STARS4Diabetes
Research type
Research Study
Full title
Study to determine the Efficacy of the Androgen Receptor Repeat Polymorphism in the Diagnosis and Treatment of Male Hypogonadism and to confirm validation of the Barnsley Diabetes Hypogonadism Questionnaire
IRAS ID
220878
Contact name
Hugh Jones
Contact email
Sponsor organisation
Barnsley Hospital HNS Foundation Trust
Duration of Study in the UK
2 years, 1 months, 21 days
Research summary
The diagnosis of male hypogonadism (testosterone deficiency) must comprise both symptoms with or without clinical signs and biochemical evidence of testosterone deficiency.The diagnosis is complicated by the fact that the symptoms of hypogonadism are non-specific and there are no clear cut-off thresholds of serum testosterone. This is further complicated with the knowledge that symptomatic men with total testosterone within the lower part of the normal healthy range can have hypogonadism which responds to testosterone replacement.
Total testosterone (TT) assays are the most commonly used in clinical practise but there are no generally accepted lower limits of normal. TT is a combination of three sub-fractions of testosterone – (1) free T, (2) albumen-bound T and (3) sex hormone-bound globulin (SHBG) bound T. The free T (FT) and albumen-bound T are biologically active (bioavailable) (BioT) whereas SHBG tightly binds the T and is considered to be inactive. Mathematical equations using complex regression analysis can estimate both FT and BioT if the TT, SHBG and albumin levels are known and are useful in clinical practise. However, there are differences between acceptable cut-off thresholds between guidelines.
The degree of tissue androgenisation in an individual male is not only dependent on the circulating level of BioT but also on the sensitivity of the Androgen Receptor (AR). There is a repeat CAG polymorphism found in exon 1 of the AR gene where the greater the number of CAG repeats the less sensitive the biological activity of the receptor. In humans the number of repeats range between 9 and 35. High receptor sensitivity (lower CAG repeat number) is for example associated with increased bone mineral density (BMD), prostate size, sperm count whereas low receptor sensitivity correlates with increased body fat content, BMI, insulin levels and lower BMD.
Not infrequently clinicians have to give a trial of testosterone replacement therapy (TRT) to assess whether there is any clinical benefit. Currently, available questionnaires are used by doctors to determine and support changes in symptoms. These again are helpful but not ideal. Resolution of symptoms of hypogonadism can take up to six months and occasionally longer.
Evidence therefore strongly supports the fact that the degree of androgen receptor sensitivity is an important factor that should be utilised clinically not only in the diagnostic assessment of hypogonadism but also as a guide to the response of treatment and also titration of testosterone dosage.
REC name
Yorkshire & The Humber - Leeds East Research Ethics Committee
REC reference
18/YH/0042
Date of REC Opinion
16 Mar 2018
REC opinion
Further Information Favourable Opinion