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Objective: To assess the incidence of testicular cancer in trans women (male sex assigned at birth, female gender identity) using gender‐affirming hormonal treatment. Patients and Methods: Data of trans women starting hormonal treatment at our gender identity clinic between 1972 and 2017 were linked to the national pathology database to obtain testicular cancer diagnoses. The standardised incidence ratio (SIR) was calculated using the number of observed testicular cancer cases in our cohort and the number of expected cases based on age‐specific Dutch incidence rates. Subgroup analyses were performed in testicular tissues sent for histopathological analysis at the time of bilateral orchidectomy, and when follow‐up exceeded 5 years. Results: The cohort consisted of 3026 trans women with a median follow‐up time of 2.3 interquartile range (IQR) (1.6–3.7) years. Two testicular cancer cases were identified whilst 2.4 cases were expected (SIR 0.8, 95% confidence interval 0.1–2.8). In addition, one testicular cancer case was encountered in an orchidectomy specimen (0.1%). In the 523 trans women with a follow‐up time of >5 years (median [IQR] 8.9 [6.4–13.9] years), no testicular cancer was observed. Conclusion: Testicular cancer risk in trans women is similar to the risk in cis men. The testicular cancer cases occurred within the first 5 years after commencing hormonal treatment, and the percentage of cases encountered at the time of bilateral orchidectomy was low. As no testicular cancer was observed in trans women with a long follow‐up period, long‐term hormonal treatment does not seem to increase testicular cancer risk. [ABSTRACT FROM AUTHOR]

ObjectiveTo study whether long-term treatment with oestrogen (E(2) ), selective E(2) receptor modulators (SERMs), or growth hormone (GH) can prevent the development of abnormal voiding patterns during filling cystometry (CMG) in a postpartum, ovariectomized (Ovx) female rat.Materials and methodsImmediately after spontaneous delivery, 60 primiparous Sprague-Dawley rats were randomly divided into six equal groups. One group served as uninjured sham controls and five groups underwent intravaginal balloon dilatation. On day seven, previously dilated rats underwent bilateral Ovx and implantation of a subcutaneous hormone-delivery pump. The five treatment groups received normal saline (control), E(2) , raloxifene, levormeloxifene, or GH for 7 weeks. Conscious CMG was performed 7 weeks after Ovx. Urethral sphincter tissue was harvested for elastin immunohistochemistry and real-time polymerase chain reaction of α(1A) -adrenoceptor mRNA.ResultsNo abnormal voiding patterns were detected in the group treated with GH. The E(2) , raloxifene and levormeloxifene groups had greater detrusor overactivity and urethral relaxation incontinence than control rats. The raloxifene group had a significantly lower baseline bladder pressure and opening pressure. GH-treated rats had higher elastin content in the urethra. Urethral α(1A) -adrenoceptor mRNA concentration was significantly lower in the SERM-treated rats compared with controls.ConclusionsGH prevents the development of abnormal voiding patterns during filling CMG in a rat model of parturition-induced incontinence; E(2) and SERMs may worsen voiding patterns.

ObjectiveTo investigate whether oestrogen, selective oestrogen receptor modulators (SERMs), and growth hormone (GH) can prevent the development of voiding dysfunction in a postpartum postmenopausal rat model of voiding dysfunction.Materials and methodsImmediately after spontaneous delivery, nine primiparous Sprague-Dawley rats served as uninjured controls (sham group) and 54 underwent intravaginal balloon dilation. On day 7, the 54 subject rats underwent bilateral ovariectomy. A week later, six treatment groups of nine rats were randomized to receive: normal saline (injured control group), 17beta-oestradiol (E(2)), raloxifene, levormeloxifene, GH, or GH + E(2). The treatment groups received daily subcutaneous injections for 3 weeks. The effects of hormone treatment were examined by conscious cystometry at the end of the study. Voiding dysfunction was defined to include overactive bladder and sphincter deficiency.ResultsThe sham rats had a mean (sd) voiding frequency of 3 (0.87) times in 10 min and a bladder capacity of 0.43 (0.13) mL with smooth cystometry curves. The number of rats in each treatment group (each group contained nine rats) that had voiding dysfunction was as follows: E(2), three; raloxifene, six; levormeloxifene, four; and controls, four (P > 0.05 among the groups). Only one rat in the GH-treated group and no rats in the GH + E(2)-treated group had voiding dysfunction, which was significantly less in the GH + E(2)-treated group than in the controls (P = 0.041).ConclusionThis functional data suggest that the development of voiding dysfunction can be prevented by short-term administration of GH and GH + E(2) in our rat model. SERMs and E(2) alone seem to have no therapeutic effect.

