Doses Of Testosterone Research Articles

Prevalence of androgen deficiency in aging male in an outpatient population and effects of testosterone gel reposition therapy

Background: Androgen deficiency in aging male (ADAM) is characterized by hypogonadism with symptoms such as reduced sexual desire, muscle mass loss, among others. The treatment with testosterone gel and the results around weight and other indicators are the research objects. Objective: Analysis of association between ADAM and obesity in the outpatient population studied and to verify the outcomes of the testosterone gel treatment. Materials & Methods: From a group of 126 outpatients of University Hospital Mário Palmério, 40 were selected with total testosterone lower than 300ng/dL, upon the signature of written informed consent form and the realization of laboratory tests. After new testosterone dosage and urologic evaluation, 6 patients were treated for an average time of 6 months. Initially the dosage was 50 mg/day, with medical consultations and laboratory tests to verify the effects and to adjust the dosage. The variables analyzed were BMI, abdominal circumference, weight, muscle mass, body and visceral fat, in addition to testosterone serum dosages, lipid profile, amongst others, considering the test t among the beginning and end of treatment, defining the significance level by p<0,05. Results: Significant increase of total testosterone levels (p<0,001) and a tendency of improvement in the free testosterone levels (p=0,061) and no significant reduction of BMI (p=0,4308), abdominal circumference (p=0,1695), weight (p=0,999), body fat (p=0,194) and muscle mass (p=0,632), while visceral fat increased (p=0,5265). Vitamin D had no significant increase (p=0,2422). Conclusion: The total testosterone level was increased after the testosterone gel treatment with statistical significance, however there must be new research with more subjects with ADAM to prove the benefits of this treatment.

Androgen abuse and the brain.

Purpose of reviewThe purpose of this review is to examine the recent evidence regarding the effects of exogenous androgens on the brain. Understanding these effects is of high importance, as the consequences of androgens on the reproductive and endocrine system are well documented, while fewer studies have focused on the neural and cerebral consequences of androgen use.Recent findingsSupraphysiological doses of androgens have been shown to contribute to neurodegeneration, decreased brain-derived neurotrophic factor, increased inflammation and decreased neuronal density in animal studies, which may correspond to changes in mood, cognition and aggression. Findings from human studies suggest that similar behavioural and cognitive deficits may occur as a result of prolonged use of androgens. Additional evidence suggests that androgen use, particularly in high doses, may contribute to brain ageing and cerebrovascular problems.SummaryFindings from recent human and animal studies indicate that androgen use likely contributes to brain alterations, which may cause the frequently observed deficits in cognitive and emotional functioning. Although exogenous testosterone in appropriate doses for therapeutic purposes likely have some neurobiological benefits for certain populations, supraphysiological doses may cause multiple mental and physical health problems, indicating a need for additional large-scale studies in humans.

Development of a single-dose intranasal testosterone administration paradigm for use in men and women

For over two decades, researchers in the field of human social neuroendocrinology have been using single-dose pharmacological challenge protocols to determine the causal effects of testosterone on psychological, behavioural, and neural processes. Most of these single-dose administration studies have so far used (1) single-sex samples and (2) varying modes of testosterone administration (intramuscular, transdermal, sublingual, and intranasal) that produced vastly different dose-response curves. Moreover, whereas studies with male participants increased men's testosterone concentrations within the high normal physiological range, studies with women typically increased testosterone concentrations to supraphysiological levels. The purpose of this study was to develop a single-dose administration protocol using intranasal testosterone that would produce a proportionally similar rise in testosterone for both sexes. We found that an 11 mg intranasal testosterone dose in men and a 0.3 mg dose in women raised testosterone concentrations to the high normal physiological range for each sex, producing similar dose-response dynamics in both sexes. This paradigm will allow researchers to design studies with mixed-sex samples that test physiologically plausible sex differences/similarities in the causal effects of testosterone. It will also provide a replicable protocol to examine the possible adaptive functions of acute increases in testosterone in both sexes.

