Exogenous Testosterone Administration Research Articles

Testosterone replacement therapy in patients with cachexia: a contemporary review of the literature.

Patients with long-term chronic illnesses frequently present with hypogonadism, which is primarily managed through exogenous testosterone. These same patients also experience a high degree of cachexia, a loss of skeletal muscle and adipose tissue. To perform a contemporary review of the literature to assess the effectiveness of testosterone replacement therapy (TRT) for managing chronic disease-associated cachexia. We performed a PubMed literature search using MeSH terms to identify studies from 2000 to 2022 on TRT and the following cachexia-related chronic medical diseases: cancer, COPD, HIV/AIDS, and liver cirrhosis. From the literature, 11 primary studies and 1 meta-analysis were selected. Among these studies, 3 evaluated TRT on cancer-associated cachexia, 3 on chronic obstructive pulmonary disease, 4 on HIV and AIDS, and 2 on liver cirrhosis. TRT showed mixed results favoring clinical improvement on each disease. Cachexia is commonly observed in chronic disease states. Its occurrence with hypogonadism, alongside the shared symptoms of these 2 conditions, points toward the management of cachexia through the administration of exogenous testosterone. Robust data in the literature support the use of testosterone in increasing lean body mass, improving energy levels, and enhancing the quality of life for patients with chronic disease. However, the data are variable, and further studies are warranted on the long-term efficacy of TRT in patients with cachexia.

Lack of association of exogenous testosterone administration with exacerbation of preexisting hidradenitis suppurativa

Lack of association of exogenous testosterone administration with exacerbation of preexisting hidradenitis suppurativa

Relationship between Androgens and Vascular and Placental Function during Pre-eclampsia.

Hypertensive disorders of pregnancy (HDP) represent a substantial risk to maternal and fetal health. Emerging evidence suggests an association between testosterone and pre-eclampsia (PE), potentially mediated through androgen receptors (AR). Nevertheless, the mechanism driving this association is yet to be elucidated. On the other hand, reports of transgender men's pregnancies offer a limited and insightful opportunity to understand the role of high androgen levels in the development of HDP. In this sense, a literature review was performed from a little over 2 decades (1998-2022) to address the association of testosterone levels with the development of HDP. Furthermore, this review addresses the case of transgender men for the first time. The main in vitro outcomes reveal placenta samples with greater AR mRNA expression. Moreover, ex vivo studies show that testosterone-induced vasorelaxation impairment promotes hypertension. Epidemiological data point to greater testosterone levels in blood samples during PE. Studies with transgender men allow us to infer that exogenous testosterone administration can be considered a risk factor for PE and that the administration of testosterone does not affect fetal development. Overall, all studies analyzed suggested that high testosterone levels are associated with PE.

Sex and Cross-Sex Testosterone Treatment Alters Gamma-Hydroxybutyrate Acid Toxicokinetics and Toxicodynamics in Rats.

Γ-hydroxybutyric acid (GHB) is widely abused due to its sedative/hypnotic and euphoric effects. In recent years, GHB use has witnessed a notable rise within the LGBTQ+ community. GHB is a substrate of monocarboxylate transporters (MCTs) and exhibits nonlinear toxicokinetics, characterized by saturable metabolism, absorption, and renal reabsorption. This study investigates the impact of exogenous testosterone administration on GHB toxicokinetics and toxicodynamics, exploring the potential of MCT1 inhibition as a strategy to counteract toxicity. Ovariectomized (OVX) females and castrated (CST) male Sprague Dawley rats were treated with testosterone or placebo for 21 days. GHB was administered at two doses (1000 mg/kg or 1500 mg/kg i.v.), and the MCT1 inhibitor AR-C 155858 (1 mg/kg i.v.) was administered 5 min after GHB (1500 mg/kg i.v.) administration. Plasma and urine were collected up to 8 h post-dose, and GHB concentrations were quantified via a validated LC/MS/MS assay. Sleep time (sedative/hypnotic effect) was utilized as the toxicodynamic endpoint. Testosterone treatment significantly affected GHB toxicokinetics and toxicodynamics. Testosterone-treated CST rats exhibited significantly lower renal clearance, higher AUC, and increased sedative effect, while testosterone-treated OVX rats demonstrated higher metabolic clearance. AR-C 155858 treatment led to an increase in GHB renal and total clearance together with an improvement in sedative/hypnotic effect. In conclusion, exogenous testosterone treatment induces significant alterations in GHB toxicokinetics and toxicodynamics, and MCT inhibition can serve as a potential therapeutic strategy for GHB overdose in both cisgender and transgender male populations.

