TRH (protirelin): diagnostic medicine, research and harms
In short
TRH, or protirelin, is the body's own three-amino-acid peptide hormone, and in synthetic form it is a diagnostic medicine given into a vein to test pituitary function [1]official [5]. It has no marketing authorisation in Finland [2]regulator, and large trials have not shown a benefit as a treatment [8]A.
- TRH makes the pituitary gland release thyroid-stimulating hormone (TSH) and prolactin [1]official [5].
- In France the protirelin product is a prescription medicine for diagnostic use only, and its withdrawal from the market has been announced [1]official.
- TRH given in pregnancy did not protect preterm babies from lung disease and increased harms for mothers and babies in a Cochrane review of 15 trials [8]A.
- Treatment trials in ALS were negative [13]A; in depression and spinal cord injury there are only small studies [14, 15, 16]A.
- In Finland protirelin is on the medicines list, but there is no marketing authorisation [2, 4]regulator. The WADA 2026 Prohibited List does not name it [20]regulator.
What is TRH (protirelin)?
TRH (thyrotropin-releasing hormone) is the body's own hormone, made in the hypothalamus of the brain. It controls the pituitary gland, which in turn makes thyroid-stimulating hormone, TSH [1]official [5]. TRH was the first hypothalamic hormone controlling the pituitary to be isolated [5].
Protirelin is the synthetic form of TRH. According to the French summary of product characteristics it is a three-amino-acid peptide (pyroglutamyl-histidyl-prolinamide) with the same structure as natural TRH [1]official.
As a medicine protirelin is used for a diagnostic test: it is given into a vein, and the TSH level in the blood is measured before and after [1]official. According to a review the TRH stimulation test is little used today [6].
Basics: What are peptides?. All substances: Peptides A-Z.
Evidence at a glance
Each cell gives the type of study and the source. The letter is the level of evidence, not the result.
| Claimed effect | Humans | Animals | Cells |
|---|---|---|---|
| Testing pituitary function | Approved diagnostic use [1]official; series of 359 tests [18]B | - | - |
| Lung maturation of preterm babies (in pregnancy) | Cochrane, 15 trials: no benefit, harms [8]A | Lungs matured in lambs and rabbits [1]official | - |
| ALS | Given into the spinal canal: no effect in 36 patients [13]A | - | - |
| Spinal cord injury | 20 patients, better result in incomplete injury, very small numbers [14]A | - | - |
| Depression | Two small studies, rapid but short effect [15, 16]A | - | - |
| Cancer-related fatigue | 8 patients, fatigue decreased [17]A | - | - |
| Safety | Transient side effects very common [1]official; bleeding into a pituitary tumour possible [1]official [19]B | - | - |
"-" = no such study is known.
What is TRH used for?
The approved use of protirelin is diagnostic. In Finland it has no marketing authorisation, so there is no approved indication here [2]regulator.
- Approved indication in France. The product is for diagnostic use only: to tell apart TSH-producing tumours of the anterior pituitary and a pituitary that resists the effect of thyroid hormones [1]official.
- The test in practice. The product is given as a slow injection into a vein, and TSH and possibly prolactin are measured before the injection and several times after it. The patient must fast before the test [1]official.
- Research use. TRH has been studied as a treatment to prevent lung disease in preterm babies [8]A, for ALS [13]A, spinal cord injury [14]A, depression [15, 16]A and cancer-related fatigue [17]A. According to a 2019 review the therapeutic use of TRH was at that time restricted to spinocerebellar degenerative disease [6].
How does TRH work?
TRH binds mainly to the pituitary and makes it release TSH, which in turn makes the thyroid produce thyroid hormones. The thyroid hormones then feed back on TSH release [1]official. According to a review the feedback also acts on the pituitary TRH receptor [5]. TRH also releases prolactin [1]official.
According to the review TRH nerve cells are activated by energy-demanding situations such as cold and exercise, and inhibited by fasting, inflammation and chronic stress [5]. Feedback from thyroid hormones also affects the breakdown of TRH [5].
TRH is widespread in the brain, and according to another review it affects feeding, arousal, anxiety and movement, among others. Its use as a treatment is limited because TRH is poorly absorbed from the gut, crosses the blood-brain barrier poorly and is rapidly broken down by an enzyme in the blood [7].
Has TRH been studied in humans?
