Male genital tract tuberculosis: clinical spectrum, diagnostic challenges, and implications for male fertility - a scoping review

¹Department of Biomedical Sciences, Faculty of Medicine, Universitas Padjadjaran, Sumedang, Indonesia, ²Aster Fertility Clinic, Hasan Sadikin General Hospital, Bandung, Indonesia, ³Faculty of Medicine, Universitas Padjadjaran, Sumedang, Indonesia, ⁴Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Padjadjaran, Sumedang, Indonesia, ⁵Department of Urology, Hasan Sadikin General Hospital, Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia, ⁶Department of Clinical Pathology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt

^&Corresponding author
Andri Rezano, Department of Biomedical Sciences, Faculty of Medicine, Universitas Padjadjaran, Sumedang, Indonesia

Introduction    

Tuberculosis (TB) is a highly contagious disease and is easily reinfected worldwide. It is estimated that approximately 25% of the world's population has been infected with TB, with the most significant impact on developing countries. In 2023, the World Health Organization (WHO) reported that more than 10.8 million people were infected with TB, including 6.0 million men, 3.6 million women, and 1.3 million children [1,2]. An increasing incidence was observed, with 5.8 million cases from 2019 to 2020 and 6.4 million cases from 2020 to 2021. The rise in incidence in the coming years is due to human immunodeficiency viruses, malnutrition, mobility, and treatment resistance. Southeast Asia records the highest number of TB cases, at 46%. Meanwhile, according to the Global Report TB 2022, Indonesia ranks second in the world for the highest prevalence of TB after India. WHO estimates 969,000 TB cases in Indonesia, with the current number being 717,941, among people aged 15 to 54 [2,3].

The two types of clinical presentations of TB are pulmonary TB and extrapulmonary TB (ETB). ETB's most commonly affected organs of ETB were the lymph nodes, gastrointestinal, bone and joints, central nervous system, and genitourinary [4]. The most common reason for chronic specific infection, which is classical forms of TB in the genital system, is present in 38-40% of all cases [5]. In the general population, genitourinary TB (GUTB) represents 20-73% of all forms of ETB [6]. GUTB may develop from primary infection, but also may develop later in a long latent period. GUTB may be present 20-30 years after primary localization [7,8]. In such cases, the source of infection might be the existing primary focus in the lung or lymph nodes, rare in bone, bowel or could be endogenous reinfection or exogenous superinfection [9]. Kidneys are the primary organs affected in GUTB with slow progression, asymptomatic, and highly destructive [10]. Male genital TB (MGTB) affects male genital tract organs, including the prostate, seminal vesicles, vas deferens, epididymis, Cowper glands, penis, and testicles. It typically shows scrotal swelling, irregular prostate nodules, genital ulcers, and perineal sinus that may lead to male infertility [11].

Male genital TB (MGTB) occurs at all ranges, but it is predominant in the fourth and fifth decades. Although urologists and andrologists have long recognized the condition, MGTB remains challenging. This review aims to summarize recent developments in the understanding of MGTB pathogenesis, evolving diagnostic approaches, and fertility-related complications. Emphasis will be placed on clinically relevant and translational aspects pertinent to urology and andrology practice.

Methods     

Search strategy and selection: the reporting of this review adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 guideline [12]. In this review, we aimed to provide clinicians with relevant information on MGTB. A comprehensive literature search was conducted using Scopus as the primary database. The search was restricted to studies published from 2015 onward. The search strategy utilized the keywords "male genital" and "tuberculosis", with the use of Boolean operators (and, or). Only English-language publications were considered to ensure accuracy in data extraction and interpretation. To minimize the risk of missing relevant evidence, supplementary search strategies were employed, including citation tracking and manual screening of reference lists from included studies and related reviews. The search was completed on 24^th August, 2025.

