Testosterone and Glucose Homeostasis in Adult Males: Current Insights and Future Prospects.

Insulin plays a central role in blood glucose regulation, with insulin resistance contributing to the progression of prediabetes to diabetes, underscoring the importance of early intervention. Androgens, primarily synthesized in the testis under pituitary gland influence, impact male reproductive function. Testosterone, crucial for sexual development and secondary male characteristics, declines with age, leading to issues like anemia, sexual dysfunction, and reduced bone density. Sex-specific differences in glucose metabolism highlight males' lower insulin sensitivity and less effective glucose utilization compared to females due to androgenic effects. Testosterone's intricate role extends to potential benefits in glycemic control, fat mass reduction, and muscle strength increase in men with diabetes. However, cautious consideration of testosterone therapy is crucial, especially in the presence of underlying health conditions, warranting further research for clear guidelines in managing hyperglycemia.

Gestational diabetes mellitus may predispose to metabolic dysfunction-associated steatotic liver disease.

The development of type 2 diabetes mellitus is a major contributing factor to the worldwide health burden of metabolic dysfunction-associated steatotic liver disease (MASLD). Insulin resistance, subclinical inflammation, dyslipidemia, obesity, and hypertension are all factors in this reciprocal interaction that contribute to the development of MASLD, which includes hepatocellular carcinoma, advanced fibrosis/cirrhosis, and non-alcoholic steatohepatitis (NASH). A new risk factor for MASLD/NASH that affects the course of the disease independently throughout life is gestational diabetes mellitus (GDM). Women with a history of GDM had a higher chance of developing NASH, according to a recent study that used a large-scale database. Although the precise etiology is yet unknown, temporary disruption of pancreatic beta cell activity during pregnancy may set off systemic inflammation, affecting distant organs including the liver. Early screening and management strategies are crucial in mitigating MASLD progression and preventing adverse cardiovascular events in affected individuals.

Artificial night light and thyroid cancer.

BACKGROUND: The occurrence of thyroid cancer (TC) has increased in recent decades. Exposure to outdoor artificial light at night (ALN) is associated with an increased risk of cancer. AIM: To investigated the impact of ALN, as a significant environmental pollutant, on TC incidence worldwide. METHODS: The assessment involved analyzing satellite ALN data in conjunction with TC incidence data [adjusted standardized rate (ASR)], while considering the quality of cancer registries (QCR), gross domestic product (GDP) per person, and health expenditure per person (HEP) for each country. RESULTS: Results indicated a correlation between higher ASR and ALN exposure percentages, particularly in countries with higher GDP or HEP quartiles (all P< 0.05). Significant differences in ASR were observed across QCR levels, both high and low quality (all P < 0.05), but not in countries without registry activity. However, when evaluating ASR against ALN exposure percentages while considering GDP/HEP quartiles or QCR levels, no significant associations were found (all P > 0.10). CONCLUSION: The findings suggest a potential link between higher GDP and adverse health conditions, serving as possible risk factors for TC, rather than a direct association with ALN. Limitations include the use of cross-sectional data, temporal misalignment, and reliance on ALN as a socioeconomic proxy. It is proposed that light pollution might be connected to a lifestyle conducive to carcinogenesis. Additionally, the presence of higher GDP/HEP could enhance access to diagnostic resources, potentially facilitating TC diagnosis and inclusion in cancer registries.

Future clinical prospects of C-peptide testing in the early diagnosis of gestational diabetes.

Gestational diabetes is typically diagnosed in the late second or third trimester of pregnancy. It is one of the most common metabolic disorders among expectant mothers, with potential serious short- and long-term complications for both maternal and offspring health. C-peptide is secreted from pancreatic beta-cells into circulation in equimolar amounts with insulin. It is a useful biomarker to estimate the beta-cell function because it undergoes negligible hepatic clearance and consequently it has a longer half-life compared to insulin. Pregnancy induces increased insulin resistance due to physiological changes in hormonal and metabolic homeostasis. Inadequate compensation by islet beta-cells results in hyperglycemia. The standard oral glucose tolerance test at 24-28 wk of gestation sets the diagnosis. Accumulated evidence from prospective studies indicates a link between early pregnancy C-peptide levels and the risk of subsequent gestational diabetes. Elevated C-peptide levels and surrogate glycemic indices at the beginning of pregnancy could prompt appropriate strategies for secondary prevention.