P–437 The ovaries of transgender men indicate effects of high dose testosterone on the primordial and early growing follicle pool

Abstract Study question Does high-dose testosterone therapy affect the stage distribution, morphological health and DNA damage repair capacity of human ovarian follicles and their survival in vitro? Summary answer Testosterone exposure is associated with reduced follicle growth activation, reduced follicle health and increased DNA damage: these further deteriorate after six days of culture. What is known already: Androgens have diverse actions within the ovary, however, there is a lack of information regarding the long-term effects of high-dose testosterone on ovarian function and reproductive potential. Cumulus-oocyte complexes recovered from transgender men have been successfully matured in-vitro but little is known regarding the impact of this gender affirming endocrine therapy on the primordial follicle pool. Study design, size, duration: Whole ovaries were obtained from four transgender men aged 25–36 years with informed consent at oophorectomy. All patients had received 1000mg testosterone undecanoate intramuscularly at 12–16 week intervals for a minimum of 4 years pre-operatively. Cortical tissues were dissected into small pieces (≈1x1x0.5mm) and either immediately fixed for histological analysis or cultured for 6 days. Testosterone-treated ovaries were compared to cortical biopsies from age-matched healthy women obtained at caesarean section (n = 4, age 26–36). Participants/materials, setting, methods: Follicle number, classification of developmental stage and morphology were evaluated by histological analysis of ovarian cortical tissue from day 0 and 6 days post culture. Immunohistochemical analysis included γH2AX as a marker of DNA damage, and meiotic recombination 11 (MRE11), ataxia telangiectasia mutated (ATM) and Rad51 as DNA repair proteins. A total of 3802 follicles from testosterone exposed and 878 from control ovaries were analysed. Main results and the role of chance: At day 0 (D0), transgender tissue had a higher proportion of non-growing follicles (92.7±1.7%) compared to control (85.4±6.2%, p < 0.05) but a lower proportion of morphologically healthy follicles (non-growing 59%, primary 61%, secondary 36%; vs 83%, 75%, 80% in controls, all p < 0.005). After 6 days in culture, the proportion of growing follicles increased (51.3% vs 46.5%) but follicle health further declined (all stages p < 0.005). DNA damage was assessed by expression of γH2AX. At D0, the proportion of oocytes showing DNA damage was significantly higher in transgender non-growing follicles (48.1±12.5%, vs 12.3±0.25%, p < 0.005). After culture, γH2AX expression increased in both transgender (p < 0.005) and controls (p < 0.005) but remained higher in transgender oocytes (non-growing 72.2%, primary 71.7% vs 27.3%, 46.2%, all p < 0.05). At D0, there was no difference in expression of DNA repair enzymes ATM and RAD51 between transgender and control oocytes, and increased expression of MRE11 in control non-growing follicles (p < 0.05). Post-culture, there was a significant increase in ATM expression in transgender non-growing oocytes compared to control (98.5% vs 77.8%, p < 0.05) and a less marked decline in RAD51 expression(p < 0.05). The expression of MRE–11 in control non-growing oocytes dramatically declined (100% to 58.2%, p < 0.05), unlike in transgender tissue where expression was comparable to D0. Limitations, reasons for caution A large number of follicles have been analysed, but only from a small number of ovaries. DNA damage at D0 and after 6 days of culture may not reflect DNA damage and repair capacity at later stages of follicle growth. The effect of duration of testosterone treatment was not investigated. Wider implications of the findings: These data indicate that high circulating concentrations of testosterone have previously unrecognised effects on the primordial and small-growing follicles of the ovary. These results may have implications for transgender men receiving gender-affirming therapy prior to considering pregnancy or fertility preservation measures. Trial registration number n/a

P-437 The ovaries of transgender men indicate effects of high dose testosterone on the primordial and early growing follicle pool

