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Female hypogonadism (FH) is a relatively common endocrine disorder in women of premenopausal age, but there are significant uncertainties and wide variation in its management. Most current guidelines are monospecialty and only address premature ovarian insufficiency (POI); some allude to management in very brief and general terms, and most rely upon the extrapolation of evidence from the studies relating to physiological estrogen deficiency in postmenopausal women. The Society for Endocrinology commissioned new guidance to provide all care providers with a multidisciplinary perspective on managing patients with all forms of FH. It has been compiled using expertise from Endocrinology, Primary Care, Gynaecology and Reproductive Health practices, with contributions from expert patients and a patient support group, to help clinicians best manage FH resulting from both POI and hypothalamo‐pituitary disorders, whether organic or functional. [ABSTRACT FROM AUTHOR]

Background: Inter‐assay variation between different immunoassays and different mass spectrometry methods hampers the biochemical confirmation of male hypogonadism. Furthermore, some laboratories utilise assay manufacturer reference ranges that do not necessarily mirror assay performance characteristics, with the lower limit of normality ranging from 4.9 nmol/L to 11 nmol/L. The quality of the normative data underlying commercial immunoassay reference ranges is uncertain. Design: A working group reviewed published evidence and agreed upon standardised reporting guidance to augment total testosterone reports. Results: Evidence‐based guidance on appropriate blood sampling, clinical action limits, and other major factors likely to affect the interpretation of results are provided. Conclusions: This article aims to improve the quality of the interpretation of testosterone results by non‐specialist clinicians. It also discusses approaches for assay harmonisation which have been successful in some but not all healthcare systems. [ABSTRACT FROM AUTHOR]

ABSTRACT Objectives Methods Results Conclusions Anaemia is a key cause of morbidity in chronic kidney disease (CKD). Androgen deficiency (AD) in males can contribute to anaemia of all causes, including in CKD. We sought to examine the prevalence of AD in men with CKD, the extent to which it contributed to anaemia and whether it was independently associated with long‐term survival.This cross‐sectional observational study was conducted among males aged 18 years and over with CKD stages 4 and 5. The study analysed morning blood samples with regard to their full blood count, urea and electrolytes, albumin, lipids, testosterone (T) and sex hormone binding globulin, with calculation of free testosterone by mass action equation. Mortality data were obtained 15 years later for survival analysis.Among 322 patients with a mean age of 63 years, the overall prevalence of AD was 68.9%. There was a statistically significant negative correlation between erythropoiesis stimulating agent (ESA) dose and testosterone concentrations (Pearson correlation −0.193, p = 0.05). There was a positive correlation between haemoglobin (Hb) and free testosterone level among patients not on ESA therapy (Pearson correlation 0.331, p < 0.001). Kaplan‐Meier plots showed p < 0.001 on log‐rank analysis, indicating that AD was significantly associated with worse survival. However, in Cox regression analysis, free testosterone was not associated with survival (95% CI for free testosterone 0.997–1.000).AD is highly prevalent among this population, and increases further with older age and more severe CKD warranting haemodialysis. Association of lower Hb and higher ESA dose with lower T concentration might be causative, which has important pharmaco‐economic as well as clinical implications. Lower survival in men with low T, more likely reflects overall poor health rather than causation. A properly constituted randomised controlled study evaluating the effect of native T replacement is warranted in men with CKD and AD. [ABSTRACT FROM AUTHOR]

Congenital hypogonadotropic hypogonadism (CHH) is a rare reproductive disorder caused by deficient secretion or action of gonadotropin‐releasing hormone (GnRH) and is a hormonally treatable form of male infertility. Both pulsatile GnRH treatment and combined gonadotropin therapy effectively induce spermatogenesis in 75%–80% of males with CHH, albeit the ejaculate does not usually approach normal semen parameters by WHO criteria. This is in some contrast to the cumulative fertility outcomes in females with CHH on gonadotropin treatment that are indistinguishable from those of reproductively normal females. Emerging data provide insights into early life determinants of male fertility (i.e., minipuberty), and research has identified key predictors of outcomes for fertility‐inducing treatment in men with CHH. Such developments provide mounting evidence for tailoring approaches to maximize fertility potential in CHH, although there is no clear consensus to date on the optimal approach to fertility‐inducing treatment. This review provides an up‐to‐date review on the current evidence underpinning therapeutic approaches for inducing spermatogenesis in males with CHH. In the absence of evidence‐based clinical guidelines, this synthesis of current evidence provides guidance for clinicians working with males with CHH seeking fertility. [ABSTRACT FROM AUTHOR]

This article discusses the use of gonadotropin treatment as an alternative to surgery for adults with congenital hypogonadotropic hypogonadism (CHH) and cryptorchidism. CHH is a condition where there is a deficiency of certain hormones, leading to absent or incomplete puberty. Cryptorchidism, or undescended testis, is more common in individuals with CHH. The article presents three case studies of adult males with CHH and persistent cryptorchidism who were successfully treated with gonadotropin therapy. The findings suggest that this treatment can be a safe and effective alternative to surgery for correcting cryptorchidism in young adult males with CHH. Further research is needed to explore this treatment in larger patient groups. [Extracted from the article]