Study Type - Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Diethylstilbestrol (DES) was the first hormone treatment used for prostate cancer and has also shown effectiveness in castration-resistant disease in small studies; however, concerns over thromboembolic toxicity have restricted its use in the past. Over 200 elderly men with castration-resistant prostate cancer were treated with 1-3 mg of DES, given with 75 mg aspirin and breast bud irradiation. Almost 30% of men showed a significant PSA response and the median time to PSA progression was 4.6 months. Almost 20% of patients with pain had a significant analgesic benefit. The most important toxicity was thromboembolism in 10% of men. Overall the drug has an acceptable toxicity profile and offers a palliative benefit in frail elderly men who may not be fit for chemotherapy. OBJECTIVE To assess the efficacy and toxicity of diethylstilbestrol (DES) in the management of castration-resistant prostate cancer (CRPC)., PATIENTS AND METHODS A total of 231 patients with CRPC received treatment with DES at the Royal Marsden Hospital between August 1992 and August 2000., The median pre-treatment prostate-specific antigen (PSA) level was 221 ng/mL., DES was used at a dose of 1-3 mg daily, with aspirin 75 mg., The primary endpoint was PSA response rate., RESULTS The PSA response rate (using PSA Working Group criteria) was 28.9%., The median time to PSA progression was 4.6 months., Of patients with bone pain, 18% had an improvement in their European Organisation for the Research and Treatment of Cancer pain score., Thromboembolic complications were seen in 9.9% of all patients., CONCLUSIONS DES has significant activity in CRPC and can be of palliative benefit., DES has an acceptable toxicity profile in the management of patients with symptomatic CRPC when used at a dose of 1-3 mg, combined with aspirin and prophylactic breast bud radiotherapy. [ABSTRACT FROM AUTHOR]