The association of testosterone with sarcopenia and frailty in chronic liver disease.

Testosterone is an important anabolic hormone responsible for maintaining body composition and muscle mass and circulates mostly albumin-bound, or sex hormone binding globulin (SHBG)-bound or free in the plasma. Of these fractions, the latter is bioactive and exerts the androgenic effects on male population. Liver cirrhosis, the advanced stage of any chronic liver disease characterized by permanent distortions to the hepatic architecture, disrupts the hypothalamic-pituitary-gonadal axis, leading to diminished levels of free testosterone and hypogonadism. We retrieved the PubMed database to provide a synopsis of testosterone's physiology and action and summarize the effect of sarcopenia in pre-cirrhotic and cirrhotic patients. Moreover, we scoped to provide insight into the relationship of testosterone levels with sarcopenia, frailty and survival in cirrhotic and non-cirrhotic population as well as to discuss the efficacy of exogenous testosterone supplementation on the anthropometric parameters and survival of those patients. Low testosterone levels have been associated with sarcopenia, reduced body lean mass, decreased bone mineral density and frailty, thus leading to increased morbidity and mortality especially among cirrhotic patients. Furthermore, exogenous testosterone administration significantly ameliorated body composition on patients with chronic hepatic disease, without significant adverse effects. However, the current literature does not suggest any significant effect on survival of those patients. Moreover, the long-term safety of testosterone use remains an open question. Low serum testosterone is strongly correlated with sarcopenia, frailty, higher rate of hepatic decompensation and mortality. Nonetheless, exogenous supplementation of testosterone did not ameliorate the liver-related outcomes and complications.

THU576 Anabolic Androgenic Steroid Abuse In Cis-gender Female Bodybuilder

Abstract Disclosure: E.M. Niedzialkowska: None. D. Shelden: None. Introduction: Anabolic androgenic steroids (AAS) are used in bodybuilders to increase muscle mass. Abuse has surged as they are regarded as potent image enhancement drugs. There are a variety of illegal AAS available. Their true content is often unknown and dosing regimens frequently include concurrent use of multiple hormonally active agents. Use among female body builders is rarely reported. Having significantly lower levels of natural testosterone, females may be more susceptible to side effects and toxicity associated with AAS abuse. Clinical case: 36 year old cis-gender female presented to the Endocrinology clinic for evaluation of fatigue. The patient worked as a personal trainer at a gym and began participating in bodybuilding competitions. A year prior to the visit the patient was started on a steroid regimen by a friend at the gym. The patient’s regimen included testosterone cypionate (250mg-350mg a week) and trenbolone acetate. Anastozole was added to limit conversion to estrogen but was not administered on a regular basis. The patient reported no gender dysphoria. She has not had a menstrual period since she started the AAS. The patient was also diagnosed with acute kidney injury at the time of AAS initiation and further work up showed negative ANA, C3, C4, normal UA and protein/creatinine ratio. Her kidney injury was deemed to be related to NSAID and testosterone use. At the time of the visit laboratory results were significant for testosterone of >1500 ng/dl (N 240-1080), IGF-1 359 ng/ml (N 63-223), LH <0.1 mUI/ml (N>0.6), FSH <0.5 mUI/ml (N>1.4), estradiol 47 pg/ml (N 21-251), prolactin 10.8 ng/ml (N 3-30), hemoglobin 17.4 g/dl (N 12-15.1), platelets 416 bil/L (150-400), TSH 0.75 uIU/ml (N 0.4-4.5), creatinine 1.33 mg/dl (N 0.5-1.1), eGFR 53 ml/min/1.73m2. The patient's testosterone regimen was gradually decreased to 100 mg weekly with plans to further decrease the dose and with close follow up and monitoring of gonadotropins. Treatment to stimulate endogenous estrogen production may be necessary despite her current value being within normal limits as this may be a function of peripheral conversion of exogenous testosterone. Conclusion: AAS abuse is infrequent among cis-gender females. Its use in female bodybuilders increases muscle strength and athletic performance. Exogenous administration of synthetic testosterone results in negative feedback on the hypothalamic-pituitary axis, inhibiting GnRH, leading to inhibition of FSH and LH production leading to amenorrhea in females. AAS has also been associated with kidney injury with reports from animal studies suggesting testosterone induced podocyte damage and apoptosis. The steroid regimens used by bodybuilders differ and include multiple hormonally active agents. Its abuse among cis-gender women is uncommon and further research is needed to evaluate its toxicity among this group. Presentation Date: Thursday, June 15, 2023

