30 HOW TO TREAT : MANAGEMENT OF LOW TESTOSTERONE IN MEN
30 HOW TO TREAT : MANAGEMENT OF LOW TESTOSTERONE IN MEN
9 AUGUST 2024 ausdoc . com . au comorbidities ( for example , depression , sleep apnoea or glycaemic control in diabetes ) and where possible removal of implicated medications ( for example , opioids , glucocorticoids ) is also very important . These strategies may safely raise testosterone concentrations and have other health benefits .
Young men with an energy deficit from either malnutrition ( for example , anorexia nervosa ) or excessive exercise ( also referred to as Relative Energy Deficiency in Sport [ RED-S ] syndrome , see figure 6 ), or a combination of restricted eating and excessive exercise , may have severe hypogonadism .
These young men display the so-called athletic triad , comprising hypogonadism , low energy availability ( with or without an eating disorder ) and decreased bone mineral density ( see figure 7 ). 2
While this energy deficit is recognised predominately in women ( and referred to as the female athletic triad , see figure 6 ), it can also occur in men . The associated hypogonadism in men is reversible on rectifying the energy deficit . 3 Obesity is the strongest risk factor for low testosterone , even overriding the effects of age . 4 This is in part because obesity blunts the age-related luteinising hormone ( LH ) rise that can compensate for the testicular dysfunction that occurs in some older men . Consistent with this , successful weight loss , whether by diet , weight-loss medication or surgery , can lead to substantial increases in testosterone in obese men . The increase in testosterone is proportional to the amount of weight lost : 10 % weight loss increases testosterone by 2-3nmol / L , whereas profound weight loss after bariatric surgery can raise testosterone by more than 10nmol / L in morbidly obese men . 5
Lifestyle measures
Most older men presenting with a low testosterone have comorbidities , especially overweight / obesity , which can supress the HPT axis and may contribute to non-specific androgen deficiency-like symptoms . For example , in the 2009 population-based European Male Ageing Study ( EMAS ) study , obesity was associated with a 13-fold increased prevalence of LOH compared with normal weight , while the presence of two or more comorbidities was associated with a ninefold increase compared with men without comorbidities . 6
Lifestyle measures for older men with a lowered testosterone include achieving a healthy body weight , personalised exercise recommendations , and optimisation of comorbidities as part of clinical care . These measures , while difficult to achieve , can be very effective .
A 2013 meta-analysis of men with a BMI of 30-40kg / m 2 showed that a low caloric diet led to a 9.8 % loss of body weight and an increase in serum testosterone of 2.87nmol / L . 7
A 2016 RCT of obese men ( baseline BMI 37kg / m 2 , serum testosterone 7.0nmol / L ) reported a 9.1 % weight loss achieved with a low caloric diet in association with a 2.9 % increase in testosterone . 8
Given that most men with so-called late-onset hypogonadism have testosterone levels that fluctuate around the lower limit of the assay range , weight loss by way of dietary changes may be sufficient to
Figure 1 . Histopathology of high-grade prostatic intraepithelial neoplasia .
Table 1 . Contraindications to testosterone treatment
Absolute contraindications
Relative contraindications
Untreated high-grade prostate cancer ( see figure 1 )
Untreated breast cancer
Severe lower urinary tract symptoms
Unevaluated prostate nodule
Idiopathic venous thromboembolism in the past 3-6 months
Treated Gleason * stage 3 + 4 or 3 + 3 prostate cancer confined to the prostate and in remission
Treated breast cancer in remission
Venous thromboembolism ( see figure 2 ) or thrombophilia
Erythrocytosis / polycythaemia ( before initiation of testosterone therapy ; see figure 3 )
Major adverse cardiovascular event ( see figure 4 ) in the past six months
normalise their serum testosterone . In addition to diet , recommending a patient-appropriate exercise program is very important . Moderate exercise can improve LOH-associated end-organ deficits such as sarcopenia , reduced bone mass and the metabolic syndrome , and may modestly improve erectile function , acting synergistically with phosphodiesterase-5 inhibitors ( PDE5-I ). 9
While it is often difficult to achieve and sustain weight loss with lifestyle measures alone , effective pharmacotherapy ( for example ,
Requires informed consent of patient
Consultation with urologist or oncologist is recommended
Consultation with oncologist is recommended
Haematological assessment and anticoagulation required
Investigate aetiology and haematological assessment as required
Requires documentation of benefit-risk analysis
Documentation of informed consent recommended
* The pathologist assigns one Gleason grade to the most predominant pattern in the biopsy and a second Gleason grade to the second most predominant pattern ( eg , 3 + 4 ). The two grades are added to determine the Gleason score . Gleason scores range from 6-10 ( 6 is low grade , 7 is intermediate grade , and 8-10 is high-grade cancer ).
