AUA Congress Report– new studies on long-term testosterone therapy

AUA 2016 annual congress San Diego, May 6-10, 2016, Congress Report
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The American Urological Association (AUA) is a premier urologic association, which provides the global urology community opportunities to present, learn and share news of discovery and advancement. In this editorial we summarize four key presentations from the AUA 2016 annual congress in San Diego, May 6-10, 2016.

Key Points

  • Long-term testosterone therapy in hypogonadal men with prediabetes results in sustained weight loss, and improves glycaemic control. Testosterone therapy may prevent progression from prediabetes to diabetes in men with testosterone deficiency.
  • Long-term treatment with testosterone undecanoate in hypogonadal men may reduce incidence of PCa and protect against high-grade PCa.
  • Long-term testosterone therapy (up to 10 years) in hypogonadal men significantly improves and preserves erectile function, as well as reduces body weight and waist circumference, all of which deteriorate in untreated hypogonadal men.
  • Long-term testosterone therapy in symptomatic hypogonadal men improves urinary function, while untreated controls experience a worsening.
  • Long-term testosterone undecanoate is well tolerated, and excellent adherence suggests a high level of patient satisfaction in a real-life urology practice.

Notable new research

Prediabetes, hypogonadism & erectile dysfunction: glycaemic control in 109 hypogonadal men treated with testosterone undecanoate injections (TU) for up to 8 years: real-life data from registry studies

Multiple studies have demonstrated that testosterone therapy improves sexual and metabolic parameters in hypogonadal men with type 2 diabetes.1-5 However, there is no information on effects of testosterone therapy in hypogonadal men with prediabetes. Yassin et al. investigated the effect of testosterone therapy on erectile function and metabolic parameters in hypogonadal men with prediabetes.6

From two registries of hypogonadal men receiving long-term testosterone therapy with testosterone undecanoate, 109 men with prediabetes, defined as a baseline HbA1c from 5.7 to 6.4%, were analysed. Testosterone undecanoate was administered in 3-month intervals for up to 8 years. At each or each other visit, questionnaires were applied and anthropometric and metabolic parameters were measured.

Results:
Mean age was 57 years. Total testosterone increased from 8.6 to trough levels between 16 and 19 nmol/L.

Mean International Index of Erectile Function (IIEF-EF) score (maximum: 30) improved from 13 to 22. The improvement was statistically significant for three years and remained statistically significant vs baseline throughout the observation time, and stable compared to previous years.

Weight decreased from 96 to 84 kg, and waist circumference from 104 to 94 cm by -7 cm (p<0.0001 for both).

Fasting glucose decreased from 5.4 to 4.6 mmol/L, reaching a plateau after 1 year. HbA1c decreased from 5.9 to 5.4%, with statistical significance compared to the previous year for the first 3 years (figure 1). The triglyceride:HDL ratio - a surrogate parameter of insulin resistance - declined from 5.6 to 2.6 (p<0.0001 for all).

Figure 1: Reduction in HbA1c from prediabetic range (5.7 to 6.4%) to normal range (final 5.4%).

Figure 1: Reduction in HbA1c from prediabetic range (5.7 to 6.4%) to normal range (final 5.4%).

No patient progressed from prediabetes to type 2 diabetes. All but 4 patients' last HbA1c was <5.7%. 3 patients dropped out, 2 due to relocation to a different city, 1 was lost to follow-up. There were no major adverse cardiovascular events during the full observation time.

Conclusion:
Long-term testosterone treatment with testosterone undecanoate in hypogonadal men with prediabetes results in significant and clinically important sustained weight loss, and improves glycaemic control. Testosterone therapy may prevent progression from prediabetes to diabetes in men with testosterone deficiency.

Prostate cancer is less frequent and severe in hypogonadal men treated adequately with testosterone undecanoate injections for up to 8 years compared to untreated hypogonadal controls

Concerns still abound that testosterone therapy in middle-aged and elderly men could increase risk of prostate cancer (PCa). In this real-life registry study, the incidence of PCa in hypogonadal patients on long-term treatment with testosterone undecanoate (T-group), in comparison to an untreated hypogonadal control group (C-group), was investigated.7

360 men (mean age: 57 years, range: 33-70) with testosterone ≤12.1 nmol/L received testosterone undecanoate 1000 mg every 12 weeks following an initial interval of 6 weeks for up to 8 years. 296 hypogonadal men (mean age: 65 years, range: 57-74) declined testosterone therapy for a variety of reasons.

Prostate volume (PV) and PSA were measured and digital rectal examination (DRE)/ transrectal ultrasound (TRUS) performed before treatment initiation and then regularly every 3-6 months. Biopsies were performed when indicated according to EAU guidelines.

