Lower urinary tract symptoms improve with testosterone replacement therapy in men with late-onset hypogonadism, "Beyond the Abstract," by Aksam A. Yassin, MD, PhD, EdD, FEBU, et al

BERKELEY, CA (UroToday.com) - Many men with “late-onset hypogonadism” (LOH) experience lower urinary tract symptoms (LUTS) that can be distressing and may decrease quality of life. LUTS often appear in men when testosterone levels begin to decline, which could be an indicator of a significant association. We investigated whether testosterone replacement could alleviate LUTS in men with LOH.

A total of 261 hypogonadal men (total testosterone concentration ≤ 3.5 ng ml-1 (12 nmol/L) on 2 blood samples) presenting with symptoms of LUTS were recruited onto the study (mean age 59.5 years). Patients had documented ED for ≥ 6 months, established using the international definition for ED, the International Index of Erectile Function (IIEF). Severity of ED was defined as IIEF erectile function score ≤ 21, where severe = 1–10, moderate = 11–16, and mild/none = 17–30. Patients with clinically significant findings on physical exam, or presence of known clinically significant diseases that would prejudice the completion of the study or contraindicate testosterone administration, were excluded from the study. Patients with severe diabetes mellitus, International Prostate Symptom Score (IPSS) > 18, prostatitis, hyperprolactinaemia (> 20 ng ml-1) or cardiovascular events within the last 6 months were also excluded from this study, as were patients with obstruction due to BPH with residual urine higher than 40 ml. Two-hundred and fifty-nine patients were eligible for final evaluation. All patients gave their written informed consent to be included in the study which was conducted according to ethical guidelines as formulated by the German "Ärztekammer" (the German Medical Association) for observational studies and followed the principles outlined in the Helsinki Declaration of 1975, as revised in 1983.

The primary efficacy outcome measure was mean reduction in IPSS from baseline at each treatment visit. Secondary outcome measures were IIEF, quality of life measures, the Aging Male Symptoms Scale (AMS) and obesity parameters (weight, waist circumference and BMI). Prostate volume and post-voiding residual volume were routinely measured with ultrasonography; bladder wall thickness was measured only in a subset of patients (n=40).

This prospective, observational and longitudinal registry study analyzed the efficacy and safety of long-acting intramuscular testosterone undecanoate (TU) 1000 mg (Nebido®, Bayer Pharma, Berlin, Germany) for the alleviation of LUTS in men with LOH. Patients were initially administered long-acting TU via intramuscular injection on day one of the study (T1), received the second dose after 6 weeks (T2) in order to reach steady state testosterone concentrations, and then every 3 months thereafter for a median period of 42.3 months. Linear regression was used to assess the change in mean IPSS of the entire cohort, over time. A path analysis divided the cohort at two independent stages. Firstly, the subgroup was divided into users and non-users of the PDE5 inhibitor vardenafil and t-test comparisons of mean IPSS and other outcome measures were made between the groups. Secondly, patients were divided into weight losers (L) and non-losers (NL) (L-patients had lost at least 5% weight at the last visit since baseline) and once again t-test comparison of outcome measures was made between the groups.

Safety assessments included all patients on the registry once they had received one year of treatment with the study medication. Monitoring of treatment-emergent adverse events occurred throughout the study. Physical exam and ultrasound of the prostate to estimate prostate volume were performed. Serum prostate specific antigen (PSA) levels were also measured at each 3-month period. Cardiovascular risk factors were also controlled throughout study. No cardiac events had been reported.

Baseline characteristics and end-of-study values for the patients who were enrolled in the study are summarized in Table I. The majority of patients were obese with a mean study baseline BMI of 31.73±4.42. This was consistent with obesity having been identified as one of the main causes of hypogonadism. Two percent of patients had Klinefelter syndrome. Most patients presented a combination of irritative and obstructive symptoms with different degrees of severity and percentage variation; 11% of patients presented overactive bladder.

The mean estimated prostate volume (PV) of patients as measured by transrectal ultrasonography at baseline was 27.9±8.2 ml, ranging from a minimum of 10 ml to a maximum of 56 ml. The prostate volume had an increasing trend with a p value by linear regression of < 0.05, however, the increase in the mean volume was less than 10 ml, from 27.9 to 34.8 ml over the period of the study (Table I). Statistically significant differences were observed in both bladder wall thickness (p < 0.001) and post-voiding residual volume (p < 0.001) following treatment when compared to baseline measurements (Table I).

Mean IPSS at baseline was 10.35±5.02 and decreased significantly with time after initiation of TU therapy (ANOVA p< 0.05). Mean IPSS between weight losers (L, n=186) and nonlosers (NL, n=68) showed an erratic pattern with no statistical difference between the 2 groups (Figure 1A). Furthermore, mean IPSS was not significantly altered by the use of vardenafil over the time-course of the treatment (Figure 1B).

 

N

Minimum

Maximum

Mean

Std. Deviation

End of observation period

Age (years)

259

32

84

59.5

8.4

 

Waist circumference (cm)

259

88

148

107.66

10.03

99.03±9.05

Weight (kg)

259

68

141

100.13

14.0

92.49±11.15

BMI kg/m2

261

21.97

43.27

31.73

4.42

29.44±3.37

IPSS score

260

1

21

10.35

5.02

6.58±3.47

IIEF score

260

1

19

7.8

3.32

20.10±6.3

AMS score

258

39

77

54.27

8.34

31.18±5.5

Post voiding residual urine volume (ml)

249

0

85

23.82

15.72

17.55±8.93

Prostate volume (ml)

253

10.0

56.0

27.90

8.15

34.79±8.69

Bladder wall thickness (cm)

Total Testosterone  (nmol/L)                   

40

261

0.30

1.39

1.20

11.82

0.78

7.72

0.22

2.07

0.42±0.16

18.41±2.37


Table I. Baseline characteristics and treatment results

bta yassin fig1 thumb
Figure 1. Effect of long-acting i.m. TU (1000 mg) on mean IPSS score over time. Patients are categorized according to weight loss (group L patients had lost at least 5% of their body weight at the end of the study) and according to concomitant use of the PDE5 inhibitor vardenafil. Mean IPSS of the overall study population at baseline was 10.35 and decreased significantly with time after initiation of TU therapy (ANOVA p < 0.05). There was no statistical difference between L and NL subgroups (A) or between patients concomitantly using vardenafil and those who were not (B).


Written by:
Dany-Jan Yassin,1 Yousef El Douaihy,2 Aksam A. Yassin,2, 3 James Kashanian,4 Ridwan Shabsigh,4 and Peter G. Hammerer1 as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.

1Department of Urology, Klinikum Braunschweig, Brunswick, Germany
2Segeberger Kliniken, Institute of Urology and Andrology, Rathausallee 94 a, 22846, Norderstedt-Hamburg, Germany
3Dresden International University, Dresden, Germany
4Division of Urology, Maimonides Medical Center, Brooklyn, NY, USA

 

Lower urinary tract symptoms improve with testosterone replacement therapy in men with late-onset hypogonadism: 5-Year prospective, observational and longitudinal registry study - Abstract

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