Prostate volume in male patients with spinal cord injury: a question of nerves?

Authors


Correspondence: Jürgen Pannek, Chefarzt Neuro-Urologie, Schweizer Paraplegiker-Zentrum, Guido A. Zäch Strasse 1, CH-6207 Nottwil, Switzerland.

e-mail: juergen.pannek@paranet.ch

Abstract

Objective

  • To assess the influence of standardized complete surgical deafferentation of the lower urinary tract by sacral deafferentation (SDAF) and sacral anterior root stimulation (SARS) on prostate volume in men with spinal cord injury (SCI).

Patients and Methods

  • In a prospective study, the prostate volume of men with SCI who underwent SDAF/SARS was measured using transrectal ultrasonography.
  • The prostate volumes of these men were compared with those of men with complete SCI but who did not undergo SDAF/SARS, those of men with incomplete SCI, and those of a historical sample of able-bodied men.

Results

  • The median [25th;75th percentile] prostate volume of men who underwent SDAF/SARS (20.0 [14.0; 29.0]) and of men with complete SCI who did not undergo SDAF/SARS (20.0 [16.5; 29.0]) was significantly smaller than in the reference group (25.0 [5.0; 84.0]).
  • The mean prostate volume was associated with age in the reference group (r = 0.185; P < 0.001) and in men with incomplete SCI (r = 0.284; P = 0.031), but not in men with complete SCI, irrespective of SDAF/SARS.

Conclusions

  • The prostate volume of men with complete SCI was significantly smaller than that of able-bodied men.
  • Our data imply that sustained central innervation of the prostate plays an important role in prostate growth.
Abbreviations
SDAF

sacral deafferentation

SARS

sacral anterior root stimulation

SCI

spinal cord injury

Introduction

As a result of substantial improvements in medical care in recent years, a patient's lifespan after a spinal cord injury (SCI) has increased substantially [1]. Today, the life expectancy of patients with paraplegia does not differ from that of the general population [2]. Most men with SCI are therefore likely to encounter problems of the aging male, including growth of the prostate.

Although it is well known that in the general population, the prostate gland grows with age [3], the exact mechanism is not completely elucidated. Hormonal factors are known to cause prostatic enlargement [4], and experiments in rats with SCI indicate that neurogenic factors also play an important role in prostate growth and function [5]. To assess the influence of autonomic denervation on prostate growth in humans, the impact of SCI on prostate size has been studied; however, these studies have provided conflicting results, partly because of the limited size of the study populations, but also because they have included men with different severity of SCI [6-9].

We hypothesized that the extent of decentralization of the prostate correlates with prostate volume. To examine a population of men with a decentralization of the prostate as standardized as possible, we evaluated the prostate volumes of men with SCI who underwent sacral deafferentation (SDAF) and sacral anterior root stimulation (SARS), a procedure that includes a standardized, complete dissection of the afferent roots of the sacral nerves S2 to S5 [10]. We compared these data with the prostate volumes of men with complete SCI who did not undergo SDAF/SARS, in whom the sacral reflex arch was still intact, leading to neural input to the lower urinary tract (e.g. reflex detrusor activity), with those of men with incomplete SCI, and with those of able-bodied men. In addition, the impact of SCI duration and age were assessed.

Patients and Methods

In a prospective study, we assessed the prostate volumes of men with SCI who underwent SDAF/SARS at our institution using TRUS. The age-related prostate volumes of these men were compared with the prostate volumes of men with complete SCI, but without SDAF/SARS, with those of men with incomplete SCI, and with those of a sample of men participating in an epidemiological study, representing the general population, assessed previously [6].

A standardized technique, described previously [10], was used to perform SDAF/SARS. In summary, in all patients intradural deafferentation (rhizotomy) of the sacral dorsal roots S2–S5 was performed. In 50 patients, an intradural anterior root stimulator was implanted, whereas three patients received an extradural device for anatomical reasons (all devices: Finetech Brindley Bladder Control System; Finetech Medical Ltd, Welwyn Garden City, UK). All stimulators were implanted in the Swiss Paraplegic Centre, Nottwil, by one surgeon, between 1991 and 2011. All patients included in the study effectively voided by the use of the stimulator with a residual urine of <100 mL.