Results:
From baseline to 8 years, PV increased from 29 to 31 ml in the T-group and remained stable from 34.5 to 33.5 in the C-group. PSA increased slightly from 1.7 to 1.8 ng/ml in the T-group and remained stable from 2.3 to 2.2 in the C-group, figure 2.

Figure 2: Changes of PSA (ng/ml) vs. baseline in hypogonadal men receiving testosterone undecanoate (n=360) and untreated controls (n=296).*

Figure 2: Changes of PSA (ng/ml) vs. baseline in hypogonadal men receiving testosterone undecanoate (n=360) and untreated controls (n=296).

* Blue bars show estimated differences between groups adjusted for baseline age, weight, waist circumference, fasting glucose, blood pressure, lipids, and AMS.

In T-treated patients, 7 men (1.9%) were diagnosed with PCa. In the control group, 12 (4.1%) were diagnosed with PCa. The incidence per 10,000 years was 30.05 in the T-group and 63.54 in C-group. The mean age of PCa patients was 64 years in the T-group and 65 years in C-group.

All patients underwent radical prostatectomy. The predominant Gleason score was 3 and grading was 2 in all patients in the T-group, lymph nodes and surgical margins were negative. In C-group, three men had a predominant Gleason score of 3, 8 had 4, and 1 had 5. Grading was 2 in 5 and 3 in 7 patients.

Conclusions:
Long-term treatment with testosterone undecanoate in hypogonadal men may reduce incidence of PCa and protect against high-grade PCa.

Effect of long-term (up to 10 years) testosterone undecanoate treatment on erectile function

Haider et al. presented “Erectile function in 656 hypogonadal men: Results of long term treatment with testosterone undecanoate injections in comparison with control group.”8

Prior studies on the effects of long-term testosterone therapy on erectile dysfunction are from observational studies without a control group. Haider et al. are the first to present registry data including an untreated hypogonadal control group.

In a registry of 656 hypogonadal men, 360 chose testosterone therapy (T-group) and 296 abstained (C-group). Since patients were not randomized to either group, there were differences at baseline between groups. Mean age was 61 years, mean follow-up time 6.5 years (minimum: 1; maximum: 10). Presented are unadjusted effects after 8 years of testosterone therapy vs. non-treatment.

Results:
In the T-group, T levels rose from 9.8 nmol/L to trough levels (measured prior to the following injection) between 16 and 18 nmol/L (p<0.0001). In the C-group, T levels dropped slightly but significantly from 9.6 to 9.0 nmol/L (p=0.0136).

In the T-group, the IIEF-EF significantly improved by 6 points. The improvement was statistically significant for the first four years and remained stable in the remaining years. In the C-group it decreased by 9 points after 8 years. Differences between groups are illustrated in figure 3.

Figure 3: Changes in IIEF-EF vs. baseline in hypogonadal men receiving testosterone undecanoate (n+360) and untreated controls (n=296).*

Figure 3: Changes in IIEF-EF vs. baseline in hypogonadal men receiving testosterone undecanoate (n+360) and untreated controls (n=296).

* Blue bars show estimated differences between groups adjusted for baseline age, weight, waist circumference, fasting glucose, blood pressure, lipids and AMS score.

Weight decreased progressively from 104 to 87 kg in the T-group (p<0.0001) and increased from 91 to 92 kg in the C group (p=0.0002). Waist circumference decreased from 106 to 100 cm in the T-group (p<0.0001) and increased from 106 to 108 cm in the C-group (p<0.0001).

Conclusion:
Long-term (up to 10 years) testosterone therapy in hypogonadal men significantly improves and preserves erectile function, as well as reduces body weight and waist circumference, all of which deteriorate in untreated hypogonadal men.

Effects of long-term testosterone undecanoate treatment on urinary and sexual function in hypogonadal men: real-life data

This registry study assessed the long-term effect and safety of injectable testosterone undecanoate (TU) in a urological setting, in comparison to an untreated hypogonadal control group.9 In an observational registry study of 656 symptomatic men, mean age: 61 years) with testosterone levels ≤12.1 nmol/L, 360 men received TU 1000 mg/12 weeks with an initial 6-week interval for up to 10 years (T-group). 296 men abstained from TU treatment and served as controls (C-group).

Measurements were taken at least twice a year, and 8-year data were analysed. Mean changes over time between the two groups were compared. Changes were adjusted for age, weight, waist circumference, blood pressure, and lipids to account for baseline differences between the two groups.