Yes. The most widely studied treatment use was TRH in pregnancy to protect the lungs of preterm babies: there are randomised, placebo-controlled trials in more than 4,600 women, and no benefit was found [8]A. For other uses the studies are small [13, 14, 15, 16, 17]A.
Pregnancy and the lungs of preterm babies
- Cochrane review (2013). 15 trials, more than 4,600 women. TRH added to corticosteroids did not reduce infant deaths, respiratory distress syndrome or chronic lung disease. In mothers all reported side effects were more common with TRH. In babies the need for breathing support and low Apgar scores increased [8]A.
- ACTOBAT (1995). An Australian trial in 1,234 women. Respiratory distress syndrome and the need for ventilation were more common in babies of the TRH group than in the placebo group. In mothers nausea, vomiting, light-headedness and a rise in blood pressure were more common. According to the authors the treatment cannot be recommended for widespread use [9]A.
- ACTOBAT, one-year follow-up (1997). At 12 months children in the TRH group had more delays in motor and social development and more sensory impairment [10]A.
- North American trial (1998). 996 women in 13 centres. There was no difference from placebo in respiratory distress syndrome, deaths or lung disease [11]A.
Nervous system and mood
- ALS (1992). 36 patients received TRH or placebo into the spinal canal by pump in six-month periods. There was no difference in disease progression. According to the authors earlier trials of TRH given by injection or infusion had been negative [13]A.
- Spinal cord injury (1995). 20 patients. In incomplete injury the TRH group did better at four months, but only 11 patients could be assessed. According to the authors the results must be interpreted with considerable caution [14]A.
- Severe depression (1997). Eight patients received protirelin into the spinal canal and a sham procedure. Five of eight responded rapidly, but the effect was short-lived [15]A.
- Bipolar disorder (2005). 20 depressed patients received TRH or saline into a vein at night. Within a day depressive symptoms fell by at least half in 60% of the TRH group and 10% of the comparison group, and the effect lasted up to two days [16]A.
- Cancer-related fatigue (2012). In a crossover study of eight patients fatigue decreased, but blood pressure and heart rate rose transiently [17]A.
Diagnostic test
In a Danish series 359 TRH tests were done in people with pituitary disease. The test helped when the thyroid hormone level was low: in about half of them a diagnosis of central hypothyroidism was rejected on the basis of the test. In people with a normal level or awaiting surgery (78% of tests) the test gave no clinically relevant information [18]B.
Who studies TRH?
TRH in pregnancy was studied by large collaborative groups in Australia and North America [9, 11]A, and the Cochrane review was written partly by the same researchers; they did not assess their own trials themselves [8]A. The nervous system and mood studies are small studies by individual US groups [13, 14, 15, 16, 17]A. The physiology has been reviewed by Mexican and German researchers [5, 6, 7].
Author of this page: editorial team
This page was written by the Molecular Recovery editorial team. The draft was made with the help of AI, and the claims were checked against the sources (AI policy). The page has not been medically reviewed. How we work: About us.
How long does TRH stay in the body?
A very short time. According to the French summary of product characteristics protirelin is rapidly broken down by enzymes in the blood, its half-life in the blood is about 2-3 minutes, and it is removed through the kidneys [1]official.
Most of the common side effects last 1-3 minutes [1]official. Protirelin is broken down in the gut, so according to the summary of product characteristics a breastfed baby is not exposed to its effects [1]official.
What are the side effects of TRH?
In the diagnostic test transient side effects are very common, but they usually last only minutes [1]official. The most serious rare harm is bleeding into or death of tissue in a pituitary tumour [1]official [19]B.
Side effects in the summary of product characteristics
- Very common and transient: headache, dizziness, feeling unwell, nausea, abdominal discomfort, urgent need to urinate, pelvic discomfort and flushing of the face and neck [1]official.
- Frequency not known: hypersensitivity, taste disturbance, seizures, bleeding in the pituitary, raised or lowered blood pressure, fast heart rate, asthma, dry mouth, vomiting, chest tightness and hunger [1]official.
- Sudden reaction: after the injection a reaction resembling hypersensitivity can occur (swelling, narrowing of the airways, exceptionally anaphylactic shock) [1]official.
Pituitary tumour. In some people with a large pituitary tumour bleeding into or death of tumour tissue has been described with the test, and some needed surgery [1]official. In a case report a 41-year-old woman had pituitary bleeding after a TRH test [19]B. In a series of 359 tests side effects were mild and transient apart from one possible case of bleeding [18]B.
