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Prostatic and testicular parameters in lepromatous

patients

ERDOGAN AGLAMIS*, CEMAL TASDEMIR**,

MEHMET OZGUR YUCEL***, CAVIT CEYLAN**** &

ILKER ERDEN*****

*Elazig Education and Research Hospital, Clinics of Urology,

Elazig, Turkey

**Inonu University Medical Faculty, Department of Urology

Malatya, Turkey

***Adiyaman University, Education and Research Hospital,

Clinics of Urology Adiyaman, Turkey

****Turkey Yuksek Ihtisas Education and Research Hospital,

Clinics of Urology, Ankara, Turkey

*****Elazig Education and Research Hospital, Clinics of

Dermatology, Elazig, Turkey

Accepted for publication 28 February 2014

Summary

Objectives: To evaluate PSA (Prostate-specific antigen) parameters in patients with

lepromatous leprosy (LL).

Design: In a retrospective study, 23 male patients with LL were evaluated. PSA

parameters (serum total PSA (tPSA), free PSA (fPSA), free-to-total PSA ratio

(f/tPSA), PSA Density (PSAD)) were assessed. PSA parameters were compared with

a control group.

Results: The mean tPSA, fPSA, f/tPSA, prostate volume, and PSAD values of the

patient group with LL were 1.87 ^ 0.81 ng/ml, 0.67 ^ 0.29 ng/ml, 0.36 ^ 0.11,

41.08 ^ 23.65ml and 0.055 ^ 0.037, respectively. The mean tPSA, fPSA, f/tPSA,

prostate volume, and PSAD values of the control group were 2.71 ^ 0.91 ng/ml,

0.80 ^ 0.34 ng/ml, 0.30 ^ 0.08, 65.0^ 28.73ml and 0.049 ^ 0.028, respectively. The

mean tPSAand prostate volumevalueswere found to be significantly lower in the patient

group with LL (p ¼ 0.002 and 0.004, respectively). No significant difference was found

between two groups in terms of mean fPSA and PSAD values (p ¼ 0.18 and 0.5,

respectively). The mean f/tPSA value was found to be significantly higher in the patient

groupwithLL (p ¼ 0.02). Testes in16 (69%)patientswithLLwerebilaterally atrophic.

Conclusions: Serum tPSA values and prostate volumes in the patients with LL were

significantly reduced and f/tPSA values were significantly increased. Testicular

Correspondence to: Erdogan Aglamis, Elazig Egitim ve Arastirma Hastanesi Uroloji Klinigi 23100, Elazig,Turkey (Tel: þ904242381000; e-mail: [email protected])

Lepr Rev (2014) 85, 48–53

48 0305-7518/14/064053+06 $1.00 q Lepra

atrophy in the lepromatous cases might be due to leprosy-related orchitis and

associated with a reduction in prostatic volume.

Introduction

Leprosy is a chronic granulomatous infection caused by Mycobacterium leprae and it is still

endemic in Third World countries.1,2 The skin, peripheral nerves, and other organs (testes,

eyes, some bones, reticuloendothelial system) may be affected in patients with leprosy.3,4

Leprosy may be divided into four types: indeterminate, tuberculoid type, borderline leprosy

and lepromatous leprosy.5,6 Testicular atrophy emerges most frequently in lepromatous

leprosy.4,5 Serum total testosterone levels in patients decrease as a result of testicular atrophy;

on the other hand, increased in levels of estradiol, follicle stimulating hormone (FSH)

and luteinizing hormone (LH) are observed.4 As a consequence, changes in secondary sex

characteristics, such as gynaecomastia, sexual dysfunction and sterility may develop in leprosy

patients.5 In addition, this change in androgenic hormonal levels of patients with lepromatous

leprosy may cause a change in prostate-specific antigen (PSA) parameters.

PSA is a glycoprotein released from prostate ductal epithelial cells.7 The normal

reference interval of PSA is defined as 0-4.0 ng/ml.8,9 Serum PSA is the most important

tumour marker in early diagnosis, clinical staging and treatment surveillance of prostate

cancer.10,11 In order to increase sensitivity and specifity of PSA in prostate cancer various

PSA parameters such as free PSA, free-to-total PSA ratio, and PSA density (PSAD) were

defined.There has been no study investigating the prostatic and PSA parameters in patients

with lepromatous leprosy published in the literature.

In our study, we aimed to evaluate the prostatic and testicular parameters of patients with

lepromatous leprosy.

Materials and methods

PATIENTS AND CLINICAL CHARACTERISTICS

Data from a total of 23 male patients with lepromatous leprosy, followed up in the leprosy

department of our hospital, were retrospectively analysed. Serum PSA levels and androgenic

hormone levels (follicle stimulating hormone (FSH), luteinizing hormone (LH), estrogen and

serum total testosterone levels), abdominal ultrasound findings and testicular dimensions

were assessed. It is considered normal if the diameter of the testis is more than 2.5 cm, and

atrophic if less than 2.5 cm.

