Age, gender, and voided volume dependency of peak urinary flow rate and uroflowmetry nomogram in the Indian population

Objectives:Objectives: The objective of this study was measurement of urine ﬂ ow parameters by a non invasive urodynamic test. Variation of ﬂ ow rates based on voided volume, age, and gender are described. Different nomograms are available for different populations and racial differences of urethral physiology are described. Currently, there has been no study from the Indian population on uro ﬂ ow parameters. So the purpose of this study was to establish normal reference ranges of maximum and average ﬂ ow rates, to see the in ﬂ uence of age, gender, and voided volume on ﬂ ow rates, and to chart these values in the form of a nomogram. Methods:Methods: We evaluated 1,011 uro ﬂ owmetry tests in different age groups in a healthy population (healthy relatives of our patients) 16-50 year old males, >50 year old males, 5-15 year old children, and >15 year pre-menopausal and postmenopausal females. The uro ﬂ owmetry was done using the gravitimetric method. Flow chart parameters were analyzed and statistical calculations were used for drawing uro ﬂ ow nomograms. Results:Results: Qmax values in adult males were signi ﬁ cantly higher than in the elderly and Qmax values in young females were signi ﬁ cantly higher than in young males. Qmax values in males increased with age until 15 years old; followed by a slow decline until reaching 50 years old followed by a rapid decline after 50 years old even after correcting voided volume. Qmax values in females increased with age until they reached age 15 followed by decline in ﬂ ow rate until a pre-menopausal age followed by no signi ﬁ cant decline in post-menopausal females. Qmax values increased with voided volume until 700 cc followed by a plateau and decline. Conclusions:Conclusions: Qmax values more signi ﬁ cantly correlated with age and voided volume than Qavg. Nomograms were drawn in centile form to provide normal reference ranges. Qmax values in our population were lower than described in literature. Patients with voided volume up to 50 ml could be evaluated with a nomogram.


INTRODUCTION
Uroflowmetry is the measurement of the rate of urine fl ow over time. The measurement of urine fl ow is non invasive and is the easiest uro-dynamic test useful as preliminary or follow-up investigation of the lower urinary tract symptom. The clinical usefulness of urofl ow rate has been attenuated by the lack of absolute values defining normal limits. [1] Urinary fl ow rates depend on voided volume in a nonlinear fashion. [2][3][4][5] Nomograms are required to see the change in fl ow rates at different voided volumes, and the use of nomograms overcome the danger of referencing fl ow rates to any one voided volume. Nomograms in centile form were constructed to provide normal reference ranges in various age groups for urinary fl ow rates covering a wide range of voided volumes. [2][3][4][6][7][8][9][10] Siroky, et al. were among the fi rst to develop a nomogram that allowed urofl ow to be corrected for voiding volume. [2] There are racial differences described in African and Caucasian women for urodynamic parameters. [11] However, there is no study for the Indian population on urofl owmetry.
The purpose of this study was to establish normal reference ranges for urinary fl ow rates over a wide range of voided volumes, to see the infl uence of age, gender, and voided volume on fl ow rates, and to chart these values in the form of nomogram charts for the standard Indian population. | October-December 2009 |

MATERIALS AND METHODS
A prospective study was conducted by the Department of Urology, K.E.M Hospital in Mumbai from August 2005 to November 2007. Healthy relatives of our admitted patients were recruited after taking valid consent. Different age groups of the healthy population were: 16 to 50 year males (Group I), > 50 year old males (Group II), 5 to 15 year olds (Group III), >15 year old pre-menopausal females (Group IV), and post-menopausal females (Group V). These fi ve groups were analyzed separately and intergroup differences were statistically analyzed.
We used the gravitimetric method for uroflowmetry, using Santron 2pl; PC-based urofloweter. Calibration was initially performed using the internal self calibration program on the apparatus and repeated at intervals to ensure consistency. [12] The checking of voided volume, fl ow time, and average fl ow rate was performed using known fl uid volumes and time (stopwatch). We descriptively analyzed fl ow chart parameters and used statistical calculation for drawing urofl ow nomograms. Nomograms were constructed depicting the normal Gaussian distribution of maximum and average urinary fl ow rate at volumes ranging from 50 to 1000 cc. These healthy populations were evaluated by history, examination, and investigations. Evaluated parameters were voided volume, maximum fl ow rate, average fl ow rate, fl ow time, and time to Qmax.
Exclusion criteria were patients with urological complaints or a history of neurological disorders. Other healthy volunteers were included in the study.

