Gonadorelin: real GnRH, and why the interval between doses is the whole protocol
The hormone one step above luteinising hormone, used off-label to keep the testis working during testosterone therapy. It has the same knife-edge property kisspeptin does: pulses stimulate, continuous exposure shuts the axis down.
- Also known as
- GnRH, LHRH, Factrel, Lutrepulse
- Class
- Sexual health peptide
- Regulatory status
- FDA APPROVED as Factrel for diagnostic use and Lutrepulse pump for hypogonadotropic hypogonadism. Off-label SubQ pulsatile use for TRT testicular maintenance.
- Modelled half-life
- 18 min
- Time to peak
- 9 min
- Formulation
- Aqueous (reconstituted powder)
- Before mixing
- Sealed powder tolerates room temperature in transit, but keep it refrigerated at 2–8 °C (36–46 °F) for anything beyond a few weeks, or frozen for months. Keep it dark — the carton it shipped in is doing a job.
- After mixing
- Once reconstituted with bacteriostatic water: refrigerate at 2–8 °C and use within about 28 days. The benzyl alcohol in bacteriostatic water is what buys that window — plain sterile water has no preservative, so a vial mixed with it should be treated as one sitting only. Kits are usually ten vials: only the one you mixed is on that 28-day clock — the sealed ones keep their own, much longer shelf life, so store them as powder, not as solution.
- What ruins it
- Do not freeze a reconstituted vial. Repeated freeze–thaw is one of the more reliable ways to degrade a peptide.
- Handling caveat
- General handling practice for this formulation. Your supplier’s own insert or COA overrides anything here.
Where it acts, and how that differs from hCG
Established clinical use Gonadotropin-releasing hormone is released by the hypothalamus in pulses roughly every ninety minutes and instructs the pituitary to secrete luteinising hormone and FSH. Gonadorelin is that decapeptide, synthesised. Given properly it raises your own LH, which then acts on the testis.
That is a different intervention from hCG, which skips the pituitary entirely and binds the LH receptor on the testis directly. Two consequences follow. Gonadorelin keeps the pituitary in the loop, so LH and FSH actually move and can be measured — the LH and FSH page covers what that looks like. And it needs a pituitary able to respond, where hCG does not.
The app models a half-life of about twenty minutes, which is the shortest of anything in this reference apart from sermorelin. That is not a flaw: native GnRH is cleared in minutes too, and the brevity is what makes a pulse a pulse.
Continuous exposure does the opposite
Established clinical use The pituitary gonadotroph responds to intermittent GnRH and desensitises under constant stimulation. This is not a subtlety — it is the basis of an entire drug class. Continuous GnRH agonists are used to suppress testosterone in prostate cancer and in precocious puberty, and they work precisely by overwhelming the receptor they stimulate.
So the schedule is the drug. Properly spaced administration maintains testicular function; administration that is too frequent, or a preparation that releases slowly, produces chemical castration. The app’s own drawbacks list says this in capitals and it is right to. It is also why the approved product is a pump that delivers a dose every ninety minutes, and why the subcutaneous schedules used in clinics are an approximation of that rather than the thing itself.
Off-label or community practice How good an approximation twice-daily injection is, against a pump running sixteen pulses a day, has not been established in trials. That is the honest gap in this protocol: the mechanism is textbook, the approved delivery is a pump, and the way it is actually used is neither.
What to measure
The app’s panel is well matched to the mechanism. LH and FSH will show activity here, unlike on hCG where they stay suppressed, and an LH rise thirty to sixty minutes after a dose is a direct test that the pituitary responded. Total testosterone and estradiol follow, and testicular volume is the clinical endpoint the protocol exists for.
Off-label or community practice The approval is for diagnostic use and for a pump in hypogonadotropic hypogonadism. Subcutaneous use alongside testosterone therapy is off-label, and the preparations used are compounded. This site names no pharmacy or clinic.
Anyone weighing this against hCG should know the comparison is not settled: hCG has far more use behind it for this purpose, gonadorelin has the more physiological mechanism, and no trial has compared them for testicular maintenance during testosterone therapy. That is a prescribing conversation, and anything on the drawbacks list below belongs in it.
How long one dose lasts
pkCurve function.
The vertical axis is relative: the shape carries across people, the absolute
concentration does not.Try other intervals on the half-life and steady-state calculator, which runs the same function against whatever cadence you type.
