Testosterone has been used therapeutically for over 70 years in men suffering from the symptoms of testosterone deficiency (TD, hypogonadism), and a strong body of evidence suggests testosterone treatment is safe and efficacious in patients for whom it is indicated. Additionally, there exists sufficient data to recognize male hypogonadism as a risk factor for cardiovascular disease. Four recently published studies suggested that testosterone therapy is associated with myocardial infarction, stroke, and death. Although these studies are afflicted with poor study design, flawed data analysis and misinterpretations, and received nearly unanimous rejection by experts in the field, the mainstream media has catapulted the studies into the public spotlight with sensationalist headlines, creating a hysteria that has had far-reaching and dangerous implications for patients and physicians. The media-driven hysteria has created an environment in which pharmaceutical companies are being sued, physicians are withholding treatment from men suffering from testosterone deficiency, and the United States Food and Drug Administration has been petitioned to place a black box warning on testosterone products. The imbalanced media coverage has crossed a grave ethical line by interfering in the patient-physician relationship to the extent that patients are being harmed.

Background: Prolactin-secreting tumours( prolactinomas) are the commonest type of pituitary tumour, accounting for approximately 30 to 40 %% of all pituitary adenomas. Although there is ample epidemiologic and clinic data from Industrialised countries there remains sparse data from Africa. Specifically, the clinical presentation, and hormonal deficiencies and treatment outcomes in the South Africa have not been described. Methods: A retrospective study of all patients with a diagnosis of prolactinoma attending the Endocrine and Pituitary Clinics at Groote Schuur Hospital over a 12-month period, between March 2019-March 2020. Patients folders were reviewed to retrieve the following information: demographic data, clinical presentation, clinical signs, prolactinoma phenotype, hormonal deficiencies, treatment modalities and clinical outcomes. Results: Over a 12-month period 52 patients were included in this study, females 73% (n=38), mean age of all participants was 46.1 ± 14.6 years. A macroprolactinoma was present in 67.3% (n=35) of patients and 32.7% (n=17) of patients had a microprolactinoma. In the macroprolactinoma group: the common presenting symptoms were headache 88.6% (n=33), altered vision 40% (n=14) and , in females, amenorrhoea 63.6% (n=14) but a cranial nerve palsy 17.1% (n=6) and apoplexy 5.7% (n=2) were uncommon. . In the microprolactinoma group the common presenting symptoms included amenorrhoea 75% (n=12), galactorrhoea 70.6% (n=12), headache 64.7% (n=11). On presentation the majority of patients with a macroadenoma had at least one hormonal abnormality with hypogonadism 73.1% (n=19) being most common, followed by hypothyroidism 53.8% (n=14) and hypoadrenalism 30% (n=8). Over 50% of patients with a giant adenoma had panhypopituitarism with hypogonadism in 100%, hypothyroidism in 77.8% (n=7) and hypoadrenalism in 66.7% (n=6). Hormonal deficiencies in the microadenoma group on presentation included hypogonadism 64.7% (n=11), hypothyroidism 35.3 (n=6) and one patient had hypoadrenalism. All patients received medical treatment, however, in the macroadenoma group 4 patients required surgical debulking of the tumour, 3 patients required a ventriculo-peritoneal (VP) shunt for hydrocephalus and 2 patients required radiation. After a median follow-up of 46.5 months, the median prolactin level decreased from 322.5 ug/l (94.0-4282.0) at presentation to 17.5 ug/l (8.6-82.5) at follow-up. In parallel there was a reduction of 12.2 ±9.7 mm in tumour size after a mean of 59.8 ±53.3 months. There was resolution of hypogonadism in 56.4% (n=22), of hypothyroidism in 2.7% (n=2) and hypoadrenalism only resolved in 1 patient. Conclusions: Most patients with a prolactinoma are symptomatic and have at least one hormone deficiency on presentation. With medical management most patients experienced a reduction in prolactin levels and tumour size. . This was associated with the resolution of hypogonadism in the majority, however, hypothyroidism and hypoadrenalism are unlikely to resolve despite a reduction in tumour size.

