Effects Of Androgens Research Articles

Testosterone, atherosclerosis and cardiovascular risks

The study highlighted the most significant scientific works that examined the influence of androgen deficiency and its drug correction in coronary heart disease. The effects of androgens on metabolic parameters, development of atherosclerosis, inflammation, coagulation and thromboembolism, blood pressure, and development of cardiovascular complications were also evaluated. The importance of conducting long-term randomized international studies evaluating the effects of testosterone in men with androgen deficiency and cardiovascular diseases, a cautious approach to androgen replacement therapy, and the need for individualization of therapy were discussed. Cardiovascular diseases are the leading cause of mortality. Thus, the study of the role of sex steroids in the development of atherosclerosis and coronary heart disease is of great interest. Testosterone is the main sex hormone that determines a mans health. With age, testosterone levels gradually decrease, and mortality from cardiovascular complications increases. Low testosterone levels are associated with erectile dysfunction, decreased libido, decreased skeletal muscle mass, metabolic disorders, osteoporosis, and depression, and the importance of androgens for the circulatory system remains insufficiently studied. Many men receive testosterone replacement therapy, which leads to the improvement of well-being, sexual function, surge of strength, and favorable metabolic changes. The scientific literature describes the possible cardioprotective effect of testosterone, and it is believed to have vasodilating properties, shorten the QT interval, and normalize the ratio of fat and muscle mass. However, the expediency and safety of prescribing testosterone drugs to patients with hypogonadism and high cardiovascular risk is debatable because only several studies have described an increase in the number of cardiovascular complications in the androgen therapy group relative to the placebo group. Most studies on testosterone replacement therapy did not assess cardiovascular risks and excluded people with a recent stroke, heart attack, or severe heart failure. In addition, data interpretation is complicated by the lack of generally accepted international standards of testosterone for men of different ages, and most studies do not consider the change in androgen status relative to peak values at a young age and features of the receptor apparatus.

FRI376 Regulation Of Theca Cell Function By Salt-Inducible Kinases

Abstract Disclosure: M. Rodriguez Esquivel: None. E. Hayes: None. O. Lakomy: None. M. Hassan: None. R. Filzen: None. C.O. Stocco: Grant Recipient; Self; NIH R01HD097202. The most common identifiable factors of female infertility are ovulatory disorders. Ovulation is the pinnacle of folliculogenesis, a process that requires an interplay between the oocyte, the granulosa cells, and the theca cells (TCs). TCs are the only source of ovarian androgens. Androgens play vital roles in female fertility acting as substrates for estrogen production in granulosa cells and directly regulating ovarian function via the activation of the androgen receptor. However, abnormally elevated androgen levels reduce fertility in humans and animals, suggesting that a delicate equilibrium exists between the beneficial and harmful effects of androgens in the ovary. Therefore, uncovering novel mechanisms regulating androgen synthesis in TCs is of great significance. The capacity of TCs to synthesize androgens relies on the expression of the rate-limiting enzyme CYP17A1, which converts progestogens into androgens, and its stimulation by the luteinizing hormone (LH). Previously, our group showed that salt-inducible kinases (SIKs) regulate granulosa cell steroidogenesis. Here, we investigated whether SIKs play any role in the regulation of androgen production in TCs. SIK2 and SIK3 were detected by IHC in the TCs of rat ovaries. Western blot confirmed this finding using isolated rat TCs. Next, rat TCs in culture were treated with LH in the presence or absence of HG, a highly specific SIK inhibitor. SIK inhibition enhanced the stimulatory effect of LH on Cyp17a1 mRNA expression. HG alone also increased Cyp17a1 expression to levels higher than those found in the presence of LH. Similarly, HG alone increased testosterone and potentiated LH stimulation of testosterone production. SIK inhibition also enhanced the stimulatory effect of LH on the expression of StAR and Cyp11a1. Concentration-response experiments for the SIK inhibitor in the presence or absence of LH show that SIK inhibition stimulates Cyp17a1 in a concentration-dependent manner from 0.1 to 1 µM. Of note, at 3 µM, HG was less effective in inducing Cyp17a1 than at 1 µM, suggesting that higher concentrations of HG may have alternative unknown effects. Activation of adenyl cyclase with forskolin or emulation of increased intracellular cAMP with dbcAMP stimulated Cyp17a1 an effect that was also enhanced by the inhibition of SIK. Since the main target of cAMP is PKA, we used lentivirus to express constitutively active PKA (caPKA). Overexpression of caPKA was sufficient to stimulate testosterone production, an effect that was significantly augmented by SIK inhibition, suggesting that SIKs regulate factors downstream of PKA. This evidence shows that TCs express SIKs and reveal novel roles for SIKs in the regulation of TC function and androgen production. This information could contribute to uncovering therapeutic targets to treat hyperandrogenic diseases such as PCOS. Presentation: Friday, June 16, 2023

THU650 Prevalence Of Hyperandrogenemia, PCOS And Obesity In Mothers Of Daughters With PCOS

Abstract Disclosure: J. Cai: None. K. Brewer: None. R. Sisk: None. R.S. Legro: None. A.E. Dunaif: None. Prenatal exposure to androgens produces phenocopies of PCOS in animal models. In mice, there is evidence for transgenerational prenatal androgen effects. Human studies considered to support the hypothesis that intrauterine actions of androgens play a major role in PCOS pathogenesis come from (1) health registries where PCOS in mothers and daughters was diagnosed by ICD codes and (2) retrospective assessment of mother’s PCOS status in cohorts of affected women. Maternal PCOS status has not been directly assessed. As part of our genetic analyses of PCOS, we have prospectively recruited 678 mothers and 540 fathers of 678 women fulfilling NIH criteria for PCOS with confirmed hyperandrogenism and ovulatory dysfunction (OD). All subjects had fasting blood samples for reproductive hormones measured in central labs. Mothers completed a validated questionnaire for reproductive history. We tested the hypothesis that maternal PCOS accounted for PCOS in her daughter. We also investigated the contribution of maternal compared to paternal obesity to daughters’ obesity. We limited the analysis to mothers age 50 yrs and younger, with FSH <40 mIU/mL; 108 fathers were available from these families. Continuous data are reported as median and data range. Age (yrs): daughters 23 (13-24), mothers 46 (34-50), fathers 48 (37-69). Daughters had significantly higher BMI (kg/m2) (35.3, 18.5-60.0) than mothers (28.9, 18.7-54.1) and fathers (29.6, 18.4-55.5) (both P <0 .0001), while BMI did not differ in mothers and fathers. Hyperandrogenemia (HA), defined as total testosterone >58 ng/dL, biologically available testosterone >15 ng/dL or DHEAS >2683ng/mL, was present in 14.4% (20/139) of mothers, of these, 2.2% (3/139) fulfilled NIH criteria for PCOS, HA+OD. The prevalence of obesity, BMI ≥ 30.0 kg/m2, (66.2% daughter, 44.8% mother, and 45.7% fathers) was increased in daughters compared to both mothers (p= 0.0004) and fathers (p< 0.0001). Mothers with HA had higher BMI than those without it (P= 0.011). The odds ratio for obesity in daughters was 5.16 (1.97, 13.48) with maternal obesity and 2.29 (0.95, 5.52) with paternal obesity. Only ∼14% of reproductive-age mothers had HA, which we have shown in an underlying reproductive phenotype in PCOS families (Legro. Proc Natl Acad Sci USA, 1998); ∼ 2% of mothers fulfilled NIH criteria for PCOS. Although the PCOS reproductive phenotype ameliorates with age, it is clear that many affected daughters did not have a mother with hormonal features of PCOS. These findings do not support the hypothesis that prenatal androgen exposure is a final common path to PCOS in humans. The prevalence of obesity was higher in daughters than in parents and in HA mothers compared mothers without HA suggesting that obesity was associated with features of PCOS. Maternal obesity conferred greater risk for obesity in daughters than paternal obesity. Presentation: Thursday, June 15, 2023

Changes to hypothalamic volume and associated subunits during gender-affirming hormone therapy.

Among its pleiotropic properties, gender-affirming hormone therapy (GHT) affects regional brain volumes. The hypothalamus, which regulates neuroendocrine function and associated emotional and cognitive processes, is an intuitive target for probing GHT effects. We sought to assess changes to hypothalamus and hypothalamic subunit volumes after GHT, thereby honouring the region's anatomical and functional heterogeneity. Individuals with gender dysphoria and cisgender controls underwent 2 MRI measurements, with a median interval of 145 days (interquartile range [IQR] 128.25-169.75 d, mean 164.94 d) between the first and second MRI. Transgender women (TW) and transgender men (TM) underwent the first MRI before GHT and the second MRI after approximately 4.5 months of GHT, which comprised estrogen and anti-androgen therapy in TW or testosterone therapy in TM. Hypothalamic volumes were segmented using FreeSurfer, and effects of GHT were tested using repeated-measures analysis of covariance. The final sample included 106 participants: 38 TM, 15 TW, 32 cisgender women (CW) and 21 cisgender men (CM). Our analyses revealed group × time interaction effects for total, left and right hypothalamus volume, and for several subunits (left and right inferior tubular, left superior tubular, right anterior inferior, right anterior superior, all p corr < 0.01). In TW, volumes decreased between the first and second MRI in these regions (all p corr ≤ 0.01), and the change from the first to second MRI in TW differed significantly from that in CM and CW in several subunits (p corr < 0.05). We did not address the influence of transition-related psychological and behavioural changes. Our results suggest a subunit-specific effect of GHT on hypothalamus volumes in TW. This finding is in accordance with previous reports of positive and negative effects of androgens and estrogens, respectively, on cerebral volumes.

Clinical Approaches to Nestorone Subdermal Implant Therapy in Women's Health.

Segesterone acetate (SA) or Nestorone, a fourth-generation progestogen, is a synthetic compound with high progestational activity and no androgenic, glucocorticoid, or anabolic effects. However, due to its oral inactivity, SA must be used by other routes, such as subcutaneous. Thus, considering its peculiar properties, the SA subdermal implant is successfully used in female contraception and postmenopausal hormone replacement therapy (HRT). In recent years, its potential uses in endometriosis, polycystic ovaries syndrome (PCOS), and a new therapeutic possibility for neuroprotection have made this treatment extremely interesting. However, the absence of a standardized dose and the long-term safety of SA implant therapy in women is still controversial. Here, we present the possible indications, doses, limitations, and side effects of SA implant therapy.

Neuronal AR Regulates Glucose Homeostasis and Energy Expenditure in Lean Female Mice With Androgen Excess.

Hyperandrogenemia and polycystic ovary syndrome are a result of the imbalance of androgen levels in females. Androgen receptor (Ar) mediates the effect of androgen, and this study examines how neuronal Ar in the central nervous system mediates metabolism under normal and increased androgen conditions in female mice. The neuron-specific ARKO mouse (SynARKO) was created from female (Ar fl/wt; synapsin promoter driven Cre) and male (Ar fl/y) mice. A glucose tolerance test revealed impaired glucose tolerance that was partially alleviated in the SynARKO-dihydrotestosterone (DHT) mice compared with Con-DHT mice after 4 months of DHT treatment. Heat production and food intake was higher in Con-DHT mice than in Con-veh mice; these effects were not altered between SynARKO-veh and SynARKO-DHT mice, indicating that excess androgens may partially alter calorie intake and energy expenditure in females via the neuronal Ar. The pAkt/Akt activity was higher in the hypothalamus in Con-DHT mice than in Con-veh mice, and this effect was attenuated in SynARKO-DHT mice. Western blot studies show that markers of inflammation and microglia activation, such as NF-kB p-65 and IBA1, increased in the hypothalamus of Con-DHT mice compared with Con-veh. These studies suggest that neuronal Ar mediates the metabolic impacts of androgen excess in females.

