Hypogonadism treatment with testosterone undecanoate injection has best long-term adherence
Kang B, Noh M, Park HJ. Compliance with Testosterone Replacement Therapy in Patients with Testosterone Deficiency Syndrome: A 10-Year Observational Study in Korea. The world journal of men's health. Jan 25 2021
The health benefits and safety of testosterone therapy is well established.1-9 However, only a few studies have examined adherence to testosterone therapy among men in real-life, and compared adherence rates for various forms of testosterone products.10 Furthermore, there is a paucity of data on long-term adherence rates.
Because testosterone therapy for most men is likely to be required lifelong for persistent symptom resolution and maintenance of health benefits,11 knowledge about long-term adherence rates for various testosterone products would be useful for physicians when counseling patients and recommending treatment options.
Here we summarise the results of a study which analyzed treatment continuation rates for various testosterone products and reasons for discontinuation, as well as patient characteristics for those who stayed on testosterone therapy long-term.12
What is known about
Long-term adherence to testosterone therapy is key for achievement of health benefits in men with hypogonadism.13, 14 Several studies have demonstrated that the beneficial effects of testosterone therapy are not maintained after discontinuation of testosterone treatment.15-21 This applies to improvements in body composition (body fat loss and gain in lean body mass), erectile function (assessed with the IIEF-EF questionnaire), HbA1c, total cholesterol, LDL, HDL, triglycerides, quality of life (assessed with the AMS questionnaire), urinary function (assessed with the IPSS questionnaire, and measured residual voiding volume and bladder wall thickness), and likely most – if not all - other testosterone-related outcomes.15-18, 20 It is therefore of interest to know testosterone treatment patterns among men with hypogonadism in real life, as this can provide insights regarding areas of improvement.
One study that examined treatment patterns in men with hypogonadism receiving testosterone gel or short-lasting testosterone injection, found that among those on uninterrupted testosterone therapy, 52% of testosterone gel users and 31% of short-lasting testosterone injection users were still on treatment after 3 months.10 At one year after start of testosterone therapy, only 18% of testosterone gel users and 5% of short-lasting testosterone injection users were still continuing treatment. At 30 months after start of testosterone therapy, almost all men who had been receiving treatment with short-lasting testosterone injection had discontinued its use, whereas less than 10% of men who had been receiving treatment with testosterone gel were still using it.10 Another study found that at 6 months, 34.7% of patients were still on testosterone treatment, and at 12 months only 15.4% of men remained on testosterone treatment.22 After 3 years, the large majority of patients had discontinued taking testosterone therapy.22
The low adherence rates reported by these studies confirm previous reports. For example, over the period of 2001-2011, in a population of 10,739,815 men aged 40 years or older, it was found that patients who initiated treatment with testosterone therapy stayed on treatment for a median of 150 days during a 12-month period following initiation of treatment, and almost 20% of all new users received treatment for only a maximum of 30 days.23 These studies suggest that adherence to hypogonadism treatment is better with testosterone gel than short-lasting testosterone injection, but that long-term adherence is poor for both.
Knowledge about adherence rates among various testosterone preparations, patient preferences and reasons for discontinuation can be helpful for health care professionals who are involved in treating men with hypogonadism.
What this study adds
Medical records were retrospectively analyzed for 640 men over 40 years of age with hypogonadism who had been treated with either short-acting testosterone (enanthate) injection, long-acting testosterone (undecanoate) injection, testosterone gel or testosterone capsules, and followed up for more than 10 years.12
It was found that treatment continuation rate at 1 year was highest in men receiving testosterone undecanoate injection (91%), followed by testosterone gel (71%), capsule (69%) and short-lasting testosterone injection (58%). The respective treatment continuation rate at year 1, year 5 and year 10 are illustrated in the figure.
Figure: Testosterone treatment continuation rate over 10 years with difference testosterone preparations.12
The first treatment period was also longest among men receiving testosterone undecanoate injection (20.5 months), followed by oral capsule (14.2 months), testosterone gel (11.3 months) and short-lasting testosterone injection (8.2 months).
