Abstract
Background
Interest in radiation-related health problems has been growing with the increase in the number of workers in radiation-related jobs. Although an occupational level of radiation exposure would not likely cause azoospermia, several studies have reported the relation between radiation exposure and azoospermia after accidental or therapeutic radiation exposure. We describe a case of azoospermia in a non-destructive testing (NDT) worker exposed to radiation and discuss the problems of the related monitoring system.
Case presentation
A 39-year-old man who was childless after 8 years of marriage was diagnosed with azoospermia through medical evaluations, including testicular biopsy. He did not have any abnormal findings on biochemical evaluations, other risk factors, or evidence of congenital azoospermia. He had been working in an NDT facility from 2005 to 2013, attaching and arranging gamma-ray films on the structures and inner spaces of ships. The patient’s thermoluminescent dosimeter (TLD) badge recorded an exposure level of 0.01781 Gy for 80 months, whereas results of his florescence in situ hybridization (FISH) translocation assay showed an exposure level of up to 1.926 Gy of cumulative radiation, which was sufficient to cause azoospermia. Thus, we concluded that his azoospermia was caused by occupational radiation exposure.
Conclusion
The difference between the exposure dose records measured through TLD badge and the actual exposure dose implies that the monitor used by the NDT worker did not work properly, and such a difference could threaten the health and safety of workers. Thus, to protect the safety and health of NDT workers, education of workers and strengthening of law enforcement are required to ensure that regulations are strictly followed, and if necessary, random sampling of NDT workers using a cytogenetic dosimeter, such as FISH, should be considered.
According to a 2012 report of the Nuclear Safety and Security Commission, 5606 workplaces handle radiation-generating devices and radioactive isotopes in Korea, and the number of workers in radiation-related jobs has been estimated to be 42,226, which is increasing every year, with interest in radiation-related health problems simultaneously increasing [1].The radiation at these workplaces influences the health and safety of workers, causing various conditions, such as cancer and genetic and hereditary effects [2, 3]. Radiation exposure can also possibly cause male infertility, which is the failure to achieve pregnancy after 12 months of intercourse [4] and is known to result from combined abnormalities in sperm count, motility, and morphology [5]. Azoospermia is the absence of spermatozoa on high-powered microscopic examination of at least two samples of seminal fluid [6]. The prevalence of azoospermia has been estimated to be approximately 1% among all men and 10%–15% among infertile men [7].
Exposure to ionizing radiation occurs in diagnostic and therapeutic medicine as well as in the industrial setting [3], and it is also known to cause damage to cells and non-lethal transformation of cells that can result in functional impairment of the testes, as these organs are very radiosensitive [8]. Although an occupational level of radiation exposure would not likely cause azoospermia [9], several previous studies have reported that therapeutic and accidental radiation exposure above certain values could induce azoospermia. We herein present a case of azoospermia in a patient who was exposed to radiation in a non-destructive testing (NDT) facility and discuss the problems of the related monitoring system.
The patient did not use birth control methods and did not have any sexual problems, such as erectile dysfunction, throughout his married life. However, he did not have a child during 8 years of marriage. Thus, he visitedan infertility clinic in July 2013. His wife did not have any fertility problems; however, he was diagnosed with azoospermia associated with Sertoli cell–only syndrome (SCOS).
Our patient’s height was 173 cm and weight was 71 kg. Semen analysis indicated azoospermia in two semen samples. His follicle-stimulating hormone level was 19.84mIU/mL (reference range, 1.27–19.26 mIU/mL), luteinizing hormone level was 5.55mIU/mL (reference range, 1.24–8.62mIU/mL), and testosterone level was 2.51 ng/mL (reference range, 1.75–7.81 ng/mL). Genetic studies showed a normal 46 XY karyotype without Y chromosome microdeletions. Thus, testicular biopsy was performed to determine the cause of azoospemia, and he was diagnosed with SCOS.