Caring for the Older Transgender Adults: Social, Nursing, and Medical Challenges.

Aging is a challenging process for people with gender nonconformity. Indeed, the older transgender population faces several disparities in accessing and using health care and social support services. Furthermore, the clinical management of gender transition in later life is empirical since clear research evidence is lacking. This paper aimed to present the problems encountered by older transgender adults in their access to social support and health care and to propose insightful solutions to address them both from a social and medical/nursing perspective. Trans elders face profound disparities in health and social care due to factors associated with limited accessibility to health services, social restrictions, administrative failures, and physical vulnerabilities. The medical treatment of older transgender adults also needs a careful approach to achieve satisfying gender affirmation without clinically significant risks. The potential induction of hormone-sensitive malignancies and the provocation of major adverse vascular events are the main concerns. Gender transition in older adults without a prior history of following gender-affirming therapy is challenging due to biological factors related to advanced age. Caring for elderly trans people unfolds at multiple levels. International organizations and governmental bodies should address the underprivileged status of elderly transgender people by creating and implementing inclusive policies. Safe and respectful clinical and residential environments and the formation of clearer medical guidelines could meet the unique needs of older trans adults. Care providers must advocate for their patients and be equipped to provide safe and effective services.

Glucose Homeostasis, Diabetes Mellitus, and Gender-Affirming Treatment.

The transgender (trans) population includes individuals with gender identities more fittingly aligned with the opposite sex or with an alternative that transcends the classical dipole of male/female. Hormonal treatment in transgender individuals aims to suppress the secretion of endogenous sex steroids and replace them with the steroids of the desired gender. The mainstay of gender-affirming treatment in transgender males is testosterone, whereas for transgender females it is estrogen, usually combined with an anti-androgen or a gonadotropin-releasing hormone agonist if testes are present. Testosterone and estrogen are involved in carbohydrate metabolism via direct effects on skeletal muscle, liver, adipose tissue, and immune cells and indirectly through changes in body fat mass and distribution. The effect of transgender treatment on glucose tolerance is not clear. The provided conflicting results demonstrate a positive, neutral, or even negative association between exogenous testosterone and insulin sensitivity in trans men. Studies show that feminizing hormonal therapy of trans women has mainly an aggravating effect on insulin sensitivity. The existing evidence is not robust and further research is needed to investigate the relationships between body fat distributions, muscle mass, and glycemia/insulin resistance in transgender people under hormonal therapy.

Barriers and Challenges in Caring for Transgender People: Implications for Clinical Practice and the Experience From a Specialized Center.

Background: Transgender people often experience social exclusion and transphobic attitudes, which have an adverse impact on their socioeconomic life and health status. Within health services, -discriminatory practices and mistreatment derive from the lack of cultural competence by -healthcare providers. Objective: This article features existing barriers in the provision of healthcare to transgender populations and suggests approaches to manage the relevant challenges. Methods: A thorough review of the literature was performed, and the operation of a specialized unit wass presented. Results: Health professionals are often unskilled or unwilling to offer transgender care, while most healthcare service institutions do not offer specialized treatments. Incomplete health insurance coverage and shortages of personal income impede trans individuals' access to healthcare. Certain practices and policies are needed for scientifically and culturally competent services. Conclusions: The social vulnerability and the unique health needs of transgender persons urgently call for accessible and effective care for gender minority individuals. The integration of gender identity issues into continuous medical and nursing education is a key component of transgender-friendly care. Implications for Nursing: The integration of diversity as a core value in health services, the ability of health personnel to deliver transgender care, and the provision of insurance coverage solely based on medical needs are necessary steps to achieve social justice in healthcare.

