Effects of long-acting testosterone undecanoate on quality of life in Asian men with testosterone deficiency syndrome

Effect of long-acting testosterone undecanoate treatment on quality of life in men with testosterone deficiency syndrome: a double blind randomized controlled trial. Tong SF, Ng CJ, Lee BC, et al. Asian J Androl 2012;14(4):604-611.

This Research News article reviews an open-access article available in full from Asian Journal of Andrology.

This 12-month double blind, randomized controlled study investigated the effects of intramuscular injections of testosterone undecanoate on overall quality of life (QoL) in men with testosterone deficiency syndrome (hypogonadism).1 The study, conducted in Malaysia, enrolled 120 men aged ≥40 years with a diagnosis of testosterone deficiency syndrome (serum total testosterone <12 nmol/L (346 ng/dL) and total Aging Males’ Symptoms (AMS) scores ≥27). Men received placebo or 1000 mg testosterone undecanoate by intramuscular injection at weeks 0, 6, 18, 30 and 42.

The primary analysis of the study, treatment effects using the AMS scale, has been published previously2 and was reported in the Research News on this website on 25 July 2012. This paper reported the secondary analysis of QoL changes, measured by the Medical Outcomes Study Short-Form-12 (SF-12) scale at baseline, week 30 and week 48. SF-12 is a self-administered validated tool designed to measure general health-related QoL. It measures 8 domains of QoL and has 2 composite scores for physical and mental health.

A total of 114 men (58 in the placebo group and 56 in the testosterone group) completed the study. Participants had low serum total testosterone levels and AMS subscale scores in the moderate-to-severe categories. Baseline characteristics were comparable for both groups, except for metabolic parameters (lower body mass index, waist circumference and diastolic blood pressure in the placebo group) and AMS scores (higher total and psychological subscale scores in the testosterone treatment group).
Key Points1

  • Serum total testosterone increased from 8.9 nmol/L (256.5 ng/dL) at baseline to 23.7 nmol/L (683.0 ng/dL) at week 48 in the testosterone group (p<0.001) and from 9.1 nmol/L (262.3 ng/dL) to 11.2 nmol/L (322.8 ng/dL) in the placebo group (p<0.001; between group difference p<0.001)
  • At week 48 unadjusted quality of life (QoL) scores of men in the testosterone treatment group improved significantly in five out of the eight domains on the Short-Form-12 survey (vitality, general health, social functioning, physical role functioning and emotional role functioning)

    • Physical health composite scores improved 4.0 points in the treatment group (from a baseline of 41.9±7.0) compared to 0.8 points in the placebo group (from a baseline of 43.7±7.1) (F=3.652, p=0.027)
    • The mental health composite scores improved 4.4 points from a baseline of 37.1±9.0 in the treatment group compared to 1.0 point from a baseline of 37.6±7.9 in the placebo group (F=4.514, p=0.018)
    • Significant improvements (p<0.05) in all domains of QoL, except for physical functioning, were seen in the testosterone group as early as week 30, with further significant improvements in general health, physical functioning and role functioning at week 48
  • After adjusting for baseline differences, significant improvement was observed in vitality and social functioning domains and mental health composite scores (Figure 1), but not in physical health composite scores
  • There were no significant changes in International Prostate Symptom Scores in either group during the study
  • No significant adverse events were observed
  • Although remaining within normal limits, haematocrit level, serum bilirubin and serum prostate-specific antigen level significantly increased in the testosterone group (p<0.01 vs placebo).

What is known

Hypogonadism (testosterone deficiency syndrome), which can be defined as serum total testosterone ≤12 nmol/L and a positive score suggestive of androgen deficiency on the AMS questionnaire, is increasingly recognized as a significant health problem in aging men.3-9 Testosterone deficiency syndrome adversely impacts physical health (including loss of physical strength, loss of muscle mass, increased visceral fat leading to a higher risk for metabolic syndrome and premature death), sexual function (loss of secondary sexual characteristics, decreased libido and erectile dysfunction) and psychological health (mood changes and sleep disturbances).6 Consequently, the quality of life (QoL) of men with low testosterone is negatively affected,10-15 and treatment with testosterone replacement therapy could be expected to improve QoL in men with testosterone deficiency syndrome. As data on the effects of testosterone replacement therapy on patient-reported QoL are limited, this study aimed to investigate the effects of testosterone replacement therapy on health-related QoL in men with testosterone deficiency syndrome over a 12-month period. The long-acting intramuscular formulation of testosterone undecanoate was chosen, as it is associated with providing a stable and physiological level of testosterone with 4-times-yearly administration.16,17

What this study adds

This double blind, randomized, placebo-controlled trial demonstrated that long-acting testosterone undecanoate significantly improved the mental health component of QoL in men with low serum testosterone and symptoms of testosterone deficiency. Improvement in SF-12 composite scores was apparent at week 30, but physical component scores continued to improve at 48 weeks of treatment, suggesting that testosterone replacement therapy may be indicated in men who have a poor quality of life related to testosterone deficiency syndrome.

