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TRH research

What published studies found for TRH: 7 papers, 7 in humans, with sample sizes and key results, plus 6 registered clinical trials.

Some human evidence

Why: Large RCTs and a Cochrane review are consistently negative, but only for antenatal lung protection; trials in mood and other uses are small and old.

TRH (protirelin) has substantial human trial data: a Cochrane review of 15 trials found antenatal TRH did not prevent neonatal lung disease and caused maternal side effects and some infant harms. Small older trials in depression, schizophrenia and fatigue report short-lived or preliminary benefits.

✓ 3 positive✗ 2 negative~ 1 mixed? 1 inconclusive

Maternal side effects in antenatal trials were significantly more common with TRH than control.

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Reported side effects

reportedNausea [ref]
reportedVomiting [ref]
reportedLight-headedness [ref]
reportedUrinary urgency [ref]
reportedFacial flushing [ref]
reportedIncreased need for respiratory support and low 5-minute Apgar score in infants after antenatal exposure [ref]
reportedMild, infrequent subjective side effects [ref]

Registered clinical trials

6 trials of TRH on ClinicalTrials.gov: 2 active, 2 completed, 2 with posted results. Registered trials include ones that haven't published yet.

Trial	Status	Phase	People	Sponsor
LISH Trial for the Hepatic Flexure and Proximal Transverse Colon CancerNCT05923255 · started 2023-05-14	Recruiting	–	568	Zhejiang University
LIRRH Trial for the Right-sided Colon CancerNCT07207317 · started 2025-05-01	Recruiting	–	120	Chaoxi Zhou
Study of Thyrotropin-Releasing Hormone in Normal Volunteers and in Patients With Thyroid or Pituitary AbnormalitiesNCT00054756 · started 2003-02-07 · results posted	Completed	Phase 2	96	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Evaluation of Synthetic Thyrotropin Releasing Hormone (TRH) as a Treatment for Cancer-related FatigueNCT00790296 · started 2006-12 · results posted	Terminated	Phase 2	11	UConn Health
Thyroid Function in Critically Ill Patients With Acute Kidney InjuryNCT04767763 · started 2019-02-19	Completed	–	32	Medical University of Gdansk
Study of Resistance to Thyroid Hormone After Long-term Exposure in People With Thyroid CancerNCT04868045 · started 2021-04-27	Withdrawn	Phase 1	–	Memorial Sloan Kettering Cancer Center

All 6 TRH trials, with countries and recruiting status

Meta-analyses & systematic reviews

✗ Negativemeta-analysisCochrane Database Syst Rev · 2013

Thyrotropin-releasing hormone added to corticosteroids for women at risk of preterm birth for preventing neonatal respiratory disease.

15 trials, over 4600 womenCochrane systematic review of randomised controlled trials

Cochrane review (15 trials, >4,600 women): antenatal TRH added to steroids did not reduce infant death, RDS or chronic lung disease and increased need for respiratory support and low Apgar scores.

Key resultNo reduction in death before discharge (RR 1.05, 95% CI 0.86 to 1.27, six trials, 3694 infants); respiratory support needed more often (RR 1.16, 95% CI 1.03 to 1.29)

Studied: Women at risk of preterm birth given prenatal corticosteroids
Compared with: Corticosteroids with or without placebo
Main outcome: Neonatal death, respiratory distress syndrome, chronic lung disease
Authors' conclusion: Prenatal TRH added to corticosteroids does not improve infant outcomes and can cause maternal side effects.
Limitations: Trials had a moderate risk of bias; only three trials gave childhood follow-up data.

PubMed 24265169 DOI Free full text

Human studies

✗ Negativehuman RCTN Engl J Med · 1998

Antenatal thyrotropin-releasing hormone to prevent lung disease in preterm infants. North American Thyrotropin-Releasing Hormone Study Group.

n = 996 humansDouble-blind placebo-controlled randomized trial

RCT of 996 women in preterm labour (<30 weeks): antenatal TRH plus steroids gave no reduction in RDS, death or chronic lung disease vs steroids alone.

Key resultChronic lung disease or death at 28 days 45 percent vs 42 percent (TRH vs placebo), not significantly different

Studied: Women in preterm labor at <30 weeks' gestation
Compared with: Placebo
Main outcome: Chronic lung disease or death of the infant by day 28 after delivery
Sample: 996 women enrolled; 981 with complete data and 1134 live-born infants
Authors' conclusion: In preterm infants at risk for lung disease, antenatal TRH plus glucocorticoid is no more beneficial than glucocorticoid alone.

