Age-specific testosterone thresholds: reconsidering diagnostic criteria for hypogonadism across generations of Vietnamese men.

The definition and diagnosis of functional hypogonadism (FH) remains challenging due to the nonspecific nature of symptoms and the inconsistency in normal testosterone thresholds. We conducted this single-center cross-sectional study on medical records of men aged 18 and above undergoing annual health check-ups to evaluate the correlation of age and metabolic components with testosterone. A total of 5,374 healthy men were included in the analysis. Total testosterone levels peaked at 18 years and gradually declined to age 40, followed by a mild increase. Based on the American Urology Association guideline, age-specific cutoffs for low testosterone were 14.61 nmol/l, 12.74 nmol/l, 12.70 nmol/l, and 13.98 nmol/l for those under 30, 30-40, 40-50, and over 50 years old respectively. Triglyceride - Glucose index showed a consistent negative correlation with testosterone across all age groups. In conclusion, testosterone levels demonstrated an age-related decline in early adulthood but a potential increase thereafter among healthy Vietnamese men. Metabolic components, rather than aging, had a consistent negative correlation with testosterone. Age-specific cutoffs for low testosterone may improve the detection of functional hypogonadism.

Safety and efficacy of enclomiphene and clomiphene for hypogonadal men.

Background: Both clomiphene citrate and its isomer, enclomiphene, have become widespread within urologic practice; thus, understanding these medications' comparative benefits and risks is crucial for optimizing treatment and providing improved therapeutic options. We sought to investigate the longitudinal benefits and risks associated with enclomiphene, compared to clomiphene, and to provide valuable insights for clinicians when making treatment decisions in the management of hypogonadism. Methods: We retrospectively studied patients at our academic center who had been prescribed clomiphene and, later, enclomiphene for hypogonadism. Baseline laboratory values were documented for each patient before being prescribed clomiphene, followed by subsequent values for each variable in the most recent visit before stopping clomiphene and any noted adverse effects experienced during this time. The same process was repeated for enclomiphene, using the clomiphene levels as an updated baseline. Two-tailed t-tests were employed using R to analyze the longitudinal impacts of clomiphene and enclomiphene on serum hormone values as well as a regression analysis to estimate the odds ratio (OR) for adverse events between the two therapies. Results: Among 66 patients, enclomiphene exhibited a median testosterone increase of 166 (vs. 98 ng/dL, P=0.20) with lower estradiol change than clomiphene (-5.92 vs. 17.50 pg/mL, P=0.001). Adverse effects were statistically significantly less frequent with enclomiphene, including decreased libido (P=0.001), reduced energy (P=0.044), and mood changes (P=0.03). Regression analysis confirmed lower odds of adverse events with enclomiphene [OR: 0.18; 95% confidence interval (CI): 0.07-0.44, P=0.02]. Conclusions: Our findings demonstrate that enclomiphene provides improvement in testosterone levels with a lower rate of documented adverse events. These findings support enclomiphene as a comparable treatment option for hypogonadal men while minimizing the risk of adverse effects. Further research and more extensive studies are warranted to validate these conclusions and explore the additional long-term effects of enclomiphene to guide future patient counseling regarding these medications.

Functional hypothalamic amenorrhoea and polycystic ovarian morphology: a narrative review about an intriguing association.

