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Growth Hormone

Sermorelin (5 mg vial)

Once nightly subcutaneous protocol for GHRH analog research, dosed at bedtime and cycled 8 to 12 weeks on with 2 to 4 weeks off.

Sermorelin is GRF(1-29), the first 29 amino acids of the native 44 amino acid GHRH molecule and the minimum fragment that fully activates the pituitary GHRH receptor to trigger a pulse of growth hormone. Its defining feature is regulatory rather than pharmacological: FDA approved in 1997 as Geref for pediatric GH deficiency and withdrawn commercially in 2008 for business reasons rather than safety, it holds the most defensible 503A compounding position of any GH secretagogue. This protocol runs a single bedtime subcutaneous injection of 200 to 300 mcg nightly, 8 to 12 weeks on followed by 2 to 4 weeks off.

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Protocol Overview

Concise summary of the regimen.

GoalActivate the pituitary GHRH receptor for pulsatile GH release, preserve the somatostatin feedback brake, and mimic the natural nocturnal GH pulse.
ScheduleDosing runs at 200 to 300 mcg subcutaneously nightly, 8 to 12 weeks on followed by 2 to 4 weeks off. The cycling pattern is derived from clinical practice rather than from published dose-duration trials.
Dose RangeThe range is 200 to 300 mcg as a single bedtime injection, given 30 to 60 minutes before sleep and at least 2 hours fasted. At the reconstituted concentration below, that range is 4 to 6 units on a U-100 syringe.
Reconstitution1.0 mL bacteriostatic water per 5 mg vial, giving 5 mg/mL. One insulin unit (0.01 mL) therefore delivers 50 mcg, so 200 mcg is 4 units and 300 mcg is 6 units.
StorageLyophilized frozen; reconstituted refrigerated; avoid freeze-thaw.

Dosing & Reconstitution

PHASENIGHTLY DOSEUNITS PER INJECTIONDURATION
Starter (assess)200 mcg4 unitsWeeks 1 to 2
Standard200 to 300 mcg4 to 6 unitsWeeks 3 to 12
Off-cycle0 mcg0 units2 to 4 weeks

Frequency is once nightly, a single subcutaneous injection rather than a weekly or every other day schedule. The peptide has a 10 to 20 minute half-life and clears in about 4 hours, but downstream GH effects persist for roughly 3 hours after receptor activation, so the dose is placed 30 to 60 minutes before sleep to land inside the natural slow-wave sleep GH pulse window. A fasted state of at least 2 hours after the last meal keeps elevated free fatty acids and glucose from blunting the GH response. The somatostatin feedback brake stays active throughout: as GH and IGF-1 rise, the hypothalamus releases somatostatin to slow pituitary output, which makes sermorelin self-limiting in a way rhGH is not. Sites are rotated systematically across abdomen, thighs, and upper arms to avoid lipohypertrophy. At 5 mg/mL every dose in this protocol is a 4 to 6 unit draw, so a 30 unit insulin syringe reads more accurately than a 100 unit barrel. The cycling pattern of 8 to 12 weeks on and 2 to 4 weeks off comes from clinical practice rather than published dose-duration optimization studies.

Results Timeline

Sequence described in the research record. Individual response varies.

  • Weeks 1 to 2: a 200 mcg starter dose nightly, 4 units, while tolerance and the flushing response are assessed.
  • Weeks 3 to 12: the standard 200 to 300 mcg nightly window, 4 to 6 units, held in the same 30 to 60 minute pre-sleep slot.
  • Every 12 weeks: IGF-1 is checked against a baseline drawn before the first injection, to confirm a physiological response and flag overshoot.
  • After 8 to 12 weeks on: a 2 to 4 week off-cycle. Khorram reported IGF-1 persisting about two weeks after cessation in elderly men, which suggests no immediate rebound or crash.

Reconstitution Steps

  1. Draw 1.0 mL bacteriostatic water with a sterile syringe.
  2. Inject slowly down the vial wall; avoid foaming.
  3. Gently swirl until dissolved (do not shake).
  4. Label with date and concentration; refrigerate at 2 to 8 °C, protected from light. At 5 mg/mL, 1 unit = 0.01 mL » 50 mcg on a U-100 insulin syringe: 200 mcg = 4 units, 250 mcg = 5 units, 300 mcg = 6 units.

Storage Instructions

Proper storage preserves peptide quality.

  • Lyophilized: store frozen at minus 20 °C (minus 4 °F) in dry, dark conditions; stable for 12 months or more.
  • Reconstituted: refrigerate at 2 to 8 °C (35.6 to 46.4 °F), protected from light; avoid freeze-thaw.
  • Allow vials to reach room temperature before opening to reduce condensation uptake.
  • At 1.0 mL per 5 mg vial, one vial covers 25 nights at 200 mcg, 20 nights at 250 mcg, or about 16 nights at 300 mcg, so vial timing is matched to the dosing block.