Testosterone supplementation improves estrogen synthesis of buffalo (Bubalus bubalis) granulosa cells.

Granulosa cells (GCs) synthesize estrogens needed for follicular growth. However, the effects of androgen on estrogen production in buffalo GCs remain unclear. In this study, the impacts of testosterone on estrogen synthesis in buffalo GCs were examined. The results showed that testosterone that was added to cell medium at a concentration of 10-7 mol/L and applied to GCs for 48 or 72 h enhanced the estrogen synthesis of buffalo GCs. This study provides a theoretical basis for further exploration of ovarian endocrine mechanism for steroidogenesis.

Dehydroepiandrosterone (DHEA) Supplementation in Rheumatic Diseases: A Systematic Review.

Dehydroepiandrosterone (DHEA) is an adrenal hormone used to treat rheumatic conditions such as systemic lupus erythematosus (SLE), Sjogren's syndrome (SS), rheumatoid arthritis (RA) with controversial results. To review the results of DHEA use in rheumatic diseases. PubMed, Scielo, Scopus, and Embase databases were systematically searched for articles on the treatment of rheumatic diseases with DHEA between 1966 and April 2023. Twenty-one studies were identified: 13 in SLE, 5 in SS, 2 in RA, and 1 in fibromyalgia. DHEA use in SLE has shown a mild to moderate effect on disease activity, a positive effect on bone mineral density (BMD), and improved fatigue. The studies on SS showed a decrease in symptoms of dry mouth, but its performance did not differ from placebo in disease activity. In RA, a questionable effect on disease activity was noted. The only study on fibromyalgia failed to show any improvement. The drug was well tolerated; mild androgenic effects were the most common complaints. DHEA seems to have a place in SLE treatment, where it improves BMD and disease activity. The use in RA, SS, and FM is questionable.

Androgens Modulate Bcl-2 Agonist of Cell Death (BAD) Expression and Function in Breast Cancer Cells.

Androgen receptor (AR) expression in estrogen receptor-positive (ER+) breast cancer (BC) correlates with lower tumor grade and a better clinical outcome. Additionally, in normal mammary epithelium or ER+ BC preclinical models, androgens counteract basal/ER-dependent proliferation. Here, we report an additional mechanism, underlining the protective role exerted by AR. Specifically, the activation of intracellular AR upregulates the Bcl-2-family protein BAD, and TCGA database analyses show that in ER+ BC, BAD expression is associated with better disease-free survival. Ligand-activated AR influences its own and BAD cellular compartmentalization by enhancing levels in the nucleus, as well as in mitochondrial fractions. In both compartments, BAD exerts unconventional functions. In the nucleus, BAD and AR physically interact and, upon androgen stimulation, are recruited at the AP-1 and ARE sites within the cyclin D1 promoter region, contributing to explaining the anti-proliferative effect of androgens in BC cells. Androgens cause an enrichment in BAD and AR content in the mitochondria, correlated with a decrease in mitochondrial function. Thus, we have defined a novel mechanism by which androgens modulate BAD expression, its mitochondria localization, and nuclear content to force its ability to act as a cell cycle inhibitor, strengthening the protective role of androgen signaling in estrogen-responsive BCs.