BACKGROUND: Functional hypothalamic amenorrhoea (FHA) is responsible for 20-35% of all cases of secondary amenorrhoea and, thus, is the second most common cause of secondary amenorrhoea after polycystic ovary syndrome (PCOS). A high number of patients with FHA reveal polycystic ovarian morphology (PCOM) on ultrasound. The combination of amenorrhoea and PCOM can lead to confusion. First, amenorrhoeic women with PCOM fulfil the revised Rotterdam criteria and, thus, can easily be misdiagnosed with PCOS. Moreover, it has been claimed that some women with FHA and concomitant PCOM differ from those without PCOM in terms of endocrine regulation and metabolic traits. OBJECTIVE AND RATIONALE: The main focus of this article was on studies about FHA, which differentiated between patients with or without PCOM. The aim was to estimate the prevalence of PCOM and to look if it has an impact on pathophysiologic, diagnostic and therapeutic issues as well as on long-term consequences. SEARCH METHODS: Peer review original and review articles were selected from PubMed searches for this review. Searches were performed using the search terms 'polycystic AND functional hypothalamic amenorrhoea'. The reference lists of publications found were searched for relevant additional studies. The inclusion criteria for publications were: English language, patients' age ≥ 18 years, year of publication >1980, original studies, validated diagnosis of FHA, and validated diagnosis of PCOM using transvaginal ultrasound. OUTCOMES: The prevalence of PCOM in women with FHA varied from 41.9% to 46.7%, which is higher than in healthy non-PCOS controls. Hypothetically, the high prevalence might be due to a mixture of silent PCOM, as in the general population, and pre-existing PCOS. Several differences in metabolic and hormonal parameters were found between FHA-PCOM and FHA-non-PCOM patients. While oestrogen deficiency is common to both groups of patients, FHA-PCOM patients have a higher BMI, higher levels of anti-Müllerian hormone (AMH) and testosterone, a higher increase in LH in the course of a GnRH test, and lower sex hormone binding globulin (SHBG) levels than FHA-non-PCOM patients. The differential diagnosis between FHA-PCOM and PCOS, especially PCOS phenotype D (PCOM and oligo-/anovulation without hyperandrogenism), can be challenging. Several parameters have been suggested, which are helpful though not absolutely reliable. They include the typical causes for FHA (excessive exercise, energy deficit, and/or psychological stress), the serum levels of LH, testosterone, and SHBG, as well as the progestin challenge test. Whether FHA-PCOM has a different risk profile for long-term consequences concerning patients' metabolic and cardiovascular situation as well as their bone mass, is unclear. Concerning therapeutic aspects, there are only few data about FHA-PCOM compared to FHA-non-PCOM. To treat anovulation, the use of pulsatile GnRH treatment seems to be equally effective in both groups. Similar to FHA-non-PCOM patients, pulsatile GnRH therapy would be more efficient than exogenous gonadotropins in FHA-PCOM patients. WIDER IMPLICATIONS: Women with FHA-PCOM present a special sub-population of FHA patients. The diagnostic pitfall of FHA-PCOM should be emphasized in clinical guidelines about FHA and PCOS. The fact that almost half of the women with FHA have an ovarian follicle excess (i.e. PCOM) in face of low gonadotropin serum levels suggests that the intra-ovarian regulation of folliculogenesis is subject to individual variations, for unknown reasons, either genetic or epigenetic. Further studies are needed to investigate this hypothesis. REGISTRATION NUMBER: Not applicable.

Kallmann syndrome: Diagnostics and management.

Kallmann syndrome is a genetic disorder characterized by delayed or absence of puberty and a reduced or absent sense of smell (anosmia). Kallmann syndrome is a form of hypogonadotropic hypogonadism due to lack of the production of sex hormones which is associated with development of secondary sexual characteristics. Kallmann Syndrome is a genetically heterogeneous disorder, characterized by the combination of hypogonadotropic hypogonadism (a deficiency in sex hormone production) and anosmia. Germline mutations in KAL1 gene causes deficiency in GnRH hormone followed by low level of circulating gonadotropin and testosterone which finally leads to the failure of puberty (development of secondary sexual characters). Kallmann Syndrome can be inherited in several manners including X-linked recessive (e.g., mutations within KAL1) and autosomal dominant and recessive forms. Germline mutation in KAL1 gene was identified among 8% of patients with Kallmann Syndrome. A review of the recent literature done reveals numerous clinical manifestations in Kallmann Syndrome patients with the KAL1 mutation, including microgenitalia, impotence, reduced libido, infertility, unilateral renal agenesis, and synkinesia. Genetic molecular diagnostics through prenatal diagnosis and preimplantation genetic testing are most significant way to reduce the risk of Kallmann syndrome in next generation. Complication associated with Kallmann syndrome can be prevented by early diagnosis, diet supplementation and medical therapy. Goal of therapeutic intervention is to the development of secondary sexual characteristics, build and sustain bone density as well as muscle mass and restore fertility. This review aims to explore the genetic diagnosis and management strategies for Kallmann Syndrome, particularly focusing on KAL1 gene mutations.

