Successful treatment of ejaculation pain with silodosin in patient with Zinner syndrome: a case report

Introduction

Zinner syndrome, first reported by Zinner in 1914 (1), is a rare congenital malformation that features development of a unilateral seminal vesicle cyst and ejaculatory duct obstruction (EDO) in association with ipsilateral renal agenesis. Affected patients are often asymptomatic while the coexisting seminal vesicle cyst is small, in which case follow-up examinations is an acceptable strategy. However, the cyst generally grows due to EDO-induced seminal fluid accumulation, resulting in development of symptoms such as perineal discomfort, difficulty with urination, and ejaculation pain, with surgical treatment often required (2). A recent systematic review of 214 cases of Zinner syndrome conducted by Liu et al. (3) showed that approximately 80% of affected patients received some form of invasive treatment, including surgery.

Reported here is a 37-year-old Japanese male patient with ejaculation pain and pelvic discomfort associated with Zinner syndrome who was successfully treated in a non-invasive manner with silodosin, an α₁-adrenoceptor antagonist. Administration of silodosin rapidly improved ejaculation pain and pelvic discomfort, allowing for avoidance of invasive treatment and conservative management with regular follow-up examinations. To the best of our knowledge, this is the first presented case report of use of an α₁-adrenoceptor antagonist for ejaculation pain associated with Zinner syndrome. We present this article in accordance with the CARE reporting checklist (available at https://tau.amegroups.com/article/view/10.21037/tau-22-746/rc).

Case presentation

A 37-year-old, unmarried, childless Japanese male patient visited a nearby urological clinic for painful ejaculation, as well as perineal discomfort and flank pain that lasted for approximately two weeks after ejaculation, which had been developing for the previous six months. Non-enhanced pelvic magnetic resonance imaging (MRI) performed as part of a detailed examination revealed a cystic lesion on the dorsal side of the bladder and bordering the prostate gland (15 mL), thus the patient was referred to our hospital for further examination and treatment. Physical examination findings revealed no abnormalities in appearance, including the genitourinary organs such as the testicles and penis, and the bilateral vas deferens were palpable. The mass on the dorsal side of the bladder was 7 cm in its greatest diameter and located slightly to the right of the midline, and MRI showed uniform high intensity in T1-weighted images (Figure 1A) and low intensity in T2-weighted images (Figure 1B), suggesting a hemorrhagic cyst. In addition, a wedge-shaped structure in the mass was partially visible in MRI images, suggesting a cystic mass arising from a seminal vesicle (Figure 1C,1D). To better explore the features of the cystic mass, enhanced abdominopelvic computed tomography (CT) was performed. Those results showed that the cystic lesion had a uniform internal structure with slightly high density and no enhancement effect (Figure 2A), while the right kidney was not visualized (Figure 2B). Based on these findings of right renal agenesis and ipsilateral seminal vesicle cyst, the diagnosis was Zinner syndrome. Semen analysis showed asthenozoospermia (semen volume 1.0 mL, motility 22%), while results of fluorescence in situ hybridization analysis of the sex-determining region Y gene, as well as routine laboratory studies of blood and urine including hormonal examinations were normal. Neither a cystoscopy nor vasospermography procedure was performed because of lack of patient consent.

Figure 1 Non-enhanced pelvic magnetic resonance imaging demonstrated mass on dorsal side of bladder, which showed uniform high-intensity in T1-weighted (A) and low-intensity in T2-weighted (B) images. A wedge-shaped structure in the mass was partially visible in both axial (C) and sagittal (D) T1 images (arrows).

Figure 2 Enhanced computed tomography scanning revealed slightly high density mass without enhancement (A) and defect in the right kidney (B).

The need for management by use of percutaneous drainage and transurethral or transrectal aspiration, or a surgical procedure, either a laparoscopic or open vesiculectomy, was discussed with the patient, who expressed a desire to avoid invasive treatment as much as possible. Thus, administrations of silodosin, an α₁-adrenoceptor antagonist for treatment of benign prostate hyperplasia (BPH), at 8 mg/day were started for the purpose of suppressing seminal vesicle contraction presumed to cause an increase in seminal vesicle pressure at the time of ejaculation as the main cause of the pain. After providing a full explanation of the risk of ejaculation disorder and orthostatic hypotension due to use of silodosin, the patient provided informed consent and the treatment was commenced. Immediately after starting treatment, the patient was relieved of ejaculation pain, and no longer experienced perineal discomfort or flan pain after ejaculation. The oral silodosin prescription was terminated at two months after initiation because the symptoms were stable and annual follow-up MRI examinations were started. At the time of writing, five years have passed without recurrence of ejaculation pain or ejaculation-related symptoms, and MRI results show a tendency for shrinkage of the right seminal vesicle cyst (Figure 3).

