HOW TO TREAT 33
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HOW TO TREAT 33
On examination , his BMI is 37kg / m 2 and blood pressure is 134 / 72mmHg . He has prominent lipomastia , but no gynaecomastia , and mildly reduced muscle bulk . His testes are 20mL bilaterally . Eye movements are full , and there is no clinical visual field defect .
Laboratory results reveal a total testosterone ( sample drawn at 8am while fasting ) of 7.8nmol / L ( 10.4-31.2nmol / L ) with a repeated total testosterone sample drawn one week later at 8am while fasting of 7.2 nmol / L . LH is 4.8mIU / mL ( 1.0-10.0mIU / L ), SHBG 9.8nmol / L ( 10-60nmol / L ), haemoglobin 154g / L ( 138-172g / L ) and HbA1c 8.1 % ( 4.0-5.6 %). Thyroid function and prolactin are normal .
Charles asks whether he needs testosterone treatment and if this would alleviate his symptoms of erectile function , fatigue and low mood .
Charles presents with nonspecific symptoms . His serum testosterone is modestly reduced and there is no evidence of organic hypogonadism . There is no clinical evidence of a pituitary mass , and thyroid function and prolactin are normal . In this scenario , pituitary imaging would only be indicated if his serum testosterone was less than 5.2nmol / L . Of note , the low-normal SHBG seen in Charles is typical because low SHBG is strongly associated with ( central ) adiposity and insulin resistance in men . The low SHBG leads to a concomitant reduction in total testosterone — a scenario known as pseudo-hypogonadism .
A meta-analysis of randomised controlled trials , which included older symptomatic men with modest age-related reductions in serum testosterone , concluded testosterone treatment had no effect on energy or mood . 23 Therefore , testosterone treatment is not expected to improve Charles ’ symptoms .
His erectile dysfunction is likely vascular in origin , given his cardiac history , and also would not be expected to respond to testosterone treatment . This is explained to Charles and an alternative treatment plan is developed . The most appropriate next step in his management would be the initiation of a long-acting GLP-1 receptor agonist to improve his HbA1c and achieve weight loss . In addition , a PDE5 inhibitor is recommended to improve his erectile function . Charles agrees to this plan .
At review six months later , he has lost 10kg , his HbA1c has improved to 6.7 %, and his testosterone has normalised ( 12.8nmol / L ). Use of a PDE5 inhibitor as required has improved his erectile function . Charles ’ fatigue and low mood have improved considerably .
This is a typical scenario of functional pseudo-hypogonadism with nonspecific symptoms unrelated to the mildly low testosterone . It illustrates the importance of weight loss in improving symptoms and reactivating the HPT axis . In addition , GLP-1 receptor agonists have proven cardiovascular benefits , an important consideration given Charles ’ cardiac history .
Case study two
Bruce , a 54-year-old man , seeks a second opinion regarding testosterone treatment . He presented to a different GP 12 months ago with low libido and fatigue . At that time , his serum total testosterone concentration was 9.0nmol / L . He was prescribed standard-dosage topical testosterone
Table 3 . Possible benefits of testosterone therapy in older men with age-related reductions in serum testosterone ( without organic hypogonadism )
Domain Testosterone effect First-line therapy Sexual
Muscle
Modest increase in overall function if total testosterone is less than 9.54nmol / L ( in some studies )
Libido improves more than erectile function In men with cardiovascular disease , erectile function does not improve
1.6-2.7kg increase in mass , and strength
No evidence for improved physical function , except for small improvement in walking distance in the six-minute walk test
gel . At follow-up with the GP three months later , he reported improved energy and libido . His serum testosterone concentration on treatment had increased to 16.1nmol / L .
At subsequent review nine months after initiating testosterone gel , he reported that his fatigue had returned and his libido had declined , similar to how he felt before testosterone treatment . His serum testosterone concentration was then 17.4nmol / L .