Pregnancy. In the pregnancy trials side effects in mothers were more common with TRH, and the need for breathing support increased in babies [8]A. Blood pressure rose briefly and slightly, but TRH did not affect uterine contractions [12]A.
More: Side effects and safety.
Who should not use it
According to the summary of product characteristics protirelin must not be given to people hypersensitive to it. With a large pituitary tumour the benefit of the test must be weighed against the risk of bleeding, and heart and vascular disease and conditions that lower the seizure threshold must be considered. In pregnancy there is no reason for the test, because measuring TSH is enough [1]official.
Interactions and who lacks data
According to the French summary of product characteristics thyroid hormones and similar substances weaken the rise in TSH during the test. It is also weakened by, among others, corticosteroids, somatostatin, dopamine, bromocriptine, levodopa, salicylates, morphine and barbiturates. Some other medicines, such as lithium, amiodarone and metoclopramide, slightly strengthen the TSH rise. These interfere with interpreting the test only very rarely [1]official.
Effects on driving have not been studied, but because of the short duration of action they are expected to be negligible [1]official. According to the summary of product characteristics there are not enough data on use in pregnancy to assess the risk of malformations [1]official.
What speaks against it and what is unknown
The largest TRH trials have been negative: TRH in pregnancy did not help preterm babies and increased harms [8, 9]A, and in ALS there was no effect [13]A.
Counter-evidence
- In a Cochrane review of 15 trials TRH in pregnancy did not improve any infant outcome [8]A.
- In the ACTOBAT trial respiratory distress syndrome and the need for ventilation were more common in the TRH group [9]A, and at one year there were more developmental delays [10]A.
- In the North American trial of 996 women there was no difference from placebo [11]A.
- TRH given into the spinal canal did not change the progression of ALS [13]A.
- In animal studies protirelin in pregnancy matured the fetal lungs [1]official, but in humans there was no benefit [8]A.
What the evidence does not support
- "TRH is an antidepressant": in two small studies the effect was rapid but lasted at most two days [15, 16]A, and there are no large trials.
- "TRH protects nerves": according to a review TRH is a neurotrophic peptide, but poor access to the brain and rapid breakdown have limited its use [7], and the ALS trial found no effect [13]A.
- "The TRH test is a routine thyroid test": according to a review the test is little used today [6], and according to the summary of product characteristics measuring TSH is enough in pregnancy [1]official.
What is unknown
- Whether repeated use of TRH brings benefit or harm: the treatment studies were small and short [14, 15, 16, 17]A.
- Whether TRH given through the nose works: according to a review new delivery routes have renewed interest [7], but we found no published treatment studies of it in humans.
- Long-term effects in children exposed in pregnancy: only three trials followed up the children, and the results differed [8]A.
TRH dosing in studies
Protirelin is a prescription medicine in France [1]official, so this site has no dose page or calculator for it. In Finland it has no marketing authorisation and no approved dosing [2]regulator. The dose is decided by the doctor doing the test according to the approved product information [1]official.
In the diagnostic test a single slow injection is given into a vein, and blood samples are taken before and after the injection [1]official. In the pregnancy trials TRH was given into a vein as at most four doses some hours apart, on top of corticosteroids [9, 11]A. These are study designs, not recommendations.
Combinations: TRH with corticosteroids in pregnancy
The best-known combination is TRH in pregnancy added to corticosteroids. The idea was that the combination would protect the lungs of preterm babies better than corticosteroids alone [8]A.
The combination was no better than corticosteroids, and it increased harms for mothers and babies [8, 9, 11]A. According to the ACTOBAT researchers TRH in pregnancy should be used only within trials [10]A.
Is TRH legal in Finland?
Protirelin is a medicine in Finland: it is in annex 1 of Fimea's medicines list as "Protireliini" [4]regulator. There is no marketing authorisation in Finland: the EMA Article 57 data of 9 October 2026 list no Finnish protirelin product [2]regulator.
- Authorisations elsewhere. There are national authorisations only in France and Germany, in both a product given into a vein named TRH (Ferring) [2]regulator.
- No central EU authorisation. The EMA data on centrally authorised medicines (14 October 2026) contain no protirelin [3]regulator.
- Prescription medicine in France. TRH Ferring (protirelin) is supplied only on prescription (list I). The date for stopping marketing was given as 30 June 2026, and according to the database the product is no longer, or will soon no longer be, available [1]official.