No rectal manipulation or urological procedure had been done within the last 3 days in

the patients included into the study (digital rectal examination, cystoscopy, urethral

catheterisation, rectal endoscopic intervention etc.). Moreover, the patients had no history of

mechanical irritation (sexual intercourse, bicycling, etc.) that can affect PSA levels. Prostate

volumes were evaluated by abdominal ultrasound. Serum total PSA levels were divided by

prostate volume to give PSA density (PSAD). The mean serum total PSA (tPSA), free PSA

(fPSA), free-to-total PSA ratio (f/tPSA) and PSAD of the patients were calculated and

compared with that of a control group. In one patient with lepromatous leprosy, urinary

infection was found and his PSA was 10.92 ng/ml. The PSA value of this patient decreased

to 2.34 ng/ml after treatment with ciprofloxacin for 4 weeks. This second PSA level was

included in the assessment.

Leprosy and prostate specific antigen 49

Twenty-three male patients (without leprosy) who were without lower urinary system

symptoms and matched for age with the patient group were included as controls. In the control

group, no rectal or urological manipulation that can affect PSA level had been done within the

last 3 days. Moreover, those patients had no history of urolithiasis or malignancy. Prostate

volumes of the patients in the control group were also evaluated by abdominal ultrasound.

The PSA levels and androgenic hormone levels were determined by immunoassay using

the Roche kit (Roche Diagnostics Mannheim Germany).

STATISTICAL ANALYSIS

All data were analysed with SPSS 16.0 for Windowsw. Differences between group means

were assessed by the t-test. Correlations were examined by the Pearson correlation test.

A statistically significant finding was considered when P , 0.05.

Results

The mean age of the patients with lepromatous leprosy was 75.39 ^ 8.73. The mean age of

the patients in the control group was 74.91 ^ 5.75. There was no statistically significant

difference between two groups in terms of age (P . 0.82) (Table 1).

Average duration since the diagnosis of leprosy was 45 ^ 23.75 years. Multidrug therapy

(MDT) was completed in all patients. Type 2 reactions were not observed in patients, thus

neither steroids nor thalidomide was being used. 20 (87%) patients complained of erectile

dysfunction. In four (17%) patients, there were lower urinary system symptoms. In 16/23

(69%) patients with lepromatous leprosy, bilateral atrophic testis was present and in 7/23

(31%) patients, testicular dimensions were noted to be normal. In 8/23 (35%), unilateral renal

cortical cysts were present and bilateral renal cysts were detected in 5/23 (22%) patients.

No suspicious finding on digital rectal examination was reported.

Seventeen out of 23 (73%) patients had a reduction in basal total testosterone levels with

a mean of 1.93 ^ 0.81 ng/ml. There was a significant positive correlation between serum total

testosterone and tPSA concentrations (r ¼ 0.84, P ¼ 0·000) (Fig. 1).

Twelve out of 23 (52 %) patients had increased basal FSH levels with a mean of

16.93 ^ 11.22 mIU/ml; 13/23 (56%) patients had increased basal LH levels with a mean of

Table 1. Characteristics of patients and controls

Variable Leprosy Control P*

No. of patients 23 23Age Median ^ SD 75.39 ^ 8.73 74.91 ^ 5.75 0.82Prostate volume (ml) Median ^ SD 41.08 ^ 23.65 65.0 ^ 28.73 0.004tPSA (ng/ml) Median ^ SD 1.87 ^ 0.81 2.71 ^ 0.91 0.002fPSA (ng/ml) Median ^ SD 0.67 ^ 0.29 0.80 ^ 0.34 0.18f/t PSA Median ^ SD 0.36 ^ 0.11 0.30 ^ 0.08 0.02PSAD Median ^ SD 0.055 ^ 0.037 0.04 ^ 0.028 0.5

* t-testAbbreviation: PSA: prostate-specific antigen, tPSA: total PSA, fPSA: free PSA, f/t PSA: free-to-total PSA, PSAD:

PSA Density

E. Aglamis et al.50

14.29 þ 11.58 mIU/ml. Similarly, 12/23 (52%) patients had increased basal estrogen levels,

with a mean of 37.93 þ 14.29 pg/ml.

When compared with that of the control group, the mean tPSA values of the patients with

leprosy were found to be significantly lower (P 0.002). When the mean fPSA values were

compared, no significant difference was found between the two groups (P 0.18). The mean

f/tPSA value was found to be significantly higher in the leprosy group (P 0.02) (Table 1).

When the mean prostate volume of the patient group was compared with that of the

control group, it was found to be significantly lower (P 0.004). When the mean PSAD was

compared, however, no difference was found between the two groups. (P 0.5) (Table 1).