19.4 Clinical and Neurobiological Effects of Exogenous Testosterone Administration on Transgender Youth: Implications for Mood and Social Development

19.4 Clinical and Neurobiological Effects of Exogenous Testosterone Administration on Transgender Youth: Implications for Mood and Social Development

Efficacy of Clomiphene Citrate Versus Enclomiphene Citrate for Male Infertility Treatment: A Retrospective Study.

Introduction Infertility and hypogonadism in males can greatly affect their reproductive health and overall well-being. Since exogenous testosterone administration for hypogonadism management may disrupt the normal hormonal cascade necessary for spermatogenesis, clomiphene citrate (CC) and enclomiphene citrate (EC) are medications often used to manage hypogonadism and male infertility. This study aims to directly compare the effects of CC and EC on serum testosterone levels and semen parameters in men to determine which medication may have an advantage in managing these conditions. Materials and methods We retrospectively analyzed ≥18-year-old men presenting with primary infertility, abnormal semen parameters, or hypogonadism who received CC or EC monotherapy for at least three months between January 2021 and December 2022. We compared baseline and follow-up hormone levels, semen parameters, and demographics. Variables were compared using paired and unpaired t-tests. Significance was assessed at p<0.05. Results A total of 46 men received EC and 32 men received CC. The median age was 42 (IQR: 34-47.75) years in men who received EC and 41 (IQR: 36-44) years in men who received CC (p=0.450). The two treatment groups exhibited a significant increase in serum total testosterone, while only EC had a statistically significant increase in FSH and LH. Semen volume and concentration did not significantly change with either treatment. Sperm motility increased in both groups, but total motile sperm count (TMSC) only significantly increased in men who received EC. Conclusions Our study found that EC and CC are effective treatments in increasing total testosterone without negatively affecting spermatogenesis. EC demonstrated to be more effective in raising gonadotropinlevels and TMSC.

Exogenous Testosterone Causes Delayed Postnatal Testicular Development and Disrupts Spermatogenesis

Proper postnatal development of testis is prerequisite for acquisition of full functional potential of testis. The initiation and maintenance of spermatogenesis depend on testosterone, and the production of mature sperm is highly reliant on androgen activity in the testis. The goal of the study was to investigate the effect of exogenous testosterone on testicular biometry and histomorphometry, and seminiferous epithelium in Black Bengal goat during the postnatal development. A total of 42 Black Bengal goats were divided into two categories: control and testosterone-treated; and each group again subdivided into seven groups (n=3) according to age, viz. group-I (at birth or day 0; d0), group-II (1 week of age), group-III (2 weeks), group-IV (1 month), group-V (2 months), group-VI (4 months), and group-VII (6 months). Goat kids of testosterone-treated group were injected with testosterone hormone @ 125 mg/kid (0.5 ml of Testanon™ 250 Injection, IM, 250 mg/ml, Nuvista Pharma Ltd., Bangladesh) IM weekly until the sample collection. The testicular development was slow up to 2 weeks of age, and after that, in control goats, a quick growth of the testicles was seen. In contrast, a slow trend of testicular development was continuous throughout the study period (postnatal 6 months) in testosterone-treated goats. A continuous and gradual developmental process of testis was observed in control goats. Seminiferous tubules were shown to have a marked increase in diameter at 4 months indicates initiation of spermatogenesis at this age, and completion of the first wave of spermatogenesis, i.e. establishment of spermatogenesis was observed by 6 months of age as confirmed by the presence of all types of cells of spermatogenic lineage in the seminiferous epithelium including spermatozoa were found attached to the Sertoli cells at their ad luminal border, and in the lumen of the seminiferous tubules. Continuous administration of exogenous testosterone exerted a negative effect on the postnatal developmental process of testis of Black Bengal goats. The postnatal developmental process of testis was very slow, and the proliferation of spermatogonia and lumenization of the seminiferous tubules, also known as seminiferous epithelium stratification, were not seen in testosterone-treated goats until they were 6 months old indicates delayed postnatal testicular development and disrupts spermatogenesis.&#x0D; J. of Sci. and Tech. Res. 4(1): 25-36, 2022

Up to the maximum-testosterone dose-dependent effects on anabolic and androgen responsive tissues in orchiectomized rats.

