Inappropriate developmental exposure to steroids is linked to metabolic disorders. Prenatal testosterone excess or bisphenol A (BPA, an environmental estrogen mimic) leads to insulin resistance and adipocyte disruptions in female lambs. Adipocytes are key regulators of insulin sensitivity and tissue-specific differences in insulin sensitivity, coupled with adipose depot-specific changes in key mRNAs, were previously observed with prenatal steroid exposure. We hypothesized that depot-specific changes in the non-coding RNA (ncRNA) - regulators of gene expression would account for the direction of changes seen in mRNAs. Non-coding RNA (lncRNA, miRNA, snoRNA, snRNA) from various adipose depots of prenatal testosterone and BPA-treated animals were sequenced. Adipose depot-specific changes in the ncRNA that are consistent with the depot-specific mRNA expression in terms of directionality of changes and functional implications in insulin resistance, adipocyte differentiation and cardiac hypertrophy were found. Importantly, the adipose depot-specific ncRNA changes were model-specific and mutually exclusive, suggestive of different regulatory entry points in this regulation.

It is difficult to get evidence from randomized trials of a causal relationship between steroid hormones produced by the adrenal gland and gonad and retinal neurodegenerative disorders (RND). In this study, genetic variations of aldosterone (Aldo), androstenedione (A4), progesterone (P4), hydroxyprogesterone (17-OHP), and testosterone/17β-estradiol (T/E2) were obtained from genome-wide association studies as instrumental variables. Mendelian randomization (MR) analysis was used to assess the impact on the risk of RND, including glaucoma (8,591 cases and 210,201 controls), diabetic retinopathy (DR, 14,584 cases and 202,082 controls) and age-related macular degeneration (AMD, 14,034 cases and 91,214 controls). As the main method, inverse variance weighted results suggest that the increased glaucoma risk was affected by T/E2 (OR = 1.11, 95% CI, 1.01-1.22, P = 0.03), which was further validated by other methods (PWM = 0.03, PMLE = 0.03, PMR-RAPS = 0.03). In the replicated stage, the causal relationship between T/E2 and glaucoma was verified based on the MRC-IEU consortium (P = 0.04). No impact of Aldo, A4, P4, 17-OHP, and T/E2 was observed for the risk of DR (P > 0.05) and AMD (P > 0.05). The heterogeneity test (P > 0.05) and pleiotropy test (P > 0.05) verified the robustness of the results. Our results suggest that T/E2 has a suggestive effect on the glaucoma risk. However, the genetic evidence based on a large sample does not support the effect of steroid hormones on DR and AMD risk. Further studies are vital to assess the possibility of steroid hormones as targets for prevention and treatment.

Recent studies have found an association between high volumes of physical activity and increased levels of coronary artery calcification (CAC) among older male endurance athletes, yet the underlying mechanisms have remained largely elusive. Potential mechanisms include greater exposure to inflammatory cytokines, reactive oxygen species and oxidised low-density lipoproteins, as acute strenuous physical activity has been found to enhance their systemic release. Other possibilities include post-exercise elevations in circulating parathyroid hormone, which can modify the amount and morphology of calcific plaque, and long-term exposure to non-laminar blood flow within the coronary arteries during vigorous physical activity, particularly in individuals with pre-existing atherosclerosis. Further, although the association has only been identified in men, the role of testosterone in this process remains unclear. This brief review discusses the association between high-volume endurance exercise and CAC in older men, elaborates on the potential mechanisms underlying the increased calcification, and provides clinical implications and recommendations for those at risk.

Increasing concerns have been raised on the health risks of parabens in the regard of their widespread applications and potential endocrine disrupting activities. In this study, four typical parabens, including methyl paraben (MeP), ethyl paraben (EtP), propyl paraben (PrP), and butyl paraben (BuP) were systematically investigated for their estrogen receptor- and steroid hormone-related endocrine disruptions using multi-level approaches. Paraben exposure promoted the proliferation of MCF-7 cells, increased the luciferase activity in MVLN cells, and induced the vitellogenin (vtg) expression in zebrafish larvae, showing the typical estrogenic effects. The in vitro protein assays further revealed that PrP and BuP could bind with two isoforms of estrogen receptors (ERs). The estrogenic activities of parabens were predicted to be positively correlated with their chemical structure complexity by using molecular docking analysis. Furthermore, the synthesis and secretion of estradiol (E2) and testosterone (T) were significantly disturbed in H295R cells and zebrafish larvae, which could be regulated by paraben-induced transcriptional disturbance in both in vitro steroidogenesis and in vivo hypothalamic-pituitary-gonadal (HPG) axis. Parabens could disturb the endocrine system by activating the ERs and disrupting the steroid hormone synthesis and secretion, suggesting their potential deleterious risks to the environment and human health.

