Advances and challenges in liquid chromatography-spectrometry (LC-MS) methodology for quantifying androgens and estrogens in human serum and plasma.

Accurate quantification of androgens and estrogens is critical for elucidating their roles in endocrine disorders and advancing research on their functions in human biology and pathophysiology. This review highlights recent advances and ongoing challenges in liquid chromatography- mass spectrometry (LC- MS) methodology for quantifying androgens and estrogens in human serum and plasma. We summarized current approaches for analyzing the different forms of androgens and estrogens, along with their reported levels in publications from 2010 to the present. These published levels pointed out the inconsistencies in reference intervals across studies. To address these issues, advances in derivatization methods and chromatographic separation techniques are reviewed. Future perspectives for improving the accuracy and consistency of hormone quantification in clinical and research settings were also proposed.

Androgens Suppress Corticosteroid Binding Globulin in Male Mice, Affecting the Endocrine Stress Response.

Biological sex affects the activity of the hypothalamus-pituitary-adrenal (HPA) axis. However, how androgen deprivation affects this axis remains largely unknown. In this study, we investigated the effect of androgen status on different components of the HPA axis in male mice. Two weeks of androgen deprivation did not affect total plasma corticosterone levels but led to increased pituitary ACTH levels. Stress-induced total plasma corticosterone levels were increased, whereas the suppression of corticosterone after dexamethasone treatment under basal conditions was attenuated. Androgen-deprived mice displayed a 2-fold increase in plasma levels of corticosteroid binding globulin (CBG). A similar increase in CBG was observed in global androgen receptor knock-out animals, compared to wild-type littermates. Androgen deprivation was associated with a 6-fold increase in CBG mRNA in the liver and enhanced transcriptional activity at CBG regulatory regions, as evidenced by increased H3K27 acetylation. We propose that the induction of CBG as a consequence of androgen deprivation, together with the unaltered total corticosterone levels, results in lower free corticosterone levels in plasma. This is further supported by mRNA levels of androgen-independent GR target genes in the liver. The reduction in negative feedback on the HPA axis under basal condition would suffice to explain the enhanced stress reactivity after androgen deprivation. Overall, our data demonstrate that, in mice, tonic androgen receptor activation affects CBG levels in conjunction with effects on gene expression and HPA-axis reactivity.

Gender-specific alteration of steroid metabolism and its impact on viral replication in a mouse model of hepatitis B virus infection.

Hepatitis B virus (HBV) is a sex-specific pathogen that is more severe in males than in females. Sex disparities in HBV infection have been attributed to hormonal differences between males and females. However, whether HBV infection affects the metabolic signatures of steroid hormones and how these influences viral replication remains unclear. In this study, we investigated whether HBV infection alters steroid metabolism and its effects on HBV replication. Serum samples from male and female mice obtained after the hydrodynamic injection of replication-competent HBV plasmids were subjected to quantitative steroid profiling. Serum steroid levels in mice were analyzed using an in vitro metabolism assay with the mouse liver S9 fraction. The alteration of steroids by HBV infection was observed only in male mice, particularly with significant changes in androgens, whereas no significant hormonal changes were observed in female mice. Among the altered steroids, dehydroepiandrosterone (DHEA) levels increased the most in male mice after HBV infection. An in vitro metabolism assay revealed that androgen levels were significantly reduced in HBV-infected male mice. Furthermore, the genes involved in DHEA biosynthesis were significantly upregulated in HBV-infected male mice. Interestingly, reduced dihydrotestosterone in male mice significantly inhibits viral replication by suppressing HBV promoter activity, suggesting a viral strategy to overcome the antiviral effects of steroid hormones in males. Our data demonstrated that HBV infection can cause sex-specific changes in steroid metabolism.

Therapeutic prospects of sex hormone receptor signaling in hormone-responsive cancers.

