puberty in subjects with hypothalamic disorders. Due to their ability to stimulate the natural production of testosterone, some peptides may also be used as part of a post-cycle therapy (PCT) protocol.

Here are some of the most notable benefits of peptides for testosterone:

• One trial in healthy men reported that kisspeptin-10 (hypothalamic neuropeptide and regulator of GnRH secretion) was able to increase mean serum testosterone levels from 479ng/dl to 692ng/dl after less than 23 hours of infusion [5].
• Gonadorelin has been successfully used to increase testosterone levels (up to 1560 ng/dl in one trial), stimulate pubertal development, and restore fertility in men with tertiary hypogonadism (low T caused by GnRH deficiency) [6, 21, 22].

Now that we have provided a high-level comparison of peptides for testosterone to TRT, let’s take a closer look into how peptides might work to increase testosterone levels.

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Best Peptides to Increase Testosterone Levels | A-Z Guide

Below we’ll delve deeper into peptides for testosterone, and discuss their structures, mechanisms of action, benefits, and research potential.

Peptides For Testosterone

These are the best peptides to increase testosterone levels in test subjects with low T, such as in cases of suppressed natural testosterone production due to TRT:

• Kisspeptin-10

 Kisspeptin-10 (metastin (45-54) or KP 45-54) is one of several kisspeptin peptides that originate from the KISS1 gene found in hypothalamic cells. Kisspeptins are critical regulators of reproduction, operating via the G protein-coupled receptor, GPR54 [23, 24, 25].

Kisspeptin-10 transmits controls the rhythmic release of GnRH, prompting an increase in the production of LH and FSH, which are synthesized by the pituitary gland and stimulate the production of testosterone in the testes, leading to enhanced fertility and a boost in T levels [24, 26].

The peptide appears to achieve LH and FSH increase without crossing the blood-brain barrier (BBB). Instead, studies suggest that peripherally administered kisspeptin-10 may interact with GnRH neuron dendritic terminals outside the BBB [27, 28].

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• Gonadorelin

Gonadorelin is a lab-made bioidentical version of GnRH. It has the exact same structure and function as native GnRH. When administered, gonadorelin passes the BBB and acts on the pituitary gland to stimulate the release of LH and FSH [29].

Gonadorelin is therapeutically used in medical practice to trigger ovulation in females suffering from dysregulated menstrual cycles as a consequence of hypothalamic problems, or as a diagnostic tool to assess HPG axis function [30].

Studies also indicate that gonadorelin can increase HPG activity in males afflicted with hypothalamic dysfunction and a lack of sufficient GnRH [6]. Gonadorelin has been found to efficiently elevate testosterone levels and enhance fertility in men with normal testicular and pituitary gland function [21, 22].

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• Testagen

This is a small synthetic peptide discovered by the esteemed Russian gerontologist and scholar Vladimir Khavinson [31].

Also known as KEDG, Testagen is a short signaling peptide and a bioregulator that is thought to affect the synthesis of testosterone and thyroid-stimulating hormone (TSH). It may enhance testosterone production in subjects with low T due to chronic abacterial prostatitis.

Indeed, one study revealed that Testagen led to the enhancement of uroflowmetry indicators, reduction in prostatic inflammation, and a noticeable elevation in the total levels of testosterone present in the serum of the subjects under examination [7].

The peptide may also upregulate thyroid function by stimulating the production of TSH in the pituitary gland. This results in elevated synthesis of T3 and T4 in the thyroid gland. Increasing thyroid hormone levels may also prove beneficial for T levels [32].

Regardless of the impressive potential of the aforementioned peptides for improving testosterone levels, researchers should note that TRT is still, far and away, the gold standard for treating low T in hypogonadal males.

TRT is the most reliable form of therapy for achieving physiological or supraphysiological serum T levels, depending on the research objective.

Click here to learn more about doctor-prescribed TRT!

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Peptides For Weight Loss

Being overweight can have a negative effect on testosterone production and especially total testosterone levels, due to the increased risk of T aromatization.

An enzyme in adipose tissue called aromatase can transform androgens such as testosterone into estrogens. The increased estrogen levels can act on the pituitary gland and trigger a negative-feedback loop suppressing the HPG axis and reducing T levels [13].

The following weight loss peptides can help shed excess body fat and therefore reduce the conversion of T into estrogens:

• Tirzepatide

This is the first FDA-approved GIP/GLP-1 agonist for human use. It is indicated for glycemic control in type 2 diabetes (T2D) and is now investigated in phase-3 trials for its weight loss benefits.

Compared to most other incretin mimetics, the peptide has enhanced pharmacokinetics which allows for once-weekly dosing. Tirzepatide has been shown to lead to over 20% weight loss from baseline within 72 weeks of therapy at doses of up to 15mg/weekly [10].

Studies also suggest that a large percentage of that weight loss is indeed fat loss. One trial reported that tirzepatide led to significant reductions in body weight, lean body mass, and body fat mass. Yet, the decline in lean body mass was mainly attributed to decreased body water. Percentage-wise, the test subjects experienced a decrease in body fat percentage by approximately 5%, accompanied by increases in body water, protein, and minerals [33].

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• Semaglutide

This is a GLP-1 agonist that has received FDA-approval for indications including weight reduction in nondiabetics and glycemic control in T2D [34, 35]. Clinical trials highlight that this peptide can cause up to 17.4% weight loss in 68 weeks in nondiabetics [35].

