Practical advice for effective testosterone therapy

Testosterone therapy confers 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), lipid profile, cardiovascular function, insulin sensitivity/glucose metabolism, bone mineral density, inflammatory parameters, quality of life and increased longevity.1-3

Despite this, many men fail to achieve these treatment benefits simply because they do not adhere to testosterone therapy or take it intermittently. This can easily be prevented by informing patients about all benefits they have to gain if they adhere to their testosterone treatment, as well as how soon they can 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 occur at different times points after the start of testosterone therapy, as summarized in table 1.

    How soon can effects from testosterone therapy be expected?

    It is essential for clinicians to know that the effects of testosterone therapy are time dependent. 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 a significant improvement in quality of life (as measured by reduction in AMS score) can occur after 3 months of testosterone therapy,6 long-term “real life” studies have shown that improvement in quality of life occurs progressively for up to 2-3 years during treatment with testosterone undecanoate injections.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 with testosterone undecanoate injections.8

    Table 1: When to expect health benefits 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

    Small increase within the normal range is a physiological response to testosterone therapy. This increase reaches a plateau at 12 months; any further increase is more likely related to aging rather than testosterone therapy.

    Lipids (primarily reduction in triglycerides and non-HDL cholesterol)

    4 weeks, but improvements can continue with uninterrupted testosterone therapy for 11 years.

    Insulin sensitivity

    Improvements in glycemic control become evident only after 3–12 months. Further improvements can be seen with uninterrupted testosterone therapy for 11 years.

    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 Aging 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.

    Aging Males’ Symptoms (AMS) questionnaire

    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 guidelines recommend that men who present with symptoms such as erectile dysfunction but have borderline low testosterone levels should be given a therapeutic trial of testosterone therapy for 3 months16 , 6 months17 or 12 months18, to see if it works. However, recent studies have shown that uninterrupted testosterone therapy can result in progressive improvement in erectile function for up to 9 years.8,19

    This underscores the critical importance of long-term uninterrupted testosterone therapy for achievement of maximal symptomatic improvement, and that a therapeutic trial of testosterone therapy for even 1 year may not be enough to “see if it works”. It should also be pointed out that maximal improvements in non-symptomatic outcomes of testosterone therapy, such as body fat loss, waist circumference reduction, muscle gain and increase in bone mineral density take many years to achieve.