Melatonin's actions are not limited to sleep.

Melatonin is widely available as a supplement, usually for sleep disorders. The consumption of melatonin supplements has increased considerably in recent years. An overlooked aspect of melatonin's administration is the resulting increase in prolactin secretion, via its action on hypothalamic dopaminergic neurons. We believe that since the effect of melatonin on prolactin is tangible, the laboratory finding of hyperprolactinemia could be encountered more often, given the increase in melatonin's use. This is an issue that merits further study.

Liver function in transgender persons: Challenges in the COVID-19 era.

Transgender persons constitute a non-negligible percentage of the general population. Physical gender-transitioning in trans persons is mainly achieved with hormonal cross-sex therapy and sex reassignment surgeries that aim to align bodily appearance with gender identity. Hormonal treatment acts via suppressing the secretion of the endogenous sex hormones and replacing them with the hormones of the desired sex. The administration of testosterone is the typical masculinizing treatment in trans men, whilst trans women are routinely treated with estradiol agents in combination with anti-androgens or gonadotrophin-releasing hormone agonists if testes are present. Exogenous androgenic steroids, estradiol agents, and anti-androgens have been implicated in a series of hepatotoxic effects. Thus, liver integrity is a major concern with the long-term administration of cross-sex therapy. Hepatic tissue is susceptible to coronavirus disease 19 (COVID-19) through various pathophysiological mechanisms. Special consideration should be paid to minimize the risk of hepatic damage from the potential cumulative effect of COVID-19 and gender-affirming treatment in transgender patients. Appropriate care is significant, with continuous laboratory monitoring, clinical observation and, if needed, specific treatment, especially in severe cases of infection and in persons with additional liver pathologies. The pandemic can be an opportunity to provide equal access to care for all and increase the resilience of the transgender population.

The metabolic effects of hormonal treatment in transgender males: Safety of the testosterone gender-affirming therapy.

BACKGROUND: Gender dysphoria is characterised by a sense of distress because of discordance between the self-perception of gender identity and the assigned sex. Hormonal treatment of transgender males uses testosterone to induce and preserve masculinisation. OBJECTIVE: The study investigated the safety of testosterone therapy in transgender males. METHODS: The present study used a retrospective file review of transgender male subjects who were treated with testosterone (initially transdermal testosterone gel and subsequently parenteral testosterone undecanoate) for at least 18 months and had subsequently achieved a serum testosterone level within the normal range of cisgender male counterparts. Changes in somatometric data and blood biomarkers were investigated. RESULTS: The mean testosterone serum levels after approximately 18 months of treatment were about 545 ng/dL (SD ± 94 ng/dL). There was a statistically significant rise in body mass index (𝜒d = +1.23 kg/m2) with a reduction in blood glucose (𝜒d = -5.33 mg/dL) as well as statistically significant increases in aspartate transaminase (𝜒d = +4.3 U/L), haemoglobin (𝜒d = +1.72 g/dL), and haematocrit (𝜒d = +4.76%). In contrast, there were no significant changes in the lipidaemic profile of the subjects. CONCLUSIONS: Treatment with testosterone is routinely used for the promotion of virilising physical changes in transgender males. However, the likelihood of adverse effects of continuous treatment is still unclear. This study contributed to the notion that achieving testosterone levels within the target range is a prerequisite for the safety of the gender-affirming treatment.

Further understanding of thyroid function in pregnant women.