All men with SCI, having undergone SDAF/SARS, who presented to our department for routine urological examination, were screened to ascertain if they qualified for participation in the study. Exclusion criteria were: time between SDAF/SARS and prostate volume measurement <1 year, previous prostatic or bladder surgery other than sphincterotomy, acute UTI, prostate cancer, and finasteride treatment or other hormone-active medication, including chronic opiod intake. Sphincterotomy was defined as an incision of the external urinary sphincter ‘at 12 o'clock’ in the lithotomy position without any further manipulation besides coagulation. Simultaneous resection/incision of the prostate or bladder neck was an exclusion criterion. The study was approved by the local ethics committee.

After informed consent had been obtained, prostate volume was assessed by TRUS using a 7.5 MHz probe (General Electrics, Glattbrugg, Switzerland) with the patient lying on his left side.

Statistics

Owing to the assumption of non-normal distributed data, median (25th; 75th quartiles) as well as frequencies of patients' characteristics and prostate volume were calculated. The prostate volumes of three groups (group A: men with complete SCI and who underwent SDAF/SARS; group B: men with complete SCI who did not undergo SDAF/SARS; group C: men with incomplete SCI) were compared with the prostate volumes in a cohort of 549 screening patients, who presented to a prostate awareness project, using a Kruskal–Wallis test for non-parametric data. In case of significant overall group differences in prostate size, we used a Mann–Whitney U-test for post hoc analysis. Correlations between prostate volume and age of each group were tested using Pearson correlation analysis. For further subanalysis, men were grouped according to their age (35–40 years, 41–50 years, 51–60 years, 61–70 years, and ≥71 years) and intergroup differences were analysed using a Kruskal–Wallis test. In addition, the interval between injury and examination was used as a discriminator (<10 years of SCI and >10 years of SCI, respectively) to test for inter-group differences. A P value of ≤0.05 was considered to indicate statistical significance.

Results

A total of 53 men with complete SCI who underwent SDAF/SARS were included. The median (25th; 75th percentile) age at the time of examination was 55.0 (47.0; 61.0) years and the median (25th; 75th percentile) time between SCI and examination was 20.0 (11.0; 24.5) years. No patient received anticholinergic treatment.

The group of men with complete SCI who did not undergo SDAF/SARS consisted of 41 men with a median (25th; 75th percentile) age at the time of examination of 55.0 (45.5; 61) years, and a median (25th; 75th percentile) time between SCI and examination of 16.0 (8.5; 24.5) years. The median (25th; 75th percentile) age of the 58 men with incomplete SCI at the time of examination was 54.0 (46.0; 62.0) years, and the median (25th; 75th percentile) time between SCI and examination was 9.0 (3.0; 13.5) years. The control group consisted of 548 able-bodied men without known lower urinary tract pathologies. The median (25th; 75th percentile) age of this group was 67.0 [61.0; 73.0] years (Table 1).

Table 1. Patient characteristics
GroupnMedian (25th; 75th percentile) prostate volume, mLMedian (25th; 75th percentile) age, yearsMedian (25th; 75th percentile) years since SCI
  1. n.a., not applicable.
SDAF/SARS5320.0 (14.0; 29.0)55.0 (47.0; 61.0)20.0 (11.0;29.5)
Complete SCI4120.0 (16.5; 29.0)55.0 (45.5; 61.0)16.0 (8.5; 24.5)
Incomplete SCI5822.5 (16.0; 28.0)54.0 (46.0; 62.0)9.0 (3.0; 13.5)
Reference group54925.0 (18.0; 33.0)67.0 (61.0; 73.0)n.a.

Surgical Outcome

In the 53 men who underwent SDAF/SARS, a defect of the stimulator cables or the receiver plate or both (n = 6) was the most common complication. The most severe complication was incomplete deafferentation, which required deafferentation at the conus medullaris (n = 1).

