Persistent hypogonadism influences estradiol synthesis, cognition and outcome in males after severe TBI

Wagner, Amy K.; Brett, Christopher A.; McCullough, Emily H.; Niyonkuru, Christian; Loucks, Tammy L.; Dixon, C. Edward; Ricker, Joseph; Arenth, Patricia; Berga, Sarah L.

doi:10.3109/02699052.2012.667594

Cited by 47Traumatic Brain Injury ResearchHormonal and reproductive studiesTraumatic Brain Injury and Neurovascular Disturbances

Persistent hypogonadism influences estradiol synthesis, cognition and outcome in males after severe TBI

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Wagner, Amy K., Brett, Christopher A., McCullough, Emily H., Niyonkuru, Christian, Loucks, Tammy L., Dixon, C. Edward, Ricker, Joseph, Arenth, Patricia +1 more·2012·Brain Injury

DOI 10.3109/02699052.2012.667594PMC PMC13045844

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Abstract

OBJECTIVE: Acute hypogonadotropic hypogonadism (AHH) occurs frequently after TBI, as does chronic hypogonadotropic hypogonadism. However, AHH and persistent hypogonadotropic hypogonadism (PHH) after TBI are not well studied. The objective of this study was to characterize longitudinal hormone profiles and the impact of AHH and PHH on outcome. METHODS: In this prospective cohort study, men with severe TBI (n = 38) had serum gonadal and gonadotropic hormones measured during weeks 1-52 post-injury. AHH, PHH and/or early resolving hypogonadotropic hypogonadism (ERHH) were based on temporal hormone assessments. PHH and hormone profiles were then compared to multiple outcome measures 6-12 months post-TBI. RESULTS: AHH affected 100% of the population, while 37% subsequently developed PHH. Acute testosterone (TEST) and estradiol/testosterone (E2/TEST) ratios were associated with PHH and outcome. Over time, post-acute TEST and E2 levels for the ERHH group approached normal range, while levels for the PHH group remained low. Post-acute gonadotrophin levels were within the normal range for both groups. PHH, along with lower post-acute TEST and E2 profiles, was associated with worse functional and cognitive outcomes at 6 and 12 months post-injury. CONCLUSIONS: These results support screening for post-acute secondary hypogonadism and further research to assess the mechanisms underlying PHH and associated functional and cognitive deficits.

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Chronic pituitary dysfunction is reported in 15-60% of adults after TBI.
“with reports of chronic pituitary dysfunction in 15-60% of adults after TBI [1-5]”
From Neuroendocrine Disruptions Following Head Injury (2023) · cites this paper as [2]
The Introduction reports chronic hypopituitarism after TBI, but gives a prevalence range of 1.4–29%, not 15–60%. The paper therefore supports the general occurrence of chronic pituitary dysfunction, but states a contrary numerical range. Page numbers are unavailable in our copy. (LLM, conf=0.88)
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In the acute period after TBI, there is no clear role for evaluating anterior pituitary axes other than the ACTH-cortisol axis because changes are thought to serve a compensatory purpose and may be temporary.
“there is no clear role for evaluating the other anterior pituitary axes (thyroid, sex hormone, and growth hormone) as changes are thought to serve a compensatory purpose and may be temporary[1, 2].”
From Neuroendocrine Disruptions Following Head Injury (2023) · cites this paper as [2]
The Introduction says the acute stress response after severe TBI produces HPG-axis deficits, and the Discussion says those deficits resolve for some patients. The paper does not say that the changes serve a compensatory purpose or that there is no clear role for evaluating the thyroid, sex-hormone, and growth-hormone axes in the acute period; its Discussion instead recommends a thorough work-up before hormone replacement. Page numbers are unavailable in our copy. (LLM, conf=0.82)
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Persistent Hypogonadotropic Hypogonadism in Men After Severe Traumatic Brain Injury: Temporal Hormone Profiles and Outcome Prediction
Barton, D. J., Kumar, R. G., McCullough, E. H., Galang, G., Arenth, P. M., Berga, S. L., & Wagner, A. K. (2015) · Journal of Head Trauma Rehabilitation · doi:10.1097/htr.0000000000000188 · Cited by 42 · see citing works
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Avaliação tardia do eixo hipofisário-gonadal em pacientes adultos que sofreram traumatismo cranioencefálico grave
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Hypogonadism after traumatic brain injury
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Hypogonadism after traumatic brain injury Hipogonadismo após traumatismo craniano encefálico
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Acute Gonadotroph and Somatotroph Hormonal Suppression after Traumatic Brain Injury
Wagner, J. J., Dusick, J. R., McArthur, D. L., Cohan, P., Wang, C., Swerdloff, R. S., Boscardin, W. J., & Kelly, D. F. (2010) · Journal of Neurotrauma · doi:10.1089/neu.2009.1092 · Cited by 79 · see citing works

Authors: Wagner, A. K., Brett, C. A., McCullough, E. H., Niyonkuru, C., Loucks, T. L., Dixon, C. E., Ricker, J., Arenth, P., & Berga, S. L.
Affiliations: University of Pittsburgh (US)
Emory University (US)
Corresponding author: Wagner, Amy K.
ORCID: Wagner, Amy K.
Loucks, Tammy L.
Dixon, C. Edward
Ricker, Joseph
Berga, Sarah L.
Venue: Brain Injury
Publisher: Informa UK Limited
Published: 2012-05-09
Volume: 26
Issue: 10
Pages: 1226-1242
ISSN: 0269-9052 (ISSN-L)
1362-301X
DOI: 10.3109/02699052.2012.667594
PMC: PMC13045844
OpenAlex: W1996125219
Cited by: 47
References: 105
Citations by year: 2026: 1 · 2025: 5 · 2023: 1 · 2022: 3 · 2021: 2 · 2020: 5 · 2019: 2 · 2018: 4 · 2017: 2 · 2016: 5 · 2015: 7 · 2014: 5 · 2013: 3 · 2012: 2
FWCI: 4.07
Type: journal article
Language: en
Open access: green
pmc.ncbi.nlm.nih.gov
Locations: Brain Injury (publishedVersion)
PubMed (publishedVersion)
PubMed Central (submittedVersion)
Funders: National Institutes of Health
Centers for Disease Control and Prevention
U.S. Public Health Service (R49 CCR323155)
National Institute of Neurological Disorders and Stroke (P01NS030318)
Topics: Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
Keywords: severe traumatic brain injury, estradiol, testosterone, testosterone/estradiol ratio, gonadotropins, cognitive outcomes, functional outcome
MeSH terms: Adolescent, Adult, Aged, Brain Injuries, Cognition, Cognition Disorders, Estradiol, Humans, Hypogonadism, Male, Middle Aged, Prospective Studies, Surveys and Questionnaires, Stress, Physiological, Glasgow Outcome Scale, Young Adult

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Persistent hypogonadism influences estradiol synthesis, cognition and outcome in males after severe TBI

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