The following search string was applied: title-ABS-key ("male genital*" or "genital*, male" or "genital organs, male" or "male genital organ" or "accessory sex organs, male" or "sex organs, accessory, male" or "reproductive system*, male" or "male reproductive system*") and title-ABS-key ("tuberculoses" or "mycobacterium tuberculosis infection" or "infection*, mycobacterium tuberculosis" or "koch* disease").

Inclusion and exclusion criteria: eligible publications included review articles, original research studies, and case reports, while articles not aligned with the objectives of the review were excluded. Only studies published or translated into English and conducted in human subjects were considered to ensure accuracy in data extraction and interpretation. Studies that included patients with comorbidities, such as acquired immune deficiency syndrome (AIDS) or benign prostatic hyperplasia (BPH), and also articles published before 2015 were excluded.

Study selection and data extraction: three reviewers jointly developed and agreed upon the search strategy prior to conducting the literature search. Systematic searches were then performed, and all retrieved records were screened for relevance using Rayyan. Initial screening was conducted independently based on titles and abstracts in accordance with the predefined search strategy. Studies deemed potentially eligible at the abstract level were subsequently assessed through full-text review against the established inclusion criteria. Any disagreements during the screening process were resolved through discussion and consensus.

The reviewers extracted relevant data from eligible studies into Microsoft Excel spreadsheets. Extracted information included key aspects of the study content, namely epidemiology, etiology, pathophysiology, diagnosis, management of male genital tuberculosis, and implications for infertility, as well as the study design. Any discrepancies between reviewers during the data extraction process were resolved through discussion and consensus.

Quality assessment: all included studies were critically appraised by using the Joanna Briggs Institute (JBI) critical appraisal tools appropriate to each study design [13]. The appraisal was conducted to evaluate the quality of the methodology and reporting of the included studies.

Results     

Study screening and selection: the Scopus search identified 1,022 records, with seven (7) duplicates removed. A total of 1,015 records underwent title and abstract screening, and 891 were excluded. One hundred and twenty-four (124) reports were sought for retrieval, 28 were not retrieved, and 96 were assessed for eligibility. After full-text assessment, 15 reports were excluded, leaving 81 studies included in the final quantitative synthesis. The study selection process is summarized in Figure 1.

Study characteristics: among the 81 included publications, most studies were case reports (51 studies; 62.9%), followed by observational studies (12 studies; 14.8%), and review articles (including literature review, narrative review, and systematic review) (8 studies; 9.8%) (Table 1). Case reports with review studies, cross-sectional studies, and case series were less frequent, representing 6 (7.4%), 3 (3.7%), and 1 (1.2%) studies. Regarding anatomical site of involvement, the epididymis was most frequently affected (30 studies; 37%), followed by prostate (10 studies; 12.3%) and multi-site involvement (11 studies; 13.6%). Penile involvement was uncommon (5 cases; 6.2%), while other sites, including the glans penis, scrotum, and seminal duct/vas deferens, were rare. Cutaneous involvement was reported with testicular or prostatic disease. In 5 cases (6.2%), the anatomical site was unspecified. Quality assessment results are shown in Figure 2, Figure 3, Figure 4, Figure 5, and Figure 6.

Epidemiology: epidemiologically, GUTB disproportionately affects men in their reproductive years, particularly 20-40 years of age, but cases in older men are not uncommon. Immunocompromised individuals, especially those with HIV, have an increased risk of male genital TB. Migration from endemic regions has also contributed to the burden in low-prevalence countries, where unfamiliarity with GUTB may delay recognition [14-18]. GUTB is more frequently reported in TB-endemic regions of Asia and Africa, but migration and travel have led to cases in low-incidence countries, often among foreign-born individuals, which results in delayed recognition and management, leading to severe complications [15,17,19-22]. Around 50% of GUTB involves both urinary and genital organs, while isolated genital TB constitutes 5-30%, with the kidney being the most frequently affected organ, followed by the epididymis and prostate.