Globally, hormone-responsive cancers afflict millions of people contributing to cancer-related morbidity and mortality. While hormone-responsive cancers overburden patients, their close families, and even health budgets at the local levels, knowledge of these cancers particularly their biology and possible avenues for therapy remains poorly exploited. Herewith, this review highlights the role of sex hormones (estrogens and androgens) in the pathophysiology of hormone-responsive cancers and the exploration of therapeutic targets. Major scientific databases including but not limited to Scopus, PubMed, Science Direct, Web of Science core collections, and Google Scholar were perused using a string of search terms: Hormone-responsive cancers, androgens and cancers, estrogens and cancer, androgen receptor signalling, estrogen receptor signalling, etc.

Prevalence of adrenal rest tumors and course of gonadal dysfunction in a clinical sample of men with congenital adrenal hyperplasia: a longitudinal analysis over 10 years.

BACKGROUND: Subfertility is prevalent in men with classic 21-hydroxylase deficiency (21OHD). We sought to characterize the long-term evolution of their gonadal function. METHODS: Retrospective longitudinal single-center study in 27 men (11 with testicular adrenal rest tissue [TART]), median observation period 12 years, testosterone (T), 11-oxygenated androgens, gonadotropins, and inhibin B measurement at each time point. RESULTS: T concentrations were below the normal range (n.s.) in 43.2% (no TART) and 54.6% (TART) per patient. After accounting for body mass index, sex hormone-binding globulin, and age, men with TART exhibited higher T (14.0 ± 0.80 nmol/L) than those without (11.9 ± 0.71 nmol/L). During the observation period, T levels rose in both groups but more in men with TART (from 10.1 ± 1.1 to 17.3 ± 1.9 nmol/L vs 10.3 ± 1.0 to 12.8 ± 1.9 nmol/L); this was accompanied by rising luteinizing hormone and diminishing hydrocortisone equivalent dosages (TART: from 38.1 ± 3.2 to 35.1 ± 1.8 mg/d; vs no TART: 28.8 ± 2.7 to 28.1 ± 1.6 mg/d) without correlation with any markers of adrenal androgen control. Inhibin B declined in men with large TART over time while TART status remained stable. CONCLUSION: T levels below the normal range are frequent in men with 21OHD, regardless of TART, but change little over time. Besides adrenal androgen control gonadal axis suppression from supraphysiological glucocorticoid dosages needs to be considered. While our results do not endorse regular screening for alterations in TART status among adults, Sertoli cell function should be monitored in men with large TART.

Effectiveness of low dose cyproterone acetate compared to standard dose in feminizing hormone treatment: a single institutional retrospective pilot study.

Background: Data regarding the effectiveness of low-dose cyproterone acetate (CPA) in testosterone suppression as feminizing hormone therapy (FHT) in individuals assigned male at birth (AMAB) are sparse. Aim: To assess the effectiveness in testosterone suppression using low-dose CPA (<25 mg/day) compared to standard-dose CPA (25-50 mg/day) in FHT. Methods: A retrospective cohort study of 59 individuals AMAB using CPA was done at a tertiary care center in Bangkok, Thailand between January 2014 and July 2022. Outcomes: The main outcomes included a median time when the testosterone was suppressed (<50 ng/dL), the proportion of individuals AMAB who achieved the targeted testosterone level at 3 months, and the testosterone level at each follow-up. Changes in clinical data were assessed. Results: Among 59 individuals AMAB, 37 initiated CPA with available testosterone levels at the 3-month follow-up. Twenty-two individuals AMAB started with low-dose CPA (12.5 mg/day), and 15 individuals AMAB started with standard-dose CPA. The median time to reach targeted testosterone was 3 months in both groups (adjusted hazard ratio 0.60, P = .489). At 3 months, 72.7% of those on low-dose CPA and 86.7% of those on standard-dose CPA achieved targeted testosterone (adjusted relative risk 0.85, P = .606). Testosterone levels at all follow-up visits were not significantly different. The standard dose group had higher high-density lipoprotein cholesterol (HDL-C) but lower low-density lipoprotein cholesterol (LDL-C) and alanine aminotransferase (ALT). Clinical Translation: This study supports a paradigm shift toward using lower-dose CPA in FHT. Strengths and Limitations: This is one of a few studies showing the effectiveness of low-dose CPA in testosterone suppression within 3 months. Limitations include a small sample size and missing data. Conclusions: Testosterone suppression is comparable between CPA 12.5 mg/day and the standard dose in FHT.