Thesis (Ph. D.)--Ohio State University, 2008. / Title from first page of PDF file.

Millions of men, as a result of the natural aging process, injury, illness, and medical therapies, experience a decline in testosterone levels that necessitate a need for testosterone supplementation therapy (TST). The signs and symptoms of testosterone decline may occur gradually, and low testosterone levels may be misdiagnosed as other medical conditions. Over the past two decades, there has been an increase in testing of testosterone levels and the use of TST. With so many men now on TST, it is essential for health care professionals to know the signs and symptoms, the causes of testosterone decline, how testosterone deficiency is diagnosed, what pathological changes are associated with testosterone decline, and the benefits and risks of TST. In addition, health care providers need to be aware of the various forms of testosterone available as well as the advantages and disadvantages of each. This article provides a brief overview of testosterone deficiency, TST treatment options and guidelines, and the risks and benefits associated with of TST.

Late-onset hypogonadism (LOH) is a pathological disorder that develops in males over the age of 40 and is diagnosed upon strict criteria that requires that the individual have total serum testosterone (T) below the normal limits as well as three symptoms of sexual dysfunction. Recommended therapy for young males with hypogonadism is testosterone replacement therapy (TRT). Treatment of LOH with TRT has increased significantly in the past several years, but studies showing adverse risks associated with TRT have led to a growing concern about the safety of such a treatment. This systematic review will give an overview of the pathology of LOH, clinical diagnosis of LOH, and comorbidities associated with this dysfunction. Benefits of TRT in elderly hypogonadal men have included improvement in cardiovascular function, reduced all-cause mortality, increased sexual function, increased bone mineral density, improved body composition, increased muscle strength, improved quality of life, and improvement in metabolic parameters. However, risks associated with TRT have included infertility, worsening lipid panel parameters, polycythemia, increased risk of prostate cancer, and in some cases, increased risk of adverse cardiovascular events.

No description available.

O Hipogonadismo hipogonadotrófico isolado (HHI) congênito é uma síndrome clínica rara causada por defeito na produção ou secreção do hormônio liberador de gonadotrofinas (GnRH) pelo hipotálamo ou por resistência hipofisária à ação do GnRH. O HHI é mais prevalente em homens e cerca de 50% a 60% dos indivíduos afetados apresentam anosmia ou hiposmia associada, caracterizando a síndrome de Kallmann. Diversos genes já foram associados à patogênese do HHI congênito, porém, a maioria dos casos ainda permanece sem diagnóstico molecular definido. Até recentemente, a identificação das causas genéticas dos pacientes com HHI era realizada por sequenciamento de genes candidatos, empregando a técnica de Sanger. No entanto, com o número crescente de genes descritos nos últimos anos, esse processo vem se tornando impraticável. Novas metodologias de sequenciamento (sequenciamento paralelo em larga escala) foram desenvolvidas permitindo a genotipagem simultânea de diversas regiões, com maior velocidade e menor custo relativo. O atual projeto foi desenvolvido com o objetivo de rastrear genes candidatos em pacientes portadores de HHI congênito utilizando-se o sequenciamento paralelo em larga escala, visando ampliar o conhecimento genético do HHI. Realizamos o sequenciamento paralelo em larga escala (SPLE) de 130 pacientes com HHI congênito utilizando um painel contendo 36 genes relacionados ao HHI. Inicialmente, identificamos 104 variantes, potencialmente patogênicas em 77 pacientes (59,2%). Após a filtragem inicial, foi realizada uma análise individualizada de cada variante e com isso foram mantidos 41 (31,5%) pacientes com variantes classificadas como patogênicas ou provavelmente patogênicas. Os genes KAL1, FGFR1, CHD7 e GNRHR foram os mais frequentemente afetados. Esses resultados confirmam a importância dos genes classicamente associados ao HHI congênito. Destaca-se a alta prevalência de variantes no CHD7 (10,8%), gene bastante extenso, levando à dificuldade técnica de sequenciá-lo pelos métodos tradicionais, até então sem estudos nessa coorte. O