Endocrine (other)

Protirelin (TRH)

Also called Thyrotropin-releasing hormone, TRH, Thyroliberin, Thyrel TRH, Thypinone, Relefact TRH, TRH Ferring, Hirtonin (protirelin tartrate, Japan)

Protirelin is a lab-made copy of TRH, a tiny three-amino-acid hormone from the brain that tells the pituitary gland to release thyroid-stimulating hormone (TSH). For decades doctors injected it as a test of the thyroid and pituitary. The US versions (Thyrel TRH, Thypinone) are discontinued, but it is still sold as a diagnostic in Germany, and in Japan it is also used to treat balance problems in spinocerebellar degeneration.

Late-stage trialsTested in large human trials (phase 2b/3) but not yet approved in the US.

New · under editorial review. Added October 31, 2026 by our automated research, with every claim sourced. A person has not checked this page yet; treat it with extra care. How we research

Drawn from its published sequence: 3 residues, one bead each.

At a glance

Type: Peptide
Size: 3 amino acids (pyroglutamyl-histidyl-prolinamide)
Sequence: QHP
Formula: C16H22N6O4 (PubChem)
Molecular weight: 362.38 g/mol (PubChem)
CAS number: 24305-27-9 (PubChem)
Origin: Identical to natural hypothalamic TRH: pGlu-His-Pro-NH2, where the first residue (Q) is a pyroglutamate ring and the end is amidated [2][1]. Japan's product is the tartrate salt hydrate [9].
Evidence: Late-stage trials
US FDA status: No FDA-approved protirelin product is marketed. Thypinone (Abbott, NDA 017638) was approved on November 5, 1976 and Thyrel TRH (Ferring, NDA 018087) on July 18, 1978; both are listed as discontinued ⁴. FDA proposed withdrawing 14 applications, including NDA 018087, in November 2013 because required annual reports had repeatedly not been filed ⁵, and withdrew approval of those applications effective November 17, 2014 ¹³.

Overview

How it works

Established: TRH is made in the hypothalamus and travels through small portal blood vessels to the front of the pituitary gland, where it triggers release of TSH, which then raises thyroid hormone output; it also releases prolactin (German label) ³. After an IV dose, protirelin peaks in blood within 2-5 minutes and is broken down fast (half-life about 3-6.5 minutes), while TSH peaks at 20-30 minutes ³. Doctors compare TSH before and 30 minutes after the injection to help sort out thyroid and pituitary problems ³. Since ultrasensitive TSH blood tests arrived, the test is rarely needed for ordinary thyroid diagnosis but can still help with TSH-secreting pituitary tumors and subtle central hypothyroidism ⁶⁷. Proposed: it is classed as a TRH receptor agonist ⁸, and how it eases ataxia in spinocerebellar degeneration (its Japanese use) is not fully understood; studies report short-term benefit ¹⁰.

What research shows

Approved diagnostic use (German label): a single IV dose with TSH measured before and after helps assess thyroid and pituitary function ³.
ACTOBAT (human RCT, n=1234 pregnant women at risk of preterm birth, all on steroids): TRH slightly increased the babies' risk of respiratory distress (RR 1.17) and need for ventilation (RR 1.15), and caused more nausea, vomiting, lightheadedness and high blood pressure in mothers ¹¹.
Cochrane review (15 trials, over 4600 women): adding TRH to corticosteroids before preterm birth did not reduce death before discharge, respiratory distress syndrome or chronic lung disease, and increased the need for respiratory support (RR 1.16) and the chance of a low 5-minute Apgar score (RR 1.48); all reported maternal side effects were more common with TRH ¹².
Japan, retrospective study (92 patients with spinocerebellar degeneration, 273 treatment courses, 2011-2025): 64% improved by at least 1 point on an ataxia scale; side effects in 2 of 92; not a randomized trial ¹⁰.
Its usefulness for routine thyroid testing has fallen since sensitive TSH tests became available ⁶.