Figure 3 The seminal vesicle cyst showed no tendency to enlarge. Magnetic resonance imaging results at five years after treatment showed that maximum diameter had decreased to approximately 5 cm.

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

Zinner syndrome is a rare anomaly occurring in the Wolffian duct, with approximately 220 cases reported worldwide to date (3). Anomalous growth of the mesonephric or Wolffian duct between four and 13 weeks of gestation is thought to affect embryological development of the kidneys and ejaculatory duct, inducing congenital conditions, such as ipsilateral renal hypoplasia, EDO, and a seminal vesicle cyst, noted in Zinner syndrome cases (4). Affected individuals are presented with a wide range of symptoms, including perineal discomfort and post-ejaculation pain, with their onset and severity related to the size of the cyst (3). Therefore, symptoms related to Zinner syndrome often appear after beginning sexual activity due to accumulation of semen in the seminal vesicle and cases are often initially diagnosed at that point (5).

Zinner syndrome symptoms are classified into urinary related, local pain, and reproductive dysfunction, of which ejaculation pain is a typical reproductive dysfunction symptom noted by approximately 10% of diagnosed patients (3). Pain and/or discomfort during ejaculation, found in 6.7% of all men over the age of 50 in a multinational survey of aging males (6), is considered to be a significant quality of life-impairing problem for those affected (7). A multitude of factors are implicated in ejaculation pain, including infection or inflammation of the urinary tract, BPH, post-surgery for inguinal hernia, and EDO, with specific treatment strategies needed according to cause (8). Ejaculation pain noted in patients with Zinner syndrome is presumed to be caused by an increase in seminal vesicle pressure caused by contraction of the seminal vesicles during orgasm, which become dilated with semen due to EDO. Therefore, these patients often undergo an invasive procedure as first-line treatment, such as transurethral resection of the ejaculatory duct, or aspiration and drainage, which reduces pressure within the seminal vesicle cyst, or surgical resection of the seminal vesicle (3,8). Among those, a seminal vesiculectomy procedure, including open, laparoscopic, and robot-assisted approaches, is performed in nearly 60% of affected cases because of the advantage of less recurrence as compared to conservative management (3). However, that report also noted that performance of a seminal vesicle resection is associated with high risk for surgical complications leading to erectile dysfunction and urinary incontinence.

The α1-adrenoceptor is involved in vasoconstriction and blood pressure regulation, and also known to play an important role in regulation of seminal vesicle contraction. Indeed, α₁-adrenoceptor antagonists, widely used as first-line drugs for BPH due to their high levels of efficacy and safety, often cause ejaculation dysfunction. This may be related to retrograde ejaculation or inhibition of seminal vesicle contraction through blockage of the α₁-adrenoceptor abundantly present in seminal vesicles (9). There are three α1-adrenoceptor subtypes (α_1A, α_1B, α_1D) as well as α₁-adrenoceptor antagonists that target these receptors, ranging from subtype nonselective to those that act selectively. The previously described α1 adrenergic receptor subtype C was later found to be a variant of α_1A and then integrated into subtype A. The α_1A and α_1D receptors are present in prostate and bladder neck smooth muscle tissues, while α_1B is abundant in vascular smooth muscle. Presently, tamsulosin, silodosin, and naftopidil are α1 blocker drugs available in Japan for treating BPH. Of those, it is well known that silodosin has a high affinity for the α_1A receptor and naftopidil a strong affinity for the α_1D receptor, which is also distributed in the bladder. Previous animal experiments showed that inhibition of α_1A-adrenoceptors in particular strongly inhibits seminal vesicle contraction (10). Such findings led us to attempt administration of 8 mg/day of silodosin, an α_1A-adrenoceptor selective antagonist, to relieve ejaculation pain in the present patient by inhibiting seminal vesicle contraction, with the result rapid improvements with associated pain and discomfort. Two months after beginning treatment, follow-up observations were started without oral administration and no recurrence of symptoms has been observed for approximately five years. We believe that this is the first case report noting successful relief of pain and discomfort associated with ejaculation pain in a patient with Zinner syndrome by administration of an oral α₁-adrenoceptor antagonist.