PubMed 9468465 DOI

✓ Positivehuman RCTLancet · 1992

Respiratory disease in very-low-birthweight infants after prenatal thyrotropin-releasing hormone and glucocorticoid. TRH Study Group.

n = 404 humansMulticentre, blinded, randomised trial

Earlier RCT (404 women): in fully treated very-low-birthweight infants, TRH plus betamethasone reduced chronic lung disease (18% vs 44%), a finding not confirmed by later larger trials.

Key resultChronic lung disease 18% vs 44% of controls (p less than 0.01); total respiratory distress syndrome 47% vs 58%, not affected

Studied: Women with threatened preterm delivery at less than 32 weeks' gestation
Compared with: Betamethasone plus placebo
Main outcome: Respiratory distress syndrome and chronic lung disease (oxygen need at 28 days)
Sample: 404 women randomized; 103 fully treated infants under 1500 g evaluated
Authors' conclusion: Prenatal TRH reduces the incidence of chronic lung disease among betamethasone-treated infants.
Limitations: Analysis based on 103 evaluated infants.

PubMed 1346877 DOI

✓ Positivehuman RCTArch Gen Psychiatry · 1978

Behavioral effects of protirelin in schizophrenia.

n = 143 humansMulti-institutional double-blind controlled study14 days

Double-blind controlled study in 143 chronic schizophrenia patients: oral protirelin added to neuroleptics was rated superior to placebo on global efficacy; no adverse reactions reported.

Studied: Chronic schizophrenic patients continuing neuroleptics
Compared with: Placebo
Main outcome: Physicians' global ratings of efficacy
Sample: 143 chronic schizophrenic patients
Authors' conclusion: Protirelin (4 mg/day orally) appeared significantly superior to placebo on physicians' global ratings, with improved motivation for work; no adverse reactions were encountered.
Limitations: Abstract gives no numerical results.

PubMed 98128 DOI

✓ Positivehuman RCTArch Gen Psychiatry · 1997

Effects of intrathecal thyrotropin-releasing hormone (protirelin) in refractory depressed patients.

Eight patients (crossover)Double-blind crossover vs sham lumbar punctureTwo procedures separated by 1 week

Crossover study in 8 refractory depressed inpatients: intrathecal TRH produced rapid but short-lived improvement in mood and suicidality in 5 of 8.

Key result5 of 8 patients responded to 500 micrograms intrathecal protirelin; suicidality reduced significantly (P < .05)

Studied: Medication-free inpatients with refractory depression
Compared with: Sham lumbar puncture
Main outcome: 50% or greater reduction in abbreviated Hamilton Rating Scale for Depression score
Authors' conclusion: Intrathecal protirelin induced rapid but short-lived improvement in mood and suicidality, supporting TRH as a possible positive modulator of mood.
Limitations: Only 8 patients; effects were short-lived.

PubMed 9075462 DOI

~ Mixedhuman RCTArch Gen Psychiatry · 1979

TRH (protirelin) in depressed alcoholic men. Behavioral changes and endocrine responses.

HumansDouble-blind placebo-controlled study

Placebo-controlled study in depressed alcoholic men: protirelin improved behaviour 3 hours after injection but not on subsequent days.

Studied: Chronic alcoholics with secondary depression
Compared with: Placebo
Main outcome: Behavioral changes and endocrine responses (TSH, growth hormone, prolactin)
Authors' conclusion: Protirelin had a beneficial behavioral effect three hours after injection but not on subsequent days, during acute alcohol withdrawal. Blunted TSH response was associated with favorable behavioral response.
Limitations: Behavioral effect was short-lived; sample size not stated in the abstract.

PubMed 107908 DOI

? Inconclusivehuman trialJ Int Med Res · 2009

Thyrotropin-releasing hormone can relieve cancer-related fatigue: hypothesis and preliminary observations.

Three patients; six TRH treatments and six saline controlsPreliminary observations from a randomized placebo-controlled crossover pilot4 consecutive weeks

Preliminary crossover observations in 3 breast cancer patients: TRH reduced fatigue in 4 of 6 treatments vs 1 of 6 saline controls.

Key resultAnti-fatigue effects in four of six TRH treatments; no response in five of six saline controls

Studied: Breast cancer patients with cancer-related fatigue
Compared with: Saline
Main outcome: Global assessment of fatigue (subjective and objective)
Authors' conclusion: These initial findings support the proposal that TRH can ameliorate cancer-related fatigue.
Limitations: Only three patients; preliminary observations from an ongoing pilot.

PubMed 19761698 DOI

Verdicts are judged on each paper's own main outcome; grades run from A (strong human evidence) to D (little or none). Details are read from the abstracts, and figures are reproduced only from openly licensed full texts. Not medical advice.