Evaluation of Association Between Testosterone Levels, Dementia, and Adverse Mental Health Outcomes

Recruiting

• Conditions: Depression; Genetic Disorder; Hematopoietic and Lymphoid Cell Neoplasm; Anxiety Disorder; Malignant Solid Neoplasm
• Interventions: Other: Electronic Health Record Review

• Registration Number: NCT04743466
• Lead Sponsor: M.D. Anderson Cancer Center

Brief Summary

This study evaluates the association between testosterone levels and risk of dementia and adverse mental health outcomes (e.g. depression and anxiety). It is not known whether low testosterone levels may be associated with an increased risk of dementia. Learning about the association between testosterone levels and risk of dementia may help determine the long-term effects of androgen deprivation therapy and may help improve quality of life.

Detailed Description

PRIMARY OBJECTIVE:

I. To use a Mendelian randomization study design to determine whether genetically predicted decreased testosterone levels are associated with an increased risk of dementia.

SECONDARY OBJECTIVE:

I. To examine whether genetically predicted decreased testosterone levels are associated with worse cognitive function and adverse mental health outcomes.

OUTLINE:

Patients' records from institutional or national biobanks are reviewed.

Study Timeline

• Study Start: 2020-02-13
• Study First Submitted: 2021-02-03
• Study First Submitted QC: 2021-02-03
• Study First Posted: 2021-02-08
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-15
• Last Update Posted: 2024-08-16
• Primary Completion: 2025-11-30
• Study Completion: 2025-11-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 700000

Inclusion Criteria

• Have volunteered to participate in institutional or national biobanks, mainly the UK Biobank and the Kaiser Permanente Research Bank, and those that have previously participated in studies that resulted in de-identified clinical and genetic data being make available on public archives, mainly the database of Genotypes and Phenotypes (dbGaP)
• No special populations (adults unable to consent, individuals not yet adults, pregnant women, or prisoners)

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Observational (biobank review)	Electronic Health Record Review	Patients' records from institutional or national biobanks are reviewed.

Primary Outcome Measures

Name	Time	Method
Association between germline genetic predictors (single nucleotide variants) of lower testosterone levels and dementia risk	Up to 2 years	Will utilize genetic variants associated with testosterone levels at genome-wide statistical significance thresholds (P \< 5 x 10-8) in published meta-analyses. Will additionally conduct a genome-wide association study with testosterone values in the UK Biobank. Will construct a weighted genetic risk score based on the strength of each variant's association with testosterone levels in published datasets. The results of the weighted method will be scaled per standard deviation (SD) of testosterone levels so that effect sizes represent the odds ratio of the outcome (e.g. dementia) per genetically predicted SD decrease in testosterone levels. Will also utilize risk scores with less stringent significance thresholds in secondary analyses (P \< 5 x 10-6).

Secondary Outcome Measures

Name	Time	Method
Anxiety	Up to 2 years	Association between low testosterone levels and anxiety will be examined. Will construct a weighted genetic risk score based on the strength of each variant's association with testosterone levels in published datasets. The results of the weighted method will be scaled per standard deviation (SD) of testosterone levels so that effect sizes represent the odds ratio of the outcome (e.g. dementia) per genetically predicted SD decrease in testosterone levels. Will also utilize risk scores with less stringent significance thresholds in secondary analyses (P \< 5 x 10-6).
Depression	Up to 2 years	Association between low testosterone levels and depression will be examined. Will construct a weighted genetic risk score based on the strength of each variant's association with testosterone levels in published datasets. The results of the weighted method will be scaled per standard deviation (SD) of testosterone levels so that effect sizes represent the odds ratio of the outcome (e.g. dementia) per genetically predicted SD decrease in testosterone levels. Will also utilize risk scores with less stringent significance thresholds in secondary analyses (P \< 5 x 10-6).
Cognitive/mental health	Up to 2 years	Association between low testosterone levels and cognitive/mental health will be examined. Will construct a weighted genetic risk score based on the strength of each variant's association with testosterone levels in published datasets. The results of the weighted method will be scaled per standard deviation (SD) of testosterone levels so that effect sizes represent the odds ratio of the outcome (e.g. dementia) per genetically predicted SD decrease in testosterone levels. Will also utilize risk scores with less stringent significance thresholds in secondary analyses (P \< 5 x 10-6).

Trial Locations

Locations (1)

M D Anderson Cancer Center; 🇺🇸 Houston, Texas, United States