CHD7 é um gene originalmente associado à complexa síndrome de CHARGE, porém, nos últimos anos vem sendo cada vez mais associados ao HHI congênito. Dentre os resultados, ressaltamos a identificação de uma mutação inédita no gene GNRH1, causa rara de HHI, e a identificação de variantes deletérias no gene IGSF10, recentemente descrito associado ao atraso puberal, mas sem papel claro no fenótipo de HHI, em dois pacientes que tiveram reversibilidade do hipogonadismo. Variantes provavelmente patogênicas em genes com poucas descrições ou até mesmo sem relatos de associação ao fenótipo de HHI (SPRY4, FLRT3, IGSF1, NSMF, SOX10 e OTX2) também foram identificadas nessa coorte, ampliando nosso conhecimento genético do HHI. A oligogenicidade, previamente descrita com prevalência de 2,5% a 7%, em nosso estudo esteve presente em 22% dos pacientes, demonstrando uma ampliação das descrições de oligogenicidade quando comparados aos estudos prévios utilizando somente a técnica de Sanger. A nova técnica de sequenciamento genético (SPLE), utilizada em nosso estudo, foi capaz de ampliar de 22% para 31,5% (41 em 130 pacientes) a porcentagem de pacientes com diagnóstico molecular definido, quando comparado aos dados prévios utilizando a técnica de Sanger, mostrando-se rápida, confiável e eficaz / Congenital isolated hypogonadotropic hypogonadism (IHH) is a rare condition caused by GnRH deficiency, due to defective hypothalamic gonadotropin-releasing hormone (GnRH) production or secretion, or by pituitary resistance to the GnRH action. Congenital IHH is more prevalent in men and about 50% to 60% of affected individuals present with associated anosmia or hyposmia, characterizing Kallmann\'s syndrome. Several genes have already been associated with the pathogenesis of congenital IHH, but most cases still remain without a molecular diagnosis. Until recently, identification of the genetic causes of IHH was performed by sequencing candidate genes using the Sanger technique. However, with the growing number of genes and the genetic complexity of IHH, it has become almost impossible to keep the screening of all candidate genes updated using the traditional techniques. The advent of next-generation sequencing (NGS) has allowed the simultaneous genotyping of several regions, faster and with lower relative cost. The present project was developed with the objective of tracking candidate genes in patients with congenital IHH using large-scale parallel sequencing, in aiming to increase the genetic knowledge of this rare condition. A total of 130 unrelated patients with IHH was studied by targeted NGS, using a panel containing 36 IHH associated genes. Initially, 104 potentially pathogenic variants were identified in 77 patients (59.2%). However, after an individualized analysis of each variant, the number of patients considered to carry pathogenic or probably pathogenic variants dropped to 41 (31.5%). The genes KAL1, FGFR1, CHD7 and GNRHR were the most frequently affected and these results confirm the importance of genes classically associated with IHH. It is noteworthy the high prevalence of variants in CHD7 (10.8%), a rather extensive gene, leading to technical difficulty of sequencing by traditional methods, which had not been studied in this cohort. CHD7 is the causative gene of CHARGE syndrome, however it has been recently identified in a growing number of congenital IHH patients with or without additional features of the syndrome. Among the results, we emphasize a novel mutation in the GNRH1 gene, a rare cause of IHH, and the identification of deleterious variants in the IGSF10 gene, recently associated with pubertal delay but without a clear role in the IHH phenotype, in two patients with reversible hypogonadism. Probably pathogenic variants in genes with few descriptions or even no reports of association with the IHH phenotype (SPRY4, FLRT3, IGSF1, NSMF, SOX10 and OTX2) were also identified in this cohort, increasing the genetic knowledge of IHH. Oligogenicity, previously described with a prevalence of 2.5% to 7%, was observed in 22% of our patients, demonstrating an increase in oligogenicity cases when compared to previous studies using only the Sanger sequencing. In conclusion, targeted NGS was able to increase the percentage of patients with molecular diagnosis from 22% to 31.5% in our cohort when compared to the previous data using the Sanger sequencing, and has been shown to be a fast, reliable and effective tool in the molecular diagnosis of congenital IHH

