Why should sermorelin be injected at bedtime?

Sermorelin is typically injected 30–60 minutes before bedtime because the body's largest natural growth hormone pulse occurs during the first few hours of deep sleep (Stage 3/4 NREM sleep). By injecting sermorelin before sleep, the exogenous GHRH stimulus combines with the endogenous nocturnal GH surge to produce a more robust pituitary response. Injecting in a fasted state is also important because insulin and elevated blood glucose suppress GH release.

How long does it take for sermorelin to work?

Subjective effects such as improved sleep quality and increased energy are commonly reported within 2–4 weeks of starting sermorelin. Measurable changes in serum IGF-1 levels are typically detected within 4–6 weeks. Body composition changes (reduced body fat, improved lean mass) are generally discussed as becoming noticeable after 3–6 months of consistent use. Full benefits are often described as continuing to develop over a 6–12 month period.

What is the difference between sermorelin and HGH?

Sermorelin stimulates the pituitary gland to produce and release its own growth hormone, while HGH (recombinant human growth hormone) directly provides exogenous GH. Sermorelin preserves the natural pulsatile GH release pattern and the hypothalamic-pituitary feedback loop, whereas exogenous HGH bypasses the pituitary entirely and can suppress natural GH production. Sermorelin is generally considered to carry a lower risk of side effects related to supraphysiological GH levels because the pituitary retains regulatory control.

Do you need to cycle sermorelin?

Cycling sermorelin is a commonly discussed but not universally agreed-upon practice. The 5-days-on/2-days-off protocol is the most popular cycling approach, with the rationale of preventing pituitary GHRH receptor desensitization. Some practitioners prescribe continuous daily use for 3–6 months followed by a break. There are no controlled clinical trials directly comparing cycled versus continuous sermorelin use, so recommendations are based on theoretical considerations and clinical experience.

Can sermorelin be combined with ipamorelin?

Yes, the sermorelin-ipamorelin combination is one of the most frequently discussed growth hormone secretagogue stacks. The proposed rationale is that sermorelin stimulates the GHRH receptor while ipamorelin stimulates the ghrelin/GHS receptor, and these two pathways have a synergistic effect on pituitary GH release when activated simultaneously. A typical combination protocol involves 200–300 mcg of each peptide administered together at bedtime.

Is sermorelin FDA approved?

Sermorelin was FDA approved in 1997 under the brand name Geref for the diagnostic evaluation of pituitary growth hormone secretion capacity in children. The branded product was subsequently discontinued by the manufacturer (not for safety reasons). Sermorelin continues to be available through 503A and 503B compounding pharmacies and is commonly prescribed off-label for age-related growth hormone decline in adults, though this use is not FDA approved.

Sermorelin Dosage Guide: Protocol & Timing

Overview

Sermorelin (sermorelin acetate, GRF 1-29 NH2) is a synthetic analog of growth hormone-releasing hormone (GHRH) consisting of the first 29 amino acids of the naturally occurring 44-amino-acid GHRH molecule. It was FDA approved in 1997 under the brand name Geref for the diagnosis of growth hormone deficiency in children, though it has since been discontinued as a branded product. Sermorelin stimulates the anterior pituitary gland to produce and release growth hormone through a physiological feedback mechanism, which is discussed in the literature as maintaining the pulsatile pattern of GH secretion and preserving the negative feedback loop — distinguishing it from exogenous GH administration. Bedtime dosing is the standard protocol because it synergizes with the natural nocturnal GH surge that occurs during deep sleep. Sermorelin remains widely available through compounding pharmacies and is one of the most commonly prescribed growth hormone secretagogues in age-management and regenerative medicine clinics.

Dosing Protocols

Standard Dose — Bedtime Protocol

Route: Subcutaneous injection (abdominal area)

Dose: 200–300 mcg

Frequency: Once daily, administered 30–60 minutes before bedtime on an empty stomach

Duration: 3–6 months initial course; ongoing use discussed in clinical practice

This is the most widely discussed sermorelin protocol. Bedtime administration is preferred because it coincides with the natural nocturnal growth hormone pulse during Stage 3 and Stage 4 sleep. Injecting on an empty stomach (at least 2 hours after eating) is recommended because insulin and blood glucose elevations may blunt GH release. Effects on sleep quality are often reported within the first 2–4 weeks, while body composition changes are typically discussed as becoming apparent after 3–6 months.

Higher Dose Protocol

Route: Subcutaneous injection (abdominal area)

Dose: 500 mcg

Frequency: Once daily at bedtime on an empty stomach

Duration: 3–6 months

A 500 mcg dose is discussed by some practitioners for individuals who do not achieve satisfactory IGF-1 elevation on the standard 200–300 mcg dose. This higher dose has been used in some clinical studies evaluating sermorelin for age-related GH decline. Response should be monitored through serum IGF-1 levels drawn 4–6 weeks after starting therapy.

5 Days On / 2 Days Off Cycling

Route: Subcutaneous injection

Dose: 200–500 mcg (per the chosen dose from the protocols above)

Frequency: Once daily at bedtime, 5 consecutive days per week with 2 days off (e.g., weekdays on, weekends off)

Duration: 3–6 months or longer

The 5-on/2-off schedule is one of the most commonly discussed cycling approaches for sermorelin. The rationale is to prevent pituitary desensitization to chronic GHRH stimulation, maintaining receptor sensitivity. This cycling pattern is also applied to other GHRH analogs and growth hormone secretagogues. Some practitioners prefer continuous daily dosing, and the superiority of either approach has not been established in controlled trials.