Is there an association between daylight hours and serum testosterone levels in men?

BACKGROUND: Studies assessing variability of serum testosterone levels associated with seasonal environmental factors have been contradictory. DESIGN: We assessed associations between the seasons and changes (δ) in seasonality indices and male serum total testosterone (δTT) variability. PATIENTS AND MEASUREMENTS: Data were collected in 144 men with paired serum TT samples (126 non-fasting/18 fasting) analysed at Walsall Manor Hospital, UK (52.3 degrees North). Seasonal factors (ambient temperature within 15 min of sampling, humidity, precipitation, duration of daylight on the day of sampling, monthly average ambient temperature, and precipitation) were obtained from local weather-station archives. Sign-rank test determined inter-sample differences between TT and seasonality indices. Linear regression analyses studied associations between δTT and δ seasonal indices in the total cohort and subgroups (stratified by medians of age, TT and men with paired non-fasting samples). Sign-rank determined whether serum TT differed between the seasons. RESULTS: Median inter-sample interval was 63 days. No significant inter-sample differences were evident regarding serum TT levels and seasonality indices. No associations were noted between δTT and δ seasonality indices in the total cohort and subgroups stratified by age and TT. Interestingly, δ ambient temperature (p = 0.012) and daylight duration (p = 0.032) were inversely associated with δTT in the 126 men in the non-fasting group (dependent variable). Only a small degree of the variability in the δTT was accounted by the above-mentioned independent variables. The seasons did not appear to influence serum TT values. CONCLUSIONS: No relation was shown between seasonality and serum TT in the total cohort, thus possibly eliminating a confounding variable that could affect laboratory and clinical practice. It may be that seasonal variation in length of day is too modest at this latitude to demonstrate significant associations, hence our findings are latitude specific. We suggest that further data analysis to address this question in areas with greater seasonal variation would be appropriate.

Metabolic, cardiac, and bone health testing in patients with prostate cancer on androgen-deprivation therapy: A population-based assessment of adherence to therapeutic monitoring guidelines.

BACKGROUND: Androgen-deprivation therapy (ADT) remains a cornerstone in treatment for patients with advanced prostate cancer. ADT is associated with several adverse effects, including osteoporosis, metabolic syndrome, and cardiovascular events, leading to guidelines recommending routine testing to monitor for these toxicities. There is a lack of data assessing adherence to these recommendations. METHODS: The authors conducted a retrospective cohort study using administrative data from Ontario, Canada between 2008 and 2021. They identified all older men (aged 65 years and older) who received ADT for prostate cancer using comprehensive provincial health databases. The primary outcomes were the use of testing for lipids, dysglycemia (glucose), bone health serum, and bone density between 6 weeks before and 1 year after the initiation of ADT. RESULTS: In total, 29,097 patients were examined, of whom 52.8% were prescribed ADT by urologists, 37.9% were prescribed ADT by radiation oncologists, 2.8% were prescribed ADT by medical oncologists, and 2.4% were prescribed ADT by other physicians. Adherence to guidelines was low: only 21.3% of patients received a bone density scan, 41.2% underwent bone health-related serum tests, 51.3% completed a lipid profile, and 65.9% underwent dysglycemia testing within 1 year of diagnosis. Overall, only 11.9% of patients received all of the recommended investigations. Adherence to testing did not appear to improve over time (2008-2021) or with guideline publication. Patient (age) and physician (specialty) factors had important associations with adherence to testing. CONCLUSIONS: Most patients receiving ADT for prostate cancer do not receive recommended testing to monitor for treatment-related toxicity. Further study is required to address barriers to therapeutic monitoring of men on ADT and to reduce treatment-associated adverse events.

Primary ovarian insufficiency: update on clinical and genetic findings.

