Testicular volume in 268 children and adolescents followed-up for childhood obesity-a retrospective cross-sectional study.

CONTEXT: Prevalence of obesity in childhood has increased over the past few decades. The impact of obesity and of obesity-related metabolic disorders on testicular growth is unknown. OBJECTIVE: To evaluate the impact of obesity, hyperinsulinemia, and insulin resistance on testicular volume (TV) in pre-pubertal (<9 years), peri-pubertal (9-14 years), and post-pubertal (14-16 years) periods. METHODS: We collected data on TV, age, standard deviation score (SDS) of the body mass index (BMI), insulin, and fasting glycemia in 268 children and adolescents followed-up for weight control. RESULTS: Peri-pubertal boys with normal weight had a significantly higher TV compared to those with overweight or obesity. No difference was found in the other age ranges when data were grouped according to BMI. Pre- and post-pubertal children/adolescents with normal insulin levels had significantly higher TV compared to those with hyperinsulinemia. Peri-pubertal boys with hyperinsulinemia had significantly higher TV compared to those with normal insulin levels. Post-pubertal adolescents with insulin resistance had lower TV and peri-pubertal boys had higher TV compared to those without insulin resistance. No difference was found in pre-puberty. CONCLUSIONS: Closer control of the body weight and the associated metabolic alterations in childhood and adolescence may maintain testicular function later in life.

Congenital adrenal hyperplasia, disorders of sex development, and infertility in patients with POR gene pathogenic variants: a systematic review of the literature.

BACKGROUND: P450 oxidoreductase (POR) deficiency (PORD) is characterized by congenital adrenal hyperplasia (CAH) and disorders of sex development (DSD) in both sexes. PORD can also associate with skeletal defects. However, the prevalence of these phenotypes is unknown. AIM: To evaluate the prevalence of CAH, DSD, and infertility of patients with POR gene pathogenic variants by a systematic review of the literature. METHODS: The literature search was performed through PubMed, MEDLINE, Cochrane, Academic One Files, Google Scholar, and Scopus databases. All studies reporting information on CAH, DSD, testicular adrenal rest tumor (TARTs), and fertility in patients with POR gene pathogenic variants were included. Finally, the prevalence of abnormal phenotypes was calculated. RESULTS: Of the 246 articles initially retrieved, only 48 were included for a total of 119 (46 males and 73 females) patients with PORD. We also included the case of a male patient who consulted us for CAH and TARTs but without DSD. This patient, found to be a carrier of combined heterozygous POR mutation, reached fatherhood spontaneously. All the patients found had CAH. The presence of DSD was found in 65.2%, 82.1%, and 82.1% of patients with compound heterozygosity, homozygosity, or monoallelic heterozygous variants, respectively. The prevalence was significantly higher in females than in males. The prevalence of TARTs in patients with PORD is 2.7%. Only 5 women with PORD became pregnant after assisted reproductive techniques and delivered a healthy baby. Except for the recently reported proband, no other studies focused on male infertility in patients with POR gene variants. CONCLUSION: This systematic review of the literature reports the prevalence of CAH, DSD, and TARTs in patients with PORD. The unknown prevalence of POR gene pathogenetic variants and the paucity of studies investigating fertility do not allow us to establish whether PORD is associated with infertility. Further studies on both women and men are needed to clarify this relationship.

The role of thyroid function in female and male infertility: a narrative review.

PURPOSE: We herein aimed to review the new insights into the impact of impaired thyroid function on male and female fertility, spacing from spontaneous pregnancy to ART, with the objective of providing an updated narrative revision of the literature. METHODS: This narrative review was performed for all available prospective, retrospective and review articles, published up to 2021 in PubMed. Data were extracted from the text and from the tables of the manuscript. RESULTS: Thyroid dysfunction is frequently associated with female infertility, whereas its link with male infertility is debated. Female wise, impaired function is detrimental to obstetric and fetal outcomes both in spontaneous pregnancies and in those achieved thanks to assisted reproduction technologies (ART). Furthermore, the reference range of TSH in natural pregnancy and ART procedures has recently become a matter of debate following recent reports in this field. On the other hand, the impact of thyroid function on the male reproductive system is less clear, although a possible role is suggested via modulation of Sertoli and Leydig cells function and spermatogenesis. CONCLUSION: Thyroid function should be carefully monitored in both male and female, in couples seeking spontaneous pregnancy as well as ART, as treatment is generally immediate and likely to improve chances of success.