Statistical Analysis
Statistical analysis was performed using SPSS software (SPSS, Inc.). Several transformations of data were assessed and the goodness-of-fi t tested to determine whether a linear, hyperbolic, parabolic, or logarithmic function best described the relationship between the maximum or average fl ow rates and the voided volume. The Quintile regression method was used to establish the percentile levels (5, 10, 25, 50, 75, 90, and 95). Nomograms were presented in centile form and prepared for each group. The difference was assessed for signifi cance using a student's t test. Data was analyzed for "goodness of fi t" using the Kolmogorov Smirnoff test (K-S-test).

RESULTS
We evaluated urofl owmetry data of 1,011 patients from a healthy population; 262 patients were in Group I (16-50 year old males), 239 patients were in Group II (> 50 year old males), 217 patients were in Group III (children 7-14 years old), 207 patients were in Group IV (pre-menopausal females), and 92 patients were in Group V (post-menopausal females).
In Group I, the median age was 31 years old. The mean voided volume was 440 ± 215 ml. The mean maximum fl ow rate and average fl ow rate were 22.5 ± 9.2 ml/sec and 13.05 ± 6.12 ml/sec, respectively. The correlation between Qmax and Qavg with voided volume were signifi cant (Pearson's correlation coeffi cient r = 0.413 and r = 0.488, p< 0.01, respectively). The higher the voided volume, the higher the fl ow rates. Qmax values showed a signifi cant correlation with age (r: -0.15, P = 0.012). Qavg is not signifi cantly correlated with age, (Pearson's correlation r: -0.11, P value = 0.08). There was a decline in Qmax by 1 ml/sec/decade. Equation for the fl ow rates based on voided volume and age in Group I √ Maximum fl ow rate (Qmax) = 3.58 + 0.482√ (VV) -0.145x (age) Nomogram charts for maximum flow rate and voided volume were prepared and plotted based on regression analysis [ Figure 1].
The median age in Group II was 67 years old. Voided volumes were 297.78 ± 142 ml. The mean maximum fl ow rate and average fl ow rate were 17 ± 7.16 ml/sec and 8.9 ± 4.06 ml/sec. Qmax and Qavg are well correlated with voided volume (r: 0.576, P value: 0.001 and r: 0.519, P value-.0001). Qmax and Qavg in this group are negatively correlated with age (r: -0.297, P value -0.001. and r:-4.00, P value -0.0001).
Equation for the fl ow rates based on voided volume and age in Group II √Maximum fl ow rate = 3.2 + 0.544 √ (VV) -0.154(age) Nomogram charts for maximum flow rate and voided volume are shown in Figure 2.
A comparison between Groups I and II and the statistical differences are discussed in Table 1.
Out of 299 females, 202 were pre-menopausal (Group IV) and 97 were post-menopausal (Group V). The two groups were analyzed separately to assess the effect of hormonal withdrawal with menopause on the physiology In the group of post-menopausal females, the median age was 61 years old. The mean voided volume was 362 ± 141 ml. The mean maximum fl ow rate and average fl ow rate were 17.59 ± 5.59 ml/sec and 10.2 ± 3.52 ml/sec, respectively. Qmax values were negatively correlated with age, but they were statistically non-signifi cant (r: 0.036, P value = .08).
Equations for the fl ow rates based on voided volume and age in Group V √Maximum fl ow rate = 1.36 + 0.575 √ (VV) -0.086(age) Nomograms for pre-menopausal and post-menopausal females are shown in Figures 3 and 4 and a comparison of pre-menopausal and post-menopausal females is discussed in Table 2.
The fl ow rate was not statistically different in nulliparous or multiparous females.
Group III consisted of 5-15 year old children; the median age was 9 years old. The mean voided volume was 220 ± 135 ml. The mean maximum fl ow rate and average fl ow rate was 17.7 ± 6.2 ml/sec and 10.08 ± 3.44 ml/sec, respectively. Qmax and Qavg positively correlated with age (r = 0.702, P value = 0.0001 and r = 0.752, P value = 0.0001    The maximum fl ow rate nomogram for boys and girls is shown in Figures 5 and 6 and a comparison of the boys and girls in Group III are discussed in Table 3.

