After including the patients, one patient in Group 1 was excluded since he had a myocardial infarction leading to death before completion of HBO treatment. Also, in Group 3, 13 patients were omitted because they could not buy PDE5I, while three patients were excluded because they could not continue PDE5I treatment due to side effects.
Overall, 102 male patients were included. They were aged between 37 and 80. The demographic data of the patients and results of the comparative analysis between the three study groups are displayed in Table 1. This comparison revealed that the baseline IIEF-5 scores of the three groups were not significantly different from each other (p = 0,364).
Table 1
| GROUP 1 | GROUP 2 | GROUP 3 | p value |
PATIENT NUMBER (n) | 40 | 31 | 31 | |
AGE | 59 ± 9,11 | 59 ± 7,29 | 54,16 ± 9,65 | 0,042† |
SMOKING HISTORY | ABSENT | 25 (62,5%) | 22 (71%) | 21 (67,7%) | 0,746* |
PRESENT | 15 (37,5%) | 9 (29%) | 10 (32,3%) |
SMOKING PACK-YEAR | 38 ± 18,59 | 22 ± 15,63 | 25,5 ± 18,02 | 0,193† |
Diabetes Mellitus (DM) | PRESENT | 31 (77,5%) | 26 (83,9%) | 10 (32,3%) | < 0,001* |
ABSENT | 9 (22,5%) | 5 (16,1%) | 21 (67,7%) |
DM DURATION (year) | 16,55 ± 10,01 | 12,58 ± 7,54 | 8,5 ± 6,88 | 0,032† |
Hypertension | Present | 19 (47,5%) | 12 (38,7%) | 11 (35,5%) | 0,562* |
Absent | 21 (52,5%) | 19 (61,3%) | 20 (64,5%) |
Coronary artery disease | Present | 15 (37,5%) | 13 (41,9%) | 3 (9,7%) | 0,010* |
Absent | 25 (62,5%) | 18 (58,1%) | 28 (90,3%) |
Peripheric vascular disease | Present | 3 (7,5%) | 7 (22,6%) | 1 (3,2%) | 0,053* |
Absent | 37 (92,5%) | 24 (77,4%) | 30 (96,8%) |
Dyslipidemia | Present | 6 (15%) | 7 (22,6%) | 8 (25,8%) | 0,508* |
Absent | 34 (85%) | 24 (77,4%) | 23 (74,2%) |
End-stage renal disease (ESRD) | Present | 8 (20%) | 2 (6,5%) | 0 | 0,015* |
Absent | 32 (80%) | 29 (93,5%) | 31 (100%) |
Hemodialysis | + | 4 (50%) | 0 | | 0,201* |
- | 4 (50%) | 2 (100%) | |
Kidney transplantation (n) | | 2 (5%) | 1 (3,2%) | 0 | 0,463* |
Patient numbers based on ED grades (n) | Severe | 16(40%) | 18(58,1%) | 7(22,6%) | 0,044* |
Moderate | 7(17,5%) | 4(12,9%) | 12(38,7%) |
Mild-moderate | 13(32,5%) | 6(19,4%) | 11(35,5%) |
Mild | 4(10%) | 3(9,7%) | 1(3,2%) |
IIEF-5 Scores | Total | 10,45 ± 5,03 | 9,10 ± 4,69 | 10,35 ± 3,51 | 0,364†† |
Severe | 5,25 ± 0,57 | 5,50 ± 0,70 | 5,86 ± 1,06 | 0,280†† |
Moderate | 10,43 ± 0,78 | 10,75 ± 0,50 | 9,33 ± 1,30 | 0,074†† |
Mild-moderate | 14,08 ± 1,75 | 14,50 ± 1,37 | 13,64 ± 1,20 | 0,520†† |
Mild | 19,50 ± 1,91 | 17,67 ± 1,15 | 18 | 0,385†† |
ED DURATION (year) | | 5,7 ± 3,56 | 4,32 ± 2,74 | 2,35 ± 2,05 | < 0,001†† |
† One-Way ANOVA |
* Chi-square test or Fisher’s Exact Test |
†† Kruskal-Wallis one-way analysis of variance |
However, there was a significant difference between the three groups regarding baseline ED severity (Table 1) (p = 0,044). The Monte Carlo simulation determined the p value as 0,046 (0,041 − 0,051) within the 99% confidence interval. The subgroup analysis performed by the Fisher’s exact test revealed that there was no difference between Group 1 and Group 2 and also between Group 1 and Group 3 regarding ED severity (p = 0,489, p = 0,134) and that the statistical significance was due to the difference between Group 2 and Group 3 (p = 0,007). There was no significant difference between the mean IIEF-5 scores of the three patient groups in comparison based on different ED grades (p > 0,05)(Table 1).