Epididymal TB is the most common site of male genital TB [23,24]. Epididymal TB occurs predominantly in middle-aged men (mean age 45-60) [15,25-27]. This type of TB usually arises from hematogenous spread from the pulmonary or kidney TB. Coexisting pulmonary or renal TB is reported in 21-48% of patients. Concurrent renal TB is observed in 80-85% of patients [28,29]. While isolated epididymal involvement occurs in 5-30% of cases [25,30]. The epididymal tail is the site most frequently involved due to its rich vascular supply. Epididymal TB can arise via hematogenous dissemination from a primary pulmonary focus, retrograde spread from the prostate or seminal vesicles, or as part of disseminated genitourinary infection [14,30]. Testicular TB is rare, accounting for approximately 3% of male genital TB cases, and its involvement usually follows contiguous spread from the epididymis [16,19,24,25,31,32]. Delayed recognition and misdiagnosis often result in unnecessary surgery, including orchiectomy [27-29]. Prostate TB accounts for 2-2.6% of male genital TB cases. It primarily affects older men (in the sixth to seventh decade). Penile TB is even rarer, <1% of GUTB cases, with only 177 primary cases reported between 1971 and 2007, mostly secondary to hematogenous spread.

Etiopathogenesis: TB infection is commonly caused by Mycobacterium tuberculosis (Mtb) and other atypical mycobacteria [33,34]. This pathogen can have many methods of transmission. The most common route is through droplet aerosols from actively infected patients that spread through coughing and sneezing. Sexual intercourse can also be a source of person-to-person transmission. Other bacilli, such as Mycobacterium bovis (M. bovis), can be an etiology of tuberculosis. M. bovis spreads through the ingestion of raw unpasteurized dairy products, vaccination with a live BCG vaccine in immunosuppressed individuals, and Bacillus Calmette-Guérin (BCG) therapy for bladder cancer [35]. There is also Mycobacterium avium intracellulare, a pathogen that usually causes infection in immunocompromised patients [36].

Tuberculosis infection may start as a pulmonary infection that spreads hematogenously from the lung parenchyma [32,37-40]. Mtb bacilli are first inhaled and phagocytised by the alveolar macrophages and polymorphonuclear leukocytes. These bacteria then reproduce within immune cells, triggering a granulomatous reaction called Gohn's focus. These foci then travel into the lymph nodes and remain latent until certain events, such as immune system suppression, occur that could activate these bacilli [23]. Mtb then reaches the thoracic duct and enters the venous circulation, leading to the dissemination of this bacterium all over the body, which then reaches the genital organs.

The most common site of male genital TB is the epididymis, which results from retrograde seeding from the seminal vesicles and the prostate or mostly from haematogenous spreading from the primary focus [30,31,41-43]. The infection is usually present on one side (unilateral). Due to its vascularity and frequent urinary reflux, a granuloma usually forms in the tail of the epididymis (globus minor) and, in 40% of cases, may be limited to this part. Necrosis can spread to the body and head, leading to an epididymal abscess. The abscess then ruptured, forming sinuses. Fibrotic tissue and calcification then form as an attempt at healing [36]. Tuberculous epididymitis usually involves the testes due to the ejaculatory duct reflux and blood supply of the testis [25,35]. Bacteria from these sites may be transmitted to the prostate.

Prostatic TB may occur from hematogenous spread or locally from epididymal TB [44]. BCG therapy also usually causes granulomatous tissue, especially in this organ. Incidental detection after transurethral resection or prostate biopsy is also a common cause of infection at this site [17,45-49]. Infection in this location can develop caseous necrosis, which can then lead to cavities or abscess formation, thus creating fistulas to nearby organs, such as the perineum, the urethra, and the scrotum. Infection from the prostate can spread to the seminal vesicles, the vas deferens, and other ejaculatory ducts. Other sites, such as TB of the penis, are usually caused by hematogenous spread from the kidney, BCG immunotherapy, sexual intercourse with an infected female partner, or through the patient's own ejaculate [36,50]. The genital involvement in TB usually manifests after 5-15 years of the primary infection [17].