Prostate Volume

The prostate volume of men who underwent SDAF/SARS did not differ significantly from those with complete SCI (P = 0.497), nor did it differ significantly from those with incomplete lesions (P = 0.274). Comparing prostate volumes of each group of men with SCI to the reference group, there were significant differences between men with complete SCI (who did or did not undergo SDAF/SARS) and the reference population, but not between men with incomplete SCI and the reference group (Fig. 1).

Figure 1.

Prostate volumes of men with SDAF/SARS, men with incomplete SCI, a reference group, and men with complete SCI. ○: outliers; *: extreme values.

Duration of SCI

When the men were grouped according to the duration of SCI, we did not find a significant difference in prostate size between men with >10 years of SCI, and those with <10 years of SCI (P > 0.05). The prostate volume of the reference group, however, was significantly higher than in men with >10 years of SCI (P = 0.005) or <10 years of SCI (P = 0.008 [Fig. 2]).

Figure 2.

Age-related prostate volumes of the different patient groups. image: SDAF/SARS; image: incomplete SCI; image: complete SCI; image: reference group.

Prostate Volume and Age

Prostate volume was significantly and positively related to age in men with incomplete SCI (r = 0.284; P = 0.031) as well as in the reference group (r = 0.185; P < 0.001), whereas this age-related increase in prostate size was not found to be significant in men with complete SCI, in either those who underwent SDAF/SARS or in those who did not; however, in the subgroup of men aged >50 years, no significant differences in prostate volume between men with complete SCI who did or did not undergo SDAF/SARS, men with incomplete SCI and men in the reference group were found (P = 0.112 [Table 2]).

Table 2. Prostate volume in men aged >50 years
GroupnMedian (25th; 75th percentile) prostate volume, mL
SDAF/SARS3523.0 (14.0; 29.0)
Complete2621.0 (15.8; 30.0)
Incomplete3724.0 (19.5; 29.5)
Reference54925.0 (18.0; 33.0)

To analyse prostate volume in relation to different periods of life we divided the study population into five age groups (35–40 years, 41–50 years, 51–60 years, 61–70 years and >70 years). Prostate volume did not differ significantly between any of the age groups in men with complete SCI who underwent SDAF/SARS, in men with complete SCI who did not undergo SDAF/SARS and in men with incomplete SCI, respectively. Only the age groups of the reference group differed significantly, with lower prostate volumes in men aged between 51 and 60 years comparedwith men in the age groups 61–70 years (P < 0.001) and >70 years (P < 0.001).

Discussion

The present study is the first to analyse prostate size in men after SCI with a standardized complete neurological lesion. We found that men with complete SCI (who did or did not undergo SDAF/SARS) had significantly smaller prostate volumes than the reference population, whereas this was not found in men with incomplete SCI. The more pronounced influence of complete SCI on prostate growth is supported by the fact that we detected age-related differences in prostate size, known to be present in able-bodied men [11], in men with incomplete SCI, but not in men with complete SCI, irrespective of whether the men had undergone the SDAF/SARS procedure. We were not able to detect significant differences among the prostate volumes of men with complete SCI who underwent SDAF/SARS, men with complete SCI without surgery or men with incomplete SCI. Neither the time since SCI nor the life decade of the men influenced these findings.

The impact of decentralization by SCI on prostate growth has been the subject of debate. Several studies in humans have obtained conflicting results. Whereas Shim et al. [7], in their study of 31 men with SCI, and Pannek et al. in 100 men [6], could not detect significant differences in prostate size and PSA values between men with SCI and men without SCI, Frisbie et al. [8] found that prostate size was smaller in nine men with severe SCI than in 21 men with less severe lesions. Hvarness et al. [12] compared 31 men at least 5 years after SCI with age-matched controls and found that median prostate size was significantly smaller in men with SCI, whereas testosterone levels were in the normal range for both groups. In a study by Benaim et al. [9], no age-related prostate volume increase was detected in men with SCI. In the most recent study, Bartoletti et al. [13] compared the prostate volumes of 113 men with SCI with those of 109 age-matched controls. The results were stratified according to the patient age at SCI onset. The prostate volume of men with SCI was significantly lower than in the control group. Furthermore, they found that prostate volume was inversely related to the men's age at SCI onset.