Overview of the law: peptides and the law in Finland. Bringing products back from travel: Travelling with peptides.
This is not legal advice. Disclaimer.
Is TRH doping?
The WADA 2026 Prohibited List does not name TRH or protirelin. The lists of peptide hormones and their releasing factors in class S2.2 name, among others, GnRH, corticorelin and growth hormone-releasing hormones, but not TRH [20]regulator.
Class S0 covers substances with no approval by any health authority for human treatment [20]regulator; protirelin is authorised in France and Germany [2]regulator.
According to the French summary of product characteristics athletes must be made aware that the product's active substance can give a positive result in anti-doping tests [1]official. An athlete should check with the Finnish Center for Integrity in Sports (SUEK).
How is the quality of a TRH product assessed?
Authorised protirelin is a solution for injection in a glass ampoule, with sodium chloride, water for injections and hydrochloric acid as excipients [1]official. We found no quality studies of products other than the authorised one.
A certificate of analysis (COA) does not show that a product is safe. More: How to read a COA and check a test result.
FAQ
What is TRH used for?
As an approved medicine only for a diagnostic test of TSH release from the pituitary [1]official. In Finland protirelin has no marketing authorisation [2]regulator.
TRH vs TSH: what is the difference?
TRH is a hypothalamic hormone that makes the pituitary release TSH. TSH in turn makes the thyroid produce thyroid hormones [1]official [5].
Does TRH help the lungs of preterm babies?
No. According to the Cochrane review TRH in pregnancy added to corticosteroids did not improve outcomes for babies and caused side effects in mothers [8]A.
What side effects can the TRH test cause?
Very commonly transient headache, dizziness, nausea, urgent need to urinate and flushing of the face [1]official. Rarely, bleeding into a pituitary tumour can occur [1]official [19]B.
What happens when TRH use is stopped?
In diagnostic use TRH is given as a single injection, so there is no ongoing treatment to stop, and the common side effects last minutes [1]official. In the depression studies the effect was short-lived [15, 16]A.
What did animal studies show about TRH?
In animals protirelin in pregnancy matured the fetal lungs of lambs and rabbits [1]official, but in humans there was no benefit [8]A. Positive animal results in spinal cord injury led to a small human study [14]A.
What can be expected from TRH research in the future?
On 15 October 2026 ClinicalTrials.gov listed no ongoing protirelin studies [21]E, not peer-reviewed. According to a review TRH given through the nose has attracted interest [7].
Is TRH legal in Finland?
Protirelin is on Fimea's medicines list [4]regulator, but it has no marketing authorisation in Finland [2]regulator. This is not legal advice.
Is TRH doping?
The WADA 2026 Prohibited List does not name it [20]regulator. According to the French summary of product characteristics the substance can give a positive result in anti-doping tests [1]official, so an athlete should check with SUEK.
What do users report about TRH?
User accounts of TRH have not been compiled on this site. Individual accounts are not study results.
Read the research yourself: sources
Every source opens the original publication or the regulator's page. The level shows what the source itself reports.
- Base de données publique des médicaments (France). TRH Ferring, solution injectable: product information and summary of product characteristics (page updated 29 Sep 2026). medicaments.gouv.fr official
- European Medicines Agency. Article 57 product data (EMA/518502/2018 Rev.90, data as of 9 Oct 2026): protirelin products in France and Germany only, none in Finland. EMA regulator
- European Medicines Agency. Medicine data (centrally authorised medicines, data set of 14 Oct 2026): no product with protirelin. EMA regulator
- Finland. Lääkeluettelo (Fimea medicines list), decision 230/2025, annex 1: "Protireliini". Finlex regulator
- Joseph-Bravo P, Jaimes-Hoy L, Uribe RM, Charli JL. 60 years of neuroendocrinology: TRH, the first hypophysiotropic releasing hormone isolated: control of the pituitary-thyroid axis. J Endocrinol. 2015;226(2):T85-T100. PMID 26101376 (review)
- Fröhlich E, Wahl R. The forgotten effects of thyrotropin-releasing hormone: Metabolic functions and medical applications. Front Neuroendocrinol. 2019;52:29-43. PMID 29935915 (review)
- Alvarez-Salas E, García-Luna C, de Gortari P. New Efforts to Demonstrate the Successful Use of TRH as a Therapeutic Agent. Int J Mol Sci. 2023;24(13):11047. PMID 37446225 (review)
- Crowther CA, Alfirevic Z, Han S, Haslam RR. Thyrotropin-releasing hormone added to corticosteroids for women at risk of preterm birth for preventing neonatal respiratory disease. Cochrane Database Syst Rev. 2013;2013(11):CD000019. PMID 24265169 A
- Australian collaborative trial of antenatal thyrotropin-releasing hormone (ACTOBAT) for prevention of neonatal respiratory disease. Lancet. 1995;345(8954):877-882. PMID 7707809 A
- Crowther CA, Hiller JE, Haslam RR, Robinson JS; ACTOBAT Study Group. Australian Collaborative Trial of Antenatal Thyrotropin-Releasing Hormone: adverse effects at 12-month follow-up. Pediatrics. 1997;99(3):311-317. PMID 9041281 A
- Ballard RA, Ballard PL, Cnaan A, et al.; North American Thyrotropin-Releasing Hormone Study Group. Antenatal thyrotropin-releasing hormone to prevent lung disease in preterm infants. N Engl J Med. 1998;338(8):493-498. PMID 9468465 A
- Devlieger R, Vanderlinden S, de Zegher F, Van Assche FA, Spitz B. Effect of antenatal thyrotropin-releasing hormone on uterine contractility, blood pressure, and maternal heart rate. Am J Obstet Gynecol. 1997;177(2):431-433. PMID 9290464 A
- Munsat TL, Taft J, Jackson IM, et al. Intrathecal thyrotropin-releasing hormone does not alter the progressive course of ALS: experience with an intrathecal drug delivery system. Neurology. 1992;42(5):1049-1053. PMID 1579228 A
- Pitts LH, Ross A, Chase GA, Faden AI. Treatment with thyrotropin-releasing hormone (TRH) in patients with traumatic spinal cord injuries. J Neurotrauma. 1995;12(3):235-243. PMID 7473798 A
- Marangell LB, George MS, Callahan AM, et al. Effects of intrathecal thyrotropin-releasing hormone (protirelin) in refractory depressed patients. Arch Gen Psychiatry. 1997;54(3):214-222. PMID 9075462 A
- Szuba MP, Amsterdam JD, Fernando AT 3rd, Gary KA, Whybrow PC, Winokur A. Rapid antidepressant response after nocturnal TRH administration in patients with bipolar type I and bipolar type II major depression. J Clin Psychopharmacol. 2005;25(4):325-330. PMID 16012274 A
- Kamath J, Feinn R, Winokur A. Thyrotropin-releasing hormone as a treatment for cancer-related fatigue: a randomized controlled study. Support Care Cancer. 2012;20(8):1745-1753. PMID 21947558 A
- Christensen SE, Smith LN, Rosendal CAH, et al. The TRH test provides valuable information in the diagnosis of central hypothyroidism in patients with known pituitary disease and low T4 levels. Front Endocrinol (Lausanne). 2023;14:1226887. PMID 37850100 B
- Wang HF, Huang CC, Chen YF, Ho DM, Lin HD. Pituitary apoplexy after thyrotropin-releasing hormone stimulation test in a patient with pituitary macroadenoma. J Chin Med Assoc. 2007;70(9):392-395. PMID 17908654 B
- World Anti-Doping Agency. 2026 Prohibited List (sections S0 and S2.2; protirelin / TRH is not named). WADA regulator
- ClinicalTrials.gov. Studies with the intervention protirelin, status recruiting, not yet recruiting or active, searched 15 Oct 2026: none. ClinicalTrials.gov E, not peer-reviewed
Sources searched and read on 15 Oct 2026: PubMed abstracts, the French public medicines database (summary of product characteristics), the EMA Article 57 data and medicine data, Fimea's medicines list, ClinicalTrials.gov and the WADA 2026 Prohibited List (local text copy). Study details are from the abstracts.
Evidence levels: A = randomised human trial or meta-analysis · B = observational human study or case series · C = animal study · D = cell or laboratory study · E = not peer-reviewed · regulator = a regulator's assessment or decision, not research evidence. The marker official means official product information (summary of product characteristics or label); it is not research evidence. For a review, the level shows what kind of research the statement rests on. No level: statements that something has not been studied, reviews' interpretations, named hypotheses and the general rules in our certificate-of-analysis guide.
Content is general information about research, not medical advice. If you have symptoms, contact a healthcare professional.