Title: Testosterone Effects and Safety in Men with Low Testosterone levels (TESTES): An evidence synthesis and economic evaluation
Funder: Department of Health and Social Care

Abstract: Levels of circulating testosterone decline by approximately 1% annually from the age of 40 years onwards. One third to one half of middle-aged men have serum testosterone levels below the reference range for young men. Low testosterone is associated with sexual dysfunction, tiredness, reduced muscle strength, osteoporosis and mood disturbance. However, these symptoms are non-specific and may be caused by co-morbidities such as obesity and depression rather than low testosterone itself. Prescriptions of androgen replacement therapy (ART) in men have nearly doubled within the last 10 years in the UK, yet the incidence of symptomatic men with low testosterone levels remains unchanged. This suggests that the threshold for treating men with ART is reducing. Previous reports on the clinical effectiveness of ART have been conflicting in terms of effectiveness whilst highlighting potential risks of cardiovascular events and prostate growth. Important questions must be addressed to determine the role of ART for the treatment of men with symptomatic low testosterone: 1. What are the clinical benefits and risks of ART? 2. Which groups of men are most likely to experience clinical benefits and risks of ART? 3. What are the experiences of men using ART? 4. What is the cost-effectiveness of ART? We propose an Individual Participants Data Meta-Analysis (IPD MA) of randomised trials investigating the clinical effectiveness and safety of ART in symptomatic men with low testosterone. This quantitative analysis will be complemented by a qualitative synthesis to ascertain the experience of patients using ART along with the views of their partners and treating clinicians. Finally, we will conduct a systematic review of economic evaluations and develop a new evaluation model based on the results of the IPD meta-analysis.

Lay abstract: Testosterone is a hormone which is vital for sexual activity, bone growth and muscle development in men. Men with low testosterone levels may experience problems with erections and may suffer from brittle bones (osteoporosis), weakness, feeling down (low mood) and tiredness. The symptoms of low testosterone can be treated with artificial testosterone (known as Androgen Replacement Therapy or ART). However, doctors are uncertain and often disagree about, how beneficial or harmful ART might be in men with symptoms of low testosterone. This is because clinical studies conducted in men with low testosterone levels have returned conflicting findings. This is likely to be caused by individual studies including different types of patients (e.g. different levels of physical health), and measuring men’s response to ART in different ways. It is also important for doctors to better understand the thoughts and experiences of men, and their partners, in relation to ART. We will for the first time ‘piece together’ all the information about patients from each clinical study on ART, in order to determine how effective and safe ART is for different groups of patients. The first step will be to identify all the published clinical studies which deal with giving ART to men with low testosterone. The second step of the study will be to obtain information about each patient who is given ART for low testosterone; to preserve patient confidentiality, they will remain anonymous. Finally, we will combine the results of all the individual studies, to create a single information resource about ART for the NHS. Having all the information about ART in men with low testosterone in one place, will enable us to answer several important questions about ART, for the benefit of patients, the public, and healthcare professionals: • Which symptoms improve during ART, and by how much do they improve? • Which common harmful effects are experienced during ART, and what is the chance of them happening? • What are the biggest factors (such as patient age) affecting the response to ART? • What are the main motivations and problems experienced by men with low testosterone taking ART? • What are the costs of low testosterone and ART for the NHS? The proposed work will have a major and immediate impact on patients and the NHS. The findings of our project will provide useful information on the risks and benefits of ART in different patient groups and will allow men and clinicians who look after them to make informed decisions about the need and use of ART.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH