|Year : 2014 | Volume
| Issue : 1 | Page : 41-45
Testicular function in male patients with lepromatous leprosy
Faten A Abd-Elkawi1, Seham A Bahgat2, Abeer M Kamel1, Asmaa S Farag1, Omima M Ashor1
1 Department of Dermatology and Venereology, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt
2 Department of Clinical Pathology, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt
|Date of Submission||01-Jan-2014|
|Date of Acceptance||01-May-2014|
|Date of Web Publication||24-Jul-2014|
Abeer M Kamel
MD, Department of Dermatology and Venereology, Faculty of Medicine for Girls, Al-Azhar University, Cairo
Source of Support: None, Conflict of Interest: None
Leprosy is a chronic granulomatous infectious disease affecting mainly the skin and peripheral nerves. Testicular affection with leprosy occurs mainly in the lepromatous type.
The aim of the study was to investigate testicular function and potential infertility in male patients with lepromatous leprosy.
Patients and methods
This study included 40 patients and 40 healthy, age-matched and sex-matched controls. All participants were subjected to careful history taking, dermatological and genital examination, complete blood count, liver and renal function tests, complete urine analysis, assessment of follicular stimulating hormone (FSH), luteinizing hormone (LH), testosterone levels, and semen analysis.
There was statistically significant difference between patients and controls regarding history, sexual examination, hormonal profile, and sperm count, with high mean FSH and LH hormonal levels among patients and high mean testosterone levels and sperm count among controls. There was statistically significant difference between patients with history of erythema nodosum leprosum and patients without history of erythema nodosum leprosum regarding sexual examination, hormonal profile, and sperm count. There was strong positive correlation between disease duration and hormonal levels of FSH and LH and strong negative correlation between disease duration and hormonal levels of testosterone and sperm count.
Lepromatous leprosy causes a pattern of primary testicular failure.
Keywords: Infertility, lepromatous leprosy, testicular function
|How to cite this article:|
Abd-Elkawi FA, Bahgat SA, Kamel AM, Farag AS, Ashor OM. Testicular function in male patients with lepromatous leprosy. Egypt J Dermatol Venerol 2014;34:41-5
|How to cite this URL:|
Abd-Elkawi FA, Bahgat SA, Kamel AM, Farag AS, Ashor OM. Testicular function in male patients with lepromatous leprosy. Egypt J Dermatol Venerol [serial online] 2014 [cited 2020 May 31];34:41-5. Available from: http://www.ejdv.eg.net/text.asp?2014/34/1/41/137307
| Introduction|| |
Leprosy is a chronic disease that remains endemic, particularly in third world countries .
In Egypt, the risk factors governing the distribution of leprosy are unknown .
Leprosy resembles many dermatologic diseases and affects multiple organs making its recognition challenging .
Many studies revealed that testicular affection with leprosy occurs mainly in the lepromatous type  and during episodes of erythema nodosum leprosum (ENL) .
In these patients, the testis are usually atrophic. Initially, the exocrine portion atrophies leading to sterility and later the interstitial cell atrophies leading to impotence . Gynecomastia is the most obvious clinical manifestation of hormone dysfunction in leprosy .
| Patients and methods|| |
This study was carried out at the Leprosy Hospital, Fayoum, Egypt during the period between March 2010 and October 2010. It included 40 lepromatous patients and 40 healthy controls. The study was approved by research ethical committee of the Faculty of Medicine for Girls, Al-Azhar University.
This group included 40 male patients with lepromatous leprosy; their ages ranged from 24 to 55 years with a mean age of 34.97 ± 8.7 years.
The diagnosis was made in each case by six or more numerous poorly demarcated raised or nodular lesions according to the WHO diagnostic features of leprosy  confirmed by biopsies.
The mean duration of the disease was 8.6 ± 7.3 years (1-26 years).
This group included 40 healthy male individuals; their ages ranged from 22 to 55 years with a mean age of 34.05 ± 8.04 years.
All patients and controls were subjected to the following:
- Written consent of approval to participate in the study.
- Careful history taking and thorough dermatological examination.
- Local genital examination.
- Laboratory investigations.
Full history taking
It was performed to determine name, age, occupation, residence, marital status, number of children and age of the youngest, and special habit of medical importance.
History of the disease
It included age at onset, course, duration of the disease, duration of treatment, history of reaction (ENL), duration and type of fertility (primary or secondary), family history of similar condition, and past history of previous operations, diseases, or drugs that may affect the fertility.