A growing body of literature has examined the role of physical activity (PA) in modifying the effects of estrogen withdrawal on cardiovascular health in postmenopausal women, but the impact of PA on androgens is less clear. Changes in androgen concentrations following regular PA may improve cardiovascular health. This narrative review summarizes the literature assessing the impact of PA interventions on androgens in postmenopausal women. The association between changes in androgen concentrations and cardiovascular health following PA programs is also examined. Randomized controlled trials were included if they (i) implemented a PA program of any type and duration in postmenopausal women and (ii) measured changes in androgen concentrations. Following PA interventions, no changes in androstenedione, conflicting changes in dehydroepiandrosterone/dehydroepiandrosterone-sulfate, and increases in sex hormone-binding globulin concentrations were found. Total testosterone decreased following aerobic PA but increased after resistance training. Most aerobic PA interventions led to reductions in free testosterone. A combination of caloric restriction and/or fat loss enhanced the influence of PA on most androgens. Evidence exploring the relationship between changes in androgens and cardiovascular health indicators was scarce and inconsistent. PA has shown promise in modifying the concentrations of some androgens (free and total testosterone, sex hormone-binding globulin), and remains a well-known beneficial adjuvant option for postmenopausal women to manage their cardiovascular health. Fat loss influences the effect of PA on androgens, but the synergistic role of PA and androgens on cardiovascular health merits further examination. Many research gaps remain regarding the relationship between PA, androgens, and cardiovascular disease in postmenopausal women.

Alexithymia is a personality trait characterized by difficulties in emotion recognition and regulation that is associated with deficits in social cognition. High alexithymia levels are considered a transdiagnostic risk factor for a range of psychiatric and medical conditions, including depression, anxiety, and autism. Hormones are known to affect social-emotional cognition and behavior in humans, including the neuropeptides oxytocin and vasopressin, the steroid hormones testosterone and estradiol, the stress hormone cortisol as well as thyroid hormones. However, few studies have investigated hormonal effects on alexithymia and on alexithymia-related impairments in emotion regulation and reactivity, stress response, and social cognition. Here, we provide a brief overview of the evidence linking alexithymia to abnormalities in hormone levels, particularly with regard to cortisol and oxytocin, for which most evidence exists, and to thyroid hormones. We address the current lack of research on the influence of sex hormones on alexithymia and alexithymia-related deficits, and lastly provide future directions for research on associations between hormonal abnormalities and deficits in emotion regulation and social cognition associated with alexithymia.

We reported that in a 29-year-old male patient with hyperthyroidism, bilateral breast swelling appeared in three days after starting methimazole and gradually aggravated. Several days later, a small amount of transparent liquid could be squeezed out from bilateral mammary glands. Breast ultrasound confirmed gynaecomastia. The level of testosterone, estradiol and luteinizing hormone increased. After the patient continued taking methimazole for a while, gynaecomastia relieved. Testosterone, luteinizing hormone and thyroid functions restored to normal. The possible mechanisms included increased levels of serum total cholesterol and relatively decreased T3 after initiating methimazole.

Citrinin, a mycotoxin existing in fruits, has nephrotoxicity, hepatotoxicity and embryotoxicity. The effects of citrinin on Leydig cell development in prepuberty remains unclear. Male Sprague-Dawley rats were gavaged with 0, 1, 2.5, and 5 mg/kg citrinin from postnatal days 21-28. Citrinin at 5 mg/kg significantly decreased serum testosterone levels, while increasing serum LH and FSH levels. Citrinin at 1-5 mg/kg markedly downregulated Hsd17b3 and HSD17B3 expression, while upregulating Srd5a1 (SRD5A1) and Akr1c14 (AKR1C14) expression at 2.5 and/or 5 mg/kg. Citrinin at 5 mg/kg also significantly increased PCNA-labeling index in Leydig cells. Citrinin at 5 mg/kg significantly raised testicular MDA amount, whiling at 2.5 and 5 mg/kg downregulating SOD1 and SOD2 expression. Citrinin at 5 mg/kg markedly decreased the ratio of Bcl2 to Bax, in consistent with the increased apoptosis in Leydig cells judged by TUNEL assay. Enzymatic assay revealed that citrinin inhibited rat testicular HSD3B1 activity at 100 µM and HSD17B3 activity at 10-100 μM. Citrinin at 50 μM and higher also induced reactive oxygen species (ROS) and apoptosis of R2C cell line. In conclusion, citrinin inhibits Leydig cell development at multiple levels via different mechanisms and oxidative stress partially plays a role.