Pediatric leiomyoma of the glans: a case report.

OBJECTIVE: The leiomyoma is a benign mesenchymal tumor originating from smooth muscle cells therefore its location is ubiquitous. The genitourinary system is not a common site and the glans localization in pediatric age has been described only three times in the literature to date. CASE REPORT: We describe a case of an 11-year-old boy who presented with a painless, non-bleeding or itchy tumor of the glans. The surgical procedure consisted in the total removal of the mass. The histological study showed spindle cells with an eosinophilic cytoplasm while the immunohistochemical studies proved cells stained strongly positive for smooth muscle actin. The clinical follow-up for more than 5 years after surgery demonstrates the absence of recurrence and discomfort for the patient and a good aesthetic appearance of the glans. RESULTS: Leiomyoma is a benign tumor that can originate anywhere there is smooth muscle. However, localization at the level of the glans can be treated with a total excision due to the presence of a cleavage plane with the surrounding tissues that allows a good reconstruction of the glans itself. CONCLUSIONS: We propose that leiomyoma ought to be considered in the differential diagnosis of any glans mass in children.

Leukocytospermia in late adolescents: possible clinical interpretations.

BACKGROUND: No data are currently available on the implication of amicrobial leukocytospermia in male adolescents. Therefore, the primary aim of this study was to evaluate the prevalence of amicrobial leukocytospermia among non-smoker late adolescents who were exposed to other risky lifestyles for the andrological health. The main andrological clinical features of adolescents with leukocytospermia were also reported. METHODS: This is a cross-sectional study carried out in 80 boys. Each adolescent underwent a physical examination, and to the assessment of sperm conventional parameters, seminal leukocytes concentration and immature germ cell evaluation. A possible correlation between seminal leukocytes and immature germ cells and testicular volume (TV) was tested. RESULTS: The adolescents enrolled in this study had 18.0 ± 0.4 (range 18.1-18.9) years. Unprotected sexual intercourse was referred by 38% of them. Sexual dysfunctions were found in 25% and isolated hypoactive sexual desire in 12.5% of boys. Low TV and penile length in flaccidity were found in 44% and 30% of them, respectively. Only 41% had normozoospermia at the sperm analysis, whereas 19% had isolated oligozoospermia, 15% oligo-asthenozoospermia, and 25% oligo-astheno-teratozoospermia. Leukocytospermia occurred in 25% (20 out of 80) of adolescents. No seminal infection was detected in 19% (15 out of 80) of them. Adolescents with leukocytospermia had lower progressive sperm motility, percentage of normal forms, TV, and a higher percentage of immature germ cells compared to those without leukocytospermia. Semen leukocyte concentration correlated negatively with TV and positively with the percentage of immature germ cells in the ejaculate. CONCLUSION: Leukocytospermia, increased immature germ cell number, and low TV identify a distinct phenotype suggestive of testicular tubulopathy. Primary prevention of male infertility and the counselling for andrological risky lifestyles is mandatory and should be started as early as possible.

The European Academy of Andrology (EAA) ultrasound study on healthy, fertile men: Scrotal ultrasound reference ranges and associations with clinical, seminal, and biochemical characteristics.