An overview on androgen-mediated actions in skeletal muscle and adipose tissue

Androgens are a class of steroid hormones primarily associated with male sexual development and physiology, but exert pleiotropic effects in either sex. They have a crucial role in various physiological processes, including the regulation of skeletal muscle and adipose tissue homeostasis. The effects of androgens are mainly mediated through the androgen receptor (AR), a ligand-activated nuclear receptor expressed in both tissues. In skeletal muscle, androgens via AR exert a multitude of effects, ranging from increased muscle mass and strength, to the regulation of muscle fiber type composition, contraction and metabolic functions. In adipose tissue, androgens influence several processes including proliferation, fat distribution, and metabolism but they display depot-specific and organism-specific effects which differ in certain context. This review further explores the potential mechanisms underlying androgen-AR signaling in skeletal muscle and adipose tissue. Understanding the roles of androgens and their receptor in skeletal muscle and adipose tissue is essential for elucidating their contributions to physiological processes, disease conditions, and potential therapeutic interventions.

Systematic reviews and meta-analyses on androgen administration in humans: an umbrella review.

The present umbrella review systematically searches and synthesizes recent (2021-2023) systematic reviews and meta-analyses (SRMA) on androgen administration in humans. Results from 19 SRMA are synthesized. Four themes were identified: market for androgens, prevalence of androgen abuse, psychological effects of androgens, and clinical/therapeutic effects of androgens. One of three androgens on the illicit market are fake or substandard. Whereas one of three androgen users experiences dependence and various serious disorders, only one of three androgen users seek physician support. Additionally, androgen administration increases self-reported aggression in healthy male individuals, and abuse positively correlates with interpersonal violence. Furthermore, androgen therapy is beneficial in treating persons suffering from various chronic diseases. In this umbrella review, we identified 19 SRMA on androgen use and abuse. Results show a high prevalence of fake androgens on the illicit market, a high prevalence of androgen abuse and dependence, and that a huge proportion of androgen users tend to avoid seeking support from clinicians. Also, androgen administration increases self-reported aggression among healthy male individuals, and there is a positive correlation between androgen abuse and violent behaviors. Finally, androgens have multiple therapeutic effects on various pathology.

Spermatogenic and Androgenic Effect of The Root of Boscia Senegalensis (Per) Plant

Spermatogenic and Androgenic Effect of The Root of Boscia Senegalensis (Per) Plant

The Impact of Menopause on Cardiovascular Aging: A Comprehensive Review of Androgen Influences.

Menopause represents a critical life stage in women, characterized by hormonal changes that significantly impact cardiovascular health. While the decline in estrogen levels has long been recognized as a major contributor to cardiovascular aging in menopausal women, the role of androgens, particularly testosterone, has gained increasing attention in recent years. This comprehensive review aims to provide a thorough understanding of the impact of menopause on cardiovascular aging, with a specific focus on the influences of androgens. A literature search was conducted to gather relevant studies and clinical evidence exploring the relationship between menopause, androgens, and cardiovascular health. The review integrates findings from various studies to present a holistic view of the topic. The review outlines the changes in hormone levels during menopause and discusses the cardiovascular risk factors associated with this transition. Furthermore, it explores the impact of menopause on cardiovascular structure and function, elucidating the underlying mechanisms that contribute to cardiovascular aging. Androgens' significance in maintaining cardiovascular homeostasis is discussed, followed by exploring the effects of androgen decline during menopause on lipid profiles, insulin sensitivity, vascular function, and other cardiovascular parameters. The review delves into the mechanisms of androgen action on the cardiovascular system, emphasizing the role of androgen receptors and the intricate interplay between androgens, estrogens, and other hormones. Clinical evidence supporting the effects of androgens on cardiovascular aging is presented, including studies investigating the association between androgen levels and cardiovascular outcomes. Additionally, the impact of androgen replacement therapy (ART) on cardiovascular risk markers and events in menopausal women is examined, along with controversies and conflicting findings surrounding the use of androgen therapy in cardiovascular aging. This structured review provides a comprehensive understanding of the impact of menopause on cardiovascular aging, with a specific focus on the role of androgens. By highlighting the significance of androgens in cardiovascular health during menopause, this review aims to create an initial impression and interest among readers, inviting potential citations in the future. The findings underscore the need for further research and offer insights into managing cardiovascular aging in menopausal women, including lifestyle interventions, pharmacological approaches, and the potential role of personalized medicine and precision therapies.

