Extragonadal LH/hCG action-Not yet time to rewrite textbooks

Gonadotropins are indispensable in both sexes in the regulation of gonadal sex steroid production and gametogenesis. In addition to their well-established classical actions, numerous recent publications have indicated the presence and function of luteinizing hormone/chorionic gonadotropin receptors (LH/hCG-R) in a variety of extragonadal tissues. However, the physiological significance of such effects has remained unclear. We have generated two genetically modified mouse models, one with excessive production of hCG and the other with targeted disruption of LH/hCG-R gene, and used them to address the functions of LH and hCG. Numerous gonadal and extragonadal phenotypes were found in the models with the two extremes of LH/hCG action. However, when the extragonadal effects were scrutinized in greater detail, they all appeared to arise through modification of gonadal function, either through enhanced or inhibited response to LH/hCG stimulation. Hence, further evidence is needed before the extragonadal LH/hCG-R expression can be considered functionally significant.Fil: Pakarainen, Tomi. University of Turku; FinlandiaFil: Ahtiainen, Petteri. University of Turku; FinlandiaFil: Zhang, Fu Ping. University of Helsinki; FinlandiaFil: Rulli, Susana Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Poutanen, Matti. University of Turku; FinlandiaFil: Huhtaniemi, Ilpo. University of Turku; Finlandia. IMperial College London; Reino Unid

EXPRESSION OF cAMP AND CREB IN THE HUMAN PENIS

The aim of this study is to investigate the expression of adenosine 3',5'-cyclic monophosphate (cAMP) and cAMP-response element-binding protein (CREB) in the human penis as it is known that luteinizing hormone (LH) regulates cellular function mostly through the cAMP signaling pathway and LH receptors are expressed by the penile endothelium. Penile tissue was obtained from three patients during partial or total penectomy due to a rectal cancer with secondary penile metastasis or squamous cell carcinoma of the penis. Immunohistochemistry was used for the detection of cAMP and CREB. Positive immunoreaction for cAMP was present in most cells of superficial, intermedial, and basal layer of urethral epithelium and in fibroblast-like cells (FLC) of interstitial tissue and endothelial cells (EC) of cavernous spaces in corpus spongiosum penis. Positive staining for cAMP was also visible in EC of cavernous spaces and in FLC of interstitial tissue in corpus cavernosum penis. Positive immunoreaction for CREB was present in the superficial and intermedial layer of urethral epithelium, and some positive immunoreaction was also noticed in EC of cavernous spaces and in FLC of interstitial tissue in corpus spongiosum penis. Positive staining was also visible in the EC of cavernous spaces and in fibroplast-like cells of the interstitial tissue in the corpus cavernosum penis. Our results show the presence of cAMP and CREB in the human penis. While LH exerts its actions through cAMP signaling system and our previous studies have shown the expression of luteinizing hormone/choriogonadotropin (LHCG) receptor in the mouse and human penis, this finding may support the hypothesis that LH could affect the spongious and cavernous tissue of the human penis and thereby influence the development of erectile dysfunction among aging men.Peer reviewe

”Nyt on kovat piipussa” – miesten kokemuksia penissyöpään sairastumisesta

Penissyöpä on harvinainen ja varsin tuntematon sairaus, jonka pääsääntöinen hoitomuoto on kirurginen hoito. Tutkimuksen tarkoituksena oli kuvata miesten kokemuksia penissyöpään sairastumisesta, mitä Suomessa ei ole aikaisemmin tutkittu. Aineisto kerättiin vuonna 2019 yksilöhaastatteluilla ja kirjallisilla vastauksilla penissyöpään sairastuneilta, kirurgisesti hoidetuilta miehiltä (n=14). Aineisto analysoitiin aineistolähtöisellä sisällönanalyysillä. Miesten voimavaroja sairaudesta selviytymisessä heikensivät ajatuksia kuormittavat tunteet, vakavan sairauden aiheuttama pelko, miehuuden menettämisen tunne, yksinjäämisen kokemus, huoli läheisten jaksamisesta sekä taloudelliset huolet. Miesten voimavaroja puolestaan tuki omien selviytymiskeinojen rakentuminen, puhumisen taito, läheisten tuki, usko tulevaisuuteen sekä sairauden hyväksyminen osana elämää. Hoidetuksi tulemisen tunnetta heikensi epäluottamusterveydenhuollon ammattilaisiin, tiedonpuute hoidon vaikutuksista sekä organisaatiokeskeinen toiminta. Hoidetuksi tulemisen tunnetta vahvisti turvallisuudentunne hoitoprosessista, rehellinen informaatio, osallisuus päätöksenteossa sekä merkityksellinen kohtaaminen

Robot-assisted versus three-dimensional laparoscopic radical prostatectomy : 12-month outcomes of a randomised controlled trial