Study Type - Prognosis (retrospective cohort analysis) Level of Evidence 2b What's known on the subject? and What does the study add? The additional use of anti-androgen (deferred combined androgen blockade [CAB] therapy) for patients with castration-resistant prostate cancer (CRPC) initially treated with androgen deprivation monotherapy (ADMT) can provide a clinical response, although the reported response rates vary widely. Our previous study, which reported a response rate of 66% to deferred CAB therapy, suggested that deferred CAB responders would also respond better to subsequent therapies than non-responders because the difference in cancer-specific survival between the deferred CAB responders and the non-responders was much larger than the progression-free survival rates for the responders. The present study showed that PSA response to deferred CAB therapy predicts clinical outcomes after subsequent oestrogen and docetaxel therapy. We propose that PSA response to deferred CAB be used for planning individualized treatment that includes secondary hormonal therapy and chemotherapy. OBJECTIVE To evaluate whether there is any association between prostate-specific antigen (PSA) response to deferred combined androgen blockade (CAB) therapy using bicalutamide in patients with castration-resistant prostate cancer (CRPC), initially treated with castration monotherapy, and the clinical outcomes after subsequent oestrogen and docetaxel therapies., PATIENTS AND METHODS Fifty-six patients with advanced prostate cancer, who were refractory to both initial castration monotherapy and subsequent deferred CAB, received oestrogen therapy (estramustine phosphate 140 or 280 mg/day in 50 patients, diethylstilbestrol diphosphate 100 mg/day orally in six patients). Of the 56 patients, 33 underwent docetaxel therapy (median dose 55 mg/m2, every 4-8 weeks, median 6 courses) when they became refractory to oestrogen therapy., A deferred CAB response was defined as a decrease of >50% in PSA levels after the addition of bicalutamide. The difference in cancer-specific survival (CSS) after confirmation of resistance to initial castration monotherapy between the deferred CAB responders and the non-responders was evaluated, and outcomes after oestrogen and docetaxel therapies were also compared between the two groups., RESULTS A response to deferred CAB was observed in 27 (48%) of the 56 patients. There was no significant difference between the responders and the non-responders in pretreatment clinical variables, including Gleason score, metastatic sites, PSA level at diagnosis, and PSA nadir during castration monotherapy., A deferred CAB response was a significant predictor of CSS after confirmation of resistance to initial castration monotherapy., The deferred CAB responders had significantly longer progression-free survival (PFS) (median 3.2 months in the responders, 2.1 month in the non-responders, P= 0.04) and CSS (median 3.0 years in the responders, 1.5 years in the non-responders, P= 0.04) after oestrogen therapy. Likewise, PFS (median 8.2 months in the responders, 2.2 months in the non-responders, P < 0.01) and CSS (median not reached in the responders, 1.4 years in the non-responders, P < 0.01) after docetaxel therapy was significantly longer in the deferred CAB responders., CONCLUSION PSA response to deferred CAB predicts clinical outcomes after subsequent oestrogen and docetaxel therapies in patients with CRPC, and provides useful information for planning individualized optimum treatment courses that include secondary hormonal therapy and chemotherapy. [ABSTRACT FROM AUTHOR]

OBJECTIVE To evaluate the effects of dietary soy isoflavone on detrusor overactivity (DO) in ovariectomized (Ovx) rats and the association between these effects and expression of the gap junction protein, connexin-43, in the urinary bladder, and to discuss the usefulness of soy isoflavones for overactive bladder (OAB). MATERIALS AND METHODS In all, 24 (8-week-old) virgin female Sprague-Dawley rats were divided equally into four groups: sham operation with control diet (with no dietary soy isoflavones; Sham-CD), bilateral Ovx with CD (Ovx-CD), sham operation with soy isoflavone diet (Sham-ID), bilateral Ovx with soy ID (Ovx-ID). Cystometry was performed after the 4-week CD or ID in each group while awake. Quantitative reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemical and Western blot analyses were also performed to examine the expression of connexin-43 in each group. RESULTS In Ovx-CD rats, there were some significant changes in cystometry variables, including shortening of the intercontraction interval and an increased number of non-voiding contractions compared with Sham-CD rats ( P < 0.05). These changes were significantly improved by 4-week soy isoflavone administration (Ovx-ID; P < 0.05). Quantitative RT-PCR, immunohistochemical and Western blot analyses showed that the expression level of connexin-43 mRNA and protein was significantly greater in the urinary bladder of Ovx-CD rats compared with Sham-CD rats. Soy isoflavone administration significantly reduced this increased expression (Ovx-ID). CONCLUSIONS Soy isoflavone replacement improved DO with alteration of the connexin-43 expression pattern in the urinary bladder of Ovx rats. Routine consumption of diet soy isoflavones may be a useful treatment to prevent and improve OAB. [ABSTRACT FROM AUTHOR]