A comparison of the groups concerning the duration of ED elucidated that the mean duration of ED was significantly shorter in Group 3 than in Group 1 and Group 2 (p < 0,001 and p = 0,001, respectively) (Table 1).
The mean post-HBO IIEF-5 score of the patients in Group 1 was calculated as 15,3 ± 6,4. The post-treatment total IIEF-5 scores were significantly higher than the pre-treatment total IIEF-5 scores (p < 0,001). In line with this, HBO treatment led to a significant increase in the IIEF-5 scores of the patients with severe, moderate, or mild-moderate ED. However, this treatment did not significantly increase the IIEF-5 scores of the patients with mild ED (Table 2). While there were no patients with normal erectile function at study participation, 6 (%15) patients wholly recovered from ED.
Table 2
The IIEF-5 scores of Group 1 patients before and after HBO treatment
GROUP 1 | Pre-HBO | Post-HBO | p value |
IIEF-5 scores | Total (n = 40) | 10,45 ± 5,03 | 15,33 ± 6,35 | < 0,001† |
Severe ED (n = 16) | 5,25 ± 0,57 | 10,13 ± 5,30 | 0,005† |
Moderate ED (n = 7) | 10,43 ± 0,78 | 17,71 ± 4,38 | 0,027† |
Mild-moderate ED (n = 13) | 14,08 ± 1,75 | 18,31 ± 4,42 | 0,008† |
Mild ED (n = 4) | 19,50 ± 1,91 | 22,25 ± 2,75 | 0,109† |
ΔIIEF scores | Total (n = 40) | 4,87 ± 4,61 (-3-+15) | 0,346* |
Severe ED (n = 16) | 4,87 ± 5,18 (0-+15) |
Moderate ED (n = 7) | 7,28 ± 4,53 (0-+15) |
Mild-moderate ED (n = 13) | 4,23 ± 4,32 (-3-+12) |
Mild ED (n = 4) | 2,75 ± 2,21 (0-+5) |
† Wilcoxon signed rank test |
* Kruskal-Wallis one-way analysis of variance |
Analysis of the IIEF score changes (ΔIIEF) revealed the mean that ΔIIEF was 4,87 ± 4,61 (-3-+15). There was no difference between the patients with different ED grades regarding ΔIIEF in the post hoc analysis (p = 0,346) (Table 2).
The results of the analysis of the patients in Group 1 concerning age, smoking history, duration of ED, and presence of the comorbidities such as diabetes mellitus (DM), hypertension (HT), dyslipidemia, coronary artery disease (CAD), and end-stage renal disease (ESRD) and pre-HBO and post-HBO treatment IIEF-5 scores are displayed in Table 3. Analysis of the patients older than 65 and younger than 65 separately showed that HBO treatment led to a significant increase in the IIEF-5 scores (p = 0,012 and p < 0,001, respectively). The IIEF-5 scores increased significantly irrespective of the smoking history (p = 0,003 and p < 0,001, respectively). Analysis of the patients who had ED for longer than and shorter than five years separately revealed that IIEF-5 scores significantly increased in both groups (p = 0,002 and p = 0,001, respectively). Categorization regarding comorbidities elucidated that the IIEF-5 scores increased significantly in patient groups with an HbA1c level of higher or lower than 7% (p < 0,05). The IIEF-5 scores also increased in patients with comorbidities such as HT, CAD, dyslipidemia, or ESRD. While there was no significant IIEF-5 score increase in 3 patients with peripheric vascular disease (PVD), the IIEF-5 scores increased significantly with the aid of HBO in patients without PVD (p = 0,285 and p < 0,001, respectively).