With the exception of long-acting testosterone undecanoate injection, “inconvenience of medication” was one of the most common reasons for stopping treatment among men receiving short-acting testosterone enanthate injection, testosterone gel and testosterone capsules. Other common reasons were concerns about side effects among men receiving testosterone enanthate injection (250 mg) and lack of efficacy in men taking oral capsules. Among men taking testosterone gel, inconvenience of medication was by far the most common reason for discontinuation. In contrast, in men receiving testosterone undecanoate, treatment cost was the most common reason for discontinuation.
Baseline patient characteristics that were associated with the highest long-term testosterone treatment continuation rate were low testosterone level before starting treatment, erectile dysfunction and use of PDE5 inhibitors.
It was concluded that among the various testosterone preparations, testosterone undecanoate injection has the highest adherence rate, both short-term (1 year) and long-term (10 years). Therefore, for patients who have coverage or get reimbursed for the cost of treatment with testosterone undecanoate injection, it is logical to offer this as the first option.
This is the first study that compared adherence rates for 4 of the most popular testosterone preparations in the same population of men. It showed that testosterone undecanoate injection had the highest treatment adherence and treatment continuation rate at 1, 5, and 10 years of treatment, compared with testosterone gel, capsules and short-acting testosterone injection. Among men who received testosterone undecanoate injection, total duration of treatment was the longest in 10 years. This suggests that the highest patient satisfaction was achieved with testosterone undecanoate injection. This is likely due to the fact that it is a long-acting form of testosterone that maintains stable target blood levels of testosterone with just 4-5 injections per year,24 making it a convenient testosterone therapy option. For more information about treatment with testosterone undecanoate injection, see “Efficacy and safety of testosterone undecanoate injection for the treatment of hypogonadism”
In the present study, among men using short-acting testosterone injection, “concern about side effects” was the most common reason for discontinuation. This could possibly be due to fluctuating serum testosterone levels, a specific characteristic of short-acting testosterone injection, which can cause mood swings and/or changes in libido, giving patients a sense of unease.25 Treatment with short-acting testosterone injection is also linked to higher risk for side effects, such as excessive elevation in hematocrit.26 For more information, see “Hematocrit elevation following testosterone therapy – does it increase risk of blood clots?”
The present study also confirmed results from previous studies, showing that testosterone gels - despite being the most commonly prescribed testosterone preparation 23 - have high rates of patient dropout.22 For more information, see “Adherence to testosterone therapy - short term treatment is not sufficient for achievement of maximal benefits”
Another negative aspect of testosterone gel is that it causes the greatest elevation in DHT levels compared to other testosterone preparations.27 Because DHT is as a key androgen in the pathogenesis of male pattern hair loss (alopecia),28 men who are concerned about hair loss should avoid testosterone gels.
In the present study, the main reason for discontinuation of treatment with testosterone undecanoate injection was cost.12 The patient cost for treatment with testosterone undecanoate injection varies between countries. As evidence regarding the long-term efficacy of using testosterone undecanoate injection for treatment of hypogonadism continues to accumulate, it is hoped that health insurance coverage will improve, so that more patients can afford it.
Previous studies found that patients rated convenience as the most important factor when considering various testosterone treatment options.29, 30 In a post-marketing surveillance study of men receiving testosterone therapy, the most frequent reasons for choosing treatment with testosterone undecanoate injection were convenience and comfort with treatment.31 For more information, see “Effectiveness and tolerability of injectable testosterone undecanoate”
As previously pointed out 32 and confirmed in the present study,12 long-acting testosterone undecanoate injection overcomes the patient burden of daily administration, offering an effective treatment of hypogonadism that does not interfere with daily life. Furthermore, administration once every 12 weeks may provide a psychological benefit by freeing the patient from a daily reminder of “being in treatment”. In summary, knowledge about treatment compliance for various testosterone preparations, and reasons for discontinuation, can be helpful for HCPs who are counseling patients with hypogonadism who need long-term testosterone therapy.