Exploring the Relationship Between Androgen Metabolism, Metabolic Disease and Skeletal Muscle Energy Balance in Men

Summary

This study relates to men with hypogonadism, a condition describing a deficiency of androgens such as testosterone. Deficiency of these hormones occurs in men due to testicular (primary) or hypothalamic-pituitary (secondary) problems or may be observed in men undergoing androgen deprivation therapy for prostate cancer.

Testosterone plays an important role in male sexual development and health, but also plays a key role in metabolism and energy balance. Men with testosterone deficiency have higher rates of metabolic dysfunction. This results in conditions such as obesity, nonalcoholic fatty liver disease, diabetes, and cardiovascular disease. Studies have confirmed that treating testosterone deficiency with testosterone can reduce the risk of some of these adverse metabolic outcomes, however cardiovascular mortality remains higher than the general population. We know that testosterone deficiency therefore causes metabolic dysfunction. However, research to date has not established the precise mechanisms behind this.

In men with hypogonadism there is a loss of skeletal muscle bulk and function. Skeletal muscle is the site of many critical metabolic pathways; therefore it is likely that testosterone deficiency particularly impacts metabolic function at this site. Men with testosterone deficiency also have excess fat tissue, this can result in increased conversion of circulating hormones to a type of hormone which further suppresses production of testosterone. The mechanism of metabolic dysfunction in men with hypogonadism is therefore multifactorial.

The purpose of this study is to dissect the complex mechanisms linking obesity, androgens and metabolic function in men. Firstly, we will carry out a series of detailed metabolic studies in men with testosterone deficiency, compared to healthy age- and BMI-matched men. Secondly, we will perform repeat metabolic assessment of hypogonadal men 6 months after replacement of testosterone in order to understand the impact of androgen replacement on metabolism. Lastly, we will perform the same detailed metabolic assessment in men with prostate cancer before and after introduction of a drug which causes testosterone deficiency for therapeutic purposes.

Conditions

• Hypogonadism, Male
• Testosterone Deficiency
• Prostate Cancer
• Androgen Deficiency
• Metabolic Disease
• Metabolic Syndrome
• Metabolic Disturbance
• Obesity
• Cardiovascular Diseases
• NAFLD
• Diabetes

Interventions

DRUG

Testosterone

In OBS1 20 men will be started on Testosterone replacement therapy as per routine clinical practice. Data collection will occur prior initiating therapy, and 6 months post

DRUG

GnRH

20 men in OBS2 planned for GnRH analogue therapy will undergo data collection prior, and 3 months post initiation of GnRH analogue therapy

Sponsors & Collaborators

• Steroid Metabolism Analysis Core, University of Birmingham

  collaborator UNKNOWN

• University of Liverpool

  collaborator OTHER

• Royal College of Surgeons, Ireland

  lead OTHER

Eligibility

Min Age

18 Years

Max Age

60 Years

Sex

MALE

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2023-03-12

Primary Completion

2024-08-31

Completion

2024-08-31

Countries

• Ireland

Study Locations