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Peptides for Testosterone Support

Testosterone levels in men decline roughly 1--2% per year after age 30. By 45, an estimated 40% of men have levels below the lower end of normal ranges.

Testosterone levels in men decline roughly 1--2% per year after age 30. By 45, an estimated 40% of men have levels below the lower end of normal ranges. The symptoms --- low energy, reduced muscle mass, increased body fat, weaker libido, brain fog, poor sleep --- overlap so much with general aging that many men don't realize testosterone is the problem.

Testosterone replacement therapy (TRT) works. It directly raises testosterone levels and relieves symptoms, often within weeks. But it comes with a trade-off: exogenous testosterone suppresses your body's own production, which means suppressed LH and FSH, shrunken testes, and reduced or eliminated sperm production.

That's where peptides enter the picture. Rather than replacing testosterone from the outside, certain peptides stimulate your body to make more of it. Others address the downstream effects of low T --- poor body composition, low growth hormone, sluggish metabolism --- through different pathways.

This guide covers each peptide with real research behind it, what the evidence actually shows, and where the gaps are.

Table of Contents

How Testosterone Production Works {#how-testosterone-production-works}

Before diving into specific peptides, you need to understand the system they act on: the hypothalamic-pituitary-gonadal (HPG) axis.

  1. Hypothalamus releases GnRH (gonadotropin-releasing hormone) in pulses
  2. Pituitary gland responds by releasing LH (luteinizing hormone) and FSH (follicle-stimulating hormone)
  3. Testes respond to LH by producing testosterone in Leydig cells, and to FSH by supporting sperm production in Sertoli cells
  4. Feedback loop --- testosterone signals back to the hypothalamus and pituitary to slow down production when levels are sufficient

When you take exogenous testosterone (TRT), the feedback loop detects high levels and shuts down steps 1--3. Your body stops making its own testosterone and stops producing sperm. In healthy men selected for TRT, intratesticular testosterone dropped by 94% [1].

Most peptides for testosterone support work by intervening at steps 1 or 2 --- stimulating the natural cascade rather than bypassing it.

Peptides That Directly Stimulate Testosterone Production {#peptides-that-directly-stimulate-testosterone-production}

Kisspeptin: The Master Switch {#kisspeptin-the-master-switch}

Kisspeptin sits at the very top of the HPG axis. It's released by specialized neurons in the hypothalamus and tells GnRH neurons to fire. Without kisspeptin signaling, reproductive hormone production doesn't happen --- mutations in the kisspeptin receptor cause complete hypogonadotropic hypogonadism [2].

Clinical evidence:

The human data for kisspeptin is among the strongest for any peptide targeting testosterone production.

In a 2011 study published in the Journal of Clinical Endocrinology & Metabolism, intravenous kisspeptin-10 produced a rapid, dose-dependent rise in LH in healthy men. A continuous 22.5-hour infusion increased testosterone from 16.6 to 24.0 nmol/L (a roughly 45% increase) while boosting both LH pulse frequency and pulse size [3].

A follow-up study in men with type 2 diabetes and mild biochemical hypogonadism --- a common real-world scenario --- showed that kisspeptin-10 increased LH pulse frequency and testosterone in these patients as well. Mean LH rose from 4.7 to 10.7 IU/L after a single bolus [4].

A 2023 JAMA Network Open randomized clinical trial found that kisspeptin-54 improved sexual brain processing and penile tumescence in men with hypoactive sexual desire disorder, showing effects beyond just hormone numbers [5].

The practical problem: Native kisspeptin has a very short half-life --- about 4 minutes for kisspeptin-10 and 28 minutes for kisspeptin-54 in humans. This limits clinical use to research settings with intravenous infusions. Longer-acting analogs like MVT-602 (TAK-448) show a prolonged duration of action (21--22 hours vs. 4.7 hours), but these are still in development and not commercially available [6].