Two Elderly Men with Myasthenia Gravis during Androgen Deprivation Therapy for Prostate Cancer.

Myasthenia gravis (MG) development is female-dominant in younger patients and male-dominant in older patients. The reason for the sex-ratio inversion in elderly MG patients remains unclear. One possible explanation is the decrease in androgen secretion that occurs with aging, as androgen has an immunosuppressive function. We experienced two elderly men who developed MG after initiating androgen deprivation therapy (ADT) for treatment of prostate cancer and whose symptoms were ameliorated after ADT cessation. Our cases indicate that MG in older male patients can be caused by an androgen effect.

Drone Larvae Homogenate (Apilarnil) as Natural Remedy: Scientific Review

For centuries, honey bee products such as honey, bee pollen, royal jelly, bee bread (perga), and bee venom have been utilized in natural medicine due to their beneficial properties. A great deal of scientific research has been dedicated to exploring their physico-chemical properties and therapeutic effects. Despite this, drone larvae have not received as much attention from the scientific community. Within a honey bee colony, drones are responsible solely for fertilizing queen bee eggs and consuming food reserves collected by worker honey bees. As a result, beekeepers commonly remove excess drone brood from the hive, which is crucial for preventing and treating varroasis. Lyophilization is the most effective method for preserving drone larvae, and the physicochemical properties of fresh and lyophilized drone larvae were compared. The therapeutic effects of drone larvae, such as androgenic, hepatoprotective, immunostimulatory, and hypolipidemic effects in humans and experimental animals, were summarized. This study aims to summarize current scientific knowledge on drone larvae (apilarnil). The author utilized well-known publication databases like SCOPUS, Google Scholar, and Pub Med to gather research on drone larvae. Furthermore, this review collected information on the chemical composition preservation and bioactive action of drone larvae. Thanks to their high levels of amino acids, fatty acids, vitamins, minerals, and hormones, drone larvae can be considered a potential potency-raising agent.

Effect of testosterone in young ice-hockey players on hematological, biochemical parameters and the level of physical performance

Ice-hockey combines intense physical activity at high speed with elements of power struggle. Testosterone is the main anabolic hormone, an increase in which during adolescence is associated with faster growth, increased muscle mass, physical strength, and increased overall and aerobic performance. Thus, it is interesting to study the effect of different testosterone levels on metabolic parameters and physical performance of young ice-hockey players.Objective: to compare hematological and biochemical parameters, as well as exercise performance in young ice-hockey players, depending on the testosterone level.Materials and methods: the study included 100 young ice-hockey players aged 15–17 years (average age 15.3 ± 1.1 years). The study group included 25 young ice-hockey players with an increased level of total blood testosterone (&gt; 27.5 nmol/l). The control group included 75 young athletes with normal testosterone levels. All athletes included in the study underwent the PWC 170 test to assess physical performance. Assessment of hematological parameters included hemoglobin (HGB), hematocrit, red blood cell, mean corpuscular volume (MCV), mean concentration hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC). β-crosslaps, myoglobin and creatine phosphokinase (CPK) activity were measured to assess the functional state of muscle and bone tissue.Results: A comparative assessment of the CBC in young ice-hockey players did not reveal significant differences depending on the level of serum testosterone level. Tolerance to physical activity in the study groups also did not differ. Young ice-hockey players with increased testosterone levels showed lower β-crosslaps values compared to the control group. The values of other biomarkers of the functional activity of muscle tissue did not depend on the level of testosterone levels.Conclusion: Increased serum testosterone level in the range from 27.5 to 40 nmol/l, detected in young ice-hockey players aged 15–17 years, is not associated with a change in hematological and biochemical parameters. High total testosterone levels do not improve physical performance. It is necessary to continue studies to assess the dynamics of the serum testosterone in young ice-hockey players to clarify the long-term effects of androgens on the metabolic and functional indicators of young athletes. Increasing serum testosterone levels in athletes is subject to wide discussion in the community of sports physicians and endocrinologists.