The lack of a significant difference in the other five QoL domains when adjusted for baseline differences may be related to this study being underpowered to detect changes in the QoL scores, with the exception of the vitality domain.1 In view of the significant differences observed between active treatment and placebo in mental health composite scores and vitality and social functioning domains, it is possible that other domains would improve with testosterone undecanoate treatment with a longer duration of follow-up. Furthermore, it is not clear if the positive effects of testosterone on QoL shown in this study would translate into men’s satisfaction with testosterone therapy and a desire to continue with therapy. These issues would need to be determined in further studies.
Figure 1: Improvement in SF-12 domain score from baseline to week 48

References


1. Tong SF, Ng CJ, Lee BC, et al. Effect of long-acting testosterone undecanoate treatment on quality of life in men with testosterone deficiency syndrome: a double blind randomized controlled trial. Asian J Androl 2012;14(4):604-611.
2. Ho CC, Tong SF, Low WY, et al. A randomized, double-blind, placebo-controlled trial on the effect of long-acting testosterone treatment as assessed by the Aging Male Symptoms scale. BJU Int 2012;110(2):260-265.
3. Ullah MI, Washington T, Kazi M, et al. Testosterone deficiency as a risk factor for cardiovascular disease. Horm Metab Res 2011;43(3):153-164.
4. Wang C, Jackson G, Jones TH, et al. Low testosterone associated with obesity and the metabolic syndrome contributes to sexual dysfunction and cardiovascular disease risk in men with type 2 diabetes. Diabetes Care 2011;34(7):1669-1675.
5. Bassil N, Morley JE. Late-life onset hypogonadism: a review. Clin Geriatr Med 2010;26(2):197-222.
6. Wang C, Nieschlag E, Swerdloff R, et al. Investigation, treatment, and monitoring of late-onset hypogonadism in males: ISA, ISSAM, EAU, EAA, and ASA recommendations. Eur Urol 2009;55(1):121-130.
7. Kazi M, Geraci SA, Koch CA. Considerations for the diagnosis and treatment of testosterone deficiency in elderly men. Am J Med 2007;120(10):835-840.
8. Traish AM, Miner MM, Morgentaler A, et al. Testosterone deficiency. Am J Med 2011;124(7):578-587.
9. Saad F, Aversa A, Isidori AM, et al. Onset of effects of testosterone treatment and time span until maximum effects are achieved. Eur J Endocrinol 2011;165(5):675-685.
10. Maggi M, Schulman C, Quinton R, et al. The burden of testosterone deficiency syndrome in adult men: economic and quality-of-life impact. J Sex Med 2007;4(4 Pt 1):1056-1069.
11. Yasuda M, Furuya K, Yoshii T, et al. Low testosterone level of middle-aged Japanese men – the association between low testosterone levels and quality-of-life. J Men's Health 2007;4(2):149-155.
12. Low WY, Tong SF, Tan HM. Erectile dysfunction, premature ejaculation and hypogonadism and men’s quality of life: an Asian perspective. J Men's Health 2008;5(4):282-288.
13. Hwang TI, Lo HC, Tsai TF, et al. Association among hypogonadism, quality of life and erectile dysfunction in middle-aged and aged male in Taiwan. Int J Impot Res 2007;19(1):69-75.
14. Moncada I. Testosterone and men's quality of life. Aging Male 2006;9(4):189-193.
15. Novak A, Brod M, Elbers J. Andropause and quality of life: findings from patient focus groups and clinical experts. Maturitas 2002;43(4):231-237.
16. Saad F, Kamischke A, Yassin A, et al. More than eight years' hands-on experience with the novel long-acting parenteral testosterone undecanoate. Asian J Androl 2007;9(3):291-297.
17. Edelstein D, Basaria S. Testosterone undecanoate in the treatment of male hypogonadism. Expert Opin Pharmacother 2010;11(12):2095-2106.


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