Testosterone therapy practical advice

Testosterone therapy may confer a wide range of health benefits for hypogonadal men, including improvements in libido, sexual function, body composition (reduction in body fat and waist size, and increase in muscle mass), bone mineral density, inflammatory parameters, quality of life and increased longevity.1-3

Despite this many men fail to achieve these treatment benefits because they do not adhere to testosterone therapy or take it intermittently. This could be prevented by informing patients about all the potential benefits they may gain if they adhere to their testosterone treatment, as well as highlighting how soon they could expect to notice the different health benefits.

Patient expectation about testosterone therapy

A survey found that nearly 40% of respondents had discontinued testosterone therapy because they felt it “failed to work”.4 In a chart review of men attending a men’s health practice, it was found that nearly 30% of men discontinued testosterone therapy within 12 months following initiation, primarily citing lack of symptomatic improvement as the reason for discontinuation.5

Testosterone therapy discontinuation due to perceptions of insufficient efficacy are likely caused by misguided expectations and/or sub-optimal dosing of testosterone therapy. Patients who have misguided expectations about testosterone therapy may discontinue treatment too soon before they can reasonably experience symptom relief. Therefore, it is critical to inform patients that improvement in hypogonadal signs and symptoms may occur at different time points after the start of testosterone therapy, as summarised in table 1.


How soon can effects from testosterone therapy be expected?


While improvement in libido and quality of life can appear after 1 month of testosterone therapy,1 maximal improvements take longer time to manifest. For example, while an improvement in quality of life (as measured by reduction in AMS score vs untreated group) can occur after 3 months of testosterone therapy a significant improvement can be seen after 8 years.1,7-10 Similarly, while some improvement in erectile function can be noticed after 6 months of testosterone therapy,1 erectile function has been shown to continue to improve for up to 9 years with continued, uninterrupted treatment for a long period of time with testosterone undecanoate injections from baseline.8 Erectile function was measured using the IIEF-EF.

Table 1: When to expect potential health benefits in most patients with testosterone therapy.1,8,11,12

Testosterone therapy effect Time required to achieve effect

Sexual interest (libido)

3 weeks, plateauing at 6 weeks, with no further increments expected beyond.


Can be noticed after 6 months, but continued improvement is seen with ongoing testosterone therapy for 9 years.

Quality of life

3–4 weeks, but maximum improvement can take 2-3 years.

Depressive mood

3–6 weeks, with a maximum after 18–30 weeks.


3 months, peaking at 9–12 months and then stabilizing.

PSA and prostate volume

Please refer to the SmPC for a full list of contraindications and special warnings and precautions for use

Small increase within the normal range is a physiological response to testosterone therapy. Ageing itself can be considered a factor in the rise of both prostate volume and PSA levels.22,23

Reduction in waist circumference

Can be detectable after 6-12 months, but continued improvement is seen with ongoing testosterone therapy for 11 years.


Reduced fat mass / increased lean body mass and strength

6 months to several years.

Bone mineral density

Can be detectable after 6 months, but continued improvement is seen for at least 5 years with ongoing testosterone therapy.

The Ageing Males’ Symptoms (AMS) questionnaire is commonly used to evaluate symptoms that may be related to low testosterone, and to monitor symptomatic improvement during testosterone therapy.13-14 When used to monitor efficacy of testosterone therapy, it is critical to know that improvement in AMS scores (symptom severity) can continue for up to 3 years.7-10 Hence, patients with hypogonadism who have been on testosterone therapy for 3-12 months but not experienced symptomatic improvement may do so if they stay on testosterone therapy without interruption for a longer time period.

