Fatherhood and sperm DNA damage in testicular cancer patients

Testicular cancer (TC) is one of the most treatable of all malignancies and the management of the quality of life of these patients is increasingly important, especially with regard to their sexuality and fertility. Survivors must overcome anxiety and fears about reduced fertility and possible pregnancy-related risks as well as health effects in offspring. There is thus a growing awareness of the need for reproductive counseling of cancer survivors. Studies found a high level of sperm DNA damage in TC patients in comparison with healthy, fertile controls, but no significant difference between these patients and infertile patients. Sperm DNA alterations due to cancer treatment persist from 2 to 5 years after the end of the treatment and may be influenced by both the type of therapy and the stage of the disease. Population studies reported a slightly reduced overall fertility of TC survivors and a more frequent use of ART than the general population, with a success rate of around 50%. Paternity after a diagnosis of cancer is an important issue and reproductive potential is becoming a major quality of life factor. Sperm chromatin instability associated with genome instability is the most important reproductive side effect related to the malignancy or its treatment. Studies investigating the magnitude of this damage could have a considerable translational importance in the management of cancer patients, as they could identify the time needed for the germ cell line to repair nuclear damage and thus produce gametes with a reduced risk for the offspring

Oncofertility and oncosexualityvin non-Hodgkin lymphoma and testicular cancer survivors

Background – Recently great attention was brought on long-term consequences of antineoplastic treatments, with special focus to reproductive and sexual health. Human testis can be severely damaged by chemo and radiotherapy but, while literature offers plenty of data regarding common malignancies in reproductive age such as testicular cancer and Hodgkin lymphoma, we know little about other neoplasias. Similarly, knowledge of male sexological alterations in cancer derives mainly from prostate cancer, which can hardly be generalized to other pathologies. Since little is known about Non-Hodgkin Lymphoma survivors’ fertility and there is incomplete information for Testicular Cancer survivors sexological counselling, the aim of this work was: (Study 1) to evaluate semen quality and fertility status before and after treatments of patients who underwent semen cryopreservation after the diagnosis of NHL; (Study 2) to evaluate the effect of TC after orchiectomy and provide a complete follow up in order to highlight possible post treatment short and long-term sexological alterations. Material and Methods – Patients attending the Laboratory of Seminology – Sperm Bank “Loredana Gandini” for sperm cryopreservation were selected for both studies after a careful medical history collection. Exclusion criteria were any comorbidity and any other known factor interfering with sperm parameters. For Study 1, 224 patients (mean age 32.7 ± 8.6 years) with diagnosis of Non-Hodgkin Lymphoma were selected, and semen analysis was performed at baseline (T0) and at least one follow up visit at 12 (T1), 24 (T2) or more than 24 months (T3; median 52 months); fertility status was ascertained with a dedicated questionnaire. For Study 2, 241 sexually active consecutive patients (mean age 31.3 ± 6.9 years) with recent diagnosis of testicular cancer were selected. IIEF questionnaire was completed for sexual function evaluation at baseline post-orchiectomy (T0) and at least one follow up control at 6 (T1), 12 (T2), 18 (T3), 24 (T4), 48 months (T5) and after 5 years (T6, median 96 months) after chemotherapy; 223 healthy controls were also recruited for IIEF scores comparisons. Moreover, both TC patient and controls underwent blood hormones analysis (FSH, LH, total Testosterone). Results – Study 1 – Non-Hodgkin Lymphoma patients showed pre-therapy mean semen parameters within WHO 2010 normal range. Longitudinal post-therapy evaluation showed that sperm parameters significantly worsened at T1 compared to T0 (p < 0.001). Total sperm number at T2 remained significantly worse than T0 (p = 0.040) whereas it returned to values comparable to baseline at T3. Progressive motility and abnormal forms returned comparable to baseline at T2. 13.7% of survivors were azoospermic at T3. Permanent spermatogenesis impairment was associated with pelvic radiotherapy (OR 14.54, 95% CI 1.90 – 111.28) and treatment intensification for bone marrow transplant (33% azoospermia at T3). Regarding fertility, 14/22 pts who desired children were able to achieve fatherhood either through natural fertility (2 pts) or through ART (12 pts). Study 2 – Baseline prevalence of erectile dysfunction is 37.8% in TC pts vs 9.9% in healthy controls (p < 0.001). IIEF-15 baseline scores were significantly worse in TC group compared to controls (p < 0.001), with the exception of the orgasmic function domain (p = 0.334). Post-chemotherapy evaluation showed that erectile function improves significantly at T2 (T0 vs T2; p < 0.001) with further improvements at T3 and T4 compared to baseline (T0 vs T3: p = 0.014; T0 vs T4: p = 0.002). However, we detected an increase in erectile dysfunction prevalence at T5 with a significant reduction of erectile function domain scores, which seemed to persist at T6. Compared to controls, erectile function remains significantly worse at T1 then return comparable to healthy controls. Sexual desire, intercourse satisfaction and general satisfaction showed trends of improvement from baseline but remained significantly worse compared to controls for the whole duration of the study. No significant variation of the orgasmic function was detected against both baseline values and controls. The evaluation of sexual hormones revealed that prevalence of biochemical hypogonadism was 5.4% in the TC group. There were no hypogonadal patients in CTR group. Total testosterone in post-orchidectomy patients (T0) is significantly lower than controls (p < 0.001), but no significant variation was detected at T1 and T2. Finally, no significant correlation was detected between total testosterone levels and scores of any IIEF15 domain. Discussion – Study 1 demonstrates that Non-Hodgkin Lymphoma survivors undergoing intensive treatments and pelvic radiotherapy risk severe and permanent impairment of spermatogenesis. However, routine NHL chemotherapy regimens are compatible with spermatogenesis recovery after 2 years from the end of treatments and, while average sperm parameters may not fully return to pretreatment values, more than a half (63%) of patient who actively desire fatherhood can conceive either through natural conception or ART. Similarly, for Testicular Cancer survivors we confirm the presence of erectile dysfunction and impairment of sexual desire and satisfaction compared to a healthy population with improvements expected within one year from the end of the treatments. Absence of clear correlations with biochemical hypogonadism suggests that psychological burden following cancer diagnosis and treatments may play an important role. Information from these studies is of extreme importance since it will allow to increase the effectiveness of patients’ counseling interventions in an oncofertility service