The following groups were excluded from the study:
- Patients with debilitating factors such as severe anemia, diabetes, and hepatic or renal affection, as those may affect the level of hormones.
- Patients with history of chemotherapy/radiotherapy or tuberculosis.
- Patients who are receiving any medications affecting fertility or hormones level.
General examination was performed to all participants with special attention to secondary sexual characters, detection of gynecomastia according to Hall's grading  then local genital examination.
The external genitalia, the epididymis, and the vas were examined. The cord was palpated with and without valsalva's maneuver to detect the presence of varicocele. Examination for testicular size and consistency was carried out in recumbent position to avoid occurrence of syncope.
Testicular size was examined and interpreted. The average testicular size after puberty measures up to around 2-inches long, 0.8 inches in breadth, and 1.2 inches in height (5 × 2 × 3 cm) according to Sherins and Howards , using the ruler measurements (cm) as follows: Normal (4.1-5.5 cm in length and 2.7-3.2 cm in width), moderate (3.1-4 cm in length and 2-2.5 cm in width), or small (<2.9 cm in length and <1.8 cm in width). Testicular consistency was also examined and interpreted as being normal or soft.
All participants were subjected to the following:
- Complete blood count (cell counter).
- Liver function tests (Hitachi Automatic Analyzer 917; Hitachi, Tokyo, Japan).
- Renal function tests (Hitachi Automatic Analyzer 917).
- Complete urine analysis.
- Quantitative determination of:
- Follicular stimulating hormone (FSH) level in serum (chemiluminescent immunoassay),
- Luteinizing hormone (LH) level in serum (chemiluminescent immunoassay),
- Total testosterone level in serum (chemiluminescent immunoassay).
A volume of 7 ml of venous blood sample was drawn from patients and controls. Thereafter, 5 ml was left to clot and serum was separated without delay after centrifugation. Hemolysis was avoided. The remaining 2 ml was collected in tubes containing EDTA for complete blood count. The routine chemical investigations were performed on the same day and the rest of each sample was stored at -20°C after careful labeling until the time of analysis for FSH, LH, and testosterone. These hormones were measured using Access Immunoassay System (Beckman coulter immmunoassay, Biosite, inc., California, USA) [competitive binding immunoenzymatic assay in case of testosterone and a sequential two-step immunoenzymatic (sandwich) assay in case of FSH and LH]. The results of FSH and LH were expressed as mIU/ml and testosterone as ng/ml. The normal ranges of hormones for men are as follows: FSH, 2-10 mIU/ml; LH, 2-20 mIU/ml; and testosterone, 3.6-9.9 ng/ml.
Urine was collected in clean container for physical and chemical examination.
Three semen analyses were performed to every participant, who were instructed to bring semen samples by masturbation after sexual abstinence of 3-5 days; semen analysis was interpreted according to the WHO recommendations .
The data were coded and entered using the statistical package SPSS (version 15; SPSS Inc., Chicago, Illinois, USA). Correlations were performed to test for linear relationship between variables. P-values less than or equal to 0.05 were considered statistically significant .
| Results|| |
There was no statistically significant difference between patients and controls with respect to the mean age (P > 0.05). Forty patients were married and 25 (62.5%) of them had children. With respect to the medical history, the duration of disease in patients ranged from 1 to 26 years with mean duration of 8.6 ± 7.3 years. In 29 (72.5%) patients the treatment had ceased and 11 (27.5%) were still on treatment. Twenty-two (55%) patients were taking early/regular treatment and 18 (45%) were taking delayed/irregular treatment. Eight of the 40 (20%) patients had a history of ENL, 16 (40%) had oligospermia, one (2.5%) had azospermia, six (15%) had primary infertility, and nine (22.5%) had secondary infertility.
Regarding clinical examination, 10 (25%) patients had gynecomastia, eight of them had a history of ENL. There were nine (22.5%) patients who had small firm testes, eight of them had history of ENL. However, all individuals in the control group were normal.