OBJECTIVE To evaluate the effects of ovariectomy (Ovx) and oestrogen therapy on the free fatty acid (FFA) content, endogenous lipase activity, and the phospholipid (PL) content of the urinary bladder, as reduced circulating oestrogen during and after the menopause has been linked to various bladder dysfunctions including incontinence and recurrent urinary tract infections. MATERIALS AND METHODS In all, 12 New Zealand White female rabbits were separated into three groups; the Ovx + oestrogen group received Ovx and treatment with conjugated β-oestradiol (3 weeks), the Ovx group received Ovx and vehicle (3 weeks), and the control group received sham operation and vehicle. Cystometry was used to evaluate compliance and in vitro muscle strip studies quantified contractility. For the bulk of the bladder, the muscle and mucosa were separated; FFA and PL concentrations were analysed using standard biochemical techniques. RESULTS The bladder contractile responses and compliance decreased after Ovx and returned to or above normal after oestrogen administration. Both FFA and PL concentrations of the mucosa were about three times greater than that of the smooth muscle. Ovx significantly reduced the FFA and PL concentrations of both muscle and mucosa, while oestrogen therapy restored them to normal. CONCLUSIONS Reduced FFA and PL content of the smooth muscle membranes would decrease their fluidity and contribute to decreased compliance and contractility. Reduced FFA and PL content of the mucosa would be consistent with mucosal damage and may contribute to the increased incidences of incontinence and bladder infection. [ABSTRACT FROM AUTHOR]

OBJECTIVE To determine whether oestrogen enhances platinum sensitivity, and if promoter CpG methylation of the oestrogen receptor-α (ER-α) gene determines the potential of cisplatin-induced apoptosis in prostate cancer, as the high-mobility group 1 (HMG1) preferentially binds to cisplatin-modified DNA and is up-regulated after oestrogen treatment in breast cancer cell line MCF-7. MATERIALS AND METHODS The study comprised prostate cancer cell lines (LNCaP and PC-3), 156 pathologically confirmed 156 radical prostatectomy samples and eight hormone-refractory prostate cancer (HRPC) samples (from needle biopsy). Expression of HMG1 in cell lines was analysed by Western blotting or differential reverse-transcription-polymerase chain reaction (PCR). The methylation status of ER-α was analysed by methylation-specific PCR using bisulphite DNA as a template or bisulphite DNA sequencing. RESULTS In LNCaP cells, treatment with oestrogen increased HMG1 expression and co-treatment with cisplatin and oestrogen reduced cell viability by accelerating apoptosis, compared with cisplatin alone. However, in PC-3, oestrogen did not up-regulate HMG1 or accelerate the cisplatin-induced apoptosis. Although ER-β was expressed in both LNCaP and PC-3, ER-α was expressed only in LNCaP. Bisulphite DNA sequencing of the ER-α promoter showed partial methylation in LNCaP but complete methylation in PC-3. ER-α AS transfection diminished the cisplatin-induced apoptosis in oestrogen-treated LNCaP cells. In clinical samples there was ER-α hypermethylation in 40% of prostate cancers this correlated with Gleason score (GS, 31% for GS < 7, 50% for GS = 7 and 56% for GS > 7). In addition, five of eight HRPC samples showed ER-α hypermethylation. CONCLUSION These findings suggest that HMG1 induction as an enhancer of platinum sensitivity is mediated through interaction between oestrogen and ER-α. As CpG hypermethylation of the ER-α promoter is a frequent event in aggressive prostate cancer, negative conversion of ER-α methylation is essential to achieve the most beneficial effect when combined chemotherapy of cisplatin with oestrogen is used in patients with prostate cancer. [ABSTRACT FROM AUTHOR]

OBJECTIVES To investigate whether circulating levels of sex hormones are associated with urological symptoms, using data from the Boston Area Community Health (BACH) Survey. SUBJECTS AND METHODS BACH used a multistage stratified-cluster approach to randomly sample 5506 adults aged 30–79 years in Boston, MA, USA. Anthropometric measures, lifestyle and psychosocial factors, comorbidities and urological symptoms were obtained using a questionnaire administered by an interviewer. Serum testosterone, sex hormone-binding globulin (SHBG), dehydroepiandrosterone sulphate (DHEAS), dihydrotestosterone (DHT) and oestradiol (E2) levels were measured, and bioavailable testosterone (BT) was calculated in 1899 men (538 Black, 651 Hispanic and 710 White). Regression analysis was used to investigate the relationships between androgen levels and American Urological Association symptom index (AUA-SI), lower urinary tract symptoms (LUTS) (≥ 8 on the AUA-SI), urinary incontinence (UI), dribble and hesitancy. RESULTS Of all subjects, 19% reported LUTS, 6% UI, 9% dribble and 4% hesitancy. Testosterone, BT and DHEAS levels were inversely related to the AUA-SI ( P = 0.009, <0.001 and <0.001, respectively); SHBG values and the AUA-SI were positively correlated ( P < 0.001). Adjusting for age, BT and DHEAS levels had negative relationships with the AUA-SI; BT and DHEAS levels were negatively related to LUTS and SHBG was positively related to LUTS (both P < 0.001); after age adjustment, only LUTS and DHEAS remained related, and only the relationship between dribble and E2 remained significant; no hormone levels were related to hesitancy. CONCLUSIONS Circulating levels of sex hormones are generally not significant predictors of urological symptoms in men after adjusting for age. The pathophysiology of LUTS is complex and probably includes factors other than circulating sex steroid levels. [ABSTRACT FROM AUTHOR]