Table 3
Relationship of past medical history and comorbidities with the IIEF-5 score changes in Group 1 patients
| Category (n) | Pre-HBO (mean IIEF) | Post-HBO (mean IIEF) | p value* |
Age | < 65 (27) | 11,26 ± 5,35 | 15,89 ± 5,64 | < 0,001 |
≥ 65 (13) | 8,77 ± 3,96 | 14,15 ± 7,74 | 0,012 |
Smoking history | Present (15) | 10,93 ± 5,65 | 15,60 ± 6,71 | 0,003 |
Absent (25) | 10,16 ± 4,72 | 15,16 ± 6,26 | < 0,001 |
Diabetes Mellitus | Present (31) | 9,61 ± 4,75 | 13,94 ± 6,08 | < 0,001 |
Absent (9) | 13,33 ± 5,14 | 20,11 ± 4,96 | 0,015 |
Diabetes duration | < 20 years (16) | 11,11 ± 5,14 | 14,28 ± 5,93 | 0,005 |
≥ 20 years (22) | 7,54 ± 3,33 | 13,46 ± 6,5 | 0,005 |
HbA1c level (n = 25) | ≤%7 (9) | 8,33 ± 4,77 | 13,00 ± 6,10 | 0,028 |
>%7 (16) | 9,25 ± 4,23 | 13,38 ± 5,87 | 0,003 |
Hypertension | Present (19) | 9,32 ± 5,52 | 13,16 ± 6,29 | 0,003 |
Absent (21) | 11,48 ± 4,42 | 17,29 ± 5,88 | < 0,001 |
Coronary artery disease | Present (15) | 8,53 ± 4,48 | 13,93 ± 5,39 | 0,002 |
Absent (25) | 11,60 ± 5,07 | 16,16 ± 6,83 | < 0,001 |
Peripheric vascular disease | Present (3) | 13,67 ± 2,08 | 18,33 ± 7,37 | 0,285 |
Absent (37) | 10,19 ± 5,12 | 15,08 ± 6,31 | < 0.001 |
Dyslipidemia | Present (6) | 9,50 ± 4,55 | 14,67 ± 4,59 | 0,043 |
Absent (34) | 10,62 ± 5,15 | 15,44 ± 6,66 | < 0,001 |
End-stage renal disease | Present (8) | 7,13 ± 5,61 | 10,75 ± 7,06 | 0,043 |
Absent (32) | 11,28 ± 4,60 | 16,47 ± 5,72 | < 0,001 |
ED duration | ≤ 5 years (%60) | 11,83 ± 5,17 | 16,38 ± 6,19 | 0,001 |
> 5 years (%40) | 8,38 ± 4,14 | 13,75 ± 6,45 | 0,002 |
* Wilcoxon signed rank test was used for p value calculations |
In Group 2, the mean IIEF-5 score of the patients who were followed conservatively for one month was calculated as 9,23 ± 5,16 at the end of the follow-up period. There was no significant difference between the pre-follow-up and post-follow-up IIEF-5 scores (p = 0,496). Also, analysis regarding patients with different grades of ED did not show a significant difference between the IIEF-5 scores before and after a 1-month conservative follow-up. (Table 4).
Table 4
The IIEF-5 scores of Group 2 patients before and after conservative follow-up
GROUP 2 | Before follow-up | After follow-up | p value |
IIEF-5 Scores | Total (n = 31) | 9,10 ± 4,69 | 9,23 ± 5,16 | 0,496† |
Severe ED (n = 18) | 5,50 ± 0,70 | 5,44 ± 0,70 | 0,317† |
Moderate ED (n = 4) | 10,75 ± 0,50 | 10,25 ± 1,50 | 0,317† |
Mild-moderate ED (n = 6) | 14,50 ± 1,37 | 15,17 ± 2,63 | 0,317† |
Mild ED (n = 3) | 17,67 ± 1,15 | 18,67 ± 2,08 | 0,180† |
† Wilcoxon signed rank test |
The mean IIEF-5 scores of the patients in Group 3 who received oral tadalafil 5 mg treatment was 17,55 ± 6,13. There was a significant increase in the total IIEF-5 scores after completing the 1-month treatment period (p < 0,001). Analysis of the patients based on ED grades revealed that oral tadalafil 5 mg treatment led to significant increases in the IIEF-5 scores of the patients with severe, moderate, and mild-moderate ED. This analysis was not performed for the patient subgroup with mild ED since there was only one patient in this group. However, it is known that this patient’s IIEF-5 score increased from 18 to 25. While there were no patients with normal erectile functions, 9 (%29) patients showed improvement in erectile functions (Table 5).