What this means for you: Kisspeptin proves the concept that stimulating the top of the HPG axis can meaningfully raise testosterone in men. But until longer-acting formulations reach the market, it's not a practical daily therapy.

Gonadorelin: The GnRH Mimic {#gonadorelin-the-gnrh-mimic}

Gonadorelin is a synthetic version of GnRH --- the hormone that kisspeptin triggers. It works one step downstream, directly stimulating the pituitary gland to release LH and FSH.

Gonadorelin became widely prescribed after the FDA reclassified HCG as a biologic in 2020, restricting compounding pharmacy production [7]. Many clinics switched patients from HCG to gonadorelin.

What the research shows:

Gonadorelin's effectiveness depends on how it's administered. Pulsatile dosing stimulates hormone production. Continuous dosing paradoxically shuts down LH and FSH --- this is how GnRH agonists suppress testosterone in prostate cancer treatment.

In men with congenital hypogonadotropic hypogonadism, pulsatile gonadorelin pump therapy achieved spermatogenesis in 90% of patients (median 6 months), compared to 83.3% with gonadotropin therapy (median 14 months) [8].

The honest assessment:

Most clinics prescribe gonadorelin via subcutaneous injection once or twice daily --- not in true physiological pulses. Whether this adequately mimics pulsatile release is debated. Gonadorelin's half-life is only 2--20 minutes, compared to HCG's 36 hours.

Clinical experience suggests gonadorelin can maintain testicular size and some LH/FSH production alongside TRT. But it likely doesn't preserve intratesticular testosterone or fertility as reliably as HCG [7]. Men who prioritize fertility preservation should discuss HCG alternatives or enclomiphene with their provider.

Enclomiphene: The SERM Alternative {#enclomiphene-the-serm-alternative}

Enclomiphene isn't technically a peptide --- it's a selective estrogen receptor modulator (SERM). But it appears in nearly every conversation about peptides for testosterone, and its mechanism is relevant enough to include here.

Enclomiphene blocks estrogen receptors in the hypothalamus. The brain interprets this as low estrogen and responds by increasing GnRH, LH, and FSH --- which drives up testosterone production. Unlike TRT, this preserves (and often increases) sperm production.

Clinical evidence:

A 2025 systematic review and meta-analysis of 10 randomized controlled trials (819 patients) published in the Archives of Endocrinology and Metabolism found [9]:

  • Clomiphene/enclomiphene increased total testosterone by 273.76 ng/dL compared to placebo
  • LH improved by 4.66 IU/L and FSH by 4.59 IU/L compared to placebo
  • Testosterone levels were comparable to those achieved with testosterone gel
  • Sperm counts were preserved --- the opposite of what happens with TRT

In a head-to-head trial, 44 hypogonadal men (testosterone below 350 ng/dL) received either enclomiphene 25 mg daily or transdermal testosterone. After six weeks, average testosterone was 604 ng/dL in the enclomiphene group and 500 ng/dL in the testosterone group --- but only the enclomiphene group maintained elevated LH, FSH, and sperm counts [10].

Enclomiphene also causes fewer estrogenic side effects than standard clomiphene (Clomid), with one study reporting an 80% reduction in adverse effects [10].

The catch: Enclomiphene is not FDA-approved. The FDA declined approval in 2007, and the developer discontinued the program in 2021. It's used off-label through specialty pharmacies.

Growth Hormone Peptides and Their Indirect Effects on Testosterone {#growth-hormone-peptides-and-their-indirect-effects-on-testosterone}

Growth hormone doesn't directly raise testosterone. But the relationship between the two is real and clinically meaningful. Higher GH and IGF-1 levels support Leydig cell steroidogenesis (the process by which Leydig cells make testosterone), improve body composition (less fat means less aromatization of testosterone to estrogen), and improve insulin sensitivity (insulin resistance is a driver of secondary hypogonadism) [11].