Discussion

The testis is one of the most commonly involved organs in lepromatous leprosy.4,5 Grabstald

et al. first reported in 1952 that leprosy affects the testis.12 In the literature, testicular

involvement is reported to be at the rate of 10-15%.4,12 However, testicular involvement was

found in 69% of the patients in our study. The reason why the rate was higher in our study

may be associated with the length of exposure to disease and clinical severity of lepromatous

leprosy in this elderly patient group.

The testis may be invaded via the blood stream and lymphatic system in patients with

leprosy.2 Basal testosterone levels decrease in the presence of testicular atrophy; in contrast,

basal LH and FSH levels increase because of the decreased negative feedback from

testosterone, and estradiol levels increase.2,4 In our study, serum basal testosterone levels in

the patient group decreased as expected; estrogen, FSH and LH levels increased. Different

results have been reported concerning the relationship between serum testosterone and risk of

prostate cancer. In one study performed on 345 hypogonadal men, the risk of prostate cancer

was reported to increase as serum testosterone level decreased.13 On the other hand, Parsons

et al. reported that the risk of prostate cancer increased as serum testosterone levels increased

and that the risk is lower in hypogonadal men.14 In our study, a positive correlation was found

between serum testosterone level and tPSA. In the light of data from our study, the risk of

prostate cancer in patients with lepromatous leprosy can be expected to be decreased.

However, cases with lepromatous leprosy, in which prostate cancer was diagnosed have been

reported.5 Serum PSA levels in these cases were found to be higher.

0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

0 1 2 3 4

Total testosterone (ng/ml)

Tota

l PS

A (

ng/m

l)

Figure 1. Correlation between concentrations of total testosterone and total prostate specific antigen (PSA) in patientswith lepromatous leprosy (r ¼ 0.84, P ¼ 0.000).


One of the parameters which is used in order to increase the sensitivity and specifity of

total PSA is free-to-total PSA ratio. The cut-off level accepted for the free-to-total PSA rate is

0.18. In patients with free-to-total PSA of less than 0.18, the risk of prostate cancer is thought

to be higher.15 The average free-to-total PSA rate was found to be 0.36 ^ 0.11 in patients

with lepromatous leprosy, which is well over the cut-off level of 0.18.

In a study by Behre et al., prostate volume and serum PSA levels were reported to be

lower in hypogonadal men who did not receive testosterone treatment. In the same study, no

significant difference was reported between prostate volume and PSA values in normal men

compared with hypogonadal men receiving testosterone treatment.16 Therefore, as the serum

testosterone level decreases, a reduction in prostate volume is expected. Similarly in our

patient group with lepromatous leprosy, prostate volumes and serum PSA values were found

to be significantly lower.

Another parameter used in order to increase the sensitivity and specifity of total PSA is

PSA density. The cut-off level accepted for PSA density is 0.15.17,18 The risk of prostate

cancer is thought to be higher in patients with a PSAD that is greater than 0.15.17,18 The

average PSA density was 0.055 ^ 0.037 in our patient group, which is well below the

0.15 cut-off value.

In our study, the serum basal testosterone levels in the patient group were low, but

estrogen, FSH and LH levels were raised. We found the prostate volume and serum tPSA

values to be decreased in the group with lepromatous leprosy compared with a control group.

Our study has limitations such as the lack of longitudinal data, and being based on only one

centre. Larger clinical studies are needed to confirm these findings.

Conclusion

Testicular involvement was found to be common in a group of 23 elderly male patients with

lepromatous leprosy. In these men serum testosterone levels were low, and serum tPSA levels

and prostate volumes were found to be significantly lower than in the control group. On the

other hand, f/tPSA values were found to be significantly higher. Testicular atrophy in the

lepromatous cases might be due to leprosy-related orchitis.

Authors’ contributions

Erdogan Aglamis, Cemal Tasdemir, Mehmet Ozgur Yucel, Cavit Ceylan, Ilker Erden

conceived and designed the study. Erdogan Aglamis, Cemal Tasdemir, Mehmet Ozgur Yucel,

Cavit Ceylan, Ilker Erden analysed the data and wrote the paper. Erdogan Aglamis, Cemal

Tasdemir, Mehmet Ozgur Yucel, Cavit Ceylan, Ilker Erden reviewed and approved the paper.

Ethical statementThe data used in this study are part of routine work; no personal identifiers were disclosed.

Ethical approval was granted by the Ethical Committee in Medical Faculty from Inonu

University, Malatya, Turkey.

Conflict of interest

The authors declare no conflict of interest.

E. Aglamis et al.52

Abbreviations

PSA: Prostate-specific antigen

tPSA: Serum total PSA

fPSA: Free PSA

f/tPSA: Free-to-total PSA ratio

PSAD: PSA Density

LL: Lepromatous leprosy

FSH: Follicle stimulating hormone

LH: Luteinizing hormone

MDT: Multidrug therapy

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