Studies into semaglutide's impact on body composition have shown its efficacy in reducing body fat. One phase-3 trial reported data from DEXA scans on a 140-subject subgroup receiving semaglutide 2.4mg/weekly. After the study, lean mass increased by 3.8% while body fat declined by 3.0%. Conversely, the placebo group only achieved a 3.6% weight reduction, primarily from a greater loss of lean mass [36, 37].

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Peptides for Hormonal Balance

Peptides may also help upregulate testosterone synthesis by improving the levels of other regulatory hormones in the body, such as growth hormone (GH). Here is one notable example:

• Sermorelin

This peptide is an analog of growth hormone-releasing hormone (GHRH) that comprise the first 29 amino acids of native GHRH.

Used both diagnostically and therapeutically for GH deficiency, sermorelin has proven its worth. One study assessed the short-term effects of 1mg sermorelin versus GHRH injections on various hormone levels in children with pulsatile GH secretion. The researchers found that apart from increasing GH and IGF-1, sermorelin uniquely prompted both FSH and LH release [38].

In alignment with this finding, a subsequent study involving GH-deficient rats showed an increase in testosterone secretion with sermorelin treatment. However, these results are yet to be corroborated by clinical trials [39].

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Peptides For Testosterone | Side Effects and Safety

Peptides for testosterone do not have the same side effects and risks as testosterone therapy. This is because peptides do not suppress natural testosterone production and testicular function.

On the other hand, each compound may have other adverse reactions depending on its specific structure and mechanisms of action. Here are the most common adverse effects observed with the aforementioned peptides for testosterone:

• Gonadorelin and Kisspeptin-10

Research involving kisspeptin-10 and gonadorelin does not disclose any unfavorable events tied to their use, except for a heightened risk of allergic responses noted with gonadorelin.

Additionally, gonadorelin could potentially cause side effects associated with elevated testosterone levels, such as facial acne and breast tissue tenderness. These effects are particularly noted when it's administered to initiate puberty in males [5, 6].

• Tirzepatide and Semaglutide

Incretin mimetics including tirzepatide and semaglutide frequently trigger gastrointestinal complications, consistent with their drug class. These side effects typically present in 40-70% of trial participants, with nausea and diarrhea being the most common [40].

On rare occasions, affecting fewer than 2% of subjects, both peptides may also cause minor to moderate hepatobiliary conditions, such as gallstones and acute pancreatitis. However, these complaints are usually self-limiting.

Both peptides are also contraindicated in subjects with a history of thyroid cancer based on increased risk observed in rat studies, although such concerns have not been confirmed in human trials [40].

• Sermorelin

The majority of studies do not report any side effects related to sermorelin use. A major advantage of sermorelin is that it does not cause side effects typical for GH therapy, such as increased insulin resistance, due to the fact that it cannot lead to a supraphysiological increase in serum GH or IGF-1 levels [41]. One study has reported an increased risk of edema and joint pain, which were transient and dose-dependent [42].

Researchers should note that the aforementioned peptides are usually applied via subcutaneous injections, so injection site reactions are possible. These tend to be mild and self-limiting, including redness, bleeding, pain, swelling, and inflammation at the injection site.

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Testosterone Peptides | FAQ

Researchers interested in investigating the effects and safety of testosterone peptides may refer to this list of frequently asked questions on the topic.

Can peptides help with testosterone?

Yes, peptides like kisspeptin-10 and gonadorelin have been tested and shown effective for increasing testosterone levels in both healthy men and men suffering from tertiary hypogonadism.

Which peptides can increase testosterone?

Peptides such as kisspeptin-10 and gonadorelin can increase testosterone levels by stimulating the production of LH and FSH in the pituitary gland. Both peptides have been shown to boost natural T production and have a favorable effect on fertility. In addition, weight loss peptides like tirzepatide and semaglutide may help improve total testosterone levels in overweight men.

What is the best peptide to add to TRT?

Peptides like kisspeptin-10 and gonadorelin are potential adjuncts to TRT to prevent the suppressing effect of exogenous testosterone on natural T synthesis, as both work by stimulating the function of the HPG axis. They may also be used as PCT for those needing to come off testosterone replacement therapy.

Should I take TRT or peptides?

Peptides may increase testosterone levels in healthy men and those suffering from tertiary hypogonadism. In addition, weight loss peptides may help improve hormonal balance and increase testosterone in overweight men. But TRT is the only reliable way to increase testosterone levels in men with low T and related symptoms due to primary hypogonadism. TRT can also reliably achieve supraphysiological serum T levels, should this be the objective of a research study.

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Peptides and Testosterone | Verdict

Peptides for testosterone work in a variety of ways to boost levels of sex hormones in males.

Compounds such as kisspeptin-10 and gonadorelin directly stimulate the HPG axis and upregulate testosterone production in the testes. Incretin mimetics tirzepatide, and semaglutide can induce substantial fat loss and thus indirectly improve testosterone levels in overweight men.

The effectiveness of peptides for testosterone is limited compared to testosterone replacement therapy. But peptides may be associated with fewer side effects compared to exogenous testosterone, or may even be used alongside it to prevent TRT side effects in research settings.

For researcher looking to investigate peptides for testosterone levels and hormone optimization in men, we recommend choosing our top-rated vendor.

For non-researcher looking for more information about doctor-prescribed testosterone replacement therapy, visit our friends at FountainTRT.

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