CJC-1295 and Ipamorelin: The GH Secretagogue Duo {#cjc-1295-and-ipamorelin-the-gh-secretagogue-duo}

CJC-1295 is a long-acting GHRH analog. Ipamorelin is a growth hormone-releasing peptide (ghrelin mimetic). They're frequently paired because they work through complementary mechanisms --- CJC-1295 provides a sustained background signal while ipamorelin triggers sharp GH pulses.

Clinical evidence for CJC-1295:

In the key Teichman et al. (2006) trial, a single CJC-1295 injection in healthy adults produced dose-dependent GH increases of 2- to 10-fold lasting 6+ days, with IGF-1 rising 1.5- to 3-fold for 9--11 days. Multiple doses showed cumulative effects [12].

Effects on testosterone:

CJC-1295 does not directly increase testosterone. Any impact is indirect: improved body composition (less fat = less aromatase converting testosterone to estrogen), IGF-1's support of Leydig cell function [11], and better insulin sensitivity. Ipamorelin specifically triggers GH release without raising cortisol or prolactin --- a cleaner profile than older secretagogues [11].

Think of CJC-1295/ipamorelin as metabolic support that creates a better environment for testosterone production, not a direct testosterone booster.

Tesamorelin: FDA-Approved Visceral Fat Fighter {#tesamorelin-fda-approved-visceral-fat-fighter}

Tesamorelin is a synthetic GHRH analog with the strongest clinical pedigree among growth hormone peptides. It's FDA-approved for reducing excess visceral abdominal fat in HIV-associated lipodystrophy.

In the landmark 2007 NEJM trial of 412 patients (86% men), tesamorelin 2 mg daily reduced visceral fat by 27.8 cm squared in 26 weeks while the placebo group gained 5.1 cm squared. Muscle quality also improved across all truncal muscle groups [13].

The trial stratified for concurrent testosterone use and found no significant interaction --- tesamorelin works just as well whether or not you're on TRT [13]. The combination is increasingly used in clinical practice for synergistic body composition improvements.

Sermorelin: The Original GHRH Analog {#sermorelin-the-original-ghrh-analog}

Sermorelin was one of the first GHRH analogs studied in humans. It's the first 29 amino acids of native GHRH --- the minimum sequence needed for full biological activity.

Its advantage over direct GH injections: sermorelin stimulates pulsatile GH release regulated by somatostatin feedback, making GH overdose essentially impossible. It also preserves the GH neuroendocrine axis --- the feedback system that exogenous GH can suppress [14].

Sermorelin may be particularly useful for men whose low T is partly driven by age-related GH decline. The body composition improvements (more lean mass, less fat) create a better hormonal baseline. And for men on TRT, adding a GH secretagogue can address the metabolic side of things that testosterone alone may not fully correct.

Supporting Peptides for Men With Low T {#supporting-peptides-for-men-with-low-t}

BPC-157: The Gut-Testosterone Connection {#bpc-157-the-gut-testosterone-connection}

BPC-157 doesn't touch the HPG axis directly. So why does it show up in testosterone optimization protocols?

Because gut health affects testosterone more than most men realize. Chronic gut inflammation increases systemic inflammatory markers, which suppress GnRH pulsatility. Poor gut barrier integrity (so-called "leaky gut") allows endotoxins into the bloodstream, driving inflammatory cascades that further suppress the HPG axis [15].

BPC-157, a gastric pentadecapeptide, has shown strong gut-healing properties in animal studies: protection against gut lesions, accelerated intestinal and stomach healing, reduced inflammatory cytokines, and strengthened mucosal barrier function [15]. It also modulates the brain-gut axis, with preclinical evidence of anxiolytic and antidepressant effects [15].

The limitation: No human clinical trials for testosterone support. The gut-inflammation-testosterone connection is well-established, and BPC-157's gut-healing properties are documented in animal models. But the leap from "heals gut in rats" to "raises testosterone in men" hasn't been validated in controlled human studies.

For men who have gastrointestinal issues alongside low T, the theoretical rationale is reasonable. For healthy-gut men, the connection becomes much weaker.