Primary ovarian insufficiency (POI) is a disorder of insufficient ovarian follicle function before the age of 40 years with an estimated prevalence of 3.7% worldwide. Its relevance is emerging due to the increasing number of women desiring conception late or beyond the third decade of their lives. POI clinical presentation is extremely heterogeneous with a possible exordium as primary amenorrhea due to ovarian dysgenesis or with a secondary amenorrhea due to different congenital or acquired abnormalities. POI significantly impacts non only on the fertility prospect of the affected women but also on their general, psychological, sexual quality of life, and, furthermore, on their long-term bone, cardiovascular, and cognitive health. In several cases the underlying cause of POI remains unknown and, thus, these forms are still classified as idiopathic. However, we now know the age of menopause is an inheritable trait and POI has a strong genetic background. This is confirmed by the existence of several candidate genes, experimental and natural models. The most common genetic contributors to POI are the X chromosome-linked defects. Moreover, the variable expressivity of POI defect suggests it can be considered as a multifactorial or oligogenic defect. Here, we present an updated review on clinical findings and on the principal X-linked and autosomal genes involved in syndromic and non-syndromic forms of POI. We also provide current information on the management of the premature hypoestrogenic state as well as on fertility preservation in subjects at risk of POI.

Fertility preservation in men with hypogonadotropic hypogonadism secondary to germinoma: two cases of gonadotropin replacement therapy before induction of anticancer chemotherapy.

Hypogonadotropic hypogonadism can be caused by brain tumors. For a malignancy such as a germ cell tumor, chemotherapy combined with radiation is administered. In patients who wish for children, the inability to undergo sperm cryopreservation before treatment because of impaired spermatogenesis and/or ejaculation dysfunction can be problematic. We herein present two cases involving a 26-year-old man and a 30-year-old man with hypogonadotropic hypogonadism due to an intracranial germinoma and both wished to have children. Gonadotropin replacement therapy prior to anticancer chemotherapy resulted in subsequent spontaneous pregnancy or assisted reproductive therapy. Subsequent treatment of the tumor resulted in no recurrence for 9 and 2 years, respectively. Close consultation with an oncologist is mandatory in such cases. Depending on the tumor prognosis, however, it may be possible to delay tumor treatment and prioritize fertility because there is a possibility of impaired spermatogenesis due to additional chemotherapy.

Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement.

The use and misuse of opioids are a growing global problem. Although the effects of these drugs on the human endocrine system have been studied for decades, attention on their related clinical consequences, particularly on the hypothalamic-pituitary system and bone health, has intensified over recent years. This Statement appraises research data related to the impact of opioids on the gonadal and adrenal function. Whereas hypogonadism is well recognized as a side effect of opioids, the significance of their inhibitory actions on the hypothalamic-pituitary-adrenal system and the occurrence of clinically relevant adrenal insufficiency is not fully elucidated. The often-inconsistent results of studies investigating how opioids affect the secretion of GH, prolactin, arginine vasopressin, and oxytocin are assessed. The accumulating evidence of opioid actions on bone metabolism and their negative sequelae on bone mineral density and risk of fracture are also reviewed. In each section, available data on diagnostic and management approaches for opioid endocrine sequelae are described. This Statement highlights a plethora of gaps in research associated with the effects and clinical consequences of opioids on the endocrine system. It is anticipated that addressing these gaps will improve the care of people using or misusing opioids worldwide. The Statement is not intended to serve as a guideline or dictate treatment decisions.

Hypogonadotropic Hypogonadism as First Presentation of the Severe Neuroendocrine Disorder Caused by RNF216.

Biallelic pathogenic variants in RNF216 cause a syndrome characterized by hypogonadotropic hypogonadism, cerebellar ataxia, chorea, and cognitive impairment, a combination first described as Gordon Holmes syndrome (MIM 212840). We report 2 siblings who were referred due to absent or delayed puberty. The older sibling, a 17-year-old male, presented with absence of secondary sexual characteristics and a high-pitched voice. He had normal cognitive development and no anosmia. Clinical examination revealed Tanner stage P1/G1 and bilateral gynecomastia. Blood tests showed low gonadotropin and morning testosterone levels. His 15-year-old sister was referred due to primary amenorrhea. She had spontaneous thelarche and presented with Tanner stage P3/B3. Pituitary magnetic resonance imaging was performed on the brother due to suspicion of Kallmann syndrome, revealing a normal anterior pituitary, a hypoplastic posterior pituitary, and an extensive supratentorial leuko-encephalopathy. Whole-exome sequencing revealed a homozygous pathogenic variant in RNF216 in both affected siblings. Both parents were heterozygous carriers. RNF216 pathogenic variants cause a disorder characterized by combined neurodegeneration and reproductive dysfunction. Although neurological symptoms are typically recognized first, they often seem to follow the onset of hypogonadism. This highlights the need for awareness, as hypogonadotropic hypogonadism may be the initial manifestation of this severe neuroendocrine disorder, especially in males.