Results:
Testosterone increased from 9.8 to trough levels between 16 and 17 nmol/L in the T-group, and decreased slightly but significantly from 9.6 to 9.0 nmol/L in the C-group.

Prostate volume increased from 29.2 to 31.1 ml (p=0.0114) in the T-group and decreased from 34.5 to 33.5 ml (p<0.0001) in C-group. All within–group and between-group changes were significant.

Post-voiding residual volume decreased in the T-group from 47.3 to 13.7 ml and increased in C-group from 48.3 to 64.5 ml. The difference between groups was 54.0 ml (p<0.0001 for all).

The IPSS decreased in the T-group from 6.4 to 2.0 and increased in the C-group from 4.5 to 6.5, figure 4. All within-group and between-group changes were significant.

Figure 4: Changes of IPSS vs. baseline in hypogonadal men receiving testosterone undecanoate (n=360) and untreated controls (n=296).*

Figure 4: Changes of IPSS vs. baseline in hypogonadal men receiving testosterone undecanoate (n=360) and untreated controls (n=296).

* Blue bars show estimated differences between groups adjusted for baseline age, weight, waist circumference, fasting glucose, blood pressure, lipids, and AMS

In the T-group, IIEF-EF improved by 6.02 points. The improvement was statistically significant for the first four years and remained stable in the remaining years. In C-group, it decreased by 9.52 points after 8 years. All within-group and between-group changes were significant.

There were two deaths in the T-group and 21 deaths in C-group. No patient dropped out. Treatment compliance in the T-group was 100% because all injections were performed in the doctor’s office and documented.

Conclusions:
Long-term testosterone therapy with testosterone undecanoate in symptomatic hypogonadal men improved urinary function, while untreated controls experienced a worsening which was independent of prostate size. Long-term testosterone undecanoate was well tolerated and excellent adherence suggested a high level of patient satisfaction in a real-life urology practice.

References

1. Dhindsa S, Ghanim H, Batra M, Kuhadiya ND, Abuaysheh S, Sandhu S, et al. Insulin Resistance and Inflammation in Hypogonadotropic Hypogonadism and Their Reduction After Testosterone Replacement in Men With Type 2 Diabetes. Diabetes Care. 2016;39:82-91.
2. Hackett G, Cole N, Bhartia M, Kennedy D, Raju J, Wilkinson P, et al. The response to testosterone undecanoate in men with type 2 diabetes is dependent on achieving threshold serum levels (the BLAST study). Int J Clin Pract. 2014;68:203-215.
3. Janjgava S, Zerekidze T, Uchava L, Giorgadze E, Asatiani K. Influence of testosterone replacement therapy on metabolic disorders in male patients with type 2 diabetes mellitus and androgen deficiency. Eur J Med Res. 2014;19:56.
4. Hackett G, Cole N, Bhartia M, Kennedy D, Raju J, Wilkinson P. Testosterone replacement therapy with long-acting testosterone undecanoate improves sexual function and quality-of-life parameters vs. placebo in a population of men with type 2 diabetes. J Sex Med. 2013;10:1612-1627.
5. Jones TH, Arver S, Behre HM, Buvat J, Meuleman E, Moncada I, et al. Testosterone replacement in hypogonadal men with type 2 diabetes and/or metabolic syndrome (the TIMES2 study). Diabetes Care. 2011;34:828-837.
6. Yassin A, Haider A, Haider H, Doros G, Traish A, Saad F. Prediabetes, hypogonadism & erectile dysfunction: glycaemic control in 109 hypogonadal men treated with testosterone undecanoate injections (TU) for up to 8 years: real-life data from registry studies. Presented at AUA 2016.
Referenz: J Urol 195(4, Part 2): e629 (2016)
7. Haider A, Haider K, Doros G, Traish A. Prostate cancer is less frequent and severe in hypogonadal men treated adequately with testosterone undecanoate injections (TU) for up to 8 years compared to untreated hypogonadal controls. Presented at AUA 2016.
Referenz: J Urol 195(4, Part 2): e236 (2016)
8. Haider A, Haider K, Saad F, Doros G, Traish A. Erectile function in 656 hypogonadal men: Results of long term treatment with testosterone undecanoate injections (TU) in comparison with control group. Presented at AUA 2016.
Referenz: J Urol 195(4, Part 2): e1007 (2016)
9. Haider A, Haider K, Doros G, Traish A. Effects of long-term testosterone undecanoate injections (TU) on urinary and sexual function in hypogonadal men: real-life data from a controlled registry study. Presented at AUA 2016.
Referenz: J Urol 195(4, Part 2): e1186 (2016)

Last updated: 2018
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