MOTS-c: Metabolic Reset {#mots-c-metabolic-reset}

MOTS-c is a mitochondrial-derived peptide that activates AMPK --- the master metabolic switch. It promotes glucose uptake, fatty acid oxidation, and conversion of white fat to brown fat [16].

Why it matters for testosterone: metabolic syndrome and insulin resistance are major drivers of secondary hypogonadism. Men with type 2 diabetes have significantly lower testosterone than age-matched controls. Anything that improves metabolic health may indirectly support testosterone production.

Animal studies show that MOTS-c improves physical performance, reverses insulin resistance from high-fat diets, and declines with age in circulation [16, 17]. Circulating MOTS-c levels are lower in type 2 diabetes patients compared with healthy controls [16].

The limitation: Same as BPC-157 --- no human trials for testosterone support. The metabolic benefits are established in animal models but the testosterone connection is theoretical.

Peptides vs. TRT: Head-to-Head Comparison {#peptides-vs-trt-head-to-head-comparison}

FactorPeptide TherapyTRT
MechanismStimulates your body's own testosterone productionDirectly replaces testosterone from outside
Testosterone increaseModerate (200--400 ng/dL typical)Large (can normalize to 600--1000+ ng/dL)
Onset4--12 weeks for noticeable effects1--6 weeks
FertilityPreserved or improved (LH/FSH maintained)Suppressed (azoospermia common)
Testicular sizeMaintainedAtrophy without HCG/gonadorelin
Severity rangeBest for mild-to-moderate hypogonadismEffective across all severity levels
Natural productionMaintained or restoredSuppressed (may not recover)
CostOften higher (especially compounded peptides)More standardized pricing
AdministrationVaries (oral, injection, or both)Injection, gel, patch, or pellet
MonitoringLabs needed (testosterone, LH, FSH, IGF-1)Labs needed (testosterone, hematocrit, PSA, E2)

Peptide Comparison Table {#peptide-comparison-table}

PeptideTestosterone EffectMechanismEvidence LevelFDA Status
KisspeptinDirect stimulationTriggers GnRH release from hypothalamusStrong (RCTs in men)Not approved
GonadorelinDirect stimulationMimics GnRH at pituitaryModerate (clinical use, limited RCTs for TRT)Approved (diagnostic)
EnclomipheneDirect stimulationBlocks estrogen feedback at hypothalamusStrong (meta-analysis, RCTs)Not approved
CJC-1295 + IpamorelinIndirect (body composition)Increases GH/IGF-1Moderate (GH data strong; T link indirect)Not approved
TesamorelinIndirect (visceral fat reduction)Stimulates endogenous GHStrong (NEJM RCT)FDA-approved (HIV)
SermorelinIndirect (body composition)Stimulates pulsatile GHModerate (GH deficiency data)Previously approved (diagnostic)
BPC-157Indirect (gut health/inflammation)Gut healing, reduces systemic inflammationPreclinical (animal studies)Not approved
MOTS-cIndirect (metabolic health)AMPK activation, metabolic regulationPreclinical (animal studies)Not approved

Who Benefits Most From Peptides vs. TRT {#who-benefits-most-from-peptides-vs-trt}

Peptides may be the better first choice if you:

  • Have mild-to-moderate low T (250--450 ng/dL) with symptoms
  • Want to preserve fertility
  • Have secondary hypogonadism (often linked to obesity, metabolic syndrome, or diabetes)
  • Prefer stimulating your own production before committing to lifelong replacement

TRT makes more sense if you:

  • Have severe or primary hypogonadism (consistently below 200 ng/dL, or testicular failure)
  • Need rapid symptom relief
  • Have tried peptides or SERMs without adequate response

Some men use both --- TRT with gonadorelin for testicular maintenance plus a GH secretagogue for body composition. For guidance on combining peptides, see our peptide stacking guide and best peptides for men over 40.