OBJECTIVE To investigate the changes in expression underlying the marked reduction of tumour growth in vivo, by analysing the effect of Belamcanda chinensis extract (BCE) on LNCaP cells in vitro, as phytoestrogens are chemopreventive in prostate cancer, and in previous studies we examined the effects of the isoflavone tectorigenin isolated from B. chinensis on LNCaP prostate cancer cells, and a BCE consisting of 13 phytoestrogenic compounds on tumour-bearing nude mice. MATERIALS AND METHODS LNCaP cells were treated with 100, 400 or 1400 µg/mL BCE; proliferation was assessed with an Alamar Blue assay. We used real-time reverse transcription-polymerase chain reaction to quantify mRNA expression of the androgen receptor (AR), the AR coactivator prostate derived Ets transcription factor (PDEF), NKX3.1, prostate specific antigen (PSA) and oestrogen receptor-β (ER-β) compared with the expression of the housekeeping gene porphobilinogen deaminase (PBGD). PSA secretion from LNCaP cells was measured and protein expression of the AR investigated by Western blot analysis. RESULTS Concomitant with a marked decrease of tumour cell proliferation BCE down-regulated the expression of the AR, PDEF, NKX3.1 and PSA. In the same experiments, the expression of PBGD was unaltered, whereas ER-β expression increased. Furthermore, AR protein and PSA secretion were markedly diminished after treatments with the BCE. CONCLUSION BCE, comprising 13 different phytoestrogens, decreases the expression of the AR and its co-activator PDEF concomitant with diminished cell proliferation and PSA secretion. NKX3.1 expression was also reduced by BCE. We hypothesise that the positive effects of BCE are initiated by up-regulation of the ER-β, a putative tumour-suppressor gene. [ABSTRACT FROM AUTHOR]

OBJECTIVE To determine the effects of cycling oestrogen in rabbits, as oestrogen is essential for physiological maintenance and integrity of the female urogenital tract. MATERIALS AND METHODS Changes in circulating oestrogen have marked effects on the bladder of experimental animals, with ovariectomy (Ovx) inducing smooth muscle (SM) and mucosal atrophy, increasing collagen synthesis and deposition, decreasing contractile function, mucosal and SM blood flow; oestrogen reverses these effects and increases bladder mass and SM density, primarily by stimulating angiogenesis and increasing blood flow. Twenty adult female New Zealand White rabbits were divided into five equal groups; group 1 served as the control group, and groups 2–5 had a bilateral Ovx. Group 2 received no oestradiol and was assessed 2 weeks after Ovx; groups 3–5 received 17-β oestradiol from a subcutaneous slow-release tablet 2 weeks after Ovx, which remained in place for a subsequent 2-week period. Group 3 was then assessed after the 2 weeks on oestradiol. Groups 4 and 5 then had their oestradiol tablets removed for 2 weeks and group 4 was assessed after this period off oestradiol. Group 5 then received a new oestradiol tablet that was left in place for an additional 2 weeks. RESULTS Both groups receiving oestrogen (3 and 5) had a statistically significantly greater bladder weight than both the control group and group 2. The volume fraction of SM paralleled the bladder weight, showing that oestrogen increased the volume fraction of SM whereas Ovx and low oestrogen decreased the SM fraction. The cross-sections of the urethra from groups 3 and 5 were significantly wider than those of either the control or group 1, also being consistent with the structural effects of oestrogen. Intra-arterial phenylephrine increased urethral pressure to a similar level in all groups. The urethral pressure response to intra-arterial acetylcholine shifted from contraction in the control to relaxation in the oestrogen-treated groups. Ovx resulted in a lower vascular density, whereas oestrogen resulted in a significant increase in vascular density (angiogenesis). CONCLUSIONS Cyclical oestrogen had pronounced structural and pharmacological effects. Low oestrogen decreased the volume fraction of SM, increased collagen, and decreased vasculature, whereas oestrogen mediated a marked hypertrophy of the SM components, decreased the collagen component, and stimulated angiogenesis. Cyclical oestrogen also had marked effects on the responses to intra-arterial acetylcholine, shifting the response from contraction to relaxation. [ABSTRACT FROM AUTHOR]