Background: Testosterone is safe and highly effective in men with organic hypogonadism, but worldwide testosterone prescribing has recently shifted towards middle‐aged and older men, mostly with low testosterone related to age, diabetes and obesity, for whom there is less established evidence of clinical safety and benefit. The value of testosterone treatment in middle‐aged and older men with low testosterone is yet to be determined. We therefore evaluated the cost‐effectiveness of testosterone treatment in such men with low testosterone compared with no treatment. Methods: A cost‐utility analysis comparing testosterone with no treatment was conducted following best practices in decision modelling. A cohort Markov model incorporating relevant care pathways for individuals with hypogonadism was developed for a 10‐year‐time horizon. Clinical outcomes were obtained from an individual patient meta‐analysis of placebo‐controlled, double‐blind randomised studies. Three starting age categories were defined: 40, 60 and 75 years. Cost utility (quality‐adjusted life years) accrued and costs of testosterone treatment, monitoring and cardiovascular complications were compared to estimate incremental cost‐effectiveness ratios and cost‐effectiveness acceptability curves for selected scenarios. Results: Ten‐year excess treatment costs for testosterone compared with non‐treatment ranged between £2306 and £3269 per patient. Quality‐adjusted life years results depended on the instruments used to measure health utilities. Using Beck depression index‐derived quality‐adjusted life years data, testosterone was cost‐effective (incremental cost‐effectiveness ratio <£20,000) for men aged <75 years, regardless of morbidity and mortality sensitivity analyses. Testosterone was not cost‐effective in men aged >75 years in models assuming increased morbidity and/or mortality. Conclusions and future research: Our data suggest that testosterone is cost‐effective in men <75 years when Beck depression index‐derived quality‐adjusted life years data are considered; cost‐effectiveness in men >75 years is dependent on cardiovascular safety. However, more robust and longer‐term cost‐utility data are needed to verify our conclusion. [ABSTRACT FROM AUTHOR]

Congenital hypogonadotropic hypogonadism (CHH) and its anosmia-associated form (Kallmann syndrome [KS]) are genetically heterogeneous. Among the >15 genes implicated in these conditions, mutations in FGF8 and FGFR1 account for ~12% of cases; notably, KAL1 and HS6ST1 are also involved in FGFR1 signaling and can be mutated in CHH. We therefore hypothesized that mutations in genes encoding a broader range of modulators of the FGFR1 pathway might contribute to the genetics of CHH as causal or modifier mutations. Thus, we aimed to (1) investigate whether CHH individuals harbor mutations in members of the so-called "FGF8 synexpression" group and (2) validate the ability of a bioinformatics algorithm on the basis of protein-protein interactome data (interactome-based affiliation scoring [IBAS]) to identify high-quality candidate genes. On the basis of sequence homology, expression, and structural and functional data, seven genes were selected and sequenced in 386 unrelated CHH individuals and 155 controls. Except for FGF18 and SPRY2, all other genes were found to be mutated in CHH individuals: FGF17 (n = 3 individuals), IL17RD (n = 8), DUSP6 (n = 5), SPRY4 (n = 14), and FLRT3 (n = 3). Independently, IBAS predicted FGF17 and IL17RD as the two top candidates in the entire proteome on the basis of a statistical test of their protein-protein interaction patterns to proteins known to be altered in CHH. Most of the FGF17 and IL17RD mutations altered protein function in vitro. IL17RD mutations were found only in KS individuals and were strongly linked to hearing loss (6/8 individuals). Mutations in genes encoding components of the FGF pathway are associated with complex modes of CHH inheritance and act primarily as contributors to an oligogenic genetic architecture underlying CHH.

This document summarizes a study on the clinical outcomes of surgical management for primary aldosteronism (PA) when adrenal vein sampling (AVS) results are inconclusive. AVS is the preferred method for subtyping PA, but it can be challenging to successfully cannulate both adrenal veins. The study found that patients who had successful AVS and underwent unilateral adrenalectomy achieved clinical and biochemical remission. Patients with inconclusive AVS results were managed either surgically or with medical therapy, and the majority of those who underwent surgery achieved biochemical remission. The study suggests that inconclusive AVS results, along with imaging findings, can help guide surgical decision-making, but further research is needed to validate these findings. It also emphasizes that patients who are not candidates for surgery should not undergo AVS. [Extracted from the article]

Patients with congenital hypogonadism will encounter many health care professionals during their lives managing their health needs; from antenatal and infantile periods, through childhood and adolescence, into adult life and then old age. The pubertal transition from childhood to adult life raises particular challenges for diagnosis, therapy and psychological support, and patients encounter many pitfalls. Many patients with congenital hypogonadism and delayed or absent puberty are only diagnosed and treated after long diagnostic journeys, and their management across different centres and countries is not well standardised. Here we reconsider the management of pubertal delay, whilst addressing problematic diagnostic issues and highlighting the limitations of historic pubertal induction protocols – from the perspective of both an adult and a paediatric endocrinologist, dealing in our everyday work with the long-term adverse consequences to our hypogonadal patients of an incorrect and/or late diagnosis and treatment in childhood. [ABSTRACT FROM AUTHOR]