O Hipogonadismo hipogonadotrófico isolado (HHI) congênito é uma síndrome clínica rara causada por defeito na produção ou secreção do hormônio liberador de gonadotrofinas (GnRH) pelo hipotálamo ou por resistência hipofisária à ação do GnRH. O HHI é mais prevalente em homens e cerca de 50% a 60% dos indivíduos afetados apresentam anosmia ou hiposmia associada, caracterizando a síndrome de Kallmann. Diversos genes já foram associados à patogênese do HHI congênito, porém, a maioria dos casos ainda permanece sem diagnóstico molecular definido. Até recentemente, a identificação das causas genéticas dos pacientes com HHI era realizada por sequenciamento de genes candidatos, empregando a técnica de Sanger. No entanto, com o número crescente de genes descritos nos últimos anos, esse processo vem se tornando impraticável. Novas metodologias de sequenciamento (sequenciamento paralelo em larga escala) foram desenvolvidas permitindo a genotipagem simultânea de diversas regiões, com maior velocidade e menor custo relativo. O atual projeto foi desenvolvido com o objetivo de rastrear genes candidatos em pacientes portadores de HHI congênito utilizando-se o sequenciamento paralelo em larga escala, visando ampliar o conhecimento genético do HHI. Realizamos o sequenciamento paralelo em larga escala (SPLE) de 130 pacientes com HHI congênito utilizando um painel contendo 36 genes relacionados ao HHI. Inicialmente, identificamos 104 variantes, potencialmente patogênicas em 77 pacientes (59,2%). Após a filtragem inicial, foi realizada uma análise individualizada de cada variante e com isso foram mantidos 41 (31,5%) pacientes com variantes classificadas como patogênicas ou provavelmente patogênicas. Os genes KAL1, FGFR1, CHD7 e GNRHR foram os mais frequentemente afetados. Esses resultados confirmam a importância dos genes classicamente associados ao HHI congênito. Destaca-se a alta prevalência de variantes no CHD7 (10,8%), gene bastante extenso, levando à dificuldade técnica de sequenciá-lo pelos métodos tradicionais, até então sem estudos nessa coorte. O CHD7 é um gene originalmente associado à complexa síndrome de CHARGE, porém, nos últimos anos vem sendo cada vez mais associados ao HHI congênito. Dentre os resultados, ressaltamos a identificação de uma mutação inédita no gene GNRH1, causa rara de HHI, e a identificação de variantes deletérias no gene IGSF10, recentemente descrito associado ao atraso puberal, mas sem papel claro no fenótipo de HHI, em dois pacientes que tiveram reversibilidade do hipogonadismo. Variantes provavelmente patogênicas em genes com poucas descrições ou até mesmo sem relatos de associação ao fenótipo de HHI (SPRY4, FLRT3, IGSF1, NSMF, SOX10 e OTX2) também foram identificadas nessa coorte, ampliando nosso conhecimento genético do HHI. A oligogenicidade, previamente descrita com prevalência de 2,5% a 7%, em nosso estudo esteve presente em 22% dos pacientes, demonstrando uma ampliação das descrições de oligogenicidade quando comparados aos estudos prévios utilizando somente a técnica de Sanger. A nova técnica de sequenciamento genético (SPLE), utilizada em nosso estudo, foi capaz de ampliar de 22% para 31,5% (41 em 130 pacientes) a porcentagem de pacientes com diagnóstico molecular definido, quando comparado aos dados prévios utilizando a técnica de Sanger, mostrando-se rápida, confiável e eficaz / Congenital isolated hypogonadotropic hypogonadism (IHH) is a rare condition caused by GnRH deficiency, due to defective hypothalamic gonadotropin-releasing hormone (GnRH) production or secretion, or by pituitary resistance to the GnRH action. Congenital IHH is more prevalent in men and about 50% to 60% of affected individuals present with associated anosmia or hyposmia, characterizing Kallmann\'s syndrome. Several genes have already been associated with the pathogenesis of congenital IHH, but most cases still remain without a molecular diagnosis. Until recently, identification of the genetic causes of IHH was performed by sequencing candidate genes using the Sanger technique. However, with the growing number of genes and the genetic complexity of IHH, it has become almost impossible to keep the screening of all candidate genes updated using the traditional techniques. The advent of next-generation sequencing (NGS) has allowed the simultaneous genotyping of several regions, faster and with lower relative cost. The present project was developed with the objective of tracking candidate genes in