Sexual Dimorphism in the Musculoskeletal System: Sex Hormones and Beyond.

Mounting evidence indicates that whereas some fundamental aspects of bone cell differentiation and function are similar in females and males, there is a clear contribution of sex/gender on the effects of signaling molecules on bone mass and strength and, consequently, on the effects of pharmacologic approaches to treat skeletal disorders. However, until recently, most studies were designed and performed using only 1 sex, resulting in a scarcity of published information on sexual dimorphism of the musculoskeletal system, including the mandible/masticatory muscles and the axial and appendicular bones and skeletal muscles. Further, it is now recognized that scientific rigor requires the study of both males and females. Therefore, there is an increasing need to understand the molecular and cellular basis for the differential outcomes of genetic manipulations and therapeutic agent administration depending on the sex of the experimental animals. Studies have shown higher muscle mass, cancellous bone mass, and long bone width in males compared with females as well as different traits in the pelvis and the skull, which are usually used for gender identification in forensic anthropology. Yet, most reports focus on the role of sex hormones, in particular, the consequences of estrogen deficiency with menopause in humans and in ovariectomized animal models. In addition, emerging data is starting to unveil the effects of gender-affirming hormonal therapy on the musculoskeletal system. We summarize here the current knowledge on the sex/gender-dependent phenotypic characteristics of the bone and skeletal muscles in humans and rodents, highlighting studies in which side by side comparisons were made.

A real-world study of hereditary angioedema patients due to C1 inhibitor deficiency treated with danazol in the Brazilian Public Health System.

Introduction: Hereditary angioedema (HAE) due to C1 inhibitor (C1-INH) deficiency is an ultra-rare autosomal dominant inherited disease that affects 1 in 67,000 people in the world. The attacks are based on subcutaneous and submucosal edema that can lead to death if not properly managed. Considering the lack of information on the clinical management of Brazilian patients with HAE, this study aimed to identify and characterize patients with HAE-C1-INH that used danazol prophylactic treatment in the Brazilian Public Health System (SUS) and the healthcare resource utilization (HCRU). Methods: This was an observational retrospective database study with patients treated with danazol from January 2011 until December 2021 within the SUS. The HAE cohort included patients with 12 years or older with at least one record for ICD-10 D84.1, one claim for danazol record, and at least 6 months of available history in the database. Results: Our study included 799 patients treated in the SUS, with a mean (SD) age at danazol initiation of 40 years (16). The number of patients with HAE showed a similar distribution over this 10-year period analyzed with the highest number of patients in 2015 (n = 509) and 2016 (n = 480). A total of 253 (32%) patients had a record of at least one attack. Of those, 45 (17.8%) had at least one procedure HAE-related hospital admission, and 128 (50.6%) had at least one HAE-related hospital admission. The mean (SD) hospitalization length of stay was 5 (8) days. Over 14% (n = 36) of HAE patients with attack (n = 253) had at least one HAE-related ICU admission. Conclusion: This database study is the strategy used to allow us to find and describe the characteristics of patients with HAE who use danazol for long-term prophylaxis in the SUS and identify HCRU outcomes of interest such as hospitalizations, inpatient, and outpatient settings. The high rate of attacks, hospitalizations, and general resource uses highlights the necessity to increase awareness of new strategies and accurate approaches to treat HAE patients. Therefore, our findings are important indicators that our health system and guidelines need to be revised and improved to properly diagnose, treat, and assist patients with HAE.

The Use of Gonadotropin Releasing Hormone to Manage Intraspecific Agonism in a Coalition of Male Lions (Panthera leo).