The endocrine manifestations of adults with spinal muscular atrophy.

INTRODUCTION/AIMS: Changes in body composition in patients with spinal muscular atrophy (SMA) can cause endocrine abnormalities that are insufficiently studied in adults. We aimed to assess the endocrine profile in a cohort of adults with SMA. Second, we compared body composition and endocrine profiles between nonambulatory and ambulatory patients and between different types of SMA. METHODS: The cross-sectional study included 29 SMA patients (18 [62.1%] males and 11 [37.9%] females) of median age 44 (IQR 30-51.5) years with type 2, 3, or 4. Body composition was measured by bioimpedance. Morning blood samples were drawn for glycated hemoglobin (HbA1c), lipid profile, testosterone, cortisol, and insulin-like growth factor-1 (IGF-1). Blood glucose, insulin, and beta-hydroxybutyrate (BHB) were measured during a 75 g oral glucose tolerance test. The homeostatic model assessment for insulin resistance index was calculated. RESULTS: In total, 75.9% of patients had increased fat mass (FM), with 51.7% having an increase despite normal body mass index. Ambulation was the most important discriminating factor of body composition. 93.1% of patients had metabolic abnormalities, including hyperglycemia, insulin resistance, and dyslipidemia. Increased BHB, a marker of ketosis, was present in more than a third of patients. Functional hypogonadism was present in half of male patients. Testosterone and IGF-1 negatively correlated with FM. DISCUSSION: Adult patients with SMA had abnormal body composition and highly prevalent metabolic disturbances that might increase cardiometabolic risk. Because treatments have modified the course of SMA, it is important to investigate whether these observations translate into clinically relevant outcomes.

Testosterone Replacement Therapy Can Improve a Biomarker of Liver Fibrosis in Hypogonadal Men: A Subanalysis of a Prospective Randomized Controlled Study in Japan (EARTH Study).

PURPOSE: We investigated the effects of testosterone replacement therapy (TRT) on the Fibrosis-4 (FIB-4) index among hypogonadal patients who were extracted from a randomized controlled study in Japan (the EARTH study). MATERIALS AND METHODS: Data of 186 patients (88 in the TRT group; 98 in the control group) were collected. The patients in the TRT group received intramuscular administration of testosterone enanthate (250 mg) every 4 weeks for 12 months. The patients' background information such as current medical history and lifestyle habits were collected. Waist circumference, body mass index, and body fat volume were measured at baseline and 12-month visit. Fasting blood sugar (FBS), hemoglobin A1c, total cholesterol, triglyceride (TG), and high-density lipoprotein cholesterol levels were collected at baseline and 12-month visit. The FIB-4 index was calculated according to age, aspartate aminotransferase, alanine transaminase, and platelet count. RESULTS: Except for serum FBS values, most of baseline characteristics were comparable between the TRT and control groups. When comparing the changes of each variable from baseline at 12-month visit in both groups, significant differences were found in waist circumference (p=0.00248), fat volume (p=0.00812), and platelet counts (p=0.0478), whereas a FIB-4 index did not change. On the contrary, in a subanalysis including only patients with a FIB-4 index ≥1.30 at baseline, a significant difference in a FIB-4 index (-0.10±0.39 vs. 0.04±0.44; p=0.0311) was observed with significant decreases in waist circumference, body fat volume, and TG levels, and an increase in platelet counts. The FIB-4 index was significantly decreased by TRT from 1.98±0.52 to 1.87±0.60 (p=0.0277). CONCLUSIONS: TRT for 12 months improved the FIB-4 index among hypogonadal men with a higher baseline FIB-4 index.