INTRODUCTION: Normal thyroid status throughout pregnancy is important for both maternal and fetal health. Despite the bulk of contemporary research honing on thyroid function in gestation and the relevant disorders, there are still gaps in our current knowledge about the etiology and treatment of thyroid diseases in pregnant women. AREAS COVERED: This article analyzes the adaptation of the thyroid gland to gestational physiological changes and attempts to explain the effect of several factors on thyroid function in pregnancy. It also stresses proper utilization and interpretation of thyroid tests during pregnancy and underlines the significance of proper screening and treatment of pregnant women aiming at favorable health outcomes. EXPERT OPINION: Appropriate strategies for diagnosing and treating thyroid disease in pregnancy are important. Laboratory thyroid testing plays a leading role, but test results should be interpreted with caution. Given the possible serious maternal and fetal/neonatal complications of thyroid disease in pregnancy, we recommend universal screening with TSH measurements of all pregnant women. Additional assessment with determination of the levels of free thyroid hormones and thyroid antibodies may be necessary under certain conditions. The economic burden of such interventions should be considered.

Glycemic profile assessment during betamethasone administration in women with twin pregnancies after IVF with or without gestational diabetes.

BACKGROUND AND AIMS: Betamethasone's effect on glycemia in twin pregnancies, with or without gestational diabetes mellitus, has not been adequately investigated. METHODS: We assessed the glycemic profile of 30 women with twin pregnancies after in-vitro-fertilization who were given betamethasone. RESULTS: The majority of women were treated eventually with insulin to maintain glycemia. In insulin-treated women the increase in insulin dosage was of 61.1%. Insulin use/dosage was not associated with betamethasone dose, age, gestational age, weight gain in pregnancy, or duration of hyperglycemia. CONCLUSION: Post-betamethasone, twin pregnancies seem to follow the same glycemia pattern as singleton pregnancies.

COVID-19 and thyroid disease: An infodemiological pilot study.

BACKGROUND: Google Trends searches for symptoms and/or diseases may reflect actual disease epidemiology. Recently, Google Trends searches for coronavirus disease 2019 (COVID-19)-associated terms have been linked to the epidemiology of COVID-19. Some studies have linked COVID-19 with thyroid disease. AIM: To assess COVID-19 cases per se vs COVID-19-associated Google Trends searches and thyroid-associated Google Trends searches. METHODS: We collected data on worldwide weekly Google Trends searches regarding "COVID-19", "severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)", "coronavirus", "smell", "taste", "cough", "thyroid", "thyroiditis", and "subacute thyroiditis" for 92 wk and worldwide weekly COVID-19 cases' statistics in the same time period. The study period was split in half (approximately corresponding to the preponderance of different SARS-COV-2 virus variants) and in each time period we performed cross-correlation analysis and mediation analysis. RESULTS: Significant positive cross-correlation function values were noted in both time periods. More in detail, COVID-19 cases per se were found to be associated with no lag with Google Trends searches for COVID-19 symptoms in the first time period and in the second time period to lead searches for symptoms, COVID-19 terms, and thyroid terms. COVID-19 cases per se were associated with thyroid-related searches in both time periods. In the second time period, the effect of "COVID-19" searches on "thyroid' searches was significantly mediated by COVID-19 cases (P = 0.048). CONCLUSION: Searches for a non-specific symptom or COVID-19 search terms mostly lead Google Trends thyroid-related searches, in the second time period. This time frame/sequence particularly in the second time period (noted by the preponderance of the SARS-COV-2 delta variant) lends some credence to associations of COVID-19 cases per se with (apparent) thyroid disease (via searches for them).

Progesterone in gender-affirming therapy of trans women.

Progesterone is an endogenous steroid hormone with an important role for the physiology of the female reproductive system and the mammary gland. It has additional significant actions in other tissues, such as the cardiovascular system, the central nervous system, and bones. The present article explores potential clinical implications from the addition of bioidentical progesterone to gender-affirming treatment of trans women. For this purpose, it provides an overview of the physiological action of progesterone in target tissues and speculates on possible benefits for gender transitioning. Progesterone is expected to exert moderate anti-androgen action through suppression of the hypothalamic-pituitary-gonadal axis and inhibition of the conversion of testosterone to dihydrotestosterone. It may also contribute to breast maturation. In the long-term, progesterone could prevent bone loss and protect cardiovascular health. The potential benefits are mainly inferred by extrapolating evidence from biological actions in cisgender women and medical assumptions and hence, clinicians need to be cautious when applying these data into practice. Further research is needed to ascertain the efficacy and safety of progesterone in current hormonal regimens.