Supplies Needed

Planning is based on a 12 week course at 250 mcg nightly, which works out to 1.75 mg of peptide per week.

Peptide Vials (Sermorelin, 5 mg vial):

  • A 12 week course at 250 mcg nightly totals 21 mg, which is 5 vials; the same course at 300 mcg nightly totals 25.2 mg, which is 6 vials. Three such courses in a year run 15 to 18 vials.

Insulin Syringes (U-100):

  • Per week: 7 syringes, one per night (U-100, 30 unit markings preferred at these small draws).
  • 12 week course: 84 syringes. Annual across three courses: about 250.

Bacteriostatic Water (10 mL bottles):

  • Each 5 mg vial takes 1.0 mL, so one 10 mL bottle covers 10 vials, which is roughly two full 12 week courses; annual use runs 1 to 2 bottles.

Alcohol Swabs:

  • Per injection: 2 swabs, one for the vial stopper and one for the site, so 14 swabs per week.
  • 12 week course: 168 swabs, which is two 100 count boxes. Annual: about 500.

Important Notes

Practical considerations for consistency and safety.

  • Bedtime timing carries the protocol. Injecting 30 to 60 minutes before sleep aligns the GH pulse with the natural slow-wave window, and food within 2 hours blunts the response through elevated free fatty acids and glucose. Daytime dosing wastes the peptide.
  • The somatostatin brake stays intact. As GH and IGF-1 rise, the hypothalamus releases somatostatin to slow the pituitary; sermorelin can ring the doorbell but cannot override the brake, which is the structural safety advantage over rhGH. Selectivity is clean at standard doses, with no elevation of cortisol, ACTH, or prolactin, unlike the ghrelin-receptor agonists GHRP-2 and GHRP-6.
  • The evidence position, stated plainly: the entire adult clinical case rests on Khorram 1997, 19 subjects, 16 weeks, single-blind, showing lean mass up 1.26 kg in men only, no fat loss and no change in bone mineral density. Sleep, recovery, fat loss, and anti-aging claims common on wellness sites are mechanism-plausible but not trial-measured for sermorelin specifically.
  • Sermorelin is less potent than tesamorelin, which retains the full 44 amino acid GHRH sequence with an N-terminal trans-3-hexenoic acid modification that protects against DPP-IV degradation and carries an 816 patient Phase III program. Sermorelin is the unmodified fragment with Khorram's 19 subjects behind it, and the magnitude gap is real. Sermorelin is chosen for recovery support during moderate caloric restriction, edema sensitivity, legal clarity, lower compounding cost, and a gentler stimulus; tesamorelin is chosen when visceral fat reduction, a stronger evidence base, or maximal potency is the goal.
  • IGF-1 is monitored at baseline and every 12 weeks during extended use to keep levels physiological and flag overshoot. At 5 mg/mL each unit carries 50 mcg, so the whole protocol sits between 4 and 6 units and a 1 unit miscount shifts the dose by 50 mcg; a new sterile syringe is used for each injection and discarded in a sharps container.
  • Regulatory Note: sermorelin was FDA approved in 1997 as Geref for pediatric growth hormone deficiency and withdrawn commercially by EMD Serono in 2008 for business reasons rather than safety, giving it the cleanest 503A compounding footing in the GH secretagogue class; CJC-1295 no-DAC and ipamorelin were never FDA approved and remain in regulatory limbo as of 2026. Sermorelin is prohibited by WADA, so competitive athletes subject to drug testing fall outside the scope of this protocol. Material is supplied for research purposes only and not for human consumption.

How This Works

Sermorelin binds the GHRH receptor (GHRH-R) on somatotrophs in the anterior pituitary, the cells that manufacture and release growth hormone. Receptor activation triggers the same cAMP and PKA intracellular signaling cascade that native GHRH uses, causing the somatotrophs to release a pulse of GH into the bloodstream. The somatostatin feedback brake remains active: as GH and IGF-1 rise, the hypothalamus releases somatostatin, the GH-inhibiting hormone, which slows pituitary output. Sermorelin cannot override that brake, and this is the structural safety advantage over rhGH, which bypasses the pituitary entirely. The pulsatile pattern mimics natural physiology, since native GH is released in bursts during slow-wave sleep rather than as a sustained elevation, and sermorelin's short half-life of 10 to 20 minutes reproduces that pulse shape while downstream GH effects persist about 3 hours. Selectivity is clean at standard doses, with no cortisol, ACTH, or prolactin elevation, which separates sermorelin from ghrelin-receptor agonists such as GHRP-2 and GHRP-6 that stimulate appetite and raise stress hormones. It is less potent than tesamorelin because it is the unmodified GRF(1-29) fragment with no DPP-IV protection.