Terapia della eiaculazione precoce

L’eiaculazione precoce (EP) è il più frequente disturbo sessuale riferito nel maschio, ed è a tutti gli effetti un sintomo auto-identificato, auto-riportato e auto-valutato da chi ne soffre. Attualmente la International Society for Sexual Medicine ha definito l’EP come un’eiaculazione che avviene sempre o quasi sempre entro 1 minuto (EP life-long) o 3 minuti (EP acquisita) dalla penetrazione, con incapacità di ritardare l’eiaculazione e conseguenze negative sul piano personale come frustrazione, sofferenza e/o condotte di rifiuto dell’atto sessuale [1]. Dal punto di vista tassonomico, possiamo riconoscere forme assolute e relazionali, organiche e psicogene (o meglio non-organiche), acquisite o life-long. Il corretto approccio all’EP consiste nel non considerarla esclusivamente una patologia a sé stante, ma un possibile sintomo di una condizione latent

Androgenetic alopecia: a review

Purpose Androgenetic alopecia, commonly known as male pattern baldness, is the most common type of progressive hair loss disorder in men. The aim of this paper is to review recent advances in understanding the pathophysiology and molecular mechanism of androgenetic alopecia. Methods Using the PubMed database, we conducted a systematic review of the literature, selecting studies pub- lished from 1916 to 2016. Results The occurrence and development of androgenetic alopecia depends on the interaction of endocrine factors and genetic predisposition. Androgenetic alopecia is character- ized by progressive hair follicular miniaturization, caused by the actions of androgens on the epithelial cells of genetically susceptible hair follicles in androgen-dependent areas. Although the exact pathogenesis of androgenetic alopecia remains to be clari fi ed, research has shown that it is a polygenetic condition. Numerous studies have unequi- vocally identi fi ed two major genetic risk loci for androge- netic alopecia, on the X-chromosome AR ⁄ EDA2R locus and the chromosome 20p11 locus. Conclusions Candidate gene and genome-wide association studies have reported that single-nucleotide polymorphisms at different genomic loci are associated with androgenetic alopecia development. A number of genes determine the predisposition for androgenetic alopecia in a polygenic fashion. However, further studies are needed before the specific genetic factors of this polygenic condition can be fully explaine

Ambulatorio Oncofertilità: gestione clinica del paziente della Banca del Seme

L’oncofertilità rappresenta un nuovo campo della medicina che comprende una rete integrata di specialisti focalizzati a sviluppare metodi e strategie in grado di preservare e/o ripristinare la potenzialità riproduttiva in soggetti che hanno avuto una diagnosi di cancro. L’oncofertilità prevede quindi l’integrazione di una serie di discipline quali l’oncologia, la medicina della riproduzione, la sessuologia clinica, la pediatria e la bioetica. Appaiono pertanto superati i tempi in cui l’unico obiettivo era la cura del tumore senza badare alle ricadute su fertilità, sessualità e, in definitiva, sulla qualità di vita del paziente. L’oncofertilità rappresenta lo sforzo degli specialisti in tale direzione

Ciproterone acetato e meningiomi: lo stato dell’arte

L’impiego di ciproterone acetato è stato associato all’insorgenza di meningiomi nella popolazione generale e in quella transgender. Il maggiore rischio sembra correlato alla dose impiegata e al tempo in cui si segue la terapia e più alta è l’incidenza di meningiomi nella popolazione transgender femminile che non nella popolazione generale. Massima attenzione deve essere posta dal clinico a eventuali sintomi presenti e, per minimizzare tale rischio, scegliere il minor dosaggio efficace possibile