Table 5
The IIEF-5 scores of the Group 3 patients before and after treatment
GROUP 3 | Before tadalafil use | After tadalafil use | p value |
IIEF-5 Scores | Total (n = 31) | 10,35 ± 3,51 | 17,55 ± 6,13 | < 0,001† |
Ağır ED (n = 7) | 5,86 ± 1,06 | 16,43 ± 7,48 | 0,027† |
Orta ED (n = 12) | 9,33 ± 1,30 | 15,25 ± 5,86 | 0,006† |
Hafif-Orta ED (n = 11) | 13,64,50 ± 1,20 | 20,09 ± 4,63 | 0,008† |
Hafif ED (n = 1) | 18 | 25 | |
ΔIIEF Score | Total (n = 31) | 7,19 ± 5,61 (-3-+18) | 0,289* |
Severe ED (n = 7) | 10,57 ± 6,82 (0-+18) |
Moderate ED (n = 12) | 5,91 ± 5,35 (-3-+16) |
Mild-moderate ED (n = 11) | 6,45 ± 4,94 (0-+13) |
† Wilcoxon signed rank test |
* Kruskal-Wallis one-way analysis of variance |
In Group 3, the mean ΔIIEF was 7,19 ± 5,61 (-3-+18). This figure was calculated as 10.57 ± 6.82 (0–+18), 5.91 ± 5.35 (-3–+16), and 6.45 ± 4.94 (0–+13) for patients with severe, moderate, and mild-moderate ED, respectively. There was no significant difference between patient subgroups with different ED grades concerning ΔIIEF in the post hoc analysis (p = 0,289) (Table 5).
A comparison of the IIEF-5 scores between the patients in Group 1 who received HBO treatment and the control group (i.e., Group 2) patients who were conservatively followed for one month revealed that the IIEF-5 scores were significantly higher in the former group than the latter (p < 0,001). In addition, the IIEF-5 scores were significantly higher in Group 3 patients than those of the Group 2 patients (p < 0,001).
There was no significant difference between Group 1 and Group 3 concerning the IIEF-5 scores calculated after completing one month (p = 0,166). Also, there was no significant difference between the ΔIIEF-5 scores of the patients with severe, moderate, and mild-moderate ED. Two groups were also similar concerning ΔIIEF (Table 6).
Table 6
Comparison of Group 1 and Group 3 regarding post-treatment IIEF-5 scores
| | Group 1 | Group 3 | p value |
IIEF-5 Score | Total | 15,33 ± 6,35 | 17,55 ± 6,13 | 0,166† |
Severe | 10,13 ± 5,30 | 16,43 ± 7,48 | 0,061† |
Moderate | 17,71 ± 4,38 | 15,25 ± 5,86 | 0,419† |
Mild-moderate | 18,31 ± 4,42 | 20,09 ± 4,63 | 0,350† |
ΔIIEF Score | Total | 4,87 ± 4,61 (-3–+15) | 7,19 ± 5,61 (-3- +18) | 0,093† |
Severe | 4,87 ± 5,18 (0–+15) | 10,57 ± 6,82 (0– +18) | 0,062† |
Moderate | 7,28 ± 4,53 (0-+15) | 5,91 ± 5,35 (-3– +16) | 0,581† |
Mild-moderate | 4,23 ± 4,32 (-3–+12) | 6,45 ± 4,94 (0– +13) | 0,280† |
† Mann Whitney U Test |
Twenty-seven in Group 1 were re-assessed by the IIEF-5 forms 1, 2, 3, 6, and 12 months after HBO treatment. Analysis of these patients who improved with HBO revealed that this treatment's median duration of action was 60 [15–480] days. This investigation revealed that the effects of treatment ceased in 8 of 27 (%29,6) patients one month after completion of the treatment, in 6 (22,2%) patients two months after treatment, in 5 (18,5%) patients three months after treatment and 5 (18,5%) patients six months after treatment. Thus, the treatment effects decreased in 14 (51,9%) of the patients. The assessment performed three months after treatment completion elucidated that the HBO treatment's beneficial effects decreased in 19 (70,4%) cases. Overall, in 90% of the patients, the treatment effects subsided before the completion of 6 months after HBO treatment. The effects of HBO lasted for longer than six months in only 3 (11,1%) patients. The mean post-treatment sixth-month IIEF-5 score of these 27 patients was 11.59 ± 5.28, and the comparison of this figure with the mean pre-treatment IIEF-5 score (i.e., 10,89 ± 4,77) did not reveal a significant difference (p = 0,401) (Table 7).
Table 7
Results of the duration of action of treatment in Group 1
| After 1 month | After 2 months | After 3 months | After 6 months | End of the 12th month |
Post-HBO erectile function status | No reduction in function (n) | 19 (70,4%) | 13 (48,1%) | 8 (29,6%) | 3 (11,1%) | 1 (3,71%) |
Reduction in function (n) | 8 (29,6%) | 14 (51,9%) | 19 (70,4%) | 24 (88,9%) | 26 (96,29%) |
IIEF-5 scores | 16,40 ± 6,29 | 14,77 ± 6,47 | 13,11 ± 5,85 | 11,59 ± 5,28* | 11,37 ± 5,12 |
*Wilcoxon signed rank test revealed no significant difference between pre-treatment IIEF-5 score and the IIEF-5 score calculated 6 months after completion of treatment (p = 0,401). |