BACKGROUND: Scrotal color Doppler ultrasound (CDUS) still suffers from lack of standardization. Hence, the European Academy of Andrology (EAA) has promoted a multicenter study to assess the CDUS characteristics of healthy fertile men (HFM) to obtain normative parameters. OBJECTIVES: To report and discuss the scrotal organs CDUS reference ranges and characteristics in HFM and their associations with clinical, seminal, and biochemical parameters. METHODS: A cohort of 248 HFM (35.3 ± 5.9years) was studied, evaluating, on the same day, clinical, biochemical, seminal, and scrotal CDUS following Standard Operating Procedures. RESULTS: The CDUS reference range and characteristics of the scrotal organs of HFM are reported here. CDUS showed a higher accuracy than physical examination in detecting scrotal abnormalities. Prader orchidometer (PO)- and US-measured testicular volume (TV) were closely related. The US-assessed TV with the ellipsoid formula showed the best correlation with the PO-TV. The mean TV of HFM was ~ 17 ml. The lowest reference limit for right and left testis was 12 and 11 ml, thresholds defining testicular hypotrophy. The highest reference limit for epididymal head, tail, and vas deferens was 12, 6, and 4.5 mm, respectively. Mean TV was associated positively with sperm concentration and total count and negatively with gonadotropins levels and pulse pressure. Subjects with testicular inhomogeneity or calcifications showed lower sperm vitality and concentration, respectively, than the rest of the sample. Sperm normal morphology and progressive motility were positively associated with epididymal head size/vascularization and vas deferens size, respectively. Increased epididymis and vas deferens sizes were associated with MAR test positivity. Decreased epididymal tail homogeneity/vascularization were positively associated with waistline, which was negatively associated with intratesticular vascularization. CDUS varicocele was detected in 37.2% of men and was not associated with seminal or hormonal parameters. Scrotal CDUS parameters were not associated with time to pregnancy, number of children, history of miscarriage. CONCLUSIONS: The present findings will help in better understanding male infertility pathophysiology, improving its management.

TSH lowering effects of metformin: a possible mechanism of action.

Preliminary clinical evidence suggests that metformin has TSH lowering effects in patients with T2DM and hypothyroidism or in those with TSH serum levels in the upper normal value. Also, metformin may exert a protective role against thyroid nodules growth in patients without insulin-resistance. The cross-talk between tyrosine kinase receptors and the G protein-coupled receptors (which the TSHR belongs to) has been already shown and IRS1 may represent the hub link between TSHR and IR pathways. By influencing IRS1 phosphorylation pattern, metformin may sensitize TSHR to TSH, thus explaining the findings of clinical studies. However, the existence of this molecular pathway must be confirmed through proper studies and further prospective randomized placebo-controlled studies are needed to confirm this hypothesis.

Management of premature ejaculation: a clinical guideline from the Italian Society of Andrology and Sexual Medicine (SIAMS).

Premature ejaculation (PE) is the most prevalent male sexual dysfunction, and the most recently defined. PE is often mistakenly considered a purely psychosexological symptom by patients: the lacking awareness in regards to the pathophysiology and treatments often lead to resignation from the patients' side, making PE the most underdiagnosed sexual complaint. However, an ever-growing body of evidence supporting several organic factors has been developed in the last decades and several definitions have been suggested to encompass all defining features of PE. In the present document by the Italian Society of Andrology and Sexual Medicine (SIAMS), we propose 33 recommendations concerning the definition, pathophysiology, treatment and management of PE aimed to improve patient care. These evidence-based clinical guidelines provide the necessary up-to-date guidance in the context of PE secondary to organic and psychosexological conditions, such as prostate inflammation, endocrine disorders, and other sexual dysfunctions, and suggest how to associate pharmacotherapies and cognitive-behavioral therapy in a couple-centered approach. New therapeutic options, as well as combination and off-label treatments, are also described.

SARS-CoV-2 infection, male fertility and sperm cryopreservation: a position statement of the Italian Society of Andrology and Sexual Medicine (SIAMS) (Società Italiana di Andrologia e Medicina della Sessualità).

PURPOSE: The recent pandemic of severe acute respiratory syndrome (SARS) due to coronavirus (CoV) 2 (SARS-CoV-2) has raised several concerns in reproductive medicine. The aim of this review is to summarize available evidence providing an official position statement of the Italian Society of Andrology and Sexual Medicine (SIAMS) METHODS: A comprehensive Pubmed, Web of Science, Embase, Medline and Cochrane library search was performed. Due to the limited evidence and the lack of studies, it was not possible to formulate recommendations according to the Oxford 2011 Levels of Evidence criteria. RESULTS: Several molecular characteristics of the SARS-CoV-2 can justify the presence of virus within the testis and possible alterations of spermatogenesis and endocrine function. Orchitis has been reported as a possible complication of SARS-CoV infection, but similar findings have not been reported for SARS-CoV-2. Alternatively, the orchitis could be the result of a vasculitis as COVID-19 has been associated with abnormalities in coagulation and the segmental vascularization of the testis could account for an orchitis-like syndrome. Finally, available data do not support the presence of SARS-CoV-2 in plasma seminal fluid of infected subjects. CONCLUSION: Data derived from other SARS-CoV infections suggest that in patients recovered from COVID-19, especially for those in reproductive age, andrological consultation and evaluation of gonadal function including semen analysis should be suggested. Studies in larger cohorts of currently infected subjects are warranted to confirm (or exclude) the presence of risks for male gametes that are destined either for cryopreservation in liquid nitrogen or for assisted reproduction techniques.