Analysis of (Anti-)Oestrogenic and (Anti-)Androgenic Activities in Wastewater from the Lodz Sewer System

This article presents the results of a study on the oestrogenicity and androgenicity of urban wastewater in Lodz, and the possibility of their removal by the Group Wastewater Treatment Plant (GWWTP). Wastewater samples were taken at five points of the sewer system in the city and at the inlet and outlet of the GWWTP. The study was conducted using Yeast Oestrogen Screen (YES)/Yeast Androgen Screen (YAS) tests, which allow a general assessment of the content of compounds with (anti-)oestrogenic and (anti-)androgenic effects in wastewater, without identifying specific substances. Wastewater samples taken from the sewage network did not show (anti-)oestrogenic activity, while oestrogenic and antagonistic properties to androgens were detected in most of them. In the influent of the treatment plant, oestrogen agonistic activity was detected only in one sample (oestrogen equivalent—EEQ equal to 1.31 × 105 ng 17 β–oestradiol/L) and was 100% removed. The purification efficiencies in GWWTP for oestrogen and androgen antagonistic activity were 51.5–99.2% and 39.4–47.1%, respectively. Although no oestrogenic activity was detected in general wastewater in Lodz, observed high-antagonistic–androgenic activities may adversely affect the water body and cause, among others, the feminization of fish, especially in the case of discharge of untreated wastewater by combined sewer overflows.

Effects of Sex and Androgenic Drugs on the Expression of Angiotensin-Converting Enzyme 2 Receptor, Cathepsin l and Transmembrane Serine Protease in Mouse Lungs

Introduction: Although males and females have the same prevalence of COVID-19, a variation in the severity of symptoms between males and females has been observed. We hypothesize that this variation can partly be explained by the effect of androgens on the infectious activity of the SARS-Cov2 virus.&#x0D; Aims: This study investigated the effect of sex and two androgenic drugs testosterone and oxandrolone on the mRNA expression of several SARS-Cov2 entry genes: angiotensin-converting enzyme 2 (ACE2), transmembrane protease serine 2 (TMPRSS2), and cathepsin l (CatL) in mouse lungs.&#x0D; Methods: Twenty-eight BALB/c mice were divided into four groups; the first three groups (all male mice) were treated with the vehicle, testosterone, and oxandrolone, respectively, while the fourth group consisted of untreated female mice. The androgenic drugs were administered for 21 days in doses equivalent to the human one. Accordingly, the expressions of ACE2, TMPRESS2, and CatL genes were measured using real-time PCR assay. In addition, the histopathological alterations in the lungs and the levels of total serum testosterone were analyzed.&#x0D; Results: We found that the expression of ACE2 was significantly upregulated in the lungs of the testosterone-treated group by 2.5 times. The expression of TMPRSS2 was also significantly upregulated in the lungs of oxandrolone-treated mice by 6.6 times. Moreover, these molecular alterations were associated with a high elevation of the serum testosterone and the induction of inflammation and oxidative stress. In addition, we found that the mRNA levels of ACE2, TMPRSS2, and CatL were significantly higher in the lungs of the female compared to male mice.&#x0D; Conclusion: We found several significant differences between the mRNA expression of ACE2, TMPRSS2, and CatL genes in the lungs of male and female mice. We showed how the administration of testosterone and oxandrolone to male mice upregulated the lungs’ mRNA expression of ACE2 and TMPRSS2, respectively. These results can expand our molecular understanding of the roles of sex and androgenic drugs on the expression of SARS-Cov2 entry genes.