While housing nonbreeding all-male social groups of African lion (panthera leo) is a necessary part of managing this polygynous species ex situ, resulting intraspecific agonistic behavior can negatively impact animal welfare and guest experience, undermining two primary objectives of modern zoological gardens. Improvest is a gonadotropin releasing factor analog-diphtheria toxoid conjugate marketed for temporary immunological castration which has proven successful in reducing aggression in other zoo-housed species. To the authors' knowledge, the use of this technique has not been described in male African lions; reticence to use GnRH agonists may stem from concern about phenotypic effects (mane loss) and zoo visitor perception. We describe the use of Improvest in conjunction with other management changes to manage agonism in a coalition of African lions (3.0) housed at the Oakland Zoo. Daily agonism scores were calculated via animal care staff records, fecal testosterone levels were measured, and monthly photos were taken to monitor phenotypic changes. While agonism scores varied seasonally in three pretreatment years, a significant (p < 0.05) reduction in the frequency of agonistic behavior began within 2 months of initial treatment. Two lions showed testosterone suppression within 2 months of receiving the first vaccine, while the third showed suppression beginning in the period 4 months after the first vaccine. Mane loss occurred in all three lions, and time to mane regrowth varied between individuals. Improvest, combined with other management strategies, decreased overall fecal testosterone and intraspecific agonism in these lions, and may be an effective tool in other male coalitions.

Serum Androgens as Predictive Biomarkers: Results From a Randomized Clinical Trial Comparing Enzalutamide and Abiraterone Acetate in Men With Metastatic Castration-Resistant Prostate Cancer.

INTRODUCTION: The purpose of this study was to investigate the association between baseline androgen concentrations and outcomes in men with metastatic castration-resistant prostate cancer (mCRPC) treated with first-line enzalutamide or abiraterone acetate plus prednisone (AAP). MATERIALS AND METHODS: We previously randomized men with mCRPC to enzalutamide or AAP to compare side-effects and measured androgen concentrations. In this post-hoc analysis, patients were grouped in quartiles (Q) based on their serum androgen values. Kaplan-Meier and Cox regression were used to analyze progression-free and overall survival for baseline androgen groups, treatment subgroups and their interaction. The trial was registered at clinicaltrialsregister.eu (2017-000099-27). RESULTS: Eighty-four patients received enzalutamide and 85 AAP. Overall, higher (Q4) compared with lower (Q1) baseline serum testosterone was associated with longer progression-free survival (24.8 vs. 10.7 months, hazard ratio [HR] 0.52, 95% confidence interval [CI] 0.33; 0.84) and overall survival (52.8 vs. 31.5 months, HR 0.49, 95% CI 0.28; 0.85). The risk reduction in death seemed to be treatment dependent (treatment subgroup interaction P = .04). For men in the AAP subgroup, the Q4 compared with Q1 group had a significant lower risk of death (HR 0.30, 95% CI 0.13; 0.73), while no difference was found for enzalutamide (HR 0.77, 95% CI 0.35; 1.69). Similar results were found for the other androgens. CONCLUSION: Pre-treatment serum testosterone levels may be a clinically useful biomarker for predicting mCRPC treatment responses and guiding treatment selection.

Cardiometabolic Aspects of Congenital Adrenal Hyperplasia.

Treatment of classic congenital adrenal hyperplasia (CAH) is directed at replacing deficient hormones and reducing androgen excess. However, even in the era of early diagnosis and lifelong hormonal substitution, the presence of CAH is still associated with numerous complications and also with increased mortality. The aim of this article was to create an authoritative and balanced review concerning cardiometabolic risk in patients with CAH. The authors searched all major databases and scanned reference lists of all potentially eligible articles to find relevant articles. The risk was compared with that in other forms of adrenal insufficiency. The reviewed articles, most of which were published recently, provided conflicting results, which can be partially explained by differences in the inclusion criteria and treatment, small sample sizes and gene-environmental interactions. However, many studies showed that the presence of CAH is associated with an increased risk of weight gain, worsening of insulin sensitivity, high blood pressure, endothelial dysfunction, early atherosclerotic changes in the vascular wall and left ventricular diastolic dysfunction. These complications were more consistently reported in patients with classic than non-classic CAH and were in part related to hormonal and functional abnormalities associated with this disorder and/or to the impact of over- and undertreatment. An analysis of available studies suggests that individuals with classic CAH are at increased cardiometabolic risk. Excess cardiovascular and metabolic morbidity is likely multifactorial, related to glucocorticoid overtreatment, imperfect adrenal hormone replacement therapy, androgen excess and adrenomedullary failure. Cardiometabolic effects of new therapeutic approaches require future targeted studies.