Despite the high number of synthetic androgenic-anabolic steroids, testosterone is still misused for doping in amateur and professional sports. However, only few studies investigated the dose-response effects of testosterone beyond its physiological concentrations and in over 90 years of research, no saturation dosage has been experimentally described for exogenous testosterone administration. We want to elucidate the physiological and pathophysiological effects of supra-physiological testosterone application and close this gap in testosterone dose-response data. Male orchiectomized rats were treated with different testosterone doses ranging from 0.1 to 50mg/kg body weight for 3 weeks. Several physiological endpoints (e.g., body weight, organ and muscle weight, muscle strength, muscle fiber size) were examined during and after the termination of the treatment with an adjusted Hershberger assay, open-field-test, and (immuno-)histologic. The wet weights of androgen responsive organs (penis, prostate, seminal vesicle) showed a significant increase in a dose-dependent manner. Histological evaluation of the prostate showed a significant higher percentage of KI67 positive prostate nuclei in the highest dosage group and an increasing hyperplasia with increasing testosterone administered. A significant anabolic effect was only observed in Levator ani wet weight, and to minor degree for the cardiac muscle. Regarding other skeletal muscles (Musculus soleus and Musculus gastrognemicus), no significant testosterone effects were observed. We showed a significant increasing dosage-response effect for testosterone in androgen responsive organs with saturation at the two highest concentration of 10 and 50mg/kg body weight. The dose-dependent androgenic effects of testosterone were well observable and the anabolic effects on muscle tissue were visible although to a lesser degree, without the support of aerobic exercise and a protein rich diet. Future studies should investigate a combinatorial effect of testosterone and training. Nevertheless, with the chosen range of applied testosterone, we showed a saturation of testosterone effects in prostate, seminal vesicle, penis, and Levator ani.

(046) Long-term Testosterone Pellet Insertion in Women with Low Libido Shows No Evidence of Erythrocytosis and a Minimal Side Effect Profile

Abstract Introduction Testosterone therapy for low libido in women has become more prevalent over recent years. While numerous testosterone formulations exist and have been studied in women, there has been little data assessing the safety and efficacy of subcutaneous testosterone pellet use in this population. Objective The aim of this study was to understand the biochemical effects and side effect profile of female patients who underwent testosterone pellet insertion by a single provider at an academic institution. Methods An Institutional Review Board approved retrospective chart review of all female patients undergoing testosterone pellet insertion from 2009-2022 was undertaken. Women taking 75 mg and 100 mg testosterone pellets were identified, and separately analyzed for biochemical and clinical data. Analysis of variance was performed to determine statistical significance of laboratory values over duration of testosterone pellet insertion. Results A total of 220 separate pellet insertion sessions were undertaken amongst the two cohorts. In the 75 mg cohort, the average number of pellets inserted per session was one. The average time between pellet insertion was 4.7 months (Standard error (SE) 0.1) over a five year period. There was no statistically significant change in testosterone trough levels over the duration of treatment (P=0.5105). There was also no statistically significant change in hematocrit levels from baseline (P=0.9696). In addition, no statistically significant change in systolic blood pressure was noted (P=0.8798). None of the patients in this cohort reported new or worsening acne. One patient reported mild increased facial hair growth. Two out of 19 (10.5%) patients reported vaginal bleeding during the study period, but both were also on systemic estrogen therapy at the time. In the 100 mg cohort, the average number of pellets inserted per session was one. The average time between pellet insertion was 4.3 months (SE 0.1) over an 18 month period. There was a statistically significant rise in testosterone trough levels over the duration of treatment (P=0.0168). There was no statistically significant change in hematocrit levels from baseline (P=0.7805). There was no statistically significant change in systolic blood pressure (P=0.7030). Two patients in this cohort were started on new blood pressure medications during the treatment course. None of the patients in this group reported new or worsening acne, changes in facial hair growth, or vaginal bleeding. Conclusions In both the 75 mg and 100 mg cohorts, testosterone pellet insertion lead to steady testosterone levels based on trough data, with a statistically significant rise amongst the 100mg cohort, and without any statistically significant rise in erythrocytosis rates, which is commonly seen with exogenous testosterone administration in the male population. In addition, no statistically significant changes in systolic blood pressure were noted in either cohort, along with minimal other side effects. This data suggests a relatively safe biochemical profile for regulated testosterone pellet administration in women with low libido, with a minimal side effect profile. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Boston Scientific