Treatment of osteoporosis using a selective androgen receptor modulator ostarine in an orchiectomized rat model

PurposeThe selective androgen receptor modulator ostarine has been shown to have advantageous effects on skeletal tissue properties, reducing muscle wasting and improving physical function in males. However, data on effects in male osteoporosis remain limited. In this study, the effects of ostarine on osteoporotic bone were evaluated in a rat model of male osteoporosis and compared with those of testosterone treatments.MethodsEight-month-old male Sprague-Dawley rats were either non-orchiectomized to serve as a healthy control (Non-Orx, Group 1) or orchiectomized (Orx, Groups 2–6) and then grouped (n = 15/group): (1) Non-Orx, (2) Orx, (3) Ostarine Therapy, (4) Testosterone Therapy, (5) Ostarine Prophylaxis and (6) Testosterone Prophylaxis. Prophylaxis treatments started directly after orchiectomy and continued for 18 weeks, whereas Therapy treatments were initiated 12 weeks after Orx. Ostarine and Testosterone were applied orally at daily doses of 0.4 and 50 mg/kg body weight, respectively. The lumbar vertebral bodies and femora were analyzed using biomechanical, micro-CT, ashing, and gene expression analyses.ResultsOstarine Prophylaxis showed positive effects in preventing osteoporotic changes in cortical and trabecular bone (femoral trabecular density: 26.01 ± 9.1% vs. 20.75 ± 1.2% in Orx and in L4: 16.3 ± 7.3% vs 11.8 ± 2.9% in Orx); biomechanical parameters were not affected; prostate weight was increased (0.62 ± 0.13 g vs 0.18 ± 0.07 g in Orx). Ostarine Therapy increased solely the cortical density of the femur (1.25 ± 0.03 g/cm3 vs. 1.18 ± 0.04 g/cm3 in Orx); other bone parameters remained unaffected. Testosteron Prophylaxis positively influenced cortical density in femur (1.24 ± 0.05 g/cm3 vs. 1.18 ± 0.04 g/cm3 in Orx); Test. Therapy did not change any bony parameters.ConclusionOstarine Prophylaxis could be further investigated as a preventative treatment for male osteoporosis, but an androgenic effect on the prostate should be taken into consideration, and combination therapies with other anti-osteoporosis agents could be considered.

Evaluation of aggression level in adolescent girls with classical congenital adrenal hyperplasia.

In patients with classical congenital adrenal hyperplasia (CAH), virilization affects the brain and external genitalia due to antenatal androgen exposure. There are few studies on how the effects of androgens on brain virilization are reflected in behavior. However, there is no study focused on the adolescence period. The aim of this study was to evaluate the level of aggression in adolescent girls with classical CAH (due to 21 hydroxylase and 11β hydroxylase deficiency) and to investigate the disease-related factors that may affect aggression. Twenty female and 20 male patients aged 13-20 years, diagnosed with classical CAH, with 21 hydroxylase deficiency and 11β hydroxylase deficiency, and 20 healthy girls and 20 boys from the same age group were included. The Buss-Perry Aggression Scale (BPAS), which consists of four subgroups measuring physical aggression, verbal aggression, hostility, and angry behaviors, was used. The ages of the male and female patients with CAH were 16.30 ± 2.65 and 16.60 ± 2.41 years, respectively. Total aggression scale scores were 73.3 ± 14.6 in adolescent girls with CAH, 74.1 ± 11.2 in healthy girls, 71.5 ± 14.8 in boys with CAH, and 75.3 ± 14.5 in healthy boys (p > .05). There was no difference between the subscale scores of patients and healthy adolescents. Aggression scores in adolescents with CAH increased significantly with age. In this study, we found no difference between the aggression scores of adolescents with classical CAH compared to their healthy peers. The total aggression score and subscale were similar in unaffected female adolescents.