Cardiovascular disease and testosterone therapy in male hypogonadism.

This review assesses the evidence of the physiological effects of testosterone on cardiovascular health, the association between male hypogonadism and cardiovascular health, and the effects of testosterone therapy on cardiovascular health in male hypogonadism. Preclinical studies suggest complex effects of testosterone on cardiovascular risk by acting on skeletal muscle, cardiomyocytes, vasculature, adipocytes, insulin action, and erythropoiesis. Furthermore, low testosterone has a bi-directional association with cardiometabolic risk. Observational studies have reported worse metabolic profiles in men with organic hypogonadism. However, a consistent association between major cardiovascular events and male hypogonadism has not been established. Hematocrit increases with testosterone therapy; however, most studies do not report an increase in venous thromboembolism risk. Although some observational studies and a small randomized controlled study reported an increased risk of cardiovascular disease, recent data confirm the medium-term cardiovascular safety of testosterone therapy in middle-aged and older men with low testosterone.

Decoding 11-oxygenated androgen synthesis: insights from enzyme gene expression and LC-MS/MS quantification.

BACKGROUND: Adrenal-origin and peripheral tissue-transformed 11-oxygenated androgens are recognized as significant androgens. However, our current understanding of the synthesis of 11-oxygenated androgens, including the organs and cell types involved, remains limited. METHODS: We performed comprehensive analyses on an extensive dataset of normal human tissues, which included bulk RNA data from 30 tissues, single-cell RNA sequencing (scRNA) data from 16 tissues and proteomics data from 29 tissues, to characterize the expression profiles of enzyme-encoding genes. To validate the findings, immunohistochemical and liquid chromatography-tandem mass spectrometry (LC-MS/MS) techniques were employed. RESULTS: Our investigation revealed that the gene expression levels of the enzymes HSD11B2 and AKR1C3 were notably elevated in the kidney and intestines. Intriguingly, within these organs, we observed an increasing trend in enzyme expression with age in women, while a decreasing trend was apparent in men. scRNA analysis revealed that HSD11B2 was predominantly expressed in collecting duct principal cells in the kidney, while AKR1C3 was primarily expressed in the proximal tubules. Intriguingly, nearly all epithelial cells in the intestine expressed these key enzymes. Further analysis using LC-MS/MS revealed that the kidney exhibited the highest levels of 11-ketoandrostenedione (11KA4) and 11-ketotestosterone (11KT) among the seven tissues examined, and substantial synthesis of 11KA4 and 11KT was also observed in the intestine. Finally, we developed the TransMap website (http://gxmujyzmolab.cn:16245/TransMap/) to provide comprehensive visualization of all currently available transcriptome data. CONCLUSION: This study offers an overarching perspective on tracing the synthesis of 11-oxygenated androgens in peripheral tissues, thereby providing valuable insights into the potential role of these androgens in humans.

Androgen Deprivation Therapy and the Risk of Newly Developed Dry Eye Syndrome in Patients with Prostate Cancer: A Nationwide Nested Case-Control Study in the Republic of Korea.