Abstract Study question Does high-dose testosterone therapy affect the stage distribution, morphological health and DNA damage repair capacity of human ovarian follicles and their survival in vitro? Summary answer Testosterone exposure is associated with reduced follicle growth activation, reduced follicle health and increased DNA damage: these further deteriorate after six days of culture. What is known already Androgens have diverse actions within the ovary, however, there is a lack of information regarding the long-term effects of high-dose testosterone on ovarian function and reproductive potential. Cumulus-oocyte complexes recovered from transgender men have been successfully matured in-vitro but little is known regarding the impact of this gender affirming endocrine therapy on the primordial follicle pool Study design, size, duration Whole ovaries were obtained from four transgender men aged 25-36 years with informed consent at oophorectomy. All patients had received 1000mg testosterone undecanoate intramuscularly at 12-16 week intervals for a minimum of 4 years pre-operatively. Cortical tissues were dissected into small pieces (≈1x1x0.5mm) and either immediately fixed for histological analysis or cultured for 6 days. Testosterone-treated ovaries were compared to cortical biopsies from age-matched healthy women obtained at caesarean section (n = 4, age 26-36). Participants/materials, setting, methods Follicle number, classification of developmental stage and morphology were evaluated by histological analysis of ovarian cortical tissue from day 0 and 6 days post culture. Immunohistochemical analysis included γH2AX as a marker of DNA damage, and meiotic recombination 11 (MRE11), ataxia telangiectasia mutated (ATM) and Rad51 as DNA repair proteins. A total of 3802 follicles from testosterone exposed and 878 from control ovaries were analysed. Main results and the role of chance At day 0 (D0), transgender tissue had a higher proportion of non-growing follicles (92.7±1.7%) compared to control (85.4±6.2%, p < 0.05) but a lower proportion of morphologically healthy follicles (non-growing 59%, primary 61%, secondary 36%; vs 83%, 75%, 80% in controls, all p < 0.005). After 6 days in culture, the proportion of growing follicles increased (51.3% vs 46.5%) but follicle health further declined (all stages p < 0.005). DNA damage was assessed by expression of γH2AX. At D0, the proportion of oocytes showing DNA damage was significantly higher in transgender non-growing follicles (48.1±12.5%, vs 12.3±0.25%, p < 0.005). After culture, γH2AX expression increased in both transgender (p < 0.005) and controls (p < 0.005) but remained higher in transgender oocytes (non-growing 72.2%, primary 71.7% vs 27.3%, 46.2%, all p < 0.05). At D0, there was no difference in expression of DNA repair enzymes ATM and RAD51 between transgender and control oocytes, and increased expression of MRE11 in control non-growing follicles (p < 0.05). Post-culture, there was a significant increase in ATM expression in transgender non-growing oocytes compared to control (98.5% vs 77.8%, p < 0.05) and a less marked decline in RAD51 expression(p < 0.05). The expression of MRE-11 in control non-growing oocytes dramatically declined (100% to 58.2%, p < 0.05), unlike in transgender tissue where expression was comparable to D0. Limitations, reasons for caution A large number of follicles have been analysed, but only from a small number of ovaries. DNA damage at D0 and after 6 days of culture may not reflect DNA damage and repair capacity at later stages of follicle growth. The effect of duration of testosterone treatment was not investigated. Wider implications of the findings These data indicate that high circulating concentrations of testosterone have previously unrecognised effects on the primordial and small-growing follicles of the ovary. These results may have implications for transgender men receiving gender-affirming therapy prior to considering pregnancy or fertility preservation measures. Trial registration number n/a

Masculinization of Nile tilapia (Oreochromis niloticus) using 17α-methyl testosteron

The biological nature of tilapia which causes uncontrolled mating and has an impact on reducing the quality of the fish has become one of the problems in tilapia aquaculture production. 5 times faster than female tilapia. The production of male monosexual tilapia can be obtained in several ways, including the application of low doses of hormones. The purpose of this study was to determine the effectiveness of using low doses of 17α Methyl Testosterone (MT) in immersing tilapia larvae and to obtain superior quality male tilapia results. This study used tilapia larvae that were 1 week old and were stocked in a tank measuring 30x60cm with a dose of MT 1 mg / l, 3 mg / l and 5 mg / l with 3 replications and 1 control. stocking density of 250 birds per cage. Soaking is carried out for 8 hours. The results of immersion of tilapia larvae using MT at a dose of 3 mg / l until the 60th day showed the highest results with the proportion of 72% compared to the untreated dose, 1 mg / l and 5 mg / l. It can be ignored that the use of low doses of 17α Methyl testosterone can affect sex changes in tilapia larvae. The results showed that the dose of 5 mg / l was the best dose with the proportion of male genitalia at 97%.

Effects of testosterone on intraocular pressure, thicknesses of retinal nerve fiber layer, ganglion cell complex, macula and on ocular blood flow in female-to-male transgender persons.