Loss of testosterone leads to impaired T cell function via glucocorticoids in mouse glioblastoma models

Abstract While sex differences in glioblastoma (GBM) are well established, the contribution of sex hormones on these differences has not been fully explored. Recently, the immunoregulatory effect of testosterone in other type of cancers has been reported. To evaluate the effect of testosterone on GBM, we performed castration or sham surgery on mice, followed by intracranial implantation of syngeneic glioma cells. Surprisingly, the castrated B6 mice had more aggressive tumors compared to sham surgery controls and the castration induced aggressive tumor growth could be rescued by exogenous testosterone administration. This was further confirmed by chemical blockade of androgen receptor signaling using enzalutamide. In contrast, castration in Rag1KO mouse models did not show a survival difference compared to controls, suggesting a role for lymphocytes. Interestingly, upregulated levels of circulating corticosterone in castrated mice was detected by mass spectrometry, and glucocorticoid receptor blocker reversed the survival of castrated mice, suggesting glucocorticoid-mediated systemic immunosuppression upon castration. Flow analysis revealed decreased cytokine production in CD4+ and CD8+ T cells from tumors and lymph nodes in castrated mice. We also found that tumor growth was delayed in castrated mice when tumor cells were subcutaneously implanted in the flank while decreased cytokine production in T cells in tumor and lymph nodes from flank tumor model as well. These data suggest brain-specific effect of steroid hormone on tumor control. Taken together, our findings demonstrate that testosterone regulates T cell function via glucocorticoids, and ultimately affects GBM tumor growth in a site-specific manner. Supported by grants from NIH (R35 NS127083, P01 CA245705).

Exogenous testosterone administration is associated with differential neural response to unfamiliar peer’s and own caregiver’s voice in transgender adolescents

Changes in gonadal hormones during puberty are thought to potentiate adolescents’ social re-orientation away from caregivers and towards peers. This study investigated the effect of testosterone on neural processing of emotional (vocal) stimuli by unfamiliar peers vs. parents, in transgender boys receiving exogenous testosterone as a gender-affirming hormone (GAH+) or not (GAH-). During fMRI, youth heard angry and happy vocal expressions spoken by their caregiver and an unfamiliar teenager. Youth also self-reported on closeness with friends and parents. Whole-brain analyses (controlling for age) revealed that GAH+ youth showed blunted neural response to caregivers’ angry voices—and heightened response to unfamiliar teenage angry voices—in the anterior cingulate cortex. This pattern was reversed in GAH- youth, who also showed greater response to happy unfamiliar teenager vs. happy caregiver voices in this region. Blunted ACC response to angry caregiver voices—a pattern characteristic of GAH+ youth—was associated with greater relative closeness with friends over parents, which could index more “advanced” social re-orientation. Consistent with models of adolescent neurodevelopment, increases in testosterone during adolescence may shift the valuation of caregiver vs. peer emotional cues in a brain region associated with processing affective information.

Effect of exogenous testosterone in the context of energy deficit on risky choice: Behavioural and neural evidence from males

Previous research has shown greater risk aversion when people make choices about lives than cash. We tested the hypothesis that compared to placebo, exogenous testosterone administration would lead to riskier choices about cash than lives, given testosterone’s association with financial risk-taking and reward sensitivity. A double-blind, placebo-controlled, randomized trial was conducted to test this hypothesis (Clinical Trials Registry: NCT02734238, www.clinicaltrials.gov). We collected functional magnetic resonance imaging (fMRI) data from 50 non-obese males before and shortly after 28 days of severe exercise-and-diet-induced energy deficit, during which testosterone (200 mg testosterone enanthate per week in sesame oil) or placebo (sesame seed oil only) was administered. Because we expected circulating testosterone levels to be reduced due to severe energy deficit, testosterone administration served a restorative function to mitigate the impact of energy deficit on testosterone levels. The fMRI task involved making choices under uncertainty for lives and cash. We also manipulated whether the outcomes were presented as gains or losses. Consistent with prospect theory, we observed the reflection effect such that participants were more risk averse when outcomes were presented as gains than losses. Brain activation in the thalamus covaried with individual differences in exhibiting the reflection effect. Testosterone did not impact choice, but it increased sensitivity to negative feedback following risky choices. These results suggest that exogenous testosterone administration in the context of energy deficit can impact some aspects of risky choice, and that individual differences in the reflection effect engage a brain structure involved in processing emotion, reward and risk.