Objectives: To compare functional and oncological outcomes of robot-assisted laparoscopic prostatectomy (RALP) to three-dimensional laparoscopic radical prostatectomy (3D-LRP) at 12 months after surgery. Patients and methods: Prospective randomised single-centre study of 145 consecutive men referred to radical prostatectomy in a tertiary referral centre in Finland. Patients were randomised 1:1 to the RALP (N = 75) and 3D-LRP (N = 70) groups. The primary outcome was urinary continence evaluated with the Expanded Prostate Cancer Index Composite 26-item version (EPIC-26) incontinence domain score at 12 months after surgery. Secondary outcomes included the use of protective pads at 12 months after surgery, EPIC-26 domain scores of irritative/obstructive, bowel, sexual and hormonal symptoms, positive surgical margin (PSM) rate, and biochemical recurrence (BCR). Complication frequency within the 3-month period after surgery was evaluated according to Clavien–Dindo classification. Statistical significance between groups was analysed using Mann–Whitney, chi-square and Fisher's exact tests. The trial was terminated after interim analysis based on no statistically significant difference in EPIC-26 urinary incontinence domain scores. Altogether 145 patients of the target accrual of 280 patients were recruited. Results: Postoperative continence at 12 months after surgery according to the EPIC-26 incontinence domain was 79.25 in both groups (P = 0.4). Between group difference was −5.8 (95% confidence interval –15.2 to 3.6). There was no statistically significant difference in the rates of PSM or BCR between the two surgical modality groups. Conclusion: We were unable to demonstrate a difference between the RALP and 3D-LRP groups for functional and oncological outcomes at 12 months after surgery.Peer reviewe

Randomised double-blind phase 3 clinical study testing impact of atorvastatin on prostate cancer progression after initiation of androgen deprivation therapy : study protocol

Introduction Blood cholesterol is likely a risk factor for prostate cancer prognosis and use of statins is associated with lowered risk of prostate cancer recurrence and progression. Furthermore, use of statins has been associated with prolonged time before development of castration resistance (CR) during androgen deprivation therapy (ADT) for prostate cancer. However, the efficacy of statins on delaying castration-resistance has not been tested in a randomised placebo-controlled setting. This study aims to test statins' efficacy compared to placebo in delaying development of CR during ADT treatment for primary metastatic or recurrent prostate cancer. Secondary aim is to explore effect of statin intervention on prostate cancer mortality and lipid metabolism during ADT. Methods and analysis In this randomised placebo-controlled trial, a total of 400 men with de novo metastatic prostate cancer or recurrent disease after primary treatment and starting ADT will be recruited and randomised 1:1 to use daily 80 mg of atorvastatin or placebo. All researchers, study nurses and patients will be blinded throughout the trial. Patients are followed until disease recurrence or death. Primary outcome is time to formation of CR after initiation of ADT. Serum lipid levels (total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and trigyserides) are analysed to test whether changes in serum cholesterol parameters during ADT predict length of treatment response. Furthermore, the trial will compare quality of life, cardiovascular morbidity, changes in blood glucose and circulating cell-free DNA, and urine lipidome during trial. Ethics and dissemination This study is approved by the Regional ethics committees of the Pirkanrnaa Hospital District, Science centre, Tampere, Finland (R18065M) and Tarto University Hospital, Tarto, Estonia (319/T-6). All participants read and sign informed consent form before study entry. After publication of results for the primary endpoints, anonymised summary metadata and statistical code will be made openly available. The data will not include any information that could make it possible to identify a given participant.Peer reviewe

Randomised double-blind phase 3 clinical study testing impact of atorvastatin on prostate cancer progression after initiation of androgen deprivation therapy: study protocol

Introduction Blood cholesterol is likely a risk factor for prostate cancer prognosis and use of statins is associated with lowered risk of prostate cancer recurrence and progression. Furthermore, use of statins has been associated with prolonged time before development of castration resistance (CR) during androgen deprivation therapy (ADT) for prostate cancer. However, the efficacy of statins on delaying castration-resistance has not been tested in a randomised placebo-controlled setting.This study aims to test statins’ efficacy compared to placebo in delaying development of CR during ADT treatment for primary metastatic or recurrent prostate cancer. Secondary aim is to explore effect of statin intervention on prostate cancer mortality and lipid metabolism during ADT.Methods and analysis In this randomised placebo-controlled trial, a total of 400 men with de novo metastatic prostate cancer or recurrent disease after primary treatment and starting ADT will be recruited and randomised 1:1 to use daily 80 mg of atorvastatin or placebo. All researchers, study nurses and patients will be blinded throughout the trial. Patients are followed until disease recurrence or death. Primary outcome is time to formation of CR after initiation of ADT. Serum lipid levels (total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and trigyserides) are analysed to test whether changes in serum cholesterol parameters during ADT predict length of treatment response. Furthermore, the trial will compare quality of life, cardiovascular morbidity, changes in blood glucose and circulating cell-free DNA, and urine lipidome during trial.Ethics and dissemination This study is approved by the Regional ethics committees of the Pirkanmaa Hospital District, Science centre, Tampere, Finland (R18065M) and Tarto University Hospital, Tarto, Estonia (319/T-6). All participants read and sign informed consent form before study entry. After publication of results for the primary endpoints, anonymised summary metadata and statistical code will be made openly available. The data will not include any information that could make it possible to identify a given participant.</p