Assessment of sexual and emotional distress in infertile couple: validation of a new specific psychometric tool.

BACKGROUND: The diagnosis of infertility strongly impacts on psychological and sexological couple health. In this regard, some feelings and psychological states were demonstrated in association with reproductive problems. Depression and anxiety are the most common psychopathologies associated with infertility, although also sexuality is strongly involved in infertility conditions. OBJECTIVES: The aim of this study is to develop a tool to probe and assess the emotional aspects, sexuality, and social relationships of the couple seeking medical care for infertility. MATERIALS AND METHODS: A self-reported questionnaire that we will refer to as SEIq (Sexuality and Emotions in Infertility questionnaire) was constructed and developed and, consequently, administered to 162 heterosexual couples (324 subjects) seeking help for reproductive problems. Hence, we performed a specific statistical analysis to assess and validate this new psychometric tool. RESULTS: About 60% of men and women (both partners in 43% of couples) declare that infertility has changed their life (Q10). Moreover, the incidence of sexual disorder declared by the subjects is quite rare in men (10%) but more frequent in women (29%) (p < 0.01). CONCLUSION AND DISCUSSION: The results of this pilot test show that the diagnosis of infertility impacts on the couple relationship affecting the emotional area, interpersonal relationships, and sexual functions of the couples. Moreover, the SEIq appears a valuable tool to coherently probe and relate sexological, psychological, relational, and emotive aspects in partners and couples facing the infertility diagnosis. The explorative factor analysis of SEIq data allows to understand the women, men, and couples' behavior in our sample, individuating a reduced set of factors, prone to an easier evaluation. On the whole, the psychometric evaluation through SEIq might be suitable for the couples during Assisted Reproductive Technologies treatments.

Effects of oral contraceptives on thyroid function and vice versa.

BACKGROUND: Thyroid gland dysfunction represents an epidemiologically relevant disease in the female gender, where treatment with oral contraceptives (OCs) is frequently prescribed. Although OCs are able to impact the thyroid gland function, scanty data have been released on this matter so far. AIM: The aim of this article was to review how hormonal OCs, including estrogen- or progesterone-only containing medications, interact with the hepatic production of thyroid-binding globulin (TBG) and, consequently, their effects on serum levels of thyroxine (T4) and triiodothyronine (T3). We also reviewed the effect of Levo-T4 (LT4) administration in women taking OCs and how they influence the thyroid function in both euthyroid women and in those receiving LT4. REVIEW: The estrogenic component of the pills is capable of increasing various liver proteins, such as TBG, sex hormone-binding protein (SHBG) and coagulation factors. On the other hand, the role of progestogens is to modulate estrogen-dependent effects mainly through their anti-androgenic action. In fact, a reduction in the effects of androgens is useful to keep the thromboembolic and cardiovascular risks low, whereas OCs increase it especially in women with subclinical hypothyroidism or in those treated with LT4. Accordingly, subclinical hypothyroidism is known to be associated with a higher mean platelet volume than normal and this increases cardiovascular risk due to platelet hyperactivity caused by incomplete thrombocytopoietic maturation.

FSH treatment for normogonadotropic male infertility: a synergistic role for metformin?