Stacking Peptides for Testosterone Support {#stacking-peptides-for-testosterone-support}

Common peptide combinations used in clinical practice:

Fertility-Preserving Protocol: Enclomiphene (oral, daily) for HPG axis stimulation + CJC-1295/Ipamorelin (injection, nightly) for body composition support.

TRT Adjunct Protocol: Testosterone (injection, 2x weekly) + gonadorelin (injection, 2--3x weekly) for testicular maintenance + tesamorelin (daily) for visceral fat.

Metabolic Optimization (Pre-TRT): GH secretagogue (sermorelin or CJC-1295/ipamorelin) for body composition + lifestyle optimization (resistance training, sleep, stress management).

These are examples from clinical practice, not prescriptions. Individual protocols should be designed and monitored by a qualified provider.

For more on sexual health, see best peptides for sexual health. For broader hormonal support including fertility, the options overlap significantly.

Safety and Monitoring {#safety-and-monitoring}

Baseline labs: Total and free testosterone, LH, FSH, estradiol, SHBG, prolactin, thyroid panel, metabolic panel, CBC, PSA (if over 40), IGF-1 (if using GH peptides).

Ongoing monitoring (every 3--6 months): Testosterone, LH, FSH, estradiol, IGF-1 (for GH peptides), hematocrit, and metabolic markers.

Known risks by category:

  • GnRH analogs (gonadorelin): Headache, injection site reactions. Continuous use can paradoxically suppress hormones
  • GH secretagogues: Water retention, joint stiffness, blood sugar changes
  • SERMs (enclomiphene): Visual disturbances (rare), mood changes
  • Kisspeptin: Well-tolerated in trials but limited long-term data
  • BPC-157, MOTS-c: Insufficient human safety data

FAQ {#faq}

Can peptides raise testosterone as much as TRT? Generally no. Peptides that stimulate the HPG axis (kisspeptin, gonadorelin, enclomiphene) typically raise testosterone by 200--400 ng/dL. TRT can bring levels to whatever target your doctor sets. The advantage of peptides is preserving your natural production and fertility --- not necessarily reaching the highest possible number.

Will peptides help if I have primary hypogonadism? Probably not. Primary hypogonadism means your testes can't produce adequate testosterone even when stimulated. Peptides work by sending stronger signals to the testes --- if the testes can't respond, the signals don't help. TRT is the standard treatment for primary hypogonadism.

Can I use peptides to come off TRT? Some men use enclomiphene, kisspeptin, or gonadorelin as part of a post-TRT recovery protocol. The goal is to restart the HPG axis. Success depends on how long you were on TRT, your age, and whether your hypothalamus and pituitary can still respond to stimulation. This should always be done under medical supervision.

How do peptides for testosterone differ from MK-677? MK-677 (ibutamoren) is an oral growth hormone secretagogue. It increases GH and IGF-1 but does not directly stimulate testosterone production. Like other GH secretagogues, any testosterone benefit is indirect --- through improved body composition and metabolic health.

What about PT-141 for low libido from low T? PT-141 (bremelanotide) works on melanocortin receptors in the brain to improve sexual desire. It doesn't raise testosterone but can complement testosterone-supporting peptides if libido is a primary concern.

How long do peptides take to show results for low T? Enclomiphene can raise testosterone within 2--4 weeks. Gonadorelin may show LH/FSH changes within days. GH secretagogues need 3--6 months for body composition changes.

The Bottom Line {#the-bottom-line}

The peptide approach to testosterone support is built on a different philosophy than TRT: work with your body's existing machinery rather than bypass it.

The science behind it is real. Kisspeptin raises testosterone in clinical trials. Enclomiphene matches testosterone gel in head-to-head studies while preserving fertility. GH secretagogues like CJC-1295 and tesamorelin improve body composition in ways that support healthier testosterone levels.

But the approach has clear limitations. If your testes can't respond to stimulation, peptides won't help. If you need rapid, significant testosterone elevation, TRT delivers faster and more reliably. And many of the supporting peptides (BPC-157, MOTS-c) are still in the preclinical stage --- promising animal data without confirmed human benefits for testosterone.