DISCUSSION
Mean maximum and average flow rate parameters in different age groups are shown in Table 4. Nomograms were constructed to provide normal reference ranges for both genders for urinary fl ow rates covering a wide range of voided volumes and in centile form. The use of statistical transformations in their construction overcame the problems created by inaccuracies when untransformed standard deviations were used i.e., the Siroky nomogram. [2,13] Among the male population, Qmax values in the 16 to 50 year old group were 22.8 ± 9.33 ml/sec -signifi cantly higher than in the > 50 year old and 5 to 15 year old groups, which were 17.04 ± 7.1 ml/sec and 16.9 ± 5.38 ml/sec, respectively. Similar statistical differences were found by Suebnukanwattana, et [14,15] Qmax values in the elderly population were 17.04 ml/sec signifi cantly lower than the study in the Thai population (27.5 ml/sec). [15] Among female groups, the Qmax values were 22.98 ml/ sec in the pre-menopausal group and 19.04 ml/sec in the post-menopausal group. There was a negative correlation with age and Qmax and Qavg. Our fi nding is different from Haylen, et al., who reported no dependence of fl ow rate with age. No correlation could be found with Qmax and parity.
A similar relation has also been confi rmed by the reports of Haylen, et al. [4] A signifi cant positive correlation with age was seen in the 5 to 15 year old age group and a negative correlation of Qmax values with age was seen in the 15 to 50 year old group and in the more than 50 year old group. Similar negative correlations with age were shown by the Liverpool nomogram and the study in the Thai population. [4,15] We found a strong relationship between Qmax and Qavg values with voided volume in all the three groups. A similar strong correlation was found by Siroky, et al. and Haylen, et al. [2,4] Urofl owmetry nomograms were drawn based on these positive correlations between voided volume and fl ow rates.
On comparing the fl ow rates of the male and female groups, Qmax values were 22.8 ± 9.33 ml/sec and 20.53 ± 7.75ml/ sec, respectively. There was no statistically difference found   [16,17,18] Normally, females have a short urethra usually with minimal outlet resistance.
Voiding time was prolonged in post-menopausal females, which is signifi cantly higher than the pre-menopausal and 5 to 15 year old groups.
Among the pediatric population, fl ow rates for girls and boys were 19.2 ± 6.95 ml/sec and 16.9 ±5.38 ml/sec, respectively (p<0.001). Similar results have been seen by Guitierrez Segura and Kajbafzadeh, et al. [19,20] Guitierrez Segura's report confi rmed that the Qmax value increased with volume and age. [19] Mean values were higher in girls than in boys. In our study, we also found a positive correlation of age with maximum fl ow rates. On comparing fl ow time and time to Qmax, there is no statistically signifi cant difference in both groups for time to Qmax but there was signifi cant difference between the two groups in voiding time (P value<0.001). Guitierrez Segura's and Jensen, et al. show that fl ow time is shorter in girls. [19] Qmax is positively correlated with voided volume that is seen up to 700 ml voided volume; after 700 ml there is a plateau followed by a decline. A similar report was conducted by Dominik, et al., who found a positive correlation until voided volumes of 350 ml in the adolescent population, but constant until 500 ml and a decrease in Qmax values after 500 ml. [21,22] Voided volume changes signifi cantly with age in the 5 to 15 year old group. To eliminate the factor of rising voided volume on rising fl ow rate with age, an analysis of fl ow rate at a constant voided volume was done. At a constant voided volume of 200 to 250 ml, the maximum fl ow rate is signifi cantly correlated with age.

CONCLUSIONS
Maximum fl ow rate (Qmax) is more signifi cantly correlated with age and voided volume than average flow rate (Qavg); hence, Qmax is the single most useful parameter of urofl owmetry. Qmax increases with age in the pediatric population and decreases with age in the adult and elderly population. Qmax in girls was signifi cantly higher than in boys. No artifi cial restriction of voided volume e.g., minimum 150 ml, is appropriate. Patients with voided volume up to 50 ml can also be evaluated with the help of a nomogram.
Qmax values in the adult population (15-50 years old) and the elderly population were lower than in the Thai and Austrian healthy population. Nomograms in centile form were constructed to provide normal reference ranges for urinary fl ow rates and covered a wide range of voided volumes.