To compare the effects of testosterone on intraocular pressure (IOP), thicknesses ofretinal nerve fiber layer (RNFL), ganglion cell complex (GCC), macula and onocular blood flow between female-to-male transgender (FMT) persons who use testosterone and healthy women and healthy men. The study included 39 eyes of 20 FMT(Group 1), 40 eyes of 20 healthy women (Group 2), and 42 eyes of 21 healthy men (Group 3). In all subjects, RNFL, GCCand, macular thicknesses (MT) were measured by optical coherence tomography (OCT). Ocular blood flow was measured by Color Doppler Ultrasonography in all subjects. IOP levels in FMT were significantly higher than men (p = 0.025). Superior (Sup),inferior (Inf)thicknessesof parafovea, and nasal thicknessof perifovea in FMT were significantly higher than the Group 2 (p = 0.024, p = 0.037, p = 0.018). Sup thickness of perifoveain FMT was significantly higher than Group 3 (p = 0.011). Inf thickness of perifoveain FMT was significantly higher than Group 2 and 3 (p = 0.038, p = 0.002). Mean thickness of RNFL Inf in FMT was significantly higher than the Group 2 and 3 (p = 0.039, p = 0.032). Avg and Inf thicknesses ofGCC in FMT were significantly higher than group 2 (p = 0.02, p = 0.005). In correlation test, systole/diastole ratio(S/D) in ophthalmic artery (OA) (r = 0.504, p = 0.028) and Inf thicknessof perifovea (r = 0.485, p = 0.035) were positively correlated with the serum levels of testosterone in FMT. We found that the use of supraphysiologic testosterone dose increased IOP and the thicknesses of macula, RNFL, and GCC in FMT. Serum testosterone level was positively correlated with S/D ratio in the OA.

Effect of Late Androgen Replacement Therapy on Erectile Function Through Structural Changes in Castrated Rats.

BackgroundBecause androgen replacement therapy (ART) is not performed immediately after the onset of androgen deficiency, the treatment is considered to be late.AimTo investigate the effects of late ART, starting 4 weeks after castration of rats, on erectile function and structural changes in the corpus cavernosum.MethodsRats were subjected to ART for 4 (Late-ART [4w]) or 8 (Late-ART [8w]) weeks. In either case, rats were assigned to the following groups: castrated (Cast), castrated with subcutaneous administration of testosterone (3 mg/kg/day; Cast+T), and sham (Sham). Cast + T rats received daily subcutaneous doses of testosterone starting 4 weeks after castration for 4 or 8 weeks whereas Sham and Cast rats received only the vehicle.OutcomesErectile function was assessed by evaluating intracavernosal pressure (ICP) and mean arterial pressure (MAP) after electrical stimulation of the cavernous nerve, corporal veno-occlusive function using dynamic infusion cavernosometry, and histology using Masson's trichrome staining.ResultsNo increase in the ICP was observed in Cast+T rats in the Late-ART (4w) group (0.47 ± 0.02, P > .05), whereas, in Cast+T rats in the Late-ART (8w) group, there was a significant increase in the ICP/MAP ratio (0.60 ± 0.02, P < .05), drop rate, and smooth muscle/collagen ratio.Clinical TranslationThe present study provides scientific evidence for the effect of late ART on erectile function.Strengths and LimitationsThis study provides insights into the influence of late ART on erectile function through improvements in the structure of corpus cavernosum. The major limitation of this study is the difference in the time required for healing between the humans and rats, which might have a bearing on the translational relevenace of the results.ConclusionsLate ART could improve erectile function. However, as improvement requires a considerable time period, it is necessary to persist with therapy patiently for optimal results.Kataoka T, Hotta Y, Yamamoto Y, et al. Effect of Late Androgen Replacement Therapy on Erectile Function Through Structural Changes in Castrated Rats. Sex Med 2021;XX:XX–XXX.

Hormone therapy in transgender adults – guidelines in practice for pathologists

Transgender (trans) people include people with a binary (i.e., male or female) and non-binary identity and are one of the most marginalised groups in our community with a high burden of mental health conditions and suicidality. Due to discrimination, many fear healthcare settings. Acceptance, understanding and gender-affirming care can significantly improve distress and allay fear which is important even within pathology departments. Whilst phlebotomists will need to abide by policies for patient identification, an individual’s preferred name and pronoun should be used in interactions. Legal sex as registered with Medicare may not reflect sex-assigned at birth or inform on use of feminising or masculinising hormone therapy which impacts upon sex-specific reference ranges (i.e., haemoglobin, eGFR). There are also impacts in anatomical pathology reporting such as in providing histology of reproductive organs which may not align with gender markers. In the ideal setting, information including legal name, preferred name, sex-assigned at birth, gender identity and use of feminising or masculinising hormone therapy should be available to allow phlebotomists, pathologists and treating clinicians to provide gender-affirming care and clinically-relevant reports. Moreover, reporting of dual male and female sex-specific reference ranges may be useful for people who have recently commenced gender-affirming hormone therapy or in those using non-standard hormone regimens (i.e., low dose testosterone). Implementation of these changes presents a myriad of information system challenges but also an opportunity to ensure the highest standards of care for the Australian trans community.