At today ’ s appointment , he describes fatigue , low libido and low mood . His serum testosterone concentration ( sample drawn several days ago ) is 15.0nmol / L . Apart from testosterone gel , he takes no regular medications and has no medical history of note .
On examination , Bruce has normal body hair and normal muscle bulk . There is mild gynaecomastia that is tender to palpation . His testes are 20mL bilaterally .
Bruce was inappropriately prescribed testosterone treatment based on nonspecific symptoms and a single testosterone measurement that was modestly low . It was not stated whether the blood for the pre-treatment testosterone level was drawn
PDE5 inhibitor
No added benefit of testosterone treatment
Exercise
Fat |
1.6-2.0kg decrease |
Weight loss by lifestyle or , where indicated , |
|
|
weight loss medications or bariatric surgery |
Glucose metabolism
Bone
Modest improvement in insulin resistance in some RCTs
Reduction of type 2 diabetes in high-risk men , if coupled with a community-based lifestyle program , as assessed by oral glucose tolerance test , but no effect on HbA1c
3.7 % increase in lumbar spine BMD
Possible increase in fracture risk in older men especially in the first 3-6 months of treatment
Optimisation of glycaemic control ( lifestyle , medications )
Antiresorptives
Mood / cognition No consistent effects Counselling , antidepressants
Figure 7 . Bone mineral density .
Figure 8 . International index of erectile function score . in the afternoon or after food intake , both of which can reduce serum testosterone by up to 30 %. It is important that the clinical impression is confirmed biochemically by documenting at least two low total testosterone concentrations , drawn in the morning , in the fasted state .
Testosterone should not be measured during an intercurrent illness , as this can lead to temporary gonadal axis suppression . If testosterone is repeatedly and unequivocally low , additional investigations are required to determine the aetiology of the hypogonadism . The diagnostic workup must be performed before testosterone treatment is started , as exogenous testosterone will make interpretation of additional investigations ( such as gonadotropins ) impossible .
In Bruce ’ s case , testosterone therapy , despite consistently achieving ‘ therapeutic ’ serum testosterone concentrations ( that is , in the mid-normal reference range ) over 12 months , did not lead to sustained improvement of his nonspecific symptoms . If sexual and subjective symptoms are due to a low testosterone , they should improve within 3-6 months . The initial improvement of his nonspecific symptoms is consistent with a placebo response , which is well documented .
Unfortunately , Bruce ’ s case is common . There is good evidence that testosterone is inappropriately and over-prescribed . 41 Consistent with this , observational studies have reported that less than 20 % of men starting testosterone therapy continue the treatment for longer than six months . 42 In Bruce , testosterone treatment was not indicated and should now be stopped . He requires investigation for other causes of his symptoms , such as undiagnosed depression or chronic disease .
SUMMARY AND CONCLUSION
ORGANIC hypogonadism may present in many ways , such as psychosexual symptomatology , unexplained osteoporosis , anaemia or sarcopenia , and the diagnosis can be missed . It is a clinical diagnosis consisting of suggestive symptoms and signs confirmed by low testosterone levels . While many of the clinical features of hypogonadism are non-specific , the combination of several features in men without risk factors for these , such as otherwise healthy lean young men , should raise suspicion . In men with organic hypogonadism , testosterone replacement has marked benefits , but may impair fertility .
Older men with chronic disease commonly present with nonspecific symptoms and modestly low testosterone levels ; this makes the diagnosis of androgen deficiency more difficult than in younger otherwise healthy men without comorbidities . Older men with specific features of androgen deficiency and unequivocally low testosterone levels should be thoroughly evaluated for an underlying pathological cause . It should not be assumed that their presentation is a non-specific consequence of age-related comorbidities or obesity .
CC BY 4.0 / Ruzić A , et al . Coll Antropol . 2007 Mar ; 31 ( 1 ): 185-8 / bit . ly / 49syVgB