In summary, the results of these previous studies are difficult to interpret because of the rather small sample sizes, the different levels and the different severity of lesions included. As the number of men included in the present study exceeds the study population of most of the previously published studies, we think that the data may well help to answer several unresolved questions. Our results support previous findings that prostate volumes in men with incomplete SCI are not significantly different from those of able-bodied men, whereas the difference was significant in men with complete SCI.

Animal studies have uniformly found a substantial reduction of prostate volumes after denervation [14-16]. In the majority of animal models, however, peripheral denervation has been performed. Whereas peripheral denervation leads to a complete loss of nerve supply, SCI results in a chronic decentralization rather than in a complete denervation, as the local nerve supply remains undamaged. As a consequence, animal studies evaluating prostate weights after SCI showed less impressive results. In SCI rats, prostate weights were persistently lower than in sham-operated controls for 3 months, but after 6 months this effect was no longer detectable [5]. Thus, the major difference between these observations was the level of denervation.

Histological examinations of prostatic tissue support this view. Selective intraprostatic denervation by botulinum toxin type A injection in the rat prostate led to significant prostate atrophy and volume reduction of the gland [17, 18]. Prostate biopsies in men with SCI revealed a normal prostate architecture in men with SCI [19]. Atrophy caused by changes of local nerve supply seems not to be present after SCI, which is another hint that decentralization may not cause the same effects in the prostate as complete peripheral denervation.

Obviously, the present findings could not answer all questions concerning the influence of decentralization on prostate volume. Our hypothesis that complete SCI achieved by SDAF/SARS leads to smaller prostate volumes was supported by the data; however, this fact was also demonstrated in men with complete SCI, but who did not undergo SARS/SDAF, making the influence of the surgical procedure on prostate volume less clear. Nevertheless, according to the present data, complete SCI seems to have a significant influence on prostate size in men. The mentioned uncertainties could at least partially be explained by the limited number of men included in the study.

The present study has several technical limitations. The sample size is not big enough to allow epidemiological studies, which would be necessary to reliably answer the question about the impact of decentralization on prostate growth. SDAF/SARS is not a very commonly used surgical technique, and to our knowledge, our study is the first to report prostate size in men after this procedure. Furthermore, owing to the limited sample size, all subgroup analyses have to be interpreted with caution. As prostatic enlargement tends to cause clinical signs and symptoms predominantly in men aged >50 years, we analysed this subset of men separately, and detected no significant differences in prostate volumes between men with SCI and those without. This finding, however, can be attributed to the small sample size and the high variation of the prostate volumes in these groups. Nevertheless, the sample size is similar to the largest studies previously published concerning this question, therefore, the present results may well augment our knowledge.

We did not measure PSA or testosterone levels in our men; however, several previous studies that included as many as 366 men with SCI, found no significant age-related differences in mean PSA values between men with SCI and control groups of men without SCI [6, 20]. Studies evaluating androgen profiles of men with chronic SCI detected no abnormalities in the pituitary-gonadal axis [9]; thus, possible differences in prostate volume between men with and men without SCI do not seem to be attributable to altered testosterone levels.

In conclusion, the prostate volumes of men with complete SCI were significantly smaller than those of able-bodied men. Furthermore, we detected age-dependent prostate growth in men with incomplete SCI, but not in those with complete lesions. Our data imply that sustained central innervation of the prostate in humans plays a role in prostate growth, but may not be the most important prerequisite for prostate growth in men. For example, decentralization does not lead to local glandular atrophy which, according to animal experiments, is caused by local denervation.

We were unable to detect age-related increases in prostate volumes in men with complete SCI. Other authors have shown that the earlier in life men suffered from SCI, the more distinct was the negative influence on prostate volume [13]. Combining these results, we hypothesize that decentralization has a significant, but not pronounced impact on prostate volume; a complete lesion early in life, lasting for a long time, is required for the impact to gain possible clinical relevance. Prospective long-term multicentre studies would be necessary to confirm this theory.

Conflict of Interest

None declared.

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