Background: We aimed to evaluate the association between androgen deprivation therapy (ADT) and newly developed dry eye syndrome (DES) in patients with prostate cancer. Methods: A nested case-control study was conducted. From the nationwide claims database of the Republic of Korea, 125,005 patients were included in the final analysis. Cases were defined as those newly diagnosed with DES during follow-up, and 12,654 patients were identified. The cases were matched with controls in a ratio of 1:4. Odds ratios (ORs) for newly developed DES associated with ADT were estimated using conditional logistic regression. Results: After matching, 7499 cases and 29,996 controls were selected. ADT was associated with a reduced risk of newly developed DES in patients with prostate cancer compared to no ADT (OR = 0.875; 95% confidence interval, 0.825-0.927; p < 0.0001). An accumulated dose of ADT < 1 year was associated with a reduced risk of incidental DES (OR = 0.811; 95% CI, 0.751-0.875; p < 0.0001), and a duration of 1-2 years was also associated with a reduced risk (OR = 0.890; 95% CI, 0.802-0.986; p = 0.026). No association was observed with an ADT duration of ≥2 years. Conclusions: The use of ADT, especially for shorter durations (<2 years), was associated with a reduced risk of newly developed DES in S. Korean patients with prostate cancer.

HSD3B1 genotype and outcomes in metastatic hormone-sensitive prostate cancer with androgen deprivation therapy and enzalutamide: ARCHES.

HSD3B1 encodes 3ß-hydroxysteroid dehydrogenase-1, which converts adrenal dehydroepiandrosterone to 5α-dihydrotestosterone and is inherited in adrenal-permissive (AP) or adrenal-restrictive forms. The AP allele is linked to castration resistance, mainly in low-volume tumors. Here, we investigate the association of HSD3B1 alleles with outcomes in ARCHES, a multinational, double-blind, randomized, placebo-controlled phase 3 trial that demonstrated clinical benefit with enzalutamide plus androgen deprivation therapy (ADT) in men with metastatic hormone-sensitive prostate cancer (mHSPC) compared to those treated with placebo plus ADT. There are no significant differences between genotypes for clinical efficacy endpoints. Enzalutamide significantly improves radiographic progression-free survival and overall survival vs. placebo irrespective of HSD3B1 status. Men with the AP genotype have higher post-progression mortality and treatment-emergent adverse events, including hypertension, cardiovascular events, and gynecomastia, but a lower fracture rate. Overall, enzalutamide is beneficial in men with mHSPC independent of the HSD3B1 genotype. Inherited polymorphisms of HSD3B1 may account for differential toxicities.

Reproductive neuroendocrine defects programmed by prenatal testosterone treatment between gestational days 60-90 are amplified by postnatal obesity in sheep.

Polycystic ovary syndrome (PCOS) is the leading cause of anovulatory infertility in women of reproductive age, and obesity can increase the severity and development of the PCOS phenotype. Prenatal testosterone (T) treatment between gestational days 30-90 advanced puberty and disrupted the reproductive and metabolic phenotype in female sheep, recapitulating attributes of women with PCOS, with postnatal obesity amplifying its severity. On the other hand, prenatal T treatment from gestational days 60-90 led to a much milder phenotype. We hypothesized that reproductive neuroendocrine defects programmed by prenatal T treatment between gestational days 60-90 are amplified by postnatal obesity in sheep. Suffolk ewes received T propionate (T; 100 mg) or corn oil (C; vehicle) twice weekly from gestational days 60-90. At 5 months of age, T lambs were assigned to either a maintenance (100% of NRC requirements) or overfed (130% NRC) diet and C lambs were fed the maintenance diet. We compared the timing of puberty (n = 15/group) determined by twice weekly measurement of progesterone concentrations, estradiol positive feedback responsiveness (n = 8/group) determined by assessing LH secretion in response to exogenous estradiol, periovulatory LH dynamics during the second breeding season (n = 8/group) following synchronization with two injections of PGF2α, and progesterone negative feedback (n = 8/group) determined by characterizing LH pulses during the mid-luteal phase between C, T-maintenance and T-overfed groups. Our findings indicate that postnatal obesity: 1) exacerbated reproductive defects and further deteriorated reproductive cyclicity during the second breeding season (adulthood); 2) did not amplify the impairment in estradiol positive feedback in delaying the timing and amplitude of the LH surge, although it reduced the total amount of LH secreted during the preovulatory LH surge; 3) amplified the reduced responsiveness to progesterone negative feedback manifested as an increase in LH pulse amplitude and peak. These observations, in addition to supporting our previous findings that prenatal T treatment results in reproductive neuroendocrine dysfunction and periovulatory disruptions, provide evidence that these neuroendocrine defects programmed between gestational days 60-90 are amplified by postnatal obesity in female sheep.