Effects of Saussurea costus on apoptosis imbalance and inflammation in benign prostatic hyperplasia

Ethnopharmacological relevanceSaussurea costus (synonym: Aucklandia lappa Decne) is a medicinal plant distributed in Yunnan, Guangxi, and Sichuan in China. In traditional Korean medicine, the plant parts (especially the root—“radix aucklandiae”) is widely used to treat vomiting, diarrhea, and inflammation. However, little has been reported on its effect on benign prostatic hyperplasia (BPH), which is common in middle-aged men. Aim of the studyBPH is caused by apoptosis imbalance and inflammation due to aging of the prostate. Therefore, the aim of this was to prove the efficacy of S. costus by analyzing its effect on the biological mechanisms leading to BPH progression. Materials and methodsWistar rats were injected subcutaneously with a single dose of testosterone (125 mg/kg) to induce BPH, and were later administered with S. costus (20, 40 mg/kg). After 12 weeks, histological changes in the prostate and hormone regulation factors were assessed in all animals. Furthermore, apoptotic protein and apoptotic body values were analyzed to confirm the improvement of apoptosis imbalance, and inflammatory cytokines were analyzed to confirm the anti-inflammatory efficacy of S. costus. ResultsIn the serum and tissue of S. costus-treated BPH rats, a significant reduction in prostate weight, prostate index, and hormone regulation factors was observed. S. costus also increased the levels of apoptosis marker proteins and reduced the levels of inflammatory cytokines. It also decreased the expression of B-cell lymphoma 2 (BCL-2) and increased the expression of BCL-2 associated X protein (BAX) in the prostate. Histological changes such as epithelial thickness significantly increased in BPH induced group but significantly decreased in the S. costus-treated groups (p < 0.001). ConclusionsS. costus may prevent and treat BPH occurrence by modulating inflammation and apoptosis imbalance.

A Novel Liver-targeted Testosterone Therapy for Sarcopenia in Androgen Deprived Men With Prostate Cancer.

ObjectiveAndrogen deprivation therapy (ADT) reduces muscle and bone mass, increasing frailty in men with prostate cancer. The liver mediates the whole body anabolic effects of testosterone. Based on first-pass metabolism, liver-targeted testosterone treatment (LTTT) entails oral delivery of a small dose of testosterone that does not raise peripheral blood testosterone levels. LTTT reduces blood urea and stimulates protein anabolism in hypogonadal men and postmenopausal women. We investigated whether LTTT prevents loss of lean and bone mass during ADT.MethodA 6-month, double-blind, placebo-controlled study of testosterone 40 mg/day in 50 men. Primary outcome measures were lean mass and bone mineral content (BMC). Testosterone, urea and prostate-specific antigen (PSA) were monitored. Patients were withdrawn if PSA exceeded 4 ng/mL.Results42 patients completed the study. Mean (95% CI) testosterone rose during LTTT but not placebo treatment [∆ 2.2 (1.3-3.0) vs −0.7 (−1.5 to 0.2) nmol/L; P < 0.01]. Mean PSA level did not change significantly during either treatment. Blood urea fell [∆ −0.4 (−0.9 to −0.1) mmol/L] during LTTT but not placebo [∆ 0.05 (−0.8 to 0.9) mmol/L]. BMC [∆ 49 (5 to 93) g; P < 0.02] and lean mass [∆ 0.8 (−0.1 to 1.7) kg; P = 0.04) increased compared to placebo. Five patients on LTTT withdrew from increased PSA levels, all returning to baseline levels.ConclusionLTTT shows promise as a simple therapy for preventing sarcopenia and bone loss during ADT. LTTT may induce reversible PSA rise in some patients. Further studies are required to optimize LTTT dose in ADT. LTTT has potential application in other catabolic states in men and women.

Age Trends in Growth and Differentiation Factor-11 and Myostatin Levels in Healthy Men, and Differential Response to Testosterone, Measured Using Liquid Chromatography-Tandem Mass Spectrometry.