OBJECTIVE To investigate the effects of ovariectomy and oestrogen replacement on the function and expression of Rho-kinase in rat bladder smooth muscle, as the actual effects of oestrogen deprivation on bladder smooth muscle are unclear. MATERIALS AND METHODS Female Sprague–Dawley rats were placed into one of three groups: sham-operated, bilateral ovariectomy-only, and bilateral ovariectomy plus oestrogen replacement groups. In the last group, oestrogen was replaced by weekly injection of β-estradiol 17-cypionate (250 µg/kg subcutaneously for 6 weeks) beginning at 1 week after ovariectomy, whereas the other groups received vehicle-only injections for 6 weeks. After treatment, the bladder was removed for muscle strip studies to evaluate the effects of Y-27632, a specific inhibitor of Rho-kinase, on baseline tension and carbachol-induced tonic contractions. Also, the protein expression of RhoA and Rho-kinase isoenzymes was assessed by Western blot analysis. RESULTS Of the three groups, incubation with 10 µm Y-27632 resulted in the largest decrease in baseline tension of strips from the bilateral ovariectomy-only group, but this was not statistically significant ( P > 0.05). For carbachol-induced tonic contractions, strips from the bilateral ovariectomy-only group were attenuated the most among the three groups after adding Y-27632 ( P < 0.05). However, there were no significant differences in the levels of RhoA and the two Rho-kinase isoenzymes in bladder tissues from the three groups. CONCLUSION Our data show that oestrogen might inhibit the function of Rho-kinase in bladder smooth muscle, while having no significant effect on its expression. This finding might help to explain the greater incidence of urinary tract symptoms suggestive of overactive bladder after the menopause in women. [ABSTRACT FROM AUTHOR]

To evaluate the effects of oestrogen, progesterone and pregnancy on bladder dynamics, and assess the associated histological and structural changes in the bladder wall in a rat model.Adult female Sprague-Dawley rats were divided into groups and treated as follows: nonpregnant controls (NC); pregnant (PG); oophorectomized and treated with oestrogen (ES); oophorectomized and treated with progesterone (PR); and oophorectomized controls (OO). Simultaneous and continuous renal pelvic and bladder pressures were recorded during bladder filling and emptying. Connective tissue and smooth muscle were analysed morphometrically and quantitatively, and immunohistochemistry used to evaluate the distribution and expression of collagen types I, III and IV.PG rats had significantly greater bladder compliance than NC, OO and PR rats (P < 0.05). This correlated with the morphometric analysis, with bladders of PG and PR rats having lower connective tissue to smooth muscle ratios than NC, ES and OO rats (P < 0.05). Collagen I was increased in the lamina propria of PG and ES rats, and the detrusor muscle layer showed greater localization of collagen III in the interfascicular space in the PG and PR rats than in the other groups. There was no change in the distribution of collagen IV.PG and PR rats had the highest bladder compliance and the changes paralleled structural changes in the bladders, specifically in the ratio of connective tissue to smooth muscle, and the distribution and expression of collagens I and III. These changes have age-related implications in the urinary tract. [ABSTRACT FROM AUTHOR]