He worked in an NDT facility between August 2005 and June 2011. He usually worked day/night shifts for 3 weeks per month. However, he worked for 4 weeks a month, as the workload increased later. His primary job was radiographic testing, which used iridium-192 as the radiation source. He performed radiographic testing of ship structures in two heavy industries (2005–2008 and 2008–2010). His job involved attaching and arranging gamma-ray films on the structures and inner spaces of ships. According to work instructions, when an NDT equipment was being used, workers should be far away from the equipment that emits radiation and should be shielded from the radiation; however, the working environment, which had a narrow working space and restricted movement, and high workload did not allow enough protection from the radiation and time to move away from it. After July 2011, he changed jobs within the same field and with decreased use of radiation-emitting equipment.
Our patient had a thermoluminescent dosimeter (TLD) badge, which monitored and recorded his radiation exposure during work. According to the records, the cumulative radiation dose was 0.01781 Gy for 80 months (Table 1).
In 2010, some workers at that NDT facility were diagnosed with leukemia and myelodysplastic syndrome. Because of this, all workers in that facility were required to undergo evaluation of radiation exposure dose through cytogenetic dosimetry. The dosimeters measured the exposure dose using specific genetic markers. Dicentric chromosome assay (DCA) and fluorescence in situ hybridization (FISH) translocation assay were performed in the workers [10–12]. Our patient’s radiation exposure dose was 0.882 Gy (95% confidence interval [CI], 0.597–1.183 Gy) in DCA and 1.913 Gy (95% CI, 1.358–2.591 Gy) in FISH at the time. In 2015, he underwent another exposure evaluation after the diagnosis of azoospermia. The radiation exposure dose was 0.491 Gy (95% CI, 0.219–0.822) in DCA and 1.926 Gy (95% CI, 1.349–2.624 Gy) in FISH (Table 2). Considering his exposure period and the fact that FISH accurately reflects long-term cumulative exposure, we concluded that the patient’s cumulative radiation exposure dose was 1.926 Gy.
This is a case of an azoospermic patient diagnosed with SCOS which was considered to be caused by occupational radiation exposure. There are many causes of SCOS, including ionizing radiation exposure [13–15]. Medical evaluation of our patient showed no reason to suspect other possible causes of SCOS; thus, considering his job, it is reasonable to assume that patient’s SCOS was caused by occupational radiation exposure.
We assessed the radiation exposure dose and evaluated whether he had fractionated or single exposure to determine whether his condition was caused by radiation, because it is known that spermatogenesis has higher radiation tolerance for single exposure than for fractionated exposure [16]. We inspected the patient’s job history and exposure measurement records (Table 1) and concluded that he was exposed to radiation protractedly for 80 months.
According to the report of the International Atomic Energy Agency, temporary male sterility could result from single short exposure and prolonged exposure doses of 0.15 and 0.4 Gy in a year, respectively, and that permanent male sterility could result from single short exposure and prolonged exposure doses of 3.5–6 and 2 Gy in a year, respectively [17].
Lu et al. showed that fractionated irradiation of 0.7–0.9 Gy was capable of causing oligospermia or azoospermia, but they assumed that spermatogenesis would recover in 1–1.5 years [18]. Howell and Shalet suggested that a fractionated dose of over 1.2 Gy could cause permanent infertility and a dose of over 2 Gy was very likely to cause permanent infertility [19].
Some studies suggested similar levels of exposure dose that cause azoospermia, and a number of studies about azoospermia caused by prolonged exposure to radiation were mainly conducted in patients undergoing radiotherapy for cancer treatment [20–22], and in these studies, some patient developed permanent azoospermia, whereas others experienced transient azoospermia at similar levels of exposure.
The findings of the above-mentioned studies suggest that radiation could induce permanent azoospermia at high exposure doses and that the threshold values vary from person to person, depending on each person’s distinct characteristics. Thus, a person will not necessarily experience azoospermia if exposed to a specific dose. In the present case, the patient was exposed to radiation of 1.926 Gy, which was among the threshold doses mentioned in previous studies, but this value is not usual in normal occupational exposure; the occupational exposure limit in Korea is 100 mSv for 5 years and 50 mSv in any given year. Furthermore, he did not have the evidence of congenital azoospermia or other risk factors. Therefore, it might be reasonable to conclude that his azoospermia was caused by occupational radiation exposure.