OBJECTIVE: The aim of this paper is to evaluate the effectiveness of follicle-stimulating hormone (FSH) administration in a cohort of insulin resistant (HOMA>2.5) patients with normogonadotropic idiopathic infertility. PATIENTS AND METHODS: We subdivided patients in two clinical groups basing on the adopted therapeutic scheme: group A (n=44) received 150 units of FSH three times a week for three months (group A); group B (n=35) received 150 units of FSH three times a week for three months and 500 mg of slow-release metformin once a day for three months (group B). We evaluated the post-treatment sperm parameters, sperm parameters normalization rate, spontaneous pregnancy rate, and sperm DNA fragmentation normalization rate. RESULTS: 40% of group A patients and 45% of group B patients became normozoospermic after the treatment, while 30% of group A patients and 32% of group B patients achieved a spontaneous pregnancy. B group patients also obtained higher sperm DNA fragmentation normalization rate (45% vs. 33%, p = 0.03). Compared to group A, group B showed a higher sperm concentration, progressive motility and morphology (p < 0.0001). CONCLUSIONS: The results of this study suggest that the addition of the low-dose slow-release metformin in insulin-resistant patients with normogonadotropic infertility improves the efficacy of FSH therapy.

High rate of detection of ultrasound signs of prostatitis in patients with HPV-DNA persistence on semen: role of ultrasound in HPV-related male accessory gland infection.

BACKGROUND: Papillomavirus (HPV) often occurs in the semen of patients with male accessory gland infection (MAGI). Ultrasound (US) evaluation has been suggested as a promising diagnostic tool for patients with HPV-related MAGI. No data on the spontaneous clearance of HPV-DNA have been reported so far in HPV-related MAGI. PURPOSE: The primary aim of the study was to assess the percentage of early HPV-DNA spontaneous clearance in patients with prostatitis. The secondary aim was to evaluate the frequency of spontaneous clearance of HPV-DNA among patients with prostatitis associated with the presence or absence of US abnormalities. METHODS: Patients with inflammatory MAGI and at least one suspicious criterion for HPV infection underwent semen HPV-DNA detection and prostate US. The presence of HPV-DNA was further investigated after a 6-month-long follow-up. MAIN RESULTS: Eighty patients satisfied the inclusion criteria and were recruited in the study. 69% of patients (55/80) showed HPV-DNA persistence in the semen. Among them, 82% (45/55) was positive for US signs of prostatitis, while they occurred only in 12% (3/25) of those patients with no sign of HPV-DNA persistence (p < 0.001). All patients with persistent high-risk HPV genotype (n = 30) showed at least two US signs of prostatitis. In 73% of patients (22/30), E6 and E7 mRNAs were detected. CONCLUSION: US signs of prostatitis more frequently occurred in patients with evidence of HPV-DNA persistence on semen, especially in those with high-risk genotypes. This highlights the importance of US in the framework of HPV-related MAGI.

Very-low-calorie ketogenic diet (VLCKD) in the management of metabolic diseases: systematic review and consensus statement from the Italian Society of Endocrinology (SIE).

BACKGROUND: Weight loss is a milestone in the prevention of chronic diseases associated with high morbility and mortality in industrialized countries. Very-low calorie ketogenic diets (VLCKDs) are increasingly used in clinical practice for weight loss and management of obesity-related comorbidities. Despite evidence on the clinical benefits of VLCKDs is rapidly emerging, some concern still exists about their potential risks and their use in the long-term, due to paucity of clinical studies. Notably, there is an important lack of guidelines on this topic, and the use and implementation of VLCKDs occurs vastly in the absence of clear evidence-based indications. PURPOSE: We describe here the biochemistry, benefits and risks of VLCKDs, and provide recommendations on the correct use of this therapeutic approach for weight loss and management of metabolic diseases at different stages of life.

Non-hormonal treatment for male infertility: the potential role of Serenoa repens, selenium and lycopene.