IMMU-24. TESTOSTERONE FUNCTIONS AS A TUMOR SUPPRESSOR IN GLIOBLASTOMA

Abstract A sex difference in the incidence and outcome of patients with glioblastoma (GBM), the most common primary malignant brain tumor, has been well established, as male patients experience a worse prognosis. However, the contribution of sex hormones to anti-tumor immunity has not been fully explored. To test this, we orthotopically implanted syngeneic mouse GBM cells into male mice after castration or sham surgery to assess survival differences. Castrated immune-competent mice succumbed to tumors significantly faster than the sham surgery group, and this was rescued by exogenous testosterone administration. This finding was further corroborated by that blockade of androgen signaling using enzalutamide reproduced the effect of castration with shortened survival. In contrast, castration on immunocompromised mice, NSG and RAG1KO, resulted in no survival difference compared to sham animals, suggesting a role for immune system. Flow cytometry analysis of tumor-infiltrating immune cells revealed decreased cytokine production in T and NK cells from castrated mice, while no difference was found in immune cell infiltration. Flank tumor experiments suggested brain-specific regulation of T cell recruitment, as tumor growth was delayed in castrated mice with increased infiltration of CD8+ T cell. It is noted that decreased cytokine production in T cells and NK cells was observed in tumor as well as lymph nodes from flank tumor model. Surprisingly, mass spectrometry of serum revealed upregulated levels of circulating corticosterone in castrated mice regardless of tumor presence, suggesting that castration may induce systemic immunosuppression and regulate T cell infiltration to brain via upregulation of glucocorticoids. Taken together, our data demonstrate that testosterone regulates T cell immunity, possibly via glucocorticoids, and ultimately affects GBM tumor growth. Given the decreased level of testosterone in aged males with higher risk of GBM, these findings further suggest the potential therapeutic intervention of testosterone in GBM.

TRPM8 contributes to sex dimorphism by promoting recovery of normal sensitivity in a mouse model of chronic migraine

TRPA1 and TRPM8 are transient receptor potential channels expressed in trigeminal neurons that are related to pathophysiology in migraine models. Here we use a mouse model of nitroglycerine-induced chronic migraine that displays a sexually dimorphic phenotype, characterized by mechanical hypersensitivity that develops in males and females, and is persistent up to day 20 in female mice, but disappears by day 18 in male mice. TRPA1 is required for development of hypersensitivity in males and females, whereas TRPM8 contributes to the faster recovery from hypersensitivity in males. TRPM8-mediated antinociception effects required the presence of endogenous testosterone in males. Administration of exogenous testosterone to females and orchidectomized males led to recovery from hypersensitivity. Calcium imaging and electrophysiological recordings in in vitro systems confirmed testosterone activity on murine and human TRPM8, independent of androgen receptor expression. Our findings suggest a protective function of TRPM8 in shortening the time frame of hypersensitivity in a mouse model of migraine.

Comparison of short and long-acting testosterone replacement therapy for better sperm production and testosterone levels in male late-onset hypogonadism

Introduction: Testosterone Replacement Therapy (TRT) is the standard treatment for male late-onset hypogonadism. Short-acting and long-acting testosterone are currently available treatments and have been approved by the Food and Drug Administration (FDA). The administration of exogenous testosterone is known to increase sperm production and T levels in men suffering from late-onset hypogonadism. However, limited research compares the efficacy of these two types of TRT. Objective: This study aims to compare the efficacy of short-acting and long-acting testosterone replacement therapy on sperm production and T levels in men suffering from late-onset hypogonadism. Methods: We searched for electronic databases including PubMed, Cochrane Library, EMBASE, Scopus, Web of Science, Allied and Complementary Medicine Database (AMED), and Google using keywords. All studies were evaluated by three independent reviewers who resolved differences by consensus. Results: We identified 21 studies that met our inclusion criteria. After applying the inclusion criteria, only 21 database sources remain for further analysis. Conclusion: Long-acting formulas affect blood more. RCTs show TU boosts libido and testosterone. Male infertility may result from long-acting TU blocking LH and FSH. TRP improves erections by increasing motile sperm and libido. Peanut allergy-related short-acting TRT causes nausea, itching, and injection-site pain.