patients with congenital IHH using large-scale parallel sequencing, in aiming to increase the genetic knowledge of this rare condition. A total of 130 unrelated patients with IHH was studied by targeted NGS, using a panel containing 36 IHH associated genes. Initially, 104 potentially pathogenic variants were identified in 77 patients (59.2%). However, after an individualized analysis of each variant, the number of patients considered to carry pathogenic or probably pathogenic variants dropped to 41 (31.5%). The genes KAL1, FGFR1, CHD7 and GNRHR were the most frequently affected and these results confirm the importance of genes classically associated with IHH. It is noteworthy the high prevalence of variants in CHD7 (10.8%), a rather extensive gene, leading to technical difficulty of sequencing by traditional methods, which had not been studied in this cohort. CHD7 is the causative gene of CHARGE syndrome, however it has been recently identified in a growing number of congenital IHH patients with or without additional features of the syndrome. Among the results, we emphasize a novel mutation in the GNRH1 gene, a rare cause of IHH, and the identification of deleterious variants in the IGSF10 gene, recently associated with pubertal delay but without a clear role in the IHH phenotype, in two patients with reversible hypogonadism. Probably pathogenic variants in genes with few descriptions or even no reports of association with the IHH phenotype (SPRY4, FLRT3, IGSF1, NSMF, SOX10 and OTX2) were also identified in this cohort, increasing the genetic knowledge of IHH. Oligogenicity, previously described with a prevalence of 2.5% to 7%, was observed in 22% of our patients, demonstrating an increase in oligogenicity cases when compared to previous studies using only the Sanger sequencing. In conclusion, targeted NGS was able to increase the percentage of patients with molecular diagnosis from 22% to 31.5% in our cohort when compared to the previous data using the Sanger sequencing, and has been shown to be a fast, reliable and effective tool in the molecular diagnosis of congenital IHH

Στην εργασία διερευνήθηκε πώς η έλλειψη του υποδοχέα της χαμηλής πυκνότητας λιποπρωτεϊνών (Ldlr-/-) τροποποιεί τις επιδράσεις της τεστοστερόνης στην παχυσαρκία και στις συναφείς μεταβολικές δυσλειτουργίες. ‘Εμμεση θερμιδομετρική ανάλυση έδειξε πως ο υπογοναδισμός σε μυς με έλλειψη του Ldlr συσχετίζεται με μείωση του βάρους του σώματος, και παράλληλα, αυξημένο μεταβολικό ρυθμό. Η έκφραση του κυτοχρώματος C και της UCP1 των μιτοχονδρίων ήταν αυξημένη στο λευκό λιπώδη ιστό, υποδεικνύοντας ότι η αυξημένη μεταβολική δραστηριότητα αντανακλά σε αυξημένο αριθμό μιτοχονδρίων με επίσης αυξημένη ικανότητα θερμογένεσης. Η αποκατάσταση της τεστοστερόνης σε ορχεκτομηθέντες μυς Ldlr-/- για διάστημα οχτώ εβδομάδων οδήγησε σε παχυσαρκία επαγόμενη από δίαιτα, υποδεικνύοντας την άμεση σχέση της τεστοστερόνης με τον παρατηρούμενο φαινότυπο. Η θεραπεία ψευδοχειρουργημένων μυών Ldlr-/- με εξεμεστάνη, έναν αναστολέα της αρωματάσης, για οχτώ εβδομάδες, έδειξε πως η αντίσταση στην παχυσαρκία των ορχεκτομηθέντων Ldlr-/- μυών είναι ανεξάρτητη από την δράση των οιστρογόνων. Συμπερασματικά, η εργασία δείχνει πως ο LDLr συσχετίζεται με μεταβολικές αλλαγές σε υπογοναδικούς μυς, οι οποίες δεν οφείλονται σε οιστρογονικές δράσεις, αλλά.στην ανεπάρκεια τεστοστερόνης. / In this work we investigated how low-density lipoprotein receptor deficiency (Ldlr-/-) modulates the effects of testosterone on obesity and related metabolic disorders. Indirect calorimetric analysis indicated that hypogonadism in Ldlr deficient mice correlates with a decrease in body weight and an increased metabolic rate. The expression of cytochrome C and UCP1 in mitochondria was increased in white adipose tissue, indicating that the increased metabolic activity reflects an increased number of mitochondria with an increased ability for thermogenesis. Testosterone replacement in orchectomized Ldlr-/- mice for a period of eight weeks led to diet induced obesity, suggesting a direct relationship between testosterone and the observed phenotype. Treatment of sham-operated Ldlr-/- mice with exemestane, an aromatase inhibitor, for eight weeks, showed that the obesity of orchectomized Ldlr-/- mice is independent of estrogen effects. In conclusion, this work demonstrates how the LDLr is associated with metabolic changes in hypogonadal mice which are not related to estrogenic effects but to testosterone deficiency.