Doses studied in people

Study or label	Dose used	Source
German label (TRH Ferring), diagnostic TRH test in adults	200 µg single slow IV injection usually sufficient; label range 200-500 µg (1-2.5 ampoules)	³
German label (TRH Ferring), diagnostic test in children from 2 weeks of age	1 µg/kg single IV injection	³
Official Japanese label (Hirtonin), improvement of ataxia in spinocerebellar degeneration	0.5-2 mg protirelin (as the tartrate hydrate) once daily, intramuscular or intravenous, given in supervised treatment courses	⁹
ACTOBAT randomised trial, women at risk of preterm birth (n=1234) - this regimen was found to cause harm and was not recommended for use	200 µg TRH intravenously every 12 hours, up to 4 doses, added to corticosteroids	¹¹

These figures come only from official labels and one published trial, and are listed for reference, not as advice. The antenatal regimen in the last row was found to harm mothers and babies and the trial authors advised against its use ¹¹¹².

Read this first: these are the amounts given to participants in published studies or written on official prescribing labels, reported for reference. They are not recommendations. Trial doses were chosen for specific patients under medical supervision, and a dose that is safe in one person can be harmful in another.

Vial math

Many research vials hold 5 or 10 mg of powder. This table shows how much ends up in each mark on a U-100 insulin syringe for common amounts of added liquid. It is arithmetic only, not a dose.

Vial	Liquid added	Concentration	Per unit (0.01 mL)
5 mg	1 mL	5 mg/mL	50 mcg	Open in calculator
5 mg	2 mL	2.5 mg/mL	25 mcg	Open in calculator
5 mg	3 mL	1.67 mg/mL	16.7 mcg	Open in calculator
10 mg	1 mL	10 mg/mL	100 mcg	Open in calculator
10 mg	2 mL	5 mg/mL	50 mcg	Open in calculator
10 mg	3 mL	3.33 mg/mL	33.3 mcg	Open in calculator

More sizes: all vial sizes · How this works: Syringes and units · Reconstitution guide.

Safety

Brief (1-3 minutes) side effects are expected after IV injection: warmth, nausea, urge to urinate, mild headache, lightheadedness, flushing and odd sensations in the belly and pelvis (German label) ³.
Uncommon: taste changes, rise in blood pressure and pulse, chest discomfort, dry mouth, vomiting (German label) ³.
Rare: seizures in people prone to them, and asthma attacks in people with asthma (German label) ³.
In a few patients with large pituitary tumors, tumor swelling or pituitary bleeding (apoplexy) has occurred around the time of TRH testing, sometimes needing surgery (German label) ³.
Not to be used after a recent heart attack, with unstable angina, raised seizure risk or severe airway obstruction (German label) ³.
In pregnancy it crosses the placenta; adding it before preterm birth harmed babies' breathing outcomes and caused maternal side effects ³¹¹¹².

Report side effects of any drug or product to the FDA through MedWatch. For a possible poisoning in the US, call Poison Control at 1-800-222-1222.

Legal status

FDA: No FDA-approved protirelin product is marketed. Thypinone (Abbott, NDA 017638) was approved on November 5, 1976 and Thyrel TRH (Ferring, NDA 018087) on July 18, 1978; both are listed as discontinued ⁴. FDA proposed withdrawing 14 applications, including NDA 018087, in November 2013 because required annual reports had repeatedly not been filed ⁵, and withdrew approval of those applications effective November 17, 2014 ¹³.
Compounding: Not on FDA's 503A bulk drug substances categories list (updated May 14, 2026) ⁹¹. On the 503B categories list (updated March 21, 2025), protirelin is in Category 3 (nominated without adequate support) ⁹³.
Sports (WADA): Not named on the 2026 WADA Prohibited List ⁹⁰. The S0 class covers substances with no current approval by any government health authority for human therapeutic use; protirelin does hold current approvals (Germany, Japan) ³⁹, so on our reading S0 does not apply — this is our interpretation of the published list, not a WADA ruling.
Other: Germany: TRH FERRING 0,2 mg/ml, prescription-only diagnostic (authorised 01.09.1998, renewed 04.08.2015; label dated August 2015) ³. France: TRH FERRING 200 micrograms, authorised 20/10/2017 for the differential diagnosis of TSH-secreting pituitary adenomas and pituitary resistance to thyroid hormones, with discontinuation of marketing declared as of 30/06/2026 ⁷. Japan: Hirtonin (protirelin tartrate hydrate) is approved for improving ataxia in spinocerebellar degeneration and for prolonged disturbance of consciousness (excluding coma and semi-coma) after head injury or subarachnoid haemorrhage ⁹.
Sold online: Protirelin (TRH) is also sold online as an unregulated "research" peptide. These products are not the licensed European diagnostic or the Japanese medicine and have unknown purity, dose and contents. US law requires a new drug to be shown safe and effective before it is marketed, and FDA notes that for unapproved products there is no way to know whether the label is complete and accurate ⁹². FDA has separately warned sellers of weight-loss peptides that labelling a product "for research purposes" or "not for human consumption" does not change its status when it is in fact sold for human use ⁹⁴. No FDA warning letter, import alert or anti-doping notice naming protirelin specifically was found.