The second-to-fourth digit ratio (2D:4D) is the putative marker of prenatal hormone exposure. The 2D:4D ratio or the right-left difference (Dr-l) are said to be negative and positive correlates, respectively, of circulating testosterone and estrogen in both adult males and females. However, previous studies on the subject have reported mixed results. This study aimed to determine the sex-moderated relationship between the 2D:4D ratio and adult circulating testosterone, estradiol, testosterone-to-estradiol ratio and the free androgen index. This was a cross-sectional study from January to June 2021 at the University for Development Studies, Ghana. The study involved 62 participants (Female = 28; Male = 34), aged between 20 and 26 years. The right (2D:4DR), the left (2D:4DL), and their difference (Dr-l) were measured by computer-assisted analysis. Fasting venous samples were assayed for total testosterone (T), estradiol (E2), and sex hormone-binding globulin (SHBG) using ELISA. The free androgen index (FAI) was then calculated (T/SHBG) and the data were analyzed using moderated and/or weighted regression. Males had significantly higher T and FAI than females while females had significantly higher E2 than males, which were independent of age and body mass index (p < 0.001). There was a significant SEX*Dr-l interaction on FAI (p = 0.007). The Dr-l correlated negatively with FAI in males but positively in females and accounted for about 94.0% of the variability of FAI in males (adjR2 = 0.940) and only 0.2% in females (adjR2 = 0.002). The 2D:4D ratio, a putative marker of prenatal hormone exposure, may have an impact on sex differences in adult free androgen index.

Male hypogonadism affects 10-30% of the male population and is often under-recognized and under-treated. Different replacement formulations exist, each with specific benefits and limitations. These replacements include gels, patches and short- and long-acting injectables. JATENZO® (oral testosterone undecanoate; Clarus Therapeutics Inc., Northbrook, IL, US) is the first oral formulation of testosterone approved by the US Food and Drug Administration. TLANDO® (oral testosterone undecanoate; Lipocine Inc., Salt Lake City, UT, US), another oral testosterone formulation, has also recently been approved by the US Food and Drug Administration. Based on unique chemistry using a self-emulsifying drug delivery system and lymphatic absorption, JATENZO and TLANDO address some of the limitations of other dosing routes while providing a safe option without evidence of liver dysfunction. This review discusses various testosterone treatment options, focusing on the role and pharmacokinetics of the new oral formulations.

Background Acne vulgaris is a common chronic inflammatory disease of the pilosebaceous units associated with long-term sequelae and complications. Currently, acne in women is classified into adolescent and post-adolescent forms. However, comparative studies evaluating the clinical and laboratory parameters across various age groups in women with acne are lacking. The aim of the study is to compare the clinical and laboratory characteristics of different groups of women with acne vulgaris. Patients and methods Over 3 years (2018-2021), a cross-sectional study was carried out on 340 women with acne consulting the Dermatology and Venereology Outpatient Clinic, Basrah Teaching Hospital, Basrah, Iraq. Eligible patients were carefully evaluated and fully examined, emphasizing on signs of hyperandrogenism and scoring of acne severity. Hormonal assays of serum total testosterone (TST), dehydroepiandrosterone sulfate (DHEAS), luteinizing hormone (LH), follicular stimulating hormone (FSH), and serum prolactin (PRL) were done. Pelvic ultrasonography was performed to identify any pelvic pathology. The patients were classified according to their age of onset. Clinical and laboratory data were compared among groups. Results Three groups were recognized: 160 patients (47%) with adolescent acne (AA) (mean age SD: 17.2±1.6 years), 80 (23.5%) with early adult-onset acne (EA) (mean age SD: 21.4±1.2 years), and 100 (29.4%) with post-adolescent acne (PA) (mean age SD: 28.7±2.9 years), which were further sub-grouped into late-onset acne (40 cases, 11.7%), and persistent acne (60 cases, 17.6%). The mean body mass index was normal in the AA group and overweight in the EA and PA groups. Moderate obesity was more frequent in PA (24%, p=0.03). While 78.5% of AA was mild to moderate acne, 77.5% of EA was moderate to moderately severe, and 72% of PA was moderately severe to severe. Clinical and biochemical markers of hyperandrogenism were seen in all groups, however, they were more frequent in PA and EA groups than in the AA group (p<005). Conclusion Clinical and biochemical hyperandrogenism were present in a significant proportion of women with acne; their prevalence was higher in post-adolescent acne than in adolescent acne. Acne that began between the ages of 20 and 25 was classified as "early adult-onset acne," and showed variable features of hyperandrogenism. A complete evaluation, regardless of age, for every female with acne, including a hormonal analysis and pelvic ultrasound examination to detect hormonal imbalances as early therapy, can help to prevent and reduce the risk of consequences.