On estimating of patient’s exposure dose, we found that the exposure dose records measured through TLD badge did not reflect the actual exposure level. The Korean government has introduced laws about radiation and its control and monitoring of workers who might be exposed and of factories/facilities that handle radioactive material. However, workers might not wear the TLD badge or might use it inappropriately. Accordingly, assessment of radiation exposure with a TLD badge might underestimate the exposure dose, which means that the monitoring of radiation in NDT workers is not working properly. An institution report shows that the mean exposure dose of NDT workers has been increasing, despite the strict government regulations for NDT facilities [23]. It appears that the factories/facilities might be neglecting the regulations and underreporting exposure dose to circumvent government penalties.
Thus, to protect the safety and health of NDT workers, education of workers and strengthening of law enforcement are required to ensure that regulations are strictly followed, and if necessary, the use of cytogenetic dosimeter, such as FISH, for random sampling of NDT workers should be considered.
In this case of azoospermia in an NDT worker who had been exposed to radiation, we noted a difference between the exposure dose on TLD measurement and the actual exposure dose of the patient. Although azoospermia is known to be rarely caused by normal occupational radiation exposure, our patient was exposed to a dose high enough to induce azoospermia in radiation workers. Thus, much attention and efforts are needed to correct this difference in exposure level and prevent health problems.
ACKNOWLEDGMENTS
This study was supported by the Occupational Safety and Health Research Institute (OSHRI), Korea Occupational Safety and Health Agency (KOSHA).
Authors’ contributions
JP: The first author of this article. He designed this research, collected and interpreted the data, prepared the draft of this manuscript, and approved the final version of the manuscript. SL: He suggested the design of this research, advised the causal relationship, revised the draft of this manuscript, and approved the final version of the manuscript. CP and HE: They revised the draft of this manuscript. All authors read and approved the final manuscript.
Notes
Ethics approval and consent to participate
Ethics approval is not applicable, but authors obtained informed consent from patient.
References
1. Nuclear Safety and Security Commission, Korea Institute of Nuclear Safety, Korea Institute of Nuclear Nonproliferation and Control. Nuclear safety yearbook. 2012. Seoul: NSSC.
2. Laurent O, Metz-Flamant C, Rogel A, Hubert D, Riedel A, Garcier Y, et al. Relationship between occupational exposure to ionizing radiation and mortality at the French electricity company, period 1961-2003. Int Arch Occup Environ Health. 2010; 83:935–944. DOI: 10.1007/s00420-010-0509-3. PMID: 20148259.
3. Occupational Safety and Health Administration.Occupational exposure to ionizing radiation – 70: 22828–22835.https://www.osha.gov/pls/oshaweb/owadisp.show_document?p_table=FEDERAL_REGISTER&p_id=18341. Accessed 19 Jun 2017.
4. Zegers-Hochschild F, Adamson GD, de Mouzon J, Ishihara O, Mansour R, Nygren K, et al. International Committee for Monitoring Assisted Reproductive Technology (ICMART) and the World Health Organization (WHO) revised glossary of ART terminology, 2009. Fertil Steril. 2009; 92:1520–1524. DOI: 10.1016/j.fertnstert.2009.09.009. PMID: 19828144.
5. World Health Organization. WHO laboratory manual for the examination of human semen and sperm-cervical mucus interaction. 1999. 4. Cambridge: Cambridge University Press.
6. American Urological Association, Male Infertility Best Practice Policy Committee, American Society for Reproductive Medicine. Report on evaluation of the azoospermic male. 2001. Baltimore: American Urological Association.
7. Stephen EH, Chandra A. Declining estimates of infertility in the United States: 1982-2002. Fertil Steril. 2006; 86:516–523. DOI: 10.1016/j.fertnstert.2006.02.129. PMID: 16952500.