Source : Grossmann M et al 2023 1 incretin-based therapies such as glucagon-like peptide-1 [ GLP-1 ] agonists ), have recently become available and are currently PBS-subsidised for men with type 2 diabetes , but not for the treatment of obesity .
GLP-1 agonists not only promote weight loss , but , in contrast to testosterone therapy ( see below ), have proven cardiovascular benefits , including the reduction of major adverse cardiovascular events ( reductions in the risk of cardiovascular death , nonfatal stroke by 16 % [ P = 0.007 ]), and all-cause mortality . 10
CC0 1.0 / Mikael Häggström , M . D ./ bit . ly / 3OXg0SM
Box 1 . Eligibility criteria for PBS-subsidised testosterone treatment
• To be eligible for PBS-subsidised testosterone treatment , men over 40 years of age who do not have an established pituitary or testicular disorder must have a circulating testosterone level of less than 6nmol / L , confirmed by at least two morning testosterone measurements .
• Treatment is also subsidised for total testosterone levels between 6nmol / L and 15nmol / L , provided the LH level is greater than 1.5 times the upper limit of the eugonadal reference range , or greater than 14 IU / L .
• There are no restrictions for testosterone replacement in men with organic hypogonadism due to an established pituitary or testicular disorder .
• PBS-subsidised testosterone therapy can only by prescribed in conjunction with a specialist endocrinologist , urologist or registered member of the Australasian Chapter of Sexual Health Medicine .
There is some evidence that ( perhaps because of weight loss ) GLP-1 agonists may increase serum total testosterone by 20-30 %. 11 Accumulating evidence indicates that GLP-1 agonists may improve sexual function , either because they increase serum testosterone or via yet to be defined direct mechanisms on penile physiology . 1
In a proportion of older men , measures to reverse functional hypogonadism may be unsuccessful , either because their implementation is not feasible ( for example , cessation of opioids ), or they are not achieved or maintained ( such as failure to lose weight ). In some men , features of LOH may persist even despite successful implementation of these measures . For example , testosterone levels will not normalise in all obese men even after successful weight loss , and therefore testosterone levels should be repeated if symptoms persist . If testosterone remains low , ensure that underlying organic HPT axis pathology has not been missed .
Testosterone treatment
If first-line measures fail , the question arises as to whether a trial of testosterone treatment , in conjunction with specialist input , is justified to determine whether there is benefit . In general , the response to testosterone therapy is inversely correlated to the pre-treatment testosterone levels , age , BMI , and the number of chronic comorbidities . If testosterone treatment is considered , it should target men with more severe and specific symptoms and signs , and an unequivocally and repeatedly low testosterone level . The risk-benefit ratio is better in the younger , leaner man with fewer comorbidities , who has specific symptoms and consistently low testosterone . Testosterone threshold levels that predict a response to testosterone treatment are not well defined ; they are likely to differ between individuals , and for different clinical endpoints . Population-based studies in healthy Australian men using gold-standard liquid chromatography / tandem mass spectrometry ( LC / MS-MS ) assay technology have reported lower limits for total testosterone of 9.8nmol / L for healthy young men , 12 and of 6.4nmol / L for older men who report excellent health . 13 However , such lower limits of reference do not represent values below which treatment should be considered .
Only start testosterone treatment in older men after seeking specialist input , offering appropriate counselling and informing the patient about the absence of high-level evidence regarding long-term benefits and risks . Document these discussions in the medical record .
Identify clear patient-specific goals and advise the patient at the outset that testosterone therapy will be stopped if there are no benefits ,