LETTER Can Short Anogenital Distance Cause Chronic Prostatitis? Ayhan Verit1, Fatma Ferda Verit2 Chronic prostatitis/Chronic pelvic pain syndromes (CP/CPPS) are a widespread pathology with unknown etiology without a proved treatment algorithm. Neurologic, endocrine and immune systems, and oxidative stress, infections are ranked in the physiopathology. Anogenital distance (AGD) as a marker for the degree of antenatal exposure of androgens that link to some disor- ders of androgen-sensitive tissues especially of urogenital system. In this study, we aimed a construct a hypothesis that improper development of perineum and pelvic bottom due to the insufficient embryologic androgen exposure, which can be detected by reduced AGD, can form histologic/clinic CP in adulthood through the physical forces that resulted in stretched prostate via chronic hypoxia induced oxidative stress and failed immune mechanisms. AGD, unlike the previous published ones, suggested as a real physical scale to detect narrowed pelvic bottom other than an endocrine related biomarker. Key Words: Chronic prostatitis; Chronic pelvic pain syndromes (CP/CPPS); Anogenital distance; etiology of CP; treatment of CP 1Univ. of Health Sciences, Fatih Sultan Mehmet Hospital, Dept. of Urology , Istanbul, Turkey. 2Univ. of Health Sciences, Istanbul Hospital, Dept. of Obstet. & Gyn. Istanbul, Turkey. Correspondence: Fatih Sultan Mehmet Hospital, Dept. of Urology, Içerenköy / Ataşehir Tr- 34752 Istanbul, Turkey. Phone : +90 216 578 30 00. Fax: + 90 216 575 04 06. E mail: veritayhan@yahoo.com. Received February 2021 & Accepted April 2021 Chronic prostatitis (CP) with largely unknown etiol-ogy is pathology without proven treatment strate- gy(1). Immune dysfunction and elevated oxidative stress that both may be triggered by local ischemia are some reported physiopathologic events in the etiology of CP besides the ranking the endocrine, neurologic and in- fectious ones(2-4). Anogenital distance (AGD) is correlated with antena- tal androgen activity and associated with some andro- gen-sensitive disorders such as prostate cancer, male infertility, hypospadias, cryptorchidism and extends to BPH and premature ejaculation(5-6). However, unlike the previous ones, our aim is to point the possibility of this physical marker as a physical dysfunction, not the endocrine related disorder, defining the etiology of CP through the physical compression inside the narrowed perineum. Perineal wall can be considered as the bottom of pelvis that roughly may be defined geometrically as the apex of the reversed cone. While the external superficial an- atomical tip of this cone was noted in an anterior-pos- terior line as AGD, the internal side of this anatomical line mark behind the perineal wall can be expressed as the place between the lower urinary tract mainly urethra and rectum. Prostate is the unique parenchymal organ without a true capsule of this location, thus, it is not illogical to hypotheses that narrowing of this internal side of cone may compress directly and chronically the parenchyma of prostate with its neurovascular bundle that result in chronic hypoxia. In this mechanism, we think that posteriorly-Denonvilliers fascia and anteri- orly-os pubis have the special role that reflecting the pressure on the prostate. Moreover, the ability of stabi- lizing effect of urethra, prostatic ligament and endopel- vic fascia, should be mentioned among the stabilizators in freezing prostate in any direction including lateral movements which prevents to avoid the direct chronic pressure on prostatic tissue. Furthermore, in the current treatment of CP, the resolving of the constipation is the initial goal of the clinician as the first step of manage- ment strategies due to the foresight to get rid of internal pressure of the colonic-rectal involvement to reduce the intra-abdominal pressure on the neighborhoods lo- cations. The strength of compressor mechanism may deem to increase by narrowing of the defined area that can be estimated by measurement of AGD in regard of the aim this study. This zone incurs the highest gravity pressure that give rise to the “pelvic organ prolapses” in women, however there is no real counterpart pathology in men related with trapped strain. In parallel, this up position may superpose the severity of lower abdomen venous pathologies such as hemorrhoids and pelvic congestion syndrome that all thought to have common origin(7-10). Moreover, flavonoids with their beneficial effects on vessels are well-known systemic medication for revealing rectal hemorrhoids also showed to be ef- fective in CP treatment that confirms varicose impair- ment extends to prostate in theory(11). As a result, the ac- cumulation of hydraulic venous pressure also seems to