Benefits & Side Effects

Observations from the published record.

  • Supported by direct evidence: GH and IGF-1 elevation. Nocturnal GH secretion rises reliably and IGF-1 follows, in Khorram 1997 and in the pediatric trials. The receptor pharmacology works.
  • Supported but limited: lean body mass. Khorram 1997 showed a gain of 1.26 kg in elderly men over 16 weeks (P<0.05), with no significant change in women, from a small single sex sample with no replication.
  • Mechanism-plausible but not measured: sleep quality and recovery. Bedtime dosing aligns with the slow-wave GH pulse and GH with IGF-1 supports protein synthesis and collagen turnover, but sermorelin's sleep and recovery outcomes have not been measured in a published trial.
  • Not supported by evidence: fat loss and functional anti-aging outcomes. Khorram found no significant change in total body fat or BMI, and across the class MK-677's two-year RCT and anamorelin's Phase III both raised lean mass without raising strength or handgrip function.
  • Evidence hierarchy in the class: tesamorelin (Phase III, n=816, 15 to 20 percent visceral fat reduction), MK-677 (two-year RCT, n=65, 1.1 kg lean mass, no strength gain), sermorelin (Khorram, n=19, 16 weeks, 1.26 kg lean mass in men only), ipamorelin (PK and PD only), CJC-1295 no-DAC (no human trials). Pediatric evidence was adequate for approval, with significant height velocity increases over 12 months extending to 36 months, consistently below rhGH at equivalent doses but with physiological regulation preserved.
  • Side effects: transient facial flushing is the most common and fades within minutes, alongside injection-site reactions, mild peripheral edema (less than tesamorelin), and occasional tingling that resolves with dose reduction. Contraindications include active malignancy, proliferative diabetic retinopathy, pregnancy or breastfeeding, severe systemic illness, and concurrent supraphysiological androgen use.

Lifestyle Factors

Complementary strategies for best outcomes.

  • Eating at least 2 hours before the injection is what receptor responsiveness depends on; free fatty acids and glucose blunt the GH response, and a large evening carbohydrate load raises insulin, which blunts the pulse as well.
  • Sleep of 7 to 9 hours is the substrate the protocol assumes, since the GH pulse fires into slow-wave sleep and sleep debt undermines the protocol directly. Alcohol within 4 hours of the injection suppresses GH secretion.
  • Resistance training is what converts any lean mass gain into function, because the class consistently improves surrogate markers without strength translation. Protein at 0.8 to 1.0 g per pound of body weight supports the GH-driven protein synthesis signal.
  • Pairing with DSIP is used where slow-wave sleep is fragmented, since sermorelin's GH pulse fires into the window DSIP deepens; IGF-1 checks at baseline and every 12 weeks confirm a physiological response.

Injection Technique

General subcutaneous guidance from clinical best-practice resources.

  1. Choose injection site: abdomen (at least 2 inches from navel), outer thigh, upper outer arm, or buttocks.
  2. Clean vial stopper and skin: swab with alcohol; allow to dry completely.
  3. Draw dose: remove needle cap; draw air equal to dose volume; inject air into vial; invert and draw prescribed dose; expel air bubbles.
  4. Pinch and insert: pinch a fold of skin; insert needle at 45 to 90 degrees into subcutaneous tissue.
  5. Inject slowly; wait 1 to 2 seconds before withdrawing needle at same angle.
  6. Post-injection: apply gentle pressure with cotton ball or alcohol pad; do not rub the site.
  7. Dispose immediately in designated sharps container; never recap needle.

References

Source citations for further reading.

  1. Khorram O et al. Endocrine and metabolic effects of long-term GRF(1-29) in age-advanced men and women (J Clin Endocrinol Metab, 1997).
  2. Walker RF. Sermorelin: a better approach to management of adult-onset GH insufficiency? (Clin Interv Aging, 2006).
  3. Keating GM, Wellington K. Sermorelin: pediatric GHD diagnosis and treatment review (BioDrugs, 2004).
  4. Falutz J et al. Tesamorelin pooled Phase III analysis, n=816 (J Clin Endocrinol Metab, 2010).
  5. Nass R et al. MK-677 two-year body composition RCT (Ann Intern Med, 2008).
  6. Sigalos JT, Pastuszak AW. Safety and efficacy of GH secretagogues review (Sex Med Rev, 2018).
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Educational and research reference only. Not medical advice. For research use only; not for human consumption.

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