Diagnosis

Epididymal and testicular tuberculosis: patients present with a history of tuberculosis that usually ranges from 20-40 years old. Patients can have a wide variety of symptoms and also be asymptomatic. The most common symptoms of this disease are the presence of scrotal masses and pain, frequently on both sides of the testes, and sinus formation in more advanced cases. Other symptoms that can be seen are irritative voiding symptoms, infertility, and history of pulmonary TB [23,25,36,43,51-56]. Due to its similarity to other bacterial epididymitis, diagnosis is often delayed. Complications of delayed diagnosis include epididymo-orchitis, abscess formation, scarring, obstruction, and infertility, with infertility reported in 22-50% of cases due to ejaculatory duct obstruction [19].

The ultrasonography (USG) finding in patients with epididymo-orchitis is a nodular enlargement of the scrotum, especially in the head and tail region of the epididymis, with homogeneous or heterogeneous hypoechoic lesions that could be accompanied by increased internal vascularity or decreased central blood flow accompanied by increased peripheral blood flow. This indicates the presence of granuloma formation and central necrosis. Hydrocele and discharging sinuses may be seen with this diagnostic method [24,32,35,41,57-61]. Another modality, scrotal Doppler ultrasound imaging, shows similar results to USG findings. Epididymis or testicles may seem enlarged with heterogeneous parenchyma, which consists of hypoechoic and hyperechoic appearance [62,63]. These findings can be accompanied by testicular infarction and absence of arterial and venous perfusion, shown by the absence of color Doppler flow [25].

Computed tomography (CT) scan and magnetic resonance imaging (MRI) can be used to establish epididymo-orchitis TB. Both of these modalities can show diffuse or focal lesions in the enlarged scrotum, which consist of irregular masses or nodules, cystic lesions, and heterogeneous or annular enhancement [23,64]. These findings also include heterogeneous echogenicity, increased blood flow, calcification, abscess, and/or sinuses in the affected areas [58]. On MRI, the lesion may be seen as a heterogeneous hypointense area in T2 and T-weighted images (TWI), an inhomogeneous hyperintense signal on T1WI, and restricted diffusion on DWI [65-67]. All of these findings suggest the presence of chronic inflammation.

Prostate, vas deferens, and seminal vesicle tuberculosis: findings in prostatic TB are usually nonspecific and mostly present with lower urinary tract symptoms (LUTS) [46,68]. Patients usually complain of recurrent abnormalities in urination, such as dysuria, hesitancy, and difficulty in urination, hematuria, nocturia, frequency, and/or urgency. Intermittent scrotal pain and swelling may also be seen in patients with prostatic TB. In some cases, patients might come to the doctor due to sexual function irregularity, such as hematospermia and sexual dysfunction [35]. Often, signs and symptoms of early prostatic TB are unrecognizable. This diagnosis often occurs accidentally through autopsy or lab work from prostate secretions, semen, or biopsy samples sent for investigation for cancer or infertility. The prostate can be normal, enlarged, elastic, firm, nodular, or even soft (due to caseous necrosis), and may be felt from digital rectal examination (DRE) [35]. The palpation itself is usually non-tender. Common symptoms of pulmonary TB, such as fever and cough, can also be present.

Overall, TB in the prostate is usually seen as a nodular enlargement or abscess in radiographic imaging [32]. USG examination demonstrates increased testicular size, inhomogeneous echogenicity, and increased vascularity in the affected area [35]. Mainly, there is increased stiffness in the infected region, but within the stiff mass, small irregular echoes can be seen, suggesting focal necrosis. Calcification in the prostate can also be seen by this method [17,35,68-71]. USG of the vas deferens and seminal vesicles TB shows diffuse or nodular thickening [27,72]. In most cases, only one side of the vas deferens was affected. There is also punctate, nodular, and irregular calcification in the lumen, representing the TB healing process. Thickening and distention of the wall may also be present. This results from granuloma formation in the walls of the vas deferens and seminal vesicles. The presence of distention is established by infection of the ejaculatory duct, which causes a stricture that eventually dilates the lumen. In the acute phase, TB in these regions can present as enlargement and wall thickening of the seminal vesicles, whereas atrophy and calcification occur in the chronic phase.