OBJECTIVE: Male infertility is a wide spread disease among couple of childbearing age. Spermatozoa are highly susceptible to oxidative stress. Reactive oxygen species (ROS) are capable of damaging the sperm membrane and DNA, inducing lipid peroxidation and sperm DNA fragmentation (SDF). Antioxidant supplementation is currently suggested after a complete diagnostic work-up, as recognized by the Italian Society of Andrology and Sexual Medicine (SIAMS). Indeed, it has been showed to improve sperm quality, DNA fragmentation and pregnancy rate. The administration of Serenoa repens extracts (SrE), including free fatty acids (FFA), methyl and ethyl esters, glycerides, flavonoids and sterols, has never been investigated for male infertility. However, their antioxidant and anti-inflammatory properties provide the rational for their possible effectiveness. The aim of this review was to collect all the evidence supporting the potential usefulness of SrE, alone or in combination with other molecules with proven antioxidant effects, like selenium and lycopene (along with which they are often commercialized), to improve sperm parameters. MATERIALS AND METHODS: A systematic search was performed using Pubmed, MEDLINE, Cochrane, Academic One Files, Google Scholar and Scopus databases. The search strategy included the following key words: Serenoa repens, selenium, lycopene, oligozoospermia, oxidative stress, DNA fragmentation, male infertility, pregnancy rate. CONCLUSIONS: By triggering multiple inflammatory and oxidative pathways, the combined administration of SrE, selenium and lycopene might likely improve the sperm quality. Proper studies are needed to test this hypothesis. Finally, since prostatitis can affect the sperm quality and considering the anti-estrogenic properties of SrE, we speculate about a possible specific indication in those patients with male infertility and "metabolic" prostatitis (where obesity and abnormal androgen/estrogen ratio concomitantly occur).

Benign prostatic hyperplasia and intraprostatic inflammation are associated with liver inflammation: it's time for prevention.

Some evidences have supported the link between benign prostatic hyperplasia (BPH)/lower urinary tract symptoms (LUTS) and inflammation. In this study, we aimed to evaluate the association between prostatic inflammation (PI) and non-alcoholic steatohepatitis (NASH) evaluated by a non-invasive scores in a cohort of patients affected by BPH/LUTS. Between January 2012 and January 2016, we conducted a prospective study in a single academic outpatient clinic on 132 consecutive patients who underwent surgery for lower urinary tract symptoms (LUTS) due to bladder outlet obstruction (BOO). A non-invasive non-alcoholic steatohepatitis score (NASH score) was calculated, and PI was evaluated through the Irani score. Patients with a NASH score > 1.05 had an average larger prostate volume (55 vs. 45 cc, p < 0.05), a greater waist circumference (103 vs. 93.5 cm, p < 0.01), and high values of blood glucose, triglycerides, insulin, and BMI compared to patients without NASH; 36% of patients with an Irani score ≥ 4 had NASH compared to 16.1% of patients who had a NASH score < 1.05 (p < 0.05). We found that non-alcoholic steatohepatitis (NASH ≥ 1.05) was an independent risk factor for Irani score ≥4 (OR: 3.24; p < 0.05) and of prostate volume ≥ 40 cc (OR: 13.99; p < 0.01). LUTS/BPH and NASH can be closely related, underlying common triggers of induction. In particular, inflammation seems to be associated with both conditions and with prostate gland overgrowth. Early identification of this class of patients could play a key role in preventing complications related to disease progression.

Androgen excess and metabolic disorders in women with PCOS: beyond the body mass index.

BACKGROUND: Insulin resistance is a common feature among women with polycystic ovary syndrome (PCOS), especially in those patients with hyperandrogenism and chronic anovulation. PCOS women are at risk for developing metabolic syndrome, impaired glucose tolerance and type II diabetes mellitus (DM II). OBJECTIVE: The aim of this review is to explore the existing knowledge of the interplay between androgen excess, pancreatic ß-cell function, non-alcoholic fatty liver disease (NAFLD), intra-abdominal and subcutaneous (SC) abdominal adipocytes in PCOS, providing a better comprehension of the molecular mechanisms of diabetologic interest. METHODS: A comprehensive MEDLINE® search was performed using relevant key terms for PCOS and DM II. RESULTS: Insulin-induced hyperandrogenism could impair pancreatic ß-cell function, the SC abdominal adipocytes' lipid storage capacity, leading to intra-abdominal adipocyte hypertrophy and lipotoxicity, which in turn promotes insulin resistance, and could enhance NAFLD. Fetal hyperandrogenism exposure prompts to metabolic disorders. Treatment with flutamide showed to partially reverse insulin resistance. CONCLUSIONS: Metabolic impairment seems not to be dependent only on the total fat mass content and body weight in women with PCOS and might be ascribed to the androgen excess.