The dosing rows the app records
Established clinical use Reproduced from the app’s reference so you can see what it holds, not as a recommendation. Which row applies to a particular person, if any, is a clinical decision this page does not make — and rows describing supraphysiological or post-cycle use are filtered out before this table is built, so what you see here is a subset.
| Label | Amount | Route and frequency | Duration recorded |
|---|---|---|---|
| TRT Testicular Maintenance | 100mcg | SubQ twice daily (minimum 8-hour gap) — pulsatile | Ongoing with TRT |
| Fertility Protocol | Pulsatile pump 5-20mcg every 90 min | Continuous pump delivery | Physician supervised |
What the app monitors alongside it
The panel below is the app’s own monitoring note for Gonadorelin, verbatim. The analytes in it that have a page here are linked; those pages cover what each one measures, which assay produced it and how to read a trend.
- Monitoring panel
- LH, FSH (will show some activity unlike HCG protocols), Total T, E2, testicular volume assessment. LH response 30-60 min post-injection confirms pituitary response.
Drawbacks and risks the app records
From the app’s own entry, and the first item is not a side effect — it is the protocol failing in the exact opposite direction from the one intended.
- Pulsatile dosing CRITICAL — continuous use suppresses the axis (pharmaceutical castration)
- Very short half-life — requires frequent pulsatile dosing
- Pulsatile pump ideal but impractical outside clinical setting
- SubQ pulsatile injection required multiple times daily
- More complex protocol than HCG
- Limited SubQ injection data vs pump delivery
Interaction rules that name Gonadorelin
From the app’s interaction data, filtered so no rule naming a compound this site does not publish appears. Not exhaustive, and not a safety clearance: a combination that is not listed is one nobody has documented here, which is not the same as one that is fine. The combination checker has the rest.
Gonadorelin and HCG — Choose One for Testicular Maintenance
Both gonadorelin and HCG serve the same purpose on TRT — preserving testicular function. Gonadorelin stimulates LH/FSH from the pituitary; HCG mimics LH directly at the testes. Using both simultaneously is redundant and may cause over-stimulation. Choose one approach.
What to watch: Total T, LH, FSH, E2, testicular volume. Monitor prolactin — over-stimulation can elevate it.
Gonadorelin + Clomid — Synergistic HPG Restoration
Gonadorelin stimulates LH/FSH at the pituitary level while Clomid blocks hypothalamic estrogen receptors to increase GnRH pulsatility. Together they address HPG restoration at two distinct points. A potentially more comprehensive HPTA restart than either alone.
What to watch: LH, FSH, Total T, E2 every 4 weeks. LH response to gonadorelin confirms pituitary function.
Kisspeptin-54 + Gonadorelin — Upstream and Downstream HPG
Kisspeptin acts upstream of GnRH neurons to trigger GnRH release, while gonadorelin IS GnRH acting directly on the pituitary. Using both covers the HPG axis at two levels but requires careful pulsatile timing for both. Both must be pulsatile — never continuous.
What to watch: LH, FSH, Total T, E2. Both compounds require pulsatile dosing — coordinate timing to avoid receptor conflicts.
Questions people actually ask
How is it different from hCG?
hCG binds the LH receptor on the testis directly and bypasses the pituitary; gonadorelin acts on the pituitary and raises your own LH. That means LH and FSH move on gonadorelin and stay suppressed on hCG, and it means gonadorelin needs a pituitary able to respond.
Why can continuous dosing cause suppression?
Because the gonadotroph desensitises under constant stimulation. That is the mechanism behind GnRH agonist therapy for prostate cancer, and it is why the interval between doses matters more here than the amount.
How do I know the pituitary responded?
An LH rise thirty to sixty minutes after a dose, which is the app’s own monitoring suggestion and the closest thing to a direct check available.
Is twice-daily injection equivalent to the pump?
Nobody has established that. The approved delivery is a pump giving a dose roughly every ninety minutes; twice daily is a practical approximation with no trial behind it.
Where the load-bearing numbers come from
Named rather than linked. Publisher URLs move, and a citation that resolves to a 404 two years from now is worse than one you can search for by name — every entry below is findable from the title and year alone.
- Pulsatile GnRH and gonadotroph desensitisation
- Standard endocrinology; the same pharmacology underlies GnRH agonist therapy for androgen suppression
- Approved indications
- The approval string in the fact box is app.html’s own field, reproduced verbatim
- Off-label subcutaneous use
- Described in hormone-therapy practice; no controlled trial has compared it with hCG for testicular maintenance
- Modelled half-life and time to peak
- app.html’s TL_PK entry
When the gap between doses decides the direction of the effect, the clock matters as much as the amount. TherapyLog records the time.
Save this dose to your log