Twice-Daily Protocol (Less Common)

Route: Subcutaneous injection

Dose: 100–200 mcg per injection

Frequency: Twice daily — morning (fasting) and bedtime (fasting)

Duration: 3–6 months

A split-dose approach is occasionally discussed, with the rationale of stimulating multiple GH pulses throughout the day. The morning dose should be administered in a fasted state (before breakfast). This protocol is less commonly used than the single bedtime injection but is mentioned in some anti-aging medicine literature.

Reconstitution & Storage

Vial sizes	6 mg (6,000 mcg) and 9 mg (9,000 mcg) lyophilized vials are the most common; 3 mg and 15 mg vials also available
Recommended water volume	Reconstitute with bacteriostatic water (BAC water). For a 6 mg vial, adding 2 mL BAC water yields 3,000 mcg/mL (3 mg/mL) — draw 0.1 mL for a 300 mcg dose. For a 9 mg vial with 3 mL BAC water, concentration is also 3 mg/mL.
Storage	Refrigerate reconstituted sermorelin at 36–46 °F (2–8 °C). Protect from light. Do not freeze.
Stability once reconstituted	Reconstituted sermorelin is generally considered stable for 28–30 days when properly refrigerated. Some compounding pharmacy labels indicate a 42-day beyond-use date. Discard if solution appears cloudy, discolored, or contains particles.

Use our reconstitution calculator to determine exact syringe units for your dose.

Cycle Guidance

Sermorelin cycling approaches vary among practitioners. The two most commonly discussed strategies are: (1) continuous daily use for 3–6 months followed by a 1–2 month break to assess natural GH production and prevent pituitary desensitization, and (2) the 5-days-on/2-days-off weekly cycling protocol used continuously. Some practitioners recommend initial continuous use for the first 3 months to establish baseline GH stimulation, followed by the 5-on/2-off maintenance pattern. Monitoring serum IGF-1 levels at 4–6 week intervals is commonly recommended to guide dosing decisions. Unlike exogenous growth hormone, sermorelin works through the body's own GH production pathway, which is discussed as carrying a lower risk of permanent pituitary suppression upon discontinuation.

Stacking Considerations

Sermorelin is frequently combined with Ipamorelin (a growth hormone-releasing peptide/GHRP) — the proposed rationale is synergistic GH release through stimulation of both GHRH and ghrelin/GHS receptor pathways simultaneously. A common combination is sermorelin 200–300 mcg + ipamorelin 200–300 mcg at bedtime.
The combination of sermorelin with CJC-1295 (another GHRH analog with a longer half-life) is discussed in some practitioner protocols, though both target the same GHRH receptor and the additional benefit of combining two GHRH analogs is debated.
Some practitioners combine sermorelin with GH-releasing peptides such as GHRP-2 or GHRP-6, though these have more pronounced effects on appetite (especially GHRP-6) and cortisol/prolactin release compared to ipamorelin.
Sermorelin should not be used concurrently with exogenous growth hormone, as exogenous GH suppresses pituitary GH production through negative feedback, which would counteract sermorelin's mechanism of action.
BPC-157 and TB-500 are sometimes discussed alongside sermorelin in recovery-focused protocols, as they target different aspects of the healing response.

Potential Side Effects

Injection site reactions (redness, swelling, pain at the injection site — the most commonly reported side effect)
Facial flushing (reported shortly after injection, typically transient)
Headache (reported in clinical studies, generally mild)
Dizziness or lightheadedness (reported infrequently)
Hyperactivity or difficulty sitting still (reported in some pediatric studies)
Transient changes in taste perception (reported in some studies)
Tightness in the chest (rare, reported in post-marketing data for the original branded product)
Nausea (infrequent, more common at higher doses)
Potential for joint pain or edema at high doses (associated with elevated GH/IGF-1 levels, not specific to sermorelin)

Contraindications & Cautions

Active malignancy — growth hormone stimulation may theoretically promote tumor growth
Known hypersensitivity to sermorelin acetate or any formulation excipients
Untreated hypothyroidism (thyroid hormone is required for normal GH axis function; untreated hypothyroidism may blunt response to sermorelin)
Pregnancy and breastfeeding (insufficient safety data)
Acute critical illness (GH secretagogues are generally not recommended during acute illness based on studies showing increased mortality with GH in critically ill patients)
Diabetic retinopathy (theoretical concern based on GH/IGF-1 effects on retinal vasculature)
Obesity may blunt response to sermorelin due to GH hyposecretion associated with visceral adiposity

Sermorelin Profile anti aging muscle growth sleep recovery ipamorelin dosage tesamorelin dosage cjc-1295 dosage

References

Sermorelin: A Review of Its Use in the Diagnosis and Treatment of Children with Idiopathic Growth Hormone Deficiency (1998) — PubMed
Effects of Thirty Months of Recombinant Growth Hormone-Releasing Hormone (GHRH 1-29) in Healthy Older Men and Women (1999) — PubMed
Two-Year Treatment with Recombinant Human Growth Hormone-Releasing Hormone (GHRH) Increases Bone Mineral Density in Men with Idiopathic Adult-Onset GH Deficiency (2005) — PubMed
Growth Hormone-Releasing Hormone in Aging (2013) — PubMed