Apart from Zinner syndrome with ejaculation pain, several studies have shown that post-ejaculation pain in patients being treated for prostate cancer or with lower urinary tract symptoms can be relieved by use of an α₁-adrenoceptor antagonist (11,12). Such positive therapeutic results are thought to be due to the relaxant effect of these antagonists on smooth muscle in the urethra, prostate, and prostate capsule, where the α₁-adrenoceptor is associated with sympathetic nerves. In addition, blocking of the α1-adrenoceptor suppresses release of neuropeptides related to neurogenic inflammatory responses, which may have a role to relieve ejaculation pain in individuals with lower urinary tract symptoms (13). It is considered possible that these effects of the prescribed α₁-adrenoceptor antagonist provided for symptomatic improvement in the present case.

The absence of other symptoms caused by compression of surrounding organs by a seminal vesicle cyst and no tendency for cyst growth are considered to explain why the symptoms were well managed by only administration of silodosin in our patient. Furthermore, since there was no recurrence of symptoms after the end of treatment and the seminal vesicle cysts showed a shrinking tendency, silodosin may have had some effect to improve EDO, though the mechanism is unknown. Nevertheless, it should also be kept in mind that there are cases in which seminal vesicle cyst growth noted during follow-up led to surgery or cancer arising from the cyst (3). Continued conservative management with regular follow-up examinations are planned for this case.

Conclusions

In conclusion, reported here is a patient with Zinner syndrome whose ejaculation pain was successfully managed with silodosin. Administration of such an α₁-adrenoceptor antagonist can be a useful non-invasive treatment option for such patients complaining mainly of symptoms associated with ejaculation who do not want to undergo surgery.

Acknowledgments

Funding: None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://tau.amegroups.com/article/view/10.21037/tau-22-746/rc

Peer Review File: Available at https://tau.amegroups.com/article/view/10.21037/tau-22-746/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-22-746/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Zinner A. Einfall von intravesikaler samenblasenzyste. Wien Med Wochenschr 1914;64:605-9.
2. Cascini V, Di Renzo D, Guerriero V, et al. Zinner Syndrome in Pediatric Age: Issues in the Diagnosis and Treatment of a Rare Malformation Complex. Front Pediatr 2019;7:129. [Crossref] [PubMed]
3. Liu T, Li X, Huang L, et al. Zinner syndrome: an updated pooled analysis based on 214 cases from 1999 to 2020: systematic review. Ann Palliat Med 2021;10:2271-82. [Crossref] [PubMed]
4. van den Ouden D, Blom JH, Bangma C, et al. Diagnosis and management of seminal vesicle cysts associated with ipsilateral renal agenesis: a pooled analysis of 52 cases. Eur Urol 1998;33:433-40. [Crossref] [PubMed]
5. Pereira BJ, Sousa L, Azinhais P, et al. Zinner's syndrome: an up-to-date review of the literature based on a clinical case. Andrologia 2009;41:322-30. [Crossref] [PubMed]
6. Rosen R, Altwein J, Boyle P, et al. Lower urinary tract symptoms and male sexual dysfunction: the multinational survey of the aging male (MSAM-7). Eur Urol 2003;44:637-49. [Crossref] [PubMed]
7. Shoskes DA, Landis JR, Wang Y, et al. Impact of post-ejaculatory pain in men with category III chronic prostatitis/chronic pelvic pain syndrome. J Urol 2004;172:542-7. [Crossref] [PubMed]
8. Waqar M, Omar K, Moubasher A, et al. Painful ejaculation - an ignored symptom. Cureus. 2020;12:e11253. [PubMed]
9. Hayashi T, Takeya M, Nakamura K, et al. Effects of Silodosin and Tamsulosin on the Seminal Vesicle Contractile Response. Low Urin Tract Symptoms 2016;8:55-61. [Crossref] [PubMed]
10. Sanbe A, Tanaka Y, Fujiwara Y, et al. Alpha1-adrenoceptors are required for normal male sexual function. Br J Pharmacol 2007;152:332-40. [Crossref] [PubMed]
11. Nickel JC, Elhilali M, Emberton MAlf-One Study Group, et al. The beneficial effect of alfuzosin 10 mg once daily in 'real-life' practice on lower urinary tract symptoms (LUTS), quality of life and sexual dysfunction in men with LUTS and painful ejaculation. BJU Int 2006;97:1242-6. [Crossref] [PubMed]
12. Barnas J, Parker M, Guhring P, et al. The utility of tamsulosin in the management of orgasm-associated pain: a pilot analysis. Eur Urol 2005;47:361-5. [Crossref] [PubMed]
13. Trevisani M, Campi B, Nicoletti P, et al. Alpha1-adrenoreceptors are expressed by and stimulate nociceptive and proinflammatory sensory neurons in the rat urinary tract. Eur Urol 2005;47:37. [Crossref]