Diode laser surgery in the treatment of oral proliferative verrucous leukoplakia associated with HPV-16 infection

Proliferative verrucous leukoplakia (PVL) is an oral potentially malignant disorder, characterized by multifocal expression, progressive clinical evolution, and a high rate of malignant transformation. Evidence-based information regarding optimal PVL management is lacking, due to the paucity of data. The present report describes a case of PVL associated with HPV-16 infection and epithelial dysplasia treated by diode laser surgery, and the outcome of disease clinical remission over a 2-year follow-up period

L-carnitine fumarate, L-acetyl-carnitine and other components in male infertility: A pilot study of nutraceutics on sperm motility

The aim of this study was to evaluate any possible effect a combination of L-carnitine, fumarate, acetyl-Lcarnitine, fructose, citric acid, selenium, coenzime Q10, vitamin C, zinc, folic acid and vitamin B12 (Proxeed®) on sperm motility in a group of patients with unexplained asthenozoospermia. Thirty two patients received 1 sachet/day of Proxeed® for three months. Sperm parameters were studied before, during and after this treatment. Motility was also studied by the means of a computerized analysis (CASA system). The results of this study indicate that Proxeed® is able to increase sperm motility, both in a quantitative and qualitative manner. We conclude that oral administration of Proxeed® may improve sperm quality, at least in patients with idiopathic asthenozoospermia

Effects of endocrine disruptors on fetal testis development, male puberty, and transition age

Purpose Endocrine disruptors (EDs) are exogenous substances able to impair endocrine system; consequently, they may cause numerous adverse effects. Over the last years, particular focus has been given to their harmful effects on reproductive system, but very little is known, especially in males. The aim of this review is to discuss the detrimental effects of EDs exposure on fetal testis development, male puberty, and transition age. Methods A search for the existing literature focusing on the impact of EDs on fetal testis development, male puberty, andrological parameters (anogenital distance, penile length, and testicular volume), and testicular cancer with particular regard to pubertal age provided the most current information available for this review. Human evidence-based reports were given priority over animal and in vitro experimental results. Given the paucity of available articles on this subject, all resources were given careful consideration. Results Information about the consequences associated with EDs exposure in the current literature is limited and often conflicting, due to the scarcity of human studies and their heterogeneity. Conclusions We conclude that current evidence does not clarify the impact of EDs on human male reproductive health, although severe harmful effects had been reported in animals. Despite controversial results, overall conclusion points toward a positive association between exposure to EDs and reproductive system damage. Further long-term studies performed on wide number of subjects are necessary in order to identify damaging compounds and remove them from the environment

Long-Term Follow Up of the Erectile Function of Testicular Cancer Survivors

The diagnosis of testicular cancer (TC) can have a considerable and persistent impact on a patient's sexuality, especially given its location. The high prevalence of TC in young adults, and the good prognosis, explain the great interest in sexual dysfunction and its influence on post-treatment quality of life. The aim of this study was to evaluate the impact of the diagnosis and treatments (inguinal orchiectomy and chemotherapy) on sex life. For this purpose, we recruited 241 TC patients attending the Laboratory of Seminology–Sperm Bank “Loredana Gandini” for sperm cryopreservation (mean age 31.3 ± 6.9 years) and 223 cancer-free healthy men who were undergoing andrological screening (mean age 32.0 ± 7.7 years). The IIEF-15 questionnaire was administered at the baseline (post-orchiectomy, pre-chemotherapy—T0) and at 6 (T1), 12 (T2), 18 (T3), 24 (T4), 48 months (T5) and &gt;5 years (T6, median 96 months) after chemotherapy to all patients, to evaluate the following domains: erectile function (EF), orgasmic function (OF), sexual desire (SD), intercourse satisfaction (IS) and overall satisfaction (OS). A subgroup of patients also underwent blood sex hormone analysis for further correlations with IIEF scores. At the baseline, 37.7% of patients had erectile dysfunction (EF score &lt;26) and all IIEF domains except OF showed significantly lower scores than in controls (p &lt; 0.001). Long-term follow-up revealed persistently lower scores in TC survivors than in controls for EF, SD, IS, and OS. Furthermore, most IIEF domains did not improve significantly in TC patients during the duration of the follow-up, with the exception of EF, which showed a significant improvement from T2. Finally, no significant correlation was found between hormone levels (gonadotropin and testosterone) and IIEF-15 scores. In conclusion, TC and its treatment have a significant effect on sexuality. The absence of a clear correlation with biochemical hypogonadism suggests that this may to a large extent be due to the surgical procedure itself, or to the psychological impact of a cancer diagnosis