8. Childrenandradiation.http://www.who.int/ceh/capacity/radiation.pdf. Accessed 18 Jun 2016.
9. Wisconsin Administrative Code Chapter HFS 157 – radiation protection regulatory guide 8.29. Instruction concerning risk from occupational radiation exposure. June 2002.https://www.dhs.wisconsin.gov/publications/p4/p45028.pdf. Accessed 15 Jun 2017.
10. Crespo RH, Domene MM, Rodríguez MJ. Biodosimetry and assessment of radiation dose. Rep Pract Oncol Radiother. 2011; 16:131–137. DOI: 10.1016/j.rpor.2011.06.003. PMID: 24376970.
11. Lloyd DC. Chromosomal analysis to assess radiation dose. Stem Cells. 1997; 15(Suppl 2):195–201. PMID: 9368304.
12. George K, Cucinotta FA. Biological dosimetry in astronauts. https://three.jsc.nasa.gov/articles/BiologicalDosimetry.pdf. Accessed 15 Jun 2017.
13. Ferlin A, Arredi B, Speltra E, Cazzadore C, Selice R, Garolla A, et al. Molecular and clinical characterization of Y chromosome microdeletions in infertile men: a 10-year experience in Italy. J Clin Endocrinol Metab. 2007; 92:762–770. DOI: 10.1210/jc.2006-1981. PMID: 17213277.
14. Nistal M, Jimenez F, Paniagua R. Sertoli cell types in the Sertoli-cell-only syndrome: relationships between Sertoli cell morphology and aetiology. Histopathology. 1990; 16:173–180. DOI: 10.1111/j.1365-2559.1990.tb01086.x. PMID: 2182507.
15. Gat Y, Gornish M, Perlow A, Chakraborty J, Levinger U, Ben-Shlomo I, et al. Azoospermia and Sertoli-cell-only syndrome: hypoxia in the sperm production site due to impairment in venous drainage of male reproductive system. Andrologia. 2010; 42:314–321. DOI: 10.1111/j.1439-0272.2010.01047.x. PMID: 20860630.
16. ICRP publication 118: ICRP statement on tissue reactions and early and late effects of radiation in normal tissues and organs: threshold doses for tissue reactions in a radiation potection context. Annals of the ICRP. http://www.nrc.gov/docs/ML1326/ML13269A319.pdf. Accessed 21 Apr 2011.
17. Niu S, Deboodt P, Zeeb H, International Atomic Energy Agency, international labour office, World Health Organization.Approaches to attribution of detrimental health effects to occupational ionizing radiation exposure and their application in compensation programmes for cancer: a practical guide.Occupational safety and health series, no. 73.Vienna: International Atomic Energy Agency; Geneva : International Labour Office: International Health Organization; 2010.
18. Lu JJ, Brady LW. Decision making in radiation oncology. 2011. Heidelberg: Springer Science & Business Media.
19. Howell SJ, Shalet SM. Spermatogenesis after cancer treatment: damage and recovery. J Natl Cancer Inst Monogr. 2005; 34:12–17. DOI: 10.1093/jncimonographs/lgi003.
20. Hahn EW, Feingold SM, Nisce L. Aspermia and recovery of spermatogenesis in cancer patients following incidental gonadal irradiation during treatment: a progress report. Radiology. 1976; 119:223–225. DOI: 10.1148/119.1.223. PMID: 943807.
21. Hahn EW, Feingold SM, Simpson L, Batata M. Recovery from aspermia induced by low-dose radiation in seminoma patients. Cancer. 1982; 50:337–340. DOI: 10.1002/1097-0142(19820715)50:2<337::AID-CNCR2820500229>3.0.CO;2-6. PMID: 7083140.
22. Speiser B, Rubin P, Casarett G. Aspermia following lower truncal irradiation in Hodgkin’s disease. Cancer. 1973; 32:692–698. DOI: 10.1002/1097-0142(197309)32:3<692::AID-CNCR2820320323>3.0.CO;2-I. PMID: 4726968.
23. Industry-University Cooperation Foundation of Kyung Hee University. Data cleaning of occupational radiation exposure and analysis of occupational radiation exposure. 2015. Seoul: Kyung Hee University.