There was statistically significant difference between the study groups (cases and controls) regarding hormonal profile (FSH, LH, and testosterone level) and sperm count (P < 0.001), with high mean FSH and LH hormonal level among patients and high mean testosterone level and sperm count among controls [Table 1].
|Table 1: Comparison between the studied groups according to hormonal profile and sperm count|
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There was statistically significant difference between patients with history of ENL and those without history of ENL regarding testicular size, consistency, and gynecomastia (P < 0.001) [Table 2].
|Table 2: Comparison among patients regarding history of erythema nodosum leprosum according to sexual examination|
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There was statistically significant difference between patients with history of ENL and those without history of ENL regarding seminal parameters and hormonal profile (FSH, LH, and testosterone level) (P < 0.001) [Table 3].
|Table 3: Comparison among patients regarding history of erythema nodosum leprosum according to hormonal profile and sperm count|
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There was a strong positive correlation between duration of the disease and hormonal level of FSH and LH. There was a negative correlation between duration of the disease and hormonal level of testosterone and also a negative correlation between duration of the disease and sperm count, with significant difference between groups (P < 0.01) [Table 4].
|Table 4: Correlation between duration of disease and hormonal profile of the patient and sperm count|
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| Discussion|| |
Leprosy is a chronic granulomatous infectious disease that typically causes manifestations in the skin and peripheral nerves. Testicular affection with leprosy occurs mainly in the lepromatous type of the disease. To detect hypogonadism and potential infertility in patients with lepromatous leprosy, careful examination and assessment of FSH, LH, testosterone levels, and semen analysis were performed.
In present study, nine (22.5%) patients had reduction in testicular size, six (15%) had moderate size, and 25 (62.5%) had normal size; these results are in agreement with other studies reporting that reduction in testicular volume occurs in more than 50% of lepromatous patients . Among nine patients with reduced testicular size, eight had an attack of ENL with testicular pain and swelling, which is in agreement with the study by Saporta and Yuksel , who reported that 51% of their patients had reduction in testicular size, and 15 of the 21 patients had an attack of ENL, suggesting that many factors may contribute to testicular dysfunction, including the degree of testicular involvement and frequency or intensity of orchitis resulting from ENL and the immune complex disorder of lepromatous leprosy.
In the present series of lepromatous leprosy patients, 10 (25%) patients had gynecomastia. Gynecomastia has been reported in 36% cases of lepromatous leprosy in Kumar et al.'s  study, and was present in 25% of cases in Nigam et al.'s  study; in all these cases, there was severe involvement of the testes.
Although there are few studies on lepromatous patients fertility, Kumar et al.  reported significant lower fertility among men with leprosy in India. Oligospermia or azoospermia has been documented by semen analysis in more than 50% of lepromatous patients . Our study showed that 16 (40%) patients had oligospermia and one (2.5%) had azoospermia; of them, 15 patients were infertile, six (15%) of them had primary infertility and nine (22.5%) had secondary infertility.
Infertility and abnormal semen parameters appeared to be associated with disease progression. These results are in accordance with those of Shilo et al. , who reported that children were born to patients with leprosy during the first few years of the disease only.
In this study, the mean basal FSH and LH levels were significantly elevated when compared with the control group. Testosterone levels were significantly lower than in the control group. Garg et al. , in a study on the hormone profile in male patients of lepromatous leprosy, found that the levels of serum FSH and LH were elevated, whereas the level of serum testosterone was depressed. Other studies have also corroborated this hormonal imbalance in male patients with leprosy ,.
High levels of serum FSH have been attributed to damage of the seminiferous tubules rather than interstitial cells .
These are also suggested by studies demonstrating that low basal levels of testosterone and the high basal LH and FSH levels occur secondary to the loss of testosterone-induced negative feedback in 30-80% of lepromatous patients investigated , although rare abnormal testicular hormonal changes in tuberculoid and borderline leprosy were observed ,.
Saporta and Yuksel  suggested that, even while taking antileprotic treatment, testicular damage can progress or may begin before presentation of treatment; this is in agreement with our analytic results for hormones and semen analysis except for testosterone, which was found to be increased in those who had regular or early treatment, but it can be explained that testosterone was measured as total testosterone, despite that the ideal test would be the measurement of free testosterone by the equilibrium dialysis method. This, however, is difficult to perform, not automated, and largely inaccessible to most clinicians. Measurement of 'free testosterone' by radioimmunoassay is widely available but should be discouraged because of its unreliability. Determination of bioavailable testosterone is attainable in some parts of the world, but it is expensive and not readily accessible .
In the present study, it was found that there was a positive correlation between duration of disease and FSH and LH, and negative correlation with testosterone, which is in agreement with the result suggested by Saporta and Yuksel .
Morley et al. , however, found a significant positive correlation between LH and duration of the disease but not with FSH levels.