Androgen Deficiency, Associations and Survival of Men With Stage 4 and 5 Chronic Kidney Disease: A Cohort Study.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

A study of long-term supraphysiologic-dose anabolic-androgenic steroid use on cognitive function in middle-aged men.

Background: Long-term use of supraphysiologic doses of anabolic-androgenic steroids (AAS) has been associated with impaired visuospatial memory in young men but little is known about its cognitive effects in middle-aged men.Objectives: We compared cognition in middle-aged men with histories of long-term AAS use and age-matched non-users.Methods: We administered cognitive tests from the CANTAB battery to 76 weightlifters aged 37-60 years (mean [SD] 48.5 [6.5] years), of whom 51 reported at least 2 years of cumulative AAS use and 25 reported no AAS exposure.Results: We found no significant AAS user versus non-user group differences on visuospatial, verbal memory, emotional recognition, or executive function tasks (corrected p's ≥ .00089; effect sizes ≤ .5).Conclusions: Our null visuospatial task findings contrast with our prior younger cohort study (mean age 37.1 [7.1] years), in which we found impaired visuospatial task performance in people who use AAS, and with other reports of cognitive impairments in younger men use AAS. Men who use AAS may develop early visuospatial memory deficits that stabilize by middle age while middle-aged non-users' performance may "catch up" due to normal age-related visuospatial declines. Similar effects could contribute to our null findings on other tasks. Between-study cohort substance use differences or environmental factor differences that modify cognition, such as study geographical location and time of year, also could contribute to our discordant findings. Since young adult male AAS users experience increased mortality from unnatural causes, improving our understanding of AAS cognitive effects in this age group is important.

Prevalence of hypogonadism in men with and without chronic obstructive pulmonary disease: A cross-sectional study.

BACKGROUND: Hypogonadism is a common finding of chronic obstructive pulmonary disease (COPD). However, the prevalence of hypogonadism in COPD varies among studies. The aim of this study was to determine and compare the prevalence of hypogonadism in men with and without COPD. METHODS: We conducted a cross-sectional study with 134 patients with stable COPD and 70 age-matched men with non-COPD. Hypogonadism was defined by the presence of symptoms according to the Androgen Deficiency in Aging Males questionnaire, along with total testosterone deficiency (<300ng/dL). RESULTS: Patients had a mean age of 68 years (SD, 6), a body mass index of 28kg/m2 (SD, 6), and 17% were current smokers. The prevalence of hypogonadism was 41.8% in COPD men (N=56, 95%CI, 33-51) and 10.0% in non-COPD men (N=7, 95%CI, 4-20), with a prevalence ratio of 4.2 (95%CI, 2.0-8.7, p<0.001). The prevalence of low total testosterone concentrations (<300ng/dL) were significantly higher in COPD patients vs the control group (47.0% vs 15.7%, p=<0.001). In the COPD group, 89.3% of patients had hypogonadotropic hypogonadism and 10.7%, hypergonadotropic hypogonadism. The prevalence of hypogonadism was higher in severe vs non-severe COPD patients (55.8% vs 35.2%; p=0.024). CONCLUSIONS: The prevalence of hypogonadism was high and greater in COPD vs non-COPD men. This study suggests that COPD patients should be screened for hypogonadism.

Replacement with sex steroids in hypopituitary men and women: implications for gender differences in morbidities and mortality.