To determine the early effects of oestrogen on the ultrastructure of the pudendal nerve and distal nerve fascicles near the external urethra sphincter (EUS) after a pudendal nerve crush injury. The pudendal nerve is one of the pelvic floor tissues injured during vaginal delivery, possibly contributing to the development of stress urinary incontinence (SUI) in women, the symptoms of which often do not appear until menopause, implicating hormonal factors. Twenty-seven virgin female Sprague-Dawley rats were anaesthetized and underwent ovariectomy. Three days later, they had one of four procedures: bilateral pudendal nerve crush plus implant of a subcutaneous oestrogen-containing capsule (NC+E); nerve crush plus implant of a sham saline-containing capsule (NC+S); no nerve crush with an oestrogen capsule; or no nerve crush with a sham capsule. After 2 weeks the pudendal nerves and urethral tissues were prepared for light and electron microscopy. The number of axons, myelin figures and endoneurial nuclei in the pudendal nerve segment distal to the lesion were counted. Nerve fascicles near the EUS were also counted and categorized as normal or showing signs of degeneration and/or regeneration. The location of each nerve fascicle was specified as either ventral or dorsal. As there were no significant differences between the two control groups they were combined to form a single control group. In the distal pudendal nerve there were significantly fewer myelinated axons and large myelinated axons in the NC+E and NC+S groups than in the control group. There were three times as many large unmyelinated axons in the NC+E group than in either the NC+S or control groups ( P < 0.05). There were only half as many nerve fascicles near the ventral side of the EUS in the NC+S group than in both the control and NC+E groups ( P < 0.05). Oestrogen appears to affect large unmyelinated axons in both the injured pudendal nerve and at the denervated EUS target. After pudendal nerve crush, nerve fascicles with evidence of degeneration or regeneration near the EUS appear to be spared with oestrogen treatment, particularly in the ventral region. These observations may reflect the early stages of a neuroregenerative effect of oestrogen. Additional studies are needed to confirm these results at later periods and with functional methods. [ABSTRACT FROM AUTHOR]

Objective To assess the incidence and distribution of both oestrogen and progesterone receptors throughout the female lower urinary tract, and to compare receptor expression in women of varying oestrogen status. Patients and methods The study included 90 women undergoing surgery for urogynaecological conditions; 33 were premenopausal, 26 postmenopausal and taking no oestrogen supplementation, and 31 postmenopausal and receiving some form of hormone-replacement therapy. Biopsies were taken during surgery from the bladder dome, trigone, proximal urethra, distal urethra, vagina and vesicovaginal fascia in the region of the bladder neck. All biopsies were routinely fixed and processed for histopathological assessment, and were then labelled immunohistochemically with monoclonal antibodies directed against human oestrogen (NCL-ERLH2) and progesterone (NCL-PGR) receptors. Both oestrogen and progesterone receptor expression were assessed in the epithelial, subepithelial and muscle/deeper fascial regions of all tissue for overall tissue positivity for each receptor, and by semiquantitative analysis of receptor concentration using histochemical scoring of the tissues. Results Oestrogen receptors were consistently detected in the squamous epithelia and were consistently absent in the urothelial tissues of the lower urinary tract of all women irrespective of oestrogen status; there was no significant variation in histological score. Progesterone receptor expression was more variable, being mostly subepithelial, and significantly lower in postmenopausal women receiving no oestrogen replacement. Conclusion These findings confirm the female lower urinary tract to be a target organ for the action of oestrogen and progesterone, and shed further light on the areas of the lower urinary tract likely to respond to hormone-replacement therapy. This may have implications for the use of oestrogen supplementation in the treatment of lower urinary tract disorders of postmenopausal women. [ABSTRACT FROM AUTHOR]