In contrast MRI, findings patterns were multiple hypointense lesions in the peripheral zone in T2WI imaging with radiating streaky areas which is called "watermelon skin sign”. The hypointensity may also be diffuse throughout the peripheral zone, though this is less common than the nodular pattern [45]. These findings suggest an enlarged prostate with central liquefaction consistent with an inflammatory response to infection. On DWI, hyperintense areas reflect restricted water mobility and indicate the presence of granulomatous tissue [69,71]. Cavities, sinus tracts, fistula, and extraprostatic spread of TB can also be seen by using MRI [35]. The disadvantage of this method is its low sensitivity for detecting early lesions.

The CT imaging for TB in the genital area is consistent with USG findings, which are vas deferens and seminal vesicles enlargement with possible wall thickening, distention, and wall calcification [32]. On a non-contrast CT scan, the lesions appeared as round or flaky hypodense shadows with blurred borders [73]. In contrast, CT shows annular enhancement around a hypodense shadow, blurring the distinction between TB and other causes [32]. Prostatic lithiasis can be detected in patients using PET/CT examination [74]. Other diagnostic methods, such as micturating cystourethrogram or urethrography, demonstrate dilatation and destruction of prostatic duct tissue [35].

Penile tuberculosis: patients may present to the doctor with painless nodules, swelling and/or hardening of the glans, ulcerations, and urethral discharge [20,75-77]. In primary TB of the penis, the disease may be seen as a superficial ulcer of the glans, erythematous papules, papulopustular lesions, subcutaneous nodules, or as persistent lymphedema resulting in a saxophone penis [78]. Tuberculosis in this area can also present as lupus vulgaris, nodulo-ulcerative/nodular papulonecrotic tuberculid, scrofulous gumma, and phagedenic ulceration with destruction of the penis [29,50]. The nodulo-ulcerative type is the most common case found in Japan. This ulcer has the characteristics of irregular depressed scars, which started as dusky red papules that eventually became an ulcer with purulent discharge. This type of ulcer is usually extragenital, predominantly over the extensor aspects of the extremities. Phimosis and/or erectile dysfunction can also be seen in patients due to cavernitis [20,35]. Urethrocutaneous fistula may also be seen as an advanced progression of this disease, which is called the 'watering can' effect [35,79]. Inguinal lymph node enlargement may also be present.

Other diagnostic methods

Microbiological: the gold standard of diagnosis in male genital TB is the identification of Mtb presence in samples, such as urine, semen, prostatic secretion, biopsies, and other body tissues or fluids [35,80-84]. The samples are first sent to the lab to be examined by smear microscopy. In this method, Ziehl-Neelsen (ZN) or auramine staining is used to search for acid-fast bacilli (AFB). However, other methods are gaining recognition, including from the WHO, such as light-emitting diode (LED)-based fluorescent microscopy. This method has higher sensitivity and specificity, yet requires less time to operate than ZN microscopy.

Patients who are suspected of having genital TB need their 3 consecutive early morning urine samples to be checked for microscopy and culture. There needs to be at least 5 x 10³ bacilli/ml AFB in the sample to be considered positive for TB. Yet the positivity rate of urine samples is low because the number of bacilli found in urine is very low. Not to mention, the urine can become contaminated with other Mycobacterium types during the process, thus producing false positivity. The method yields only 40% sensitivity. Other methods of sample retrieval, such as biopsies, yielded higher accuracy than urine samples.

