Testosterone replacement therapy with Nebido shows superior long-term adherence compared to gels and short-acting testosterone injectables
15 February 2019
STUDY: Kirby, Hackett: Testosterone deficiency: guiding patients through the management options. Trends in Urology & Men's Health. 2018; Supplement 1: 1-8
Several options are available for the treatment of hypogonadism. Adherence to testosterone therapy is critical for the achievement of health benefits, such as improved sexual function, wellbeing, weight loss, muscle gain and glycemic control.1 Therefore, when choosing which testosterone preparation to prescribe, patient preference, tolerability and convenience need to be taken into account.
What is known about testosterone therapy options and barriers to treatment
The symptoms associated with hypogonadism, also known as testosterone deficiency, are not specific to low testosterone levels; the same symptoms also occur with aging, obesity and other comorbidities. For example, erectile dysfunction can be a marker of coronary heart disease. Therefore, initial management of symptomatic men should include lifestyle changes with the goal to achieve weight loss and reduced waist size by increasing physical activity, improving food choices and reducing alcohol consumption. Nevertheless, while lifestyle changes and weight loss may increase endogenous testosterone levels and confer overall health benefits, it is commonly not enough for achievement of resolution of symptoms associated with hypogonadism.2,3
The major barrier to testosterone therapy is failure to consider the diagnosis of hypogonadism by general practitioners, and specialists who feel that treatment of hypogonadism is not their responsibility. Although general practitioners are ideally placed to provide care for men with hypogonadism, they have received no training in how to diagnose hypogonadism, and may be reluctant to take on the burden of long-term follow-up for a potentially large number of men. Furthermore, while accumulating evidence confirms the safety of testosterone therapy, common myths about increased risk of prostate cancer or cardiovascular events have not been completely dispelled and concern still exists amongst healthcare professionals.
The British Society for Sexual Medicine (BSSM) guideline on testosterone deficiency management provides evidence-based guidelines that help healthcare professionals diagnose and manage men with hypogonadism.4 Evidence reviewed by the BSSM shows that testosterone therapy consistently improves sexual function and preserves lean mass in men with hypogonadism; studies also show increases in bone mass, improvements in lipid profile and anemia, attenuation of insulin resistance, improved mood and increased exercise capacity.4,5 The BSSM recommends initiating testosterone therapy only in conjunction with weight-loss advice and lifestyle modification, so this should be discussed with patients.4
New data on adherence to testosterone therapy
Testosterone therapy in symptomatic men with hypogonadism should aim to restore testosterone levels and target a serum total testosterone level of 15-30 nmol/mL.4 A prerequisite for successful testosterone therapy is that this therapeutic target level of testosterone is maintained long-term in order for symptom resolution and health benefits to occur. This is why adherence to testosterone therapy is critical.
The most commonly used testosterone preparations for the treatment of hypogonadism are transdermal (gel) and injectable testosterone preparations. While transdermal preparations are easy to use, some people may find the need for daily gel application to the skin burdensome. Adherence rates with gels are disappointingly low, falling to 52% after 3 months6, 35% after 6 months7 and as low as 15-17% after 1 year.7,8
In contrast, a survey of 150 general practitioner practices in the UK showed that 58% of patients who were started on treatment with testosterone undecanoate injections stayed on treatment after 1 year, see figure. After 2-3 years, 40–44% of patients continued, and after 4–5 years about one-third were still being treated with testosterone undecanoate injections.9 Figure 1 shows the proportion of 2299 men prescribed intramuscular testosterone undecanoate who continued treatment, 2012–17.9 Adherence to treatment with long-acting testosterone undecanoate injections is also higher than the adherence rates reported with short-acting testosterone injections.6,9
These results highlight the importance of both physician and patient education and communication between the physician and patient; for expression of all benefits with testosterone therapy it is critical to inform patients about what effects to expect and when, and encourage patients to stay on testosterone therapy even after sexually related symptoms have receded. This can be done by regular comprehensive blood testing, body weight and waist circumference assessments, which provide objective proof of treatment effects and health benefits. Continuous monitoring may also be supported by use of questionnaires such as the Aging Males’ Symptoms Scale (AMS).10
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 weeks1,11, noticeable effects on body fat, muscle mass and bone mineral density may take at least 6 months to years to manifest.1 Importantly, these long-term improvements keep continuing with continuing testosterone therapy.12-18 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 long-term effects.