Key papers ✓ 3✗ 2~ 1? 1

• ✗ Negative meta-analysisCochrane Database Syst Rev · 2013

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

  Humans15 trials, over 4600 women15 trials pooledRandomized trials

  Cochrane 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)

  Study details

  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.

  DOI 10.1002/14651858.CD000019.pub3PubMed 24265169Free full text
• ✗ Negative human RCTN Engl J Med · 1998

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

  Humans996 peopleRandomizedPlacebo-controlledDouble-blind

  Double-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

  Study details

  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.

  DOI 10.1056/NEJM199802193380802PubMed 9468465
• ✓ Positive human RCTLancet · 1992

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

  Humans404 peopleRandomizedPlacebo-controlled

  Multicentre, 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

  Study details

  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.

  DOI 10.1016/0140-6736(92)90337-3PubMed 1346877
• ✓ Positive human RCTArch Gen Psychiatry · 1978

  Behavioral effects of protirelin in schizophrenia.

  Humans143 peopleRandomizedPlacebo-controlledDouble-blind14 days

  Multi-institutional double-blind controlled study

  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.

  Study details

  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.

  DOI 10.1001/archpsyc.1978.01770320105010PubMed 98128
• ✓ Positive human RCTArch Gen Psychiatry · 1997

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

  HumansEight patients (crossover)RandomizedSham/vehicle controlDouble-blindTwo procedures separated by 1 week

  Double-blind crossover vs sham lumbar puncture

  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)

  Study details

  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.

  DOI 10.1001/archpsyc.1997.01830150034007PubMed 9075462
• ~ Mixed human RCTArch Gen Psychiatry · 1979

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

  Humanssize not reportedRandomizedPlacebo-controlledDouble-blind

  Double-blind placebo-controlled study

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

  Study details

  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.

  DOI 10.1001/archpsyc.1979.01780050050005PubMed 107908
• ? Inconclusive human trialJ Int Med Res · 2009

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

  Humanssize not reportedRandomizedPlacebo-controlled4 consecutive weeks

  Preliminary observations from a randomized placebo-controlled crossover pilot

  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

  Study details

  Studied

  Breast cancer patients with cancer-related fatigue

  Compared with

  Saline

  Main outcome

  Global assessment of fatigue (subjective and objective)

  Sample

  Three patients; six TRH treatments and six saline controls

  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.

  DOI 10.1177/147323000903700420PubMed 19761698

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]

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

6 registered human trials (2 active)

✓ positive · ✗ negative · ~ mixed · ? inconclusive, judged on each paper's own main outcome. Grades: A strong human evidence → D little or none. Papers and verdicts are drawn from PubMed, Europe PMC and Russian journals (CyberLeninka); not medical advice.