Culture is the gold standard for diagnosing active TB, with a sensitivity of 65% and specificity of 100%. Lewenstein-Jensen culture was once used as the medium for Mtb, but due to its time-consuming process (estimated at 6-8 weeks), a newer medium is now recommended by the WHO. The automated liquid mycobacteria growth indicator tube (MGIT) culture using the BACTEC MGIT 960 System (Becton Dickinson-BD) is now recommended as the Mtb medium. This method only needed 9-10 days to show positive results and 6 weeks for negative results. By using this technique, drug susceptibility testing can be done simultaneously, thereby enhancing the advantages of this method.

Histological: samples for histological confirmation were collected by fine-needle aspiration (FNA) cytology or biopsies to identify AFB or granulomas [23,35,85,86]. AFB were seen as slender red rods after ZN staining. The presence of these rods doesn't confirm the diagnosis of TB. Culture and molecular testing are still needed to confirm the diagnosis. In addition to AFB detection, histology may reveal granulomas characterized by central caseous necrosis with epithelioid histiocytes, Langhans giant cells, and lymphocytes.

Molecular analyses: WHO recommended the use of polymerase chain reaction (PCR), often known as the GeneXpert MTB/RIF assay, for rapid detection of Mtb in specimens, outpacing microscopy [35]. Although as specific as smear microscopy, molecular analysis was more sensitive for sputum samples. The result also required less time to detect bacteria, which only needed less than 24 hours, while smear microscopy needed at least 1 day to be able to detect pathogens, 17 days for liquid culture, and > 30 days for solid culture. This method also has a setback. Mycobacterium DNA may still persist in bodily tissues, which can be detected by PCR, resulting in false positivity.

Other: blood tests can be done to monitor the CRP and PSA levels [35]. Increased CRP levels indicate high pathogen activity and the severity of the disease. PSA level can help indicate abnormality in the prostate due to pathogenic events, one of which is infection, but the increase of PSA may also blur the line between prostatic TB and benign prostatic hyperplasia (BPH) or prostate cancer [68,71,73]. To diagnose latent TB, the tuberculin skin test (TST) or IGRAs are needed, yet these methods cannot differentiate between active and latent infection.

Treatment: the standard treatment of genital TB is identical to that used for pulmonary tuberculosis, consisting of isoniazid (H), rifampicin (R), pyrazinamide (Z), and ethambutol (E) given daily for 6-9 months [32,44,50,65,87]. Patients receive two months of intensive therapy with rifampicin, isoniazid, pyrazinamide, and ethambutol, followed by four months of continuing phase with rifampicin and isoniazid, giving a total duration of six months for most uncomplicated cases [32,88]. The extended 9-12-month regimen is reserved for complex situations, including recurrent disease, comorbidities, immunosuppression, or HIV infection. Anti-tuberculous therapy (2RHZE/4RH) was initiated because isolated epididymal TB was uncomplicated, with clinical improvement including a resolving cough, weight gain of 5 kg, and decreased testicular size with no signs of inflammation.

In severe cases, infertility and deformity might happen; the condition may not be fully reversible with medical therapy. When abscesses are present, surgical drainage is required, and discrete nodules may need to be excised. However, there are inherent limitations to what can be achieved surgically. Due to the nature of multiple lesions, reconstruction is impossible to be done to treat infertility, thus in vitro fertilization may be the only way to conceive a child [33]. Surgery might be needed for abscesses, nodules, or obstruction [89]. Patients who require surgery, antituberculosis chemotherapy might be needed, which consists of preoperative chemotherapy for 2-4 weeks before surgery and postoperative antituberculosis therapy for 6-12 months with a standard first-line antituberculosis regimen, there are isoniazid, rifampicin, ethambutol, and pyrazinamide [23,58].

