Testosterone therapy confers a wide range of health benefits for hypogonadal men, including improvements in body composition (reduction in body fat, increase in muscle mass), lipid profile cardiovascular function, insulin sensitivity/glucose metabolism, bone mineral density, inflammatory parameters, quality of life and longevity.
Despite this, there is a high discontinuation rate with testosterone therapy.[2, 3]
In this article I summarize results from two studies that investigated adherence to testosterone therapy and treatment patterns.[2, 3]
* The rates of testosterone therapy treatment discontinuation are similar between men using topical testosterone formulations and short-lasting testosterone injections.
* 66% of patients discontinued testosterone therapy with a topical gel after 2 months, and only 31% and 14% of patients remained on therapy for 6 months and 1 year, respectively.
* Of the patients who discontinued testosterone gel therapy, almost half reinitiated therapy, and the majority of these men restarted therapy using the same medication at the same dose. Only 5% of men restarted therapy by using another testosterone product.
* A large proportion of patients stop and restart therapy every 2 to 3 months.
* Majority of patients who begin testosterone therapy discontinue its use within 3 years.
* Because continuous therapy over a longer period (years, if not indefinitely) is necessary to derive all the benefits of testosterone therapy [4-7], these low adherence rates mean that the majority of men who start testosterone therapy will not get maximum benefits from it.
What is known
Severe hypogonadism (below 231 ng/dL or 8 nmol/L), as well as borderline low testosterone levels (231 to 346 ng/dL or 8 to 12 nmol/L), is associated with multiple end-organ deficits compatible with testosterone deficiency, including insulin resistance, reduced muscle mass and bone mineral density, low hemoglobin, impaired physical function, increased fat mass, enlarged waist circumference, and poorer general health.[8-10]
The cardinal symptoms and signs of hypogonadism are decreased frequency of morning erection, decreased frequency of sexual thoughts, and erectile dysfunction. These sexual symptoms are also among the first ones to improve with testosterone therapy.[4, 12] However, improvements in other parameters take longer to manifest, and many of them (e.g. insulin resistance, HbA1c, blood lipids, bone mineral density) need to be objectively measured and monitored.
What these studies add
While hypogonadism is often irreversible, it appears that most men who initiate testosterone therapy do not remain on medication for a prolonged period. Only 14% of patients remain on therapy for 1 year, and the large majority of patients who begin testosterone therapy discontinue its use within 3 years. This is an important concern because continuous therapy over a longer period (years, if not indefinitely) is necessary to derive all the benefits of testosterone therapy.[4-7] This is congruent with the well documented presence of multiple symptom-specific testosterone thresholds, which take different durations to reach, and the notion that different thresholds exist for the various androgen-dependent targets.[13-15]
The low adherence rates reported by these studies are in line with previous other reports. For example, it has been found that patients who initiated treatment with testosterone therapy stayed on treatment for a median of 150 days during the 12 months following initiation of treatment, and almost 20% of all new users received treatment for only a maximum of 30 days.
One study used a long-term follow-up period (up to 30 months) in order to better understand treatment patterns among men on testosterone therapy. The analysis found that most patients used testosterone therapy in a cyclic fashion; on treatment for a few months, stopped treatment for 2–3 months, and then restarted testosterone treatment with the same dose and medication.  This cycle repeated, but with each successive cycle, the number of men who restarted testosterone therapy decreased. This cyclic pattern was observed with both topical testosterone gels and short-lasting testosterone injections, indicating that treatment patterns are not related to a specific testosterone preparation or route of administration. Or, it may be that patients were prescribed their preferred testosterone treatment modality (i.e. gel over injection, or vice versa).
Reasons for poor adherence are not fully understood but possible explanations, as reported for other therapies, may be cost of therapy, preference for different preparations (e.g., topical, injectable) that they are not getting from their doctor, perceived low efficacy, concerns about therapy safety, inadequate patient education, and unrealistic patient expectations for alleviation of symptoms. After TRT initiation, patients may not have been informed about the time course of symptom improvement or may not have experienced rapid symptom improvement and so discontinued therapy. Alternatively, patients may have experienced symptom improvement but then questioned the need to remain on therapy. After stopping treatment, some may not have had symptoms reappear, or symptoms may no longer have been bothersome, therefore giving them no incentive to restart testosterone, whereas, for other patients, it may be that the recurrence of symptoms prompted the restart of therapy.
The exclusive focus on symptom improvement neglects the wide range of health benefits with testosterone therapy. While symptomatic relief can be experienced as soon as after 3-4 weeks [4, 18], noticeable effects on body fat, muscle mass and bone mineral density may take at least 6 months to years to manifest. Importantly, these long-term improvements keep continuing with continuing testosterone therapy.[19-25] Therefore, merely asking patients whether they "feel better" after 3-6 months might lead to these important health benefits being underestimated, and to discontinuation of testosterone therapy. It is equally important to measure and monitor these long-term effects.
These results highlight the importance of both physician education and communication between the patient and physician; for expression of all benefits with testosterone therapy it is critical to inform patients about what effects to expect and when, and encouraging patients to remain on therapy even after sexually related symptoms have receded. This can be done by regular comprehensive blood testing, body composition and waist circumference assessments, which provide objective proof of treatment effects and health benefits.
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