Levis et al.  found a significant positive correlation between FSH and duration of disease only. The positive correlation between these hormones and the duration of leprosy could be because of progressive testicular damage as the disease advances .
| Conclusion|| |
Our results provided evidence that lepromatous leprosy causes a pattern of primary testicular failure and hypergonadotropic hypogonadism, where testosterone in the patients group was significantly lower compared with the control group and serum levels of LH and FSH was significantly higher compared with the control group. In addition, this study provides evidence that many factors may contribute to testicular dysfunction, including the duration of disease, degree of testicular involvement, frequency or intensity of orchitis resulting from ENL, and early and regularity of taking treatment.
| Acknowledgements|| |
Conflicts of interest
There are no conflicts of interest.
| References|| |
|1.||Walker SL, Lockwood DNJ. The clinical and immunological features of leprosy. Br Med Bull 2006; 77-78 :103-121. |
|2.|| Hegazy AA, Abdel-Hamid IA, Ahmed El-SF, Hammad SM, Hawas SA. Leprosy in a high-prevalence Egyptian village: epidemiology and risk factors. Int J Dermatol 2002; 41 :681-686. |
|3.|| Britton WJ, Lockwood DNJ. Leprosy. Lancet 2004; 363 :1209-1219. |
|4.|| Nigam P, Mukhija RD, Gupta AK, Dayal SG, Goyal BM. Gonadal involvement in leprosy, study of gynaecomastia, testicular and epididymal involvement and therapeutic efficacy of indigenous drugs. Hansenol Int 1984; 9 :10-20. |
|5.|| Ghorpade A, Ramanam C. Primary penile tuberculoid leprosy. Indian J Lepr 2000; 72 :499-500. |
|6.|| Neena K, Ammini AC, Singh M, Pandhi RK. Ovarian function in female patients with multibacillary leprosy. Int J Lepr Other Mycobact Dis 2003; 71 :10-15. |
|7.|| Saporta L, Yuksel A. Androgenic status in patients with lepromatous leprosy. Br J Urol 1994; 74 :221-224. |
|8.|| WHO. Expert committee on leprosy, seventh report. Geneva, Switzerland: WHO; 1998. 874. |
|9.|| Hall PF. Gynecomastia. In: Astwood E, editor. Clinical endocrinology. New York: Grune & Stratton; 1960. 1 :468-481. |
|10.||1Sherins RJ, Howards S. Male infertility. In: Walsh P, Gittes RF, Perlmutter AD, et al. Camphell′s urology. 5th ed. Philadelphia: W. B. Saunders Company; 1986. 640-697. |
|11.||1World Health Organization. WHO laboratory manual for the examination of human semen and semen - cervical mucus interaction. 3rd ed. Cambridge: Cambridge University Press; 1992. |
|12.||1Dawson B, Trapp RG. Basic and clinical biostatistics. 3rd ed. New York, McGraw-Hill Inc.; 2001. |
|13.||1Abraham A, Sharma VK, Kaur S. Assessment of testicular volume in bacilliferous leprosy: correlation with clinical parameters. Indian J Lepr 1990; 62 :310-315. |
|14.||1Kumar B, Ralna A, Kaur S, Dash RJ, Samuel E, Datta BN. Clinico-pathological study of testicular involvement in leprosy. Lepr India 1982; 54 :48-55. |
|15.||1Leal AM. Foss NT. Endocrine dysfunction in leprosy. Eur J Clin Microbiol Infect Dis 2009; 28 :1-7. |
|16.||1Shilo S, Livshin Y, Sheskin J, Spitz IM. Gonadal function in lepromatous leprosy. Lepr Rev 1981; 52 :127-134. |
|17.||1Garg R, Agarwal JK, Singh G, Bajpaih HS. Hormone profile in leprosy. Indian J Lepr 1989; 61 :428-431. |
|18.||1Levis WR, Lanza AP, Swersie S, Meeker HC, Schuller-Levis GB, Bardin CW. Testicular dysfunction in leprosy: relationships of FSH, LH and testosterone to disease classification, activity and duration. Lepr Rev 1989; 60 :94-101. |
|19.||1Kaufman JM. Hypothalamic-pituitary-gonadal function in aging men. Aging Male 1999; 2 :157-165. |
|20.||2Morely JE, Distiller LA, Sagel J, Kok SH, Kay G, Carr P, Katz M. Hormone changes associated with testicular atrophy and gynaecomastia in patients with leprosy. Clin Endocrinol 1977; 6 :299-303. |
[Table 1], [Table 2], [Table 3], [Table 4]
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