Reproductive health relevance: delayed diagnosis or inappropriate management of MGTB may worsen the progression of this disease, leading to severe complications, especially infertility. In 10% of the cases, patients came to the physicians with chief complaints of infertility. After thorough examination, only 4-9.1% of these patients experience obstructive azoospermia [16]. While extensive studies have explored the anatomical changes involved in infertility in MGTB, fewer studies have reported on the physiological and endocrinological abnormalities [90]. Granulomas and scarring resulted in structural changes of the genital tract, leading to tubular and ductal occlusion [16,31-33,35,36,89-91]. The occlusion of the ejaculatory ducts due to inflammation causes infertility in 22-50% of males with MGTB. Obstruction will eventually lead to low-volume ejaculate with no detectable sperm found in the semen [33]. Furthermore, structural deformity in the penile and glans may also make sexual intercourse more difficult, thus causing infertility [92]. Primary infection may also create an abnormality in physiological function by producing anti-gonadotropic effects that result in the decrease or even loss of libido [90].

Although it is a key tool in evaluating infertility, semen analysis is not routinely used to diagnose MGTB. Included studies suggest that this testing is only done in patients with infertility concerns. The recommendation for TB screening in infertile men is still conflicting. In a study done on 100 couples with infertility, 56% of the infertile men had MGTB. This implies that infertile patients should be considered a high-risk group for having TB [90]. However, other studies caution against TB screening in patients with idiopathic obstructive azoospermia, given its low incidence in the general population [16,45].

Infertility in MGTB cases can be treated with pharmacological or surgical procedures. Pharmacological therapy is only effective in the early stage of this disease. However, a study showed that teratozoospermia may occur as a result of the anti-TB drug therapy [66]. Most of the patients usually present at the late stage when the destruction of organs has already occurred, meaning that drug therapy rarely treats MGTB. This condition requires a surgical procedure, yet this method is only beneficial in patients with discrete organ damage [19]. Although the management of this disease, infertility, and sexual dysfunction can result from a surgical procedure [23]. Therefore, most of the patients with infertility can consider assisted reproductive technology (ART), in vitro fertilization (IVF), or intracytoplasmic sperm injection due to extensive organ damage [89,91]. The success of sperm retrieval and pregnancy is the same in tuberculous or other causes of obstructive azoospermia. If the infection involves the testis, the infertility is irreversible due to atrophy caused by the infection, even after ATB treatment. Thus, patients with this condition needed a third-party reproduction.

Discussion     

This scoping review mapped information from existing studies surrounding the topic of male genital tuberculosis, encompassing its clinical manifestation, diagnostic obstacles, and relevance to male infertility. The available evidence suggests consistent findings of the clinical aspects of this disease with well characterization of diagnostic approach. However, some difficulties still persist in diagnosing this disease due to its resemblance to other urogenital diseases. Furthermore, the articles included in this study mainly focus on the management of the infectious aspects of MGTB, while its reproductive consequences are rarely explored.

Male genital tuberculosis is quite commonly found in GUTB. The step back in diagnosing this disease, mostly due to its unspecified clinical manifestations, which the patients themself can be asymptomatic or with unspecified symptoms, such as pelvic pain, abnormal masses in genital areas, and problems in urination, such as dysuria, hematuria, urgency, etc. Further examination, such as an imaging study, may also demonstrate similarities to other diseases, including nonspecific infection, neoplasm, and benign prostatic hyperplasia [55,56,74,80]. This implies the need for lab tests, especially culture, as the gold standard for this disease. Culture examination yields sufficient sensitivity and excellent specificity. However, this method takes some time to show results. Other tests, such as ZN staining, may overcome this drawback, but it has poor sensitivity for detecting MGTB. In countries with a low incidence of tuberculosis, due to these challenges, MGTB may have been overlooked as a differential diagnosis. Furthermore, the latency between pulmonary infection and MGTB can exceed 20 years, thus contributing to delayed diagnosis [25,32].