The practical path for most men: get comprehensive bloodwork done first. Understand why your testosterone is low --- primary vs. secondary hypogonadism, metabolic contributors, lifestyle factors. If the cause is secondary and the deficit is mild-to-moderate, peptides offer a legitimate option that preserves your natural production. If the cause is primary or the deficit is severe, TRT remains the more reliable choice.

Whatever route you take, work with a provider who monitors labs, adjusts doses, and understands that testosterone optimization is a process, not a prescription.

References {#references}

  1. Coviello AD, et al. Effects of graded doses of testosterone on erythropoiesis in healthy young and older men. J Clin Endocrinol Metab. 2008. Intratesticular testosterone data referenced via: https://pmc.ncbi.nlm.nih.gov/articles/PMC6087849/

  2. de Roux N, et al. Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54. Proc Natl Acad Sci. 2003. Referenced via: PMC12112093

  3. George JT, et al. Kisspeptin-10 Is a Potent Stimulator of LH and Increases Pulse Frequency in Men. J Clin Endocrinol Metab. 2011;96(8):E1228-36. PMC3380939

  4. George JT, et al. Exploring the pathophysiology of hypogonadism in men with type 2 diabetes: kisspeptin-10 stimulates serum testosterone and LH secretion. Clin Endocrinol. 2013. PMID: 23153270

  5. Mills EG, et al. Effects of Kisspeptin on Sexual Brain Processing and Penile Tumescence in Men With Hypoactive Sexual Desire Disorder. JAMA Netw Open. 2023. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2800937

  6. Kisspeptins Regulating Fertility: Potential Future Therapeutic Approach in Infertility Treatment. PMC. PMC12112093

  7. Gonadorelin vs. HCG for Men on TRT. Referenced via clinical review: https://pmc.ncbi.nlm.nih.gov/articles/PMC6087849/

  8. Mao JF, et al. The Pulsatile Gonadorelin Pump Induces Earlier Spermatogenesis Than Cyclical Gonadotropin Therapy in Congenital Hypogonadotropic Hypogonadism Men. Front Endocrinol. 2019. PMC6775549

  9. Clomiphene and enclomiphene show comparable efficacy to testosterone in functional hypogonadism. Archives of Endocrinology and Metabolism. 2025. Meta-analysis: PMC12510335

  10. Wiehle RD, et al. Enclomiphene citrate stimulates testosterone production while preventing oligospermia: a randomized phase II clinical trial comparing topical testosterone. Fertil Steril. 2014. https://www.fertstert.org/article/S0015-0282(14)00537-8/abstract

  11. Papadopoulos V, et al. Peptide Targeting of Mitochondria Elicits Testosterone Formation. Mol Ther. 2015. PMC4428411

  12. Teichman SL, et al. Prolonged stimulation of growth hormone and insulin-like growth factor I secretion by CJC-1295, a long-acting analog of GH-releasing hormone, in healthy adults. J Clin Endocrinol Metab. 2006. PMID: 16352683

  13. Falutz J, et al. Metabolic Effects of a Growth Hormone-Releasing Factor in Patients with HIV. N Engl J Med. 2007;357:2359-70. https://www.nejm.org/doi/full/10.1056/NEJMoa072375

  14. Walker RF. Sermorelin: A better approach to management of adult-onset growth hormone insufficiency? Clin Interv Aging. 2006. PMC2699646

  15. Sikiric P, et al. Brain-gut Axis and Pentadecapeptide BPC 157: Theoretical and Practical Implications. Curr Neuropharmacol. 2017. PMC5333585

  16. Lu H, et al. Mitochondria-derived peptide MOTS-c: effects and mechanisms related to stress, metabolism and aging. J Transl Med. 2023. PMC9854231

  17. Reynolds JC, et al. MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. Nat Commun. 2021. https://www.nature.com/articles/s41467-020-20790-0