increase the intraprostatic strain, or vice versa. Present defined condensed physical pressure on prostate facili- tates to occur intra/periprostatic varicose disorder may appear clinically as CP. All in all, as a sub hypothesis, we claimed that prostate also the target of varicose dis- turbance as its anatomically neighborhoods structures. We think that the histological appearance of this mech- anism, that resulted from local inflammatory reaction related with improper immune response and oxidative stress due to the chronic hypoxia, reported as CP (60- 80%) and no bacterial induction confirmed in most of them and even this hypoxic media can also induce bac- terial one(12). Urology Journal/Vol 18 No. 3/ May-June 2021/ pp. 353-354. [DOI: 10.22037/uj.v18i.6687] In-utero anti-androgens/estrogens were also showed to induce dose dependent histologic postpubertal prosta- titis in animal models(13). Actually it may be presumed that early androgen insufficiency which the cause of shortened AGD, also prepare the histologic/clinical basement for CP that superpose impact of ischemia in- duce CP later in adulthood life described in the pres- ent hypotheses. Nevertheless, do we also speculate that there is no separate endocrinologic etiology in CP with- out the mechanism of shortening AGD and the present mechanism begin to work in intrauterine life and pro- gress life-long via accumulation of the ischemic inflam- mation? It should be reminded that perineal “pain” and “tender- ness” are some of the common symptoms of CP that may arise prostate itself or the perineum which surely be the direct target of synchronous above mentioned physical forces and chronic ischemia at the external side of prostate location(14). To conclude, AGD can not only supply information about the male disorders of urogenital system via em- bryologic hormonal pathways, but also, may be a phys- ical sign of the histologic/clinical prostatitis and this may lead novel decompression surgeries. REFERENCES: 1. Mändar R, Korrovits P, Rahu K, et al. Dramatically deteriorated quality of life in men with prostatitis-like symptoms. Andrology. 2020;8:101-109. 2. Ihsan AU, Khan FU, Khongorzul, et al. Role of oxidative stress in pathology of chronic prostatitis/chronic pelvic pain syndrome and male infertility and antioxidants function in ameliorating oxidative stress. Biomed Pharmacother. 2018;106:714-723. 3. Zhao Q, Yang F, Meng L, et al. Lycopene attenuates chronic prostatitis/chronic pelvic pain syndrome by inhibiting oxidative stress and inflammation via the interaction of NF- κB, MAPKs, and Nrf-2 signaling pathways in rats. Andrology. 2020;8:747-755. 4. Liu Y, Mikrani R, Xie D, et al. Chronic prostatitis/chronic pelvic pain syndrome and prostate cancer: study of immune cells and cytokines. Fundam Clin Pharmacol. 2020;34:160-172. 5. Cowin PA, Gold E, Aleksova J, et al. Vinclozolin exposure in utero induces postpubertal prostatitis and reduces sperm production via a reversible hormone-regulated mechanism. Endocrinology. 2010;151:783- 792. 6. Kutluhan MA, Şahin A, Ürkmez A, et al. The relationship between anogenital distance and benign prostate hyperplasia-related lower urinary tract symptoms. Andrologia. 2020 Apr 9:e13589. doi: 10.1111/and.13589. 7. Yetkin E. Hemorrhoid, internal iliac vein reflux and peripheral varicose vein: Affecting each other or affected vessels? Phlebology. 2015;30:145. 8. Gearhart SL. “Surgery” (chp.13), in Oxford American Handbook of Clinical Medicine. Eds Flynn AJ, Choi MJ, Dwight L. (New York NY: 2nd edition, Oxford University Press), 2013;438-517. 9. Venbrux AC, Lambert DL. Embolization of the ovarian veins as a treatment for patients with chronic pelvic pain caused by pelvic venous incompetence (pelvic congestion syndrome). Curr Opin Obstet Gynecol. 1999;11:395-399. 10. Gami B. Hemorrhoids – A common ailment among adults, causes & treatment: A review. Int J Pharm Pharm Sci. 2011;3:5-12. 11. Sahin A, Kutluhan MA, Yildirim C, Urkmez A, Akan S, Verit A. Results of purified micronized flavonoid fraction in the treatment of categorized type III chronic pelvic pain syndrome: a randomized controlled trial. Aging Male. 2019;16:1‐6. 12. Villeda-Sandoval CI, Herrera-Cáceres JO, Ruiz-Hernández JA, Castillo-de-León J, Castillejos-Molina RA, Rodriguez- Covarrubias F. The significance of histological chronic prostatitis in transrectal prostate biopsy. Austin J Urol. 2014;1:5. 13. Schreiber E, Alfageme O, Garcia T, et al. Oral exposure of rats to dienestrol during gestation and lactation: Effects on the reproductive system of male offspring. Food Chem Toxicol. 2019;128:193‐201. 14. Issberner U, Reeh PW, Steen KH. Pain due to tissue acidosis: a mechanism for inflammatory and ischemic myalgia? Neurosci Lett. 1996;208:191-194. Letter 354