Polycystic ovarian syndrome (PCOS) is considered the most frequent gynecological endocrine disorder that causes anovulatory infertility. The current study aimed to investigate the potential significance of selenium nanoparticles (SeNPs), an IL-1 inhibitor, in the treatment of letrozole-induced PCOS in rats that satisfied the metabolic and endocrine parameters found in PCOS patients. Letrozole (2 ppm, per orally, p.o.) was given orally to female Wistar rats for 21 days to develop PCOS. After PCOS induction, rats were given SeNPs (25 ppm/day, p.o.), SeNPs (50 ppm/day, p.o.), or metformin (2 ppm/day, p.o.) for 14 days. PCOS was associated with an increase in body weight, ovarian weight, ovarian size, and cysts, as well as an increase in blood testosterone, luteinizing hormone (LH), and insulin, glycaemia, and lipid profile levels. The SeNP administration decreased all of these variables. Furthermore, SeNPs significantly reduced letrozole-induced oxidative stress in the ovaries, muscles, and liver by decreasing elevated levels of malondialdehyde and total nitrite while raising suppressed levels of superoxide dismutase and catalase. SeNPs increased the amounts of the protective proteins Kelch-like ECH-associated protein 1 (Keap-1), nuclear factor erythroid 2-related factor 2 (Nrf2), and OH-1. It was depicted from the study that SeNPs reduce the upregulation of inflammatory cytokines that are interleukin 6 (IL-6), tumour necrosis factor α (TNF-α), and the interleukin 1 (IL-1). Our findings show that SeNPs, through their antioxidant and anti-inflammatory characteristics, alleviate letrozole-induced PCOS.

With an increasing number of patients seeking gender-affirming hormone therapy (GAHT), the clinical impact of testosterone treatments on headache needs to be determined. Our case report looks at the potential effect of testosterone on migraine among transgender patients. We present two transmasculine patients who used masculinising hormone therapy with testosterone. Both patients described their headache as moderate-to-severe pain with features that fulfilled the criteria for chronic migraine without aura. Following GAHT, one patient improved in both frequency and intensity of headache symptoms while the other noted improvement in headache intensity alone. Our report postulates that testosterone therapy may have a positive impact on headaches in individuals participating in GAHT, highlighting the need for further research on the role of testosterone therapy on headache in transmasculine individuals.

The present study aimed to determine the clinical predictive significance of HIF-1α in follicular development and assisted reproductive technology (ART). We collected follicular fluid (FF) and granulosa cells (GCs) from PCOS (polycystic ovary syndrome) patients (experimental group) and other patients who were infertile due to tubal factors or male factors (control group) with IVF/ICSI-ET. The localization and expression of HIF-1α in GCs were determined by immunofluorescence staining. HIF-1α protein and mRNA expression were detected by enzyme-linked immunosorbent assay and quantitative real-time PCR, respectively. To clarify the regulation of HIF-1α by TGF-β1, we added the HIF-1α-specific blocker YC-1 to GCs. The serum AMH, LH, LH/FSH, testosterone, BMI and the number of oocytes retrieved in the PCOS group were significantly higher, while the cleavage rate was significantly lower, than those in the control group. HIF-1α protein was expressed in the cytoplasm of GCs. The expression of HIF-1α protein in the FF of the PCOS group was significantly lower than that in the control group. However, the expression of HIF-1α protein in GCs between the two groups was not significantly different. HIF-1α protein was highly expressed in large FF (follicular diameter ≥ 14 mm). Compared with the control group, the expression of HIF-1α mRNA in GCs of the PCOS group was significantly lower. The results showed a significant positive correlation between HIF-1α and TGF-β1 expression. We found that both HIF-1α and TGF-β1 were involved in the development of PCOS follicular development. The mutual regulation of HIF-1α and TGF-β1 may be one of the important mechanisms of the occurrence and development of PCOS.