Hypopituitarism is a heterogenous disorder characterised by a deficiency in one or more anterior pituitary hormones. There are marked sex disparities in the morbidity and mortality experienced by patients with hypopituitarism. In women with hypopituitarism, the prevalence of many cardiovascular risk factors, myocardial infarction, stroke and mortality are significantly elevated compared to the general population, however in men, they approach that of the general population. The hypothalamic-pituitary-gonadal axis (HPG) is the most sexually dimorphic pituitary hormone axis. Gonadotropin deficiency is caused by a deficiency of either hypothalamic gonadotropin-releasing hormone (GnRH) or pituitary gonadotropins, namely follicle-stimulating hormone (FSH) and luteinising hormone (LH). HPG axis dysfunction results in oestrogen and testosterone deficiency in women and men, respectively. Replacement of deficient sex hormones is the mainstay of treatment in individuals not seeking fertility. Oestrogen and testosterone replacement in women and men, respectively, have numerous beneficial health impacts. These benefits include improved body composition, enhanced insulin sensitivity, improved atherogenic lipid profiles and increased bone mineral density. Oestrogen replacement in women also reduces the risk of developing type 2 diabetes mellitus. When women and men are considered together, untreated gonadotropin deficiency is independently associated with an increased mortality risk. However, treatment with sex hormone replacement reduces the mortality risk comparable to those with an intact gonadal axis. The reasons for the sex disparities in mortality remain poorly understood. Potential explanations include the reversal of women's natural survival advantage over men, premature loss of oestrogen's cardioprotective effect, less aggressive cardiovascular risk factor modification and inadequate oestrogen replacement in women with gonadotropin deficiency. Regrettably, historical inertia and unfounded concerns about the safety of oestrogen replacement in women of reproductive age have impeded the treatment of gonadotropin deficiency.

Adrenal hypoplasia congenita and hypogonadotropic hypogonadism due to a novel NR0B1 (DAX1) gene mutation associated with common variable immunodeficiency and Hashimoto's thyroiditis.

Not required for Clinical Vignette.

Association of Obesity, Inflammation, and Hypogonadism: A Cross-Sectional Study in Males Under 60 Years of Age.

Background Obesity is a significant global health issue closely associated with numerous metabolic disorders, including hypogonadism. Male obesity-related secondary hypogonadism (MOSH) is characterized by reduced testosterone levels, leading to various health complications. The bidirectional relationship between obesity and hypogonadism creates a vicious cycle, with obesity exacerbating hypogonadism and hypogonadism contributing to further obesity. Chronic inflammation, indicated by elevated C-reactive protein (CRP) levels, plays a crucial role in this interplay. The primary aim of this study is to investigate the role of obesity as an isolated factor contributing to hypogonadism. Materials and methods This observational, cross-sectional study was conducted from September 2022 to July 2024 at Dr. D.Y. Patil Medical College and Hospitals in Pune, India. A total of 80 male participants, all under 60 years of age with a BMI greater than 25 kg/m², were included in the study and classified as overweight or obese according to WHO criteria. Exclusion criteria included diabetes, age over 60 years, a BMI less than 25 kg/m², any testicular pathologies, and significant risk factors. After obtaining informed consent, participants underwent thorough clinical examinations and laboratory investigations. Patients who met the criteria were included in the study, with measurements taken for central obesity (waist circumference (WC) and waist-hip ratio (WHR)) and BMI. CRP levels were measured as an inflammatory marker indicative of chronic disease states. Statistical analyses, including correlation and regression analyses, were performed using SPSS software, version 22 (IBM SPSS Statistics, Version 22). Statistical significance was set at p < 0.05. Results The majority of participants fell within the 50-59 age group, with a mean age of 45.95 years. The study found strong positive correlations between BMI (r = 0.76), WC (r = 0.81), and WHR (r = 0.78) with CRP levels, indicating that central obesity is closely linked to systemic inflammation. Additionally, there were significant negative correlations between free testosterone and these anthropometric measures: BMI (r = -0.65), WC (r = -0.70), and WHR (r = -0.67), suggesting that increased adiposity is associated with lower testosterone levels. The strongest negative correlation observed was between CRP and free testosterone (r = -0.82), highlighting the impact of chronic inflammation on hypogonadism. Regression analysis further confirmed that CRP was a significant predictor of free testosterone levels (R-squared = 0.674), emphasizing the crucial role of inflammation in the pathophysiology of hypogonadism in obese individuals. Conclusion This study underscores the intricate relationship between obesity, chronic inflammation, and hypogonadism in men. The bidirectional nature of this relationship suggests that managing obesity and reducing systemic inflammation could potentially alleviate hypogonadism. Interventions focusing on weight loss, improving insulin sensitivity, and anti-inflammatory treatments may thus hold promise in restoring normal testosterone levels in obese men. Understanding and addressing the impact of obesity on male reproductive health is crucial, given the rising prevalence of obesity worldwide. Future research should explore therapeutic avenues and further elucidate the underlying mechanisms of this complex interplay.