Infertility in tuberculosis of the male genital is rarely explored, as most of the studies only focus on TB infection control. This may be because infertility analysis is not part of the standard diagnostic algorithm. Semen analysis is usually only employed when the patients have a concern about infertility. The use of semen to effectively detect TB also needs to be established further [90]. Furthermore, the incidence of infertility as the primary symptom is very low. The precise mechanism of the relationship between MGTB and endocrinology is not well understood, but studies show that this happens due to the role of proinflammatory cytokines. This condition increases corticotropin-releasing hormone (CRH), leading to higher concentrations of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), which eventually decrease testosterone [92]. Additionally, anti-tuberculosis drug therapy can cause infertility, especially teratozoospermia [89]. This resulted from increased oxidative stress that impairs spermatogenesis, which may potentially alter sperm count, motility, and morphology.

There are several limitations in this study. The predominant study type in this study is case reports. This may result in a high risk of bias due to the lack of generalization of MGTB presentation in the general population. Language restriction also limits the studies that can be included, as the results are relevant to the aim of this study. There are also limited studies mentioning infertility in this group. Available studies that demonstrate this phenomenon rarely discuss it comprehensively, providing only certain aspects in the literature. Despite these limitations, the articles at hand are sufficient to provide a comprehensive clinical perspective on tuberculosis of the male genital tract.

Conclusion     

Male genital tract tuberculosis is an underrecognized form of extrapulmonary tuberculosis that can result in significant and often irreversible impairment of male reproductive function. Its nonspecific and insidious clinical presentation frequently leads to delayed diagnosis, particularly in tuberculosis-endemic regions, where it is commonly mistaken for nonspecific infections, malignancy, or idiopathic infertility. Granulomatous inflammation, fibrosis, and ductal obstruction represent the main pathological mechanisms contributing to infertility, which may persist despite adequate anti-tuberculous therapy. This review highlights the importance of considering male genital tract tuberculosis in the differential diagnosis of men with chronic scrotal symptoms, recurrent epididymitis, obstructive azoospermia, or previous tuberculosis. A multidisciplinary diagnostic approach integrating clinical evaluation, imaging, microbiological, histopathological, and molecular tools is essential to improve diagnostic accuracy and prevent unnecessary interventions. Early recognition and timely treatment are crucial to limit irreversible reproductive tract damage and enable appropriate fertility counselling. Further research is needed to clarify long-term reproductive outcomes and optimize fertility-preservation strategies in affected men.

Competing interests     

The authors declare no competing interests.

Authors' contributions     

Andri Rezano was responsible for conceptualizing the study and supervised all stages of the research process; Andri Rezano and Qonita Adzkia developed the study methodology and drafted the initial manuscript; Qonita Adzkia, Julia Mukharomah, and Dwi Fitri Annisa conducted the literature search and article screening; Melia Juwita Adha, Aaron Tigor Sihombing, and Mohamed Osama Ali Abdalla performed data extraction, interpretation, and methodological validation. All the authors read and approved the final version of this manuscript.

Table and figures     

Table 1: baseline characteristics of the studies included in the scoping review of male genital tract tuberculosis, detailing study design, and specific sites of genital tract involvement among reported participants (N=81)

Figure 1: PRISMA flow diagram illustrating the study selection process for scoping review of male genital tract tuberculosis, including database searches, screening, eligibility assessment, and final inclusion of studies

Figure 2: Joanna Briggs Institute critical appraisal of included case reports and case series, with quality assessment results using the 8-item tool for case reports and the 10-item tool for case series, and evaluations of clinical reporting, diagnostic validity, and methodological quality

Figure 3: Joanna Briggs Institute critical appraisal of included narrative and systematic reviews, with quality assessment results using the 6-item tool for narrative reviews and the 11-item tool for systematic reviews, and evaluations of narrative coherence, search strategy adequacy, and methodological transparency

Figure 4: Joanna Briggs Institute critical appraisal of included cohort and cross-sectional studies, with quality assessment results using the 11-item tool for cohort studies, and the 8-item tool for cross-sectional studies, and evaluations of participant selection, exposure measurement, control of confounding factors, and statistical analysis

References