Exogenous testosterone administration decreases rates of ovarian follicle growth in domestic chickens

Avian egg yolks provide critical nutrients and energy reserves for a growing embryo. Once a follicle is selected into the ovulatory hierarchy, rings of yolk precursors are deposited daily until the yolk is large enough to ovulate. The composition of hen egg yolk and the mechanisms responsible for deposition in the ovarian follicle are well-studied. However, the factors that affect the rate of yolk deposition, and the number of days it takes for follicles to grow to the optimal size for ovulation, are less well-known. Social interactions appear to impact the rate of yolk deposition in many avian species and testosterone is a key hormone involved in regulating those interactions. Therefore, we hypothesized that testosterone would influence the rate of follicle growth. We tested the influences of exogenous testosterone treatment by rubbing either testosterone propionate cream (1.25 %) or a control cream to hen combs daily for 7 days to increase plasma testosterone concentrations. We then collected eggs and measured egg and yolk weight, yolk diameters, and stained and counted the number of concentric rings in each yolk. Testosterone-treated hens laid fewer eggs and grew their yolks more slowly than control hens. Testosterone also caused an increase in yolk weight but not yolk diameter. These results indicate that testosterone may play a role in the rate of yolk deposition in birds.

Testosterone functions as a tumor suppressor in glioblastoma

Abstract A sex difference in the incidence and outcome of patients with glioblastoma (GBM), the most common primary malignant brain tumor, has been well established, as male patients experience a worse prognosis. However, the contribution of sex hormones to anti-tumor immunity has not been fully explored. To test this, we orthotopically implanted syngeneic mouse GBM cells into male mice after castration or sham surgery to assess survival differences. Castrated immune-competent mice succumbed to tumors significantly faster than the sham surgery group, and this was rescued by exogenous testosterone administration. In contrast, immune-deficient NSG castrated mice survived longer than sham animals, suggesting a role for immune cells in the survival difference. Flow cytometry analysis of tumor-infiltrating immune cells further showed decreased cytokine production in T cells from castrated mice, while no difference was found in immune cell infiltration. Flank tumor experiments suggested brain-specific regulation of T cell recruitment, as tumor growth was delayed in castrated mice, with higher infiltration of CD8+ T cells but decreased cytokine production. Surprisingly, mass spectrometry of serum revealed upregulated levels of circulating corticosterone in castrated mice regardless of tumor presence, suggesting that castration may induce systemic immunosuppression via upregulation of glucocorticoids. Taken together, our data demonstrate that testosterone regulates T cell immunity, possibly via glucocorticoids, and ultimately affects GBM tumor growth. Given the decreased level of testosterone in aged males with higher risk of GBM, these findings further suggest the potential therapeutic intervention of testosterone in GBM. Supported by grants from NIH (P01 CA245705)

Effects of testosterone and exercise training on bone microstructure of rats.

Background and Aim:Male hypogonadism results from failure to produce physiological levels of testosterone. Testosterone in men is essential in masculine development, sperm production, and adult man’s health. Osteoporosis is one of the consequences of hypogonadism. Regular physical exercise and exogenous testosterone administration are frequently used to prevent or treat this condition. This study aimed to understand the effects of lifelong exercise training and testosterone levels (isolated and together) in the main bone structure parameters.Materials and Methods:A total of 24 rats were used and randomly divided into four groups: Control group (CG; n=6), exercised group (EG, n=6), testosterone group (TG, n=6), and testosterone EG (TEG, n=6). A micro-computed tomography equipment was used to evaluate 15 bone parameters.Results:Both factors (exercise training and testosterone) seem to improve the bone resistance and microstructure, although in different bone characteristics. Testosterone influenced trabecular structure parameters, namely, connectivity density, trabecular number, and trabecular space. The exercise promoted alterations in bone structure as well, although, in most cases, in different bone structure parameters as bone mineral density and medullar mineral density.Conclusion:Overall, exercise and testosterone therapy seems to have a synergistic contribution to the general bone structure and resistance. Further studies are warranted, comparing different individual factors, as gender, lifestyle, or testosterone protocols, to constantly improve the medical management of hypogonadism (and osteoporosis).