Erectile dysfunction is one of the primary symptoms of hypogonadism.15 It was previously believed that maximal improvements in erectile function are achieved after 3-6 months of testosterone therapy.1 Based on this belief, several clinical guidelines17 recommend that men who present with symptoms of hypogonadism such as erectile dysfunction but have borderline low testosterone levels should be given a therapeutic trial of testosterone therapy for 3 months16, 6 months or 12 months18, to see if it works. However, recent studies have shown that uninterrupted testosterone therapy for a long period of time can result in progressive improvement in erectile function for up to 9 years.8,19 This may show the importance of long-term uninterrupted testosterone therapy for a long period of time for achievement of potential maximal improvement in some symptoms. It should also be pointed out that maximal improvements in outcomes of testosterone therapy, such as body fat loss, waist circumference reduction, muscle gain and increase in bone mineral density may take many years to achieve.

Nebido is indicated for testosterone replacement therapy for male hypogonadism when testosterone deficiency has been confirmed by clinical features and biochemical tests.


Importance of uninterrupted testosterone therapy

Achievement of potential maximal benefits from testosterone therapy may require uninterrupted treatment.19-21,24 If testosterone therapy is interrupted, achieved metabolic and symptomatic benefits may disappear.20,21,24 It is critical to inform patients about this, as many patients stop and restart therapy every 2 to 3 months.25 Although the beneficial effects may reappear when testosterone therapy is resumed,21,24 these patients may not experience the full benefits of testosterone therapy. Not surprisingly, majority of patients who begin testosterone therapy discontinue its use within 3 years.25

Therefore, patient education about the potential timelines for symptom improvement and need for long-term adherence to achieve the potential wide range of health benefits of testosterone therapy is one of the essential factors for successful treatment of hypogonadism.


Importance of achieving effective testosterone levels

Besides treatment duration, a prerequisite for effective testosterone therapy is achievement of a large enough elevation in testosterone levels, that is sustained over time.26-29

There is no universal threshold level of testosterone that triggers response to testosterone therapy; due to differences in androgen receptor sensitivity and variations on sex hormone binding globulin (SHBG) (which can cause different levels of free testosterone for any given level of total testosterone), some men may need more frequent interval doses of testosterone therapy and higher on-treatment testosterone levels in order to respond. Therefore, what constitutes a large enough elevation in testosterone levels must be determined individually for each patient by regularly monitoring testosterone levels and symptomatic response during testosterone therapy, and if needed, adjusting the dose frequency based on response.

Serum levels should be within the lower third of the normal range.



While clinical guidelines recommend that testosterone therapy should aim to elevate testosterone levels into the middle tertile of the normal range28 (the exact values will vary between testosterone assays and laboratories).

Serum levels should be within the lower third of the normal range.



For how long should testosterone therapy be given?

A common question among HCPs and patients is how long testosterone therapy should be given. Several studies have demonstrated that the beneficial effects of testosterone therapy are not maintained after discontinuation of testosterone treatment.21,24,31-34 This applies to improvements in body composition, erectile function, HbA1c, total cholesterol, LDL, HDL, triglycerides, AMS, IPSS, IIEF-EF, residual voiding volume and bladder wall thickness, and quality of life, and likely most other testosterone-related outcomes.25,26,33-35

An exception may be young men with extreme obesity. In a case-report of a 20-year old man with grade III obesity, testosterone therapy for 20 months reduced BMI from 44 kg/m2 to overweight 27 kg/m2.35 During a follow-up period of 19 months after discontinuation of testosterone therapy, improvements in testosterone levels, body weight, waist circumference, blood glucose, lipids remained. Nevertheless, in middle-age and older men, studies consistently show that the beneficial effects of testosterone therapy are not maintained after discontinuation of testosterone treatment.31-34

If testosterone therapy is discontinued, beneficial effects will appear again when testosterone therapy is resumed.24 As pointed out in the British Society for Sexual Medicine guidelines on Adult Testosterone Deficiency, discontinuation of testosterone therapy results in reappearance of symptoms and reversal of benefits within 6 months, so testosterone therapy is likely to be required lifelong for persistent symptom resolution and maintenance of health benefits.17


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