Rules change often. See Legal status of peptides for how these categories work.

Storage and stability

Do not store above 25 °C; shelf life 4 years (German label) ³.

General lab handling, not instructions for personal use. See Storage and stability.

History

In 1969 Schally, Folkers and colleagues showed that TRH is pyroglutamyl-histidyl-proline amide ². In the US, Abbott's Thypinone was approved in 1976 and Ferring's Thyrel TRH in 1978; both are now listed as discontinued ⁴. Ferring halted production of Thyrel TRH in July 2002 to change its manufacturing process ⁶, in 2013 FDA proposed withdrawing the Thyrel TRH application because required annual reports had not been filed ⁵, and that withdrawal took effect on November 17, 2014 ¹³. TRH Ferring is authorised in Germany (first 1998; label dated August 2015) ³; in France, the 200 µg product (authorised in October 2017 for two narrow pituitary diagnoses) was declared discontinued as of June 30, 2026 ⁷. In Japan, Hirtonin is approved for improving ataxia in spinocerebellar degeneration and for prolonged disturbance of consciousness after head injury or subarachnoid haemorrhage ⁹. In the 1990s, trials added TRH to steroids in pregnant women at risk of preterm birth to help babies' lungs, but it did not help and caused harm ¹¹¹².

Common questions

Is protirelin (TRH) still FDA-approved?

No. No protirelin product is marketed in the US. Thypinone (1976) and Thyrel TRH (1978) are listed as discontinued ⁴, production of Thyrel stopped in 2002 ⁶, and FDA withdrew the Thyrel TRH approval effective November 17, 2014 ¹³.

What is the TRH test?

A single IV dose of protirelin is given and TSH is measured before and about 30 minutes after, to help assess thyroid and pituitary function ³. Modern TSH tests have made it rarely needed ⁶.

Is it used as a treatment anywhere?

Yes, in Japan. Hirtonin injections are approved for ataxia in spinocerebellar degeneration and some prolonged disorders of consciousness ⁹.

What are the risks?

Brief flushing, nausea, urge to urinate and headache are common after injection; rare risks include seizures, asthma attacks and pituitary bleeding in people with large pituitary tumors ³. Given before preterm birth, it harmed babies' breathing outcomes ¹¹¹².

Is TRH banned in sport?

It is not named on the 2026 WADA Prohibited List ⁹⁰.

Related compounds

Hormonal & reproductiveFDA-approvedFlashcard

Gonadorelin

GnRH · LHRH

Gonadorelin is a synthetic copy of GnRH, the brain hormone that tells the pituitary to release LH and FSH.

Growth hormone axisLate-stage trialsNew

GHRH (1-44)

Growth hormone-releasing hormone · Somatorelin

GHRH is the brain hormone that tells the pituitary gland to release growth hormone.

Growth hormone axisFDA-approvedFlashcard

Sermorelin

Sermorelin acetate · GRF 1-29 NH2

Sermorelin is a short, lab-made piece of the body's growth-hormone-releasing hormone.

Sources

Last reviewed 2026-10-31 · How we research · Found an error? See our corrections policy.