Health-Related Quality of Life, Self-esteem and Sexual Functioning Among Patients Operated for Penile Cancer - A Cross-sectional Study

Background: Penile cancer surgery affects physical, psychological, and sexual well-being, but the patient-and treatment-related factors predisposing to worse health-related quality of life (HRQoL) have not been well characterized. Aim: We report treatment-related HRQoL changes among penile cancer survivors compared to the general population and the specific deficits that have the most profound effect, and we identify patient-related factors that predispose to a worse perceived HRQoL. Methods: Patients (n = 107) who underwent operations for invasive penile cancer in two Finnish university hospitals from 2009 to 2019 were sent the Patient Reported Outcomes (PROs) questionnaire designed to measure HRQoL, self-esteem, overall sexual functioning, erections, and change in sexual function. We collected clinical information and socio-demographic characteristics, including age, partner status, children, vocational education, and employment status. Associations between patient-and treatment-related factors and HRQoL were analyzed using descriptive statistics and non-parametric tests. Linear regression models were used to compare the HRQoL differences between patients with penile cancer and the age-standardized average for the Finnish population. Outcomes: A generic measure of HRQoL (15D), the Rosenberg Self-Esteem Scale, Overall Sexual Functioning Questionnaire, the Erection Hardness Score, and self-reported change in sexual functioning. Results: Low scores in overall sexual functioning, erectile function, and changes in sexual functioning were associated with a lower HRQoL. An association was found between HRQoL and age, educational level, employment status, and place of residence. The HRQoL had a negative correlation with age. Patients with a high educational level, who were employed, or who lived in urban areas reported higher HRQoL. The mean HRQoL of penile cancer survivors was significantly lower than the age-standardized average HRQoL of the Finnish population. Clinical Implications: Enhanced support and counseling is needed among penile cancer patients to improve the HRQoL during survivorship. Strengths & Limitations: A nationwide sample with detailed information allowed comparisons of HRQoL between penile cancer patients and the general population. Due to cross-sectional nature of the study, the time between the surgery and the study intervention was heterogeneous, and this may have affected the results. Conclusion: Penile cancer patients exhibit significant physical and psychological dysfunction, and the lack of sexual activity in general is what most compromises the QoL of penile cancer survivors. Copyright (C) 2021 The Authors. Published by Elsevier Inc. on behalf of the International Society for Sexual Medicine.Peer reviewe

Fertility in luteinizing hormone receptor-knockout mice after wild-type ovary transplantation demonstrates redundancy of extragonadal luteinizing hormone action

The luteinizing hormone receptor (LHR), mainly expressed in gonads, is essential for normal reproduction. However, numerous recent studies have also demonstrated LHR expression in multiple extragonadal reproductive and nonreproductive tissues. Although some effects of luteinizing hormone (LH) or its agonist, human chorionic gonadotropin, have been shown in extragonadal sites, their physiological significance remains open. In the present study, we have addressed the function of the extragonadal LHR using LHR-KO mice (LuRKO mice), in which the ovaries of prepubertal mice were orthotopically replaced with pieces of WT ovary using similarly transplanted WT mice as controls. Most ovarian transplants attained normal endocrine function in both groups of mice, as demonstrated by normal age at vaginal opening, estrous cycles, and sexual behavior. Both the LuRKO and WT mice repeatedly became pregnant (9/16 vs. 16/20 after first mating; difference not significant) and delivered similarly sized litters, which grew normally after birth, indicating normal lactation. In conclusion, fertility is restored in LuRKO mice by transplantation of WT ovarian tissue. This is achieved in the absence of extragonadal LHR expression, which indicates physiological redundancy for such receptor sites

” Now it’s hard in the barrel” – men’s experiences with penile cancer

Penile cancer is a rare and quite unknown disease whose main method of treatment is surgery. The purpose of the study was to describe men’s experiences with penile cancer, which has not been studied in Finland before. The data were collected in 2019 through individual interviews and letter responses from surgically treated men with penile cancer (n=14). The data were analyzed by content analysis. Men’s resources to cope with the disease were weakened by emotions that burden thoughts, fear of serious disease, feelings of losing manhood, the experience of being alone, worries about coping with family members, and financial worries. On the other hand, they were supported by building their own means of coping, having the ability to speak, having the support of family members, faith in the future, and accepting illness as part of life. The feeling of being cared for was weakened by distrust in healthcare professionals, lack of treatment options, lack of information about the effects of treatment, and organization-centered caring. The feeling of being cared for was reinforced by a sense of security about the caring process, honest information, involvement in decision-making, a meaningful encounter. More information about the disease is needed for both men and healthcare professionals. The information produced by this study can be utilized to develop of the treatment process for penile cancer patients and in the education of healthcare professionals.publishedVersionPeer reviewe

Number of Screening Rounds and Postscreening Prostate Cancer Incidence : Results from the Finnish Section of the European Randomized Study of Screening for Prostate Cancer Study

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