Addition of testosterone to endocrine care for transgender women: a dose-finding and feasibility trial.

OBJECTIVE: Transgender women who underwent gonadectomy have lower serum testosterone concentrations than cisgender women. There is uncertainty regarding the dosing and side effects of supplementation of testosterone in transgender women. This study aimed to assess the feasibility of dosing testosterone to the cisgender female physiological range in transgender women. In addition, we explored changes in cardiovascular parameters, virilizing side effects, and clinical symptoms. DESIGN: This is an open-label, single-arm feasibility study. Participants initially went through a dose-titration phase with 2-week intervals of 0.07-0.09-0.13 mL (277-318-403 µg bioavailable testosterone) testosterone 2% gel to establish a dose leading to serum testosterone concentrations between 1.5 and 2.5 nmol/L. This dose was then continued for 8 weeks. METHODS: Participants applied daily transdermal testosterone 2% gel (Tostran®) at the prescribed dosage. Testosterone was measured every 2-4 weeks. Laboratory analyses, side effects, and clinical symptoms were evaluated. RESULTS: In total, 12 participants were included. Most participants required a dose of 0.07 mL (277 µg bioavailable testosterone) or 0.09 mL (318 µg bioavailable testosterone) to reach serum testosterone concentrations of 1.5-2.5 nmol/L. Continuing this dose, testosterone concentrations remained stable throughout the study. Changes in clinical outcomes were in the desired direction, and side effects were mild. CONCLUSIONS: The use of testosterone supplementation in transgender women seems feasible and safe in the short term. Although dosing requires personalized titration, stable testosterone levels can be established. A blinded, placebo-controlled, randomized clinical trial is needed to study the clinical benefit.

Beyond reproduction: unraveling the impact of sex hormones on cardiometabolic health.

This review thoroughly explores the multifaceted roles of sexual hormones, emphasizing their impact beyond reproductive functions and underscoring their significant influence on cardiometabolic regulation. It analyzes the broader physiological implications of estrogen, testosterone, and progesterone, highlighting their effects on metabolic syndrome, lipid metabolism, glucose homeostasis, and cardiovascular health. Drawing from diverse molecular, clinical, and therapeutic studies, the paper delves into the intricate interplay between these hormones and cardiometabolic processes. By presenting a comprehensive analysis that goes beyond traditional perspectives, and recognizing sexual hormones as more than reproductive agents, the review sheds light on their broader significance in health and disease management, advocating for holistic and personalized medical approaches.

Role of sex steroids in colorectal cancer: pathomechanisms and medical applications.

Given that the colon represents the most extensive hormone-responsive tissue in the human body, it prompts a compelling inquiry into whether the progression of its cancer is intimately linked to hormonal dynamics. Consequently, the interplay between sex steroids - a pivotal constituent of hormones - and colorectal cancer has increasingly captivated scientific interest. Upon a comprehensive review of pertinent literature both domestically and internationally, this study delineates the present landscape of three pivotal steroids - estrogen, progestin, and androgen - in the context of colorectal cancer. More specifically, this investigation probes into the potential utility of these steroids in providing therapeutic interventions, diagnostic insights, and prognostic indicators. Furthermore, this study also delves into the mechanistic pathways through which sex steroid interventions exert influence on colorectal cancer. It was discovered that the trio of sex steroid hormones partakes in an array of biological processes, thereby influencing the onset and progression of colorectal cancer. In conclusion, this study posits that a profound interconnection exists between colorectal cancer and sex steroids, suggesting that elucidating the targets of their action mechanisms could unveil novel avenues for the diagnosis and prevention of colorectal cancer.