Study on the Interaction between Serum Thyrotropin and Semen Parameters in Men.

The effect of thyroid function on semen parameters has been studied in pathological conditions in small studies. With this research work, we aimed to study thyroid hormone effects on semen parameters in 130 men who were evaluated for couple subfertility. Our study was cross-sectional. We noted semen volume, sperm concentration, total sperm count, testosterone levels and thyrotropin (TSH) levels. The analysis included ordinary least squares regression (OLS-R), quantile regression (QR) and segmented line regression (SR). Using OLS-R, a weak negative correlation was found between the logTSH levels and semen volume (r = -0.16, r2 = 0.03, p = 0.05). In Q-R, each incremental unit increase in logTSH decreased the mean semen volume between -0.78 ± 0.44 and -1.33 ± 0.34 mL (40-60th response quantile) and between -1.19 ± 0.71 and -0.61 ± 0.31 mL (70-90th response quantile) (p = 0.049). With SR, a biphasic relationship of sperm concentration with TSH was noted (positive turning to negative, peaking at TSH = 1.22 µIU/mL). Thus, a weak negative association between the TSH levels and semen volume was noted, showing a trough within the usual normal range for TSH. Moreover, a biphasic relationship between the sperm concentration and TSH was also noted, peaking at approximately mid-normal TSH levels. Based on our results, TSH explained slightly less than 3% of the variation in semen volume and 7% of the sperm concentration (thus, other factors, which were not studied here, have a more important effect on it).

Dream Recall/Affect and Cortisol: An Exploratory Study.

The effect of cortisol on dreams has been scarcely studied. The aim of this exploratory study was to assess the possible effect of cortisol levels on dream recall/affect, considering, in female subjects, their menstrual cycle phase. Fifteen men and fifteen women were recruited. Saliva samples were used for the detection of cortisol levels. Participants were instructed to provide four saliva samples, during three consecutive days. After awakening, on the second and third day, they were asked whether they could recall the previous night's dreams and whether these were pleasant or unpleasant. Female subjects followed this procedure twice: firstly, during the luteal phase and, secondly, during the follicular phase of the menstrual cycle. Subjects with higher evening or higher morning cortisol levels tended to show increased dream recall; a non-statistically significant association between morning cortisol levels and positive dream affect was also found. This association acquired statistical significance for salivary morning cortisol levels exceeding the upper normal level of 19.1 nmol/L (OR: 4.444, 95% CI: 1.108-17.830, p-value: 0.039). No connection between menstrual cycle stages and dream recall/affect was detected. In conclusion, cortisol may be a crucial neuromodulator, affecting dream recall and content. Therefore, its effects on sleep and dreams should be further studied.

Alpha-Methyldopa May Attenuate Insulin Demand in Women with Gestational Diabetes Treated with Betamethasone.

Gestational diabetes mellitus (GDM) is associated with hypertensive disorders in pregnancy. Alpha-methyl-DOPA (αMD) is a commonly used medication for hypertension in pregnant women. This medication may be associated with alteration in insulin resistance and glucose homeostasis. The aim of the present study was to investigate in 152 pregnant women whether the demands of exogenous insulin in glucocorticoid-treated women during pregnancy are different between those with GDM and hypertension treated with αMD and those without hypertension. In the group of women with GDM under insulin treatment, who received αMD for hypertension, the increase in insulin needs was relatively lower by at least 30% of the pre-admission insulin dose compared to all of the remaining women not receiving αMD in the same group (9 women vs. 50 women, p = 0.035). Our work raises the hypothesis that αMD can favorably modulate insulin sensitivity in the third trimester of pregnancy in previously insulin-treated women with gestational diabetes who receive glucocorticoids.