Epidemiologiniais tyrimais nustatytos androgenų sąsajos su įvairiais metaboliniais veiksniais bei širdies ir kraujagyslių ligų rizika paskatino susidomėjimą naujais vyrų reprodukcinės sveikatos aspektais. Iki šiol Lietuvoje nebuvo nustatytos normalios vyrų androgenų koncen¬tracijos ribos, nebuvo atlikta reprodukcinės sveikatos, antropometrinių ir metabolinių rodiklių sąsajų analizės tyrimų. Pasaulyje iki šiol trūksta nuoseklios informacijos apie metabolinių ir antropometrinių rodiklių ryšius su lytiniais hormonais, ypač homogeniškose tiriamųjų imtyse. Trūksta informacijos apie androgenų sąsajas su pažintinėmis funkcijomis, emocine būkle ir gyvenimo kokybės vertinimu. Daugelis tyrimų, kuriais vertintas pakaitinio gydymo testosteronu efektyvumas – trumpalaikiai, juose dau¬giausiai dėmesio skirta struktūriniams, o ne funkciniams rodikliams. Šiuo tyrimu siekta aprašyti jaunų bei vidutinio amžiaus vyrų reprodukcinės sveikatos sąsajas su antro¬pometrijos, metabolinės bei psichologinės būklės rodikliais. Tai iki šiol didžiausia savo apimtimi Lietuvos vyrų androgenų sąsajų analizė. Šiuo darbu siekiama sistemingai atsakyti į iškeltus aktualius klau¬simus, nustatyti normalios ir optimalios androgenų koncentracijos ribas, homogeniškose amžiumi tiriamųjų grupėse įvertinti šių hormonų koncen¬tracijos grupių sąsajas su kūno sudėties ir medžiagų apykaitos rodikliais bei nustatyti, kokius sergančiųjų androgenų nepakankamumu funkcinius pokyčius sąlygoja ilgalaikis optimalus pakaitinis... [toliau žr. visą tekstą] / Associations between androgens and various metabolic factors, as well as cardiovascular morbidity shown in recent epidemiological studies sparked interest in new aspects of male reproductive health. Reference values for normal androgen levels in Lithuanian population have not yet been established and no relationship studies on reproductive health and anthropometric, as well as metabolic parameters have been performed. Unequivocal information on associations among the aforementioned factors is lacking globally, especially those performed in homogenous populations. More information on androgen associations with cognitive function, emotional state and evaluation of quality of life is required. Most of the studies on effectiveness of testosterone replacement therapy were of short duration and mostly focused on structural, rather than functional parameters. The purpose of the study was to describe associations between reproductive health and anthropometric, metabolic, as well as psychological parameters in young and middle-aged men. This is the largest androgen association analysis in Lithuanian population. This work seeks for systematic responses to questions of interest: to establish reference values for normal and optimal androgen levels, to evaluate their relationship with anthropometric and metabolic factors in populations that are homogenous by age, and to assess the functional changes that long-term optimal testosterone replacement therapy may induce in patients with... [to full text]