Growth and differentiation factor (GDF)-11 controls embryonic development and has been proposed as an antiaging factor. GDF-8 (myostatin) inhibits skeletal muscle growth. Difficulties in accurately measuring circulating GDF-11 and GDF-8 have generated controversy. We developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for simultaneous measurement of circulating GDF-8 and GDF-11 that employs denaturation, reduction, and alkylation; cation-exchange solid-phase extraction; tryptic digestion; followed by separation and quantification using 2 signature peptides for multiple reaction monitoring and C-terminal [13C615N4]-Arg peptides as internal standards. We evaluated age trends in serum GDF-11 and GDF-8 concentrations in community-dwelling healthy men, 19 years or older, and determined the effects of graded testosterone doses on GDF-8 and GDF-11 concentrations in healthy men in a randomized trial. The assay demonstrated linearity over a wide range, lower limit of quantitation 0.5 ng/mL for both proteins, and excellent precision, accuracy, and specificity (no detectable cross-reactivity of GDF-8 in GDF-11 assay or of GDF-11 in GDF-8 assay). Mean ± SD (median ± 1QR) GDF-8 and GDF-11 levels in healthy community-dwelling men, 19 years and older, were 7.2 ± 1.9 (6.8 ± 1.4) ng/mL. Neither GDF-8 nor GDF-11 levels were related to age or body composition. Testosterone treatment significantly increased serum GDF-8 but not GDF-11 levels. The LC-MS/MS method for the simultaneous measurement of circulating total GDF-8 and GDF-11 demonstrates the characteristics of a valid assay. Testosterone treatment increased GDF-8 levels, but not GDF-11. Increase in GDF-8 levels by testosterone treatment, which increased muscle mass, suggests that GDF-8 acts as a chalone to restrain muscle growth.

Anabolic-androgenic steroids impair mitochondrial function and redox status in the heart and liver of mice

Supraphysiological doses of anabolic–androgenic steroids (AAS) may cause long-term functional abnormalities, particularly in the heart and liver, which may only represent the later-stage of the cumulative damage caused by dysfunctional organelles. We investigated whether mid-term supraphysiological doses of Testosterone and Nandrolone impair mitochondrial Ca2+ and membrane potential (ΔΨm) dynamics, and redox machinery in the heart and liver of mice. CF1 albino mice were treated daily with 15 mg/kg of Nandrolone (ND) or Testosterone (T), or oil (vehicle) for 19 days. Preparations enriched in mitochondria from the heart or liver were used to perform assays of Ca2+ influx/efflux, ΔΨm, and H2O2 production. ND significantly impaired mitochondrial Ca2+ influx in the heart, and ΔΨm in both organs. ND and T increased H2O2 levels in the heart and liver relative to controls. Also, ND increased oxidative damage to lipids and proteins (TBARS and carbonyls) in the heart, and both AAS decreased glutathione peroxidase activity in the heart and liver. In summary, supraphysiological doses of ND, and in a lesser extend T, impaired mitochondrial Ca2+ influx and ΔΨm, and redox homeostasis being early mechanistic substrates for inducing heart and liver tissue damage.

Salivary Estrogens Androgens and Aromatase Inhibitors by LC-MS/MS in Breast Cancer Patients Treated With Testosterone Pellets Combined With Aromatase Inhibitors

Introduction: High dose testosterone (T) has been used for treating hormone-sensitive breast cancers for many years. However, a drawback to T therapy is its propensity to convert to estradiol (E2) via aromatase, which can override the growth inhibitory effects of T and stimulate estrogen sensitive tumors. Aromatase is higher in some women than others, particularly those with active tumors, truncal obesity, and inflammatory conditions contributing to and caused by cancer. Oral aromatase inhibitors (AI) have been used to prevent conversion of T to E2. While this effectively reduces E2 burden, systemic oral AI require higher dosing, which often leads to severe side effects. As an alternative to oral AI therapy, researchers have found that T combined with a much lower dose of AI in a solitary pellet implant placed in the subcutaneous (SC) tissue, or alternatively, into the breast adjacent to a primary tumor, is effective in reducing tumor burden and maintaining a low systemic level of E2, while reducing the adverse side effects of very low E2. Study Design: In this case study we report on the use of an LC-MS/MS method to monitor salivary levels of E2, Estrone (E1), T, and the AIs Letrozole (LET) and Anastrozole (ANZ) following T + AI therapy in a breast cancer patient (intolerant of oral LET) with active (measurable) tumor in the breast and metastatic disease. Steroids and AIs were measured in saliva at baseline, 1 week, and 4 weeks after insertion of subcutaneous pellets containing ‘60 mg T + 4 mg ANZ’ and ‘60 mg T + 6 mg LET’. Results: LC-MS/MS (range values-pg/ml) for postmenopausal women, and baseline, week 1 and week 4 post treatment values for each steroid and AI were: E2: (range 0.3-0.9), 0.4, < 0.3, < 0.3; E1: (range 0.9-3.1), 1.0, <0.4, <0.4; T: (range 7-22), 6, 96, 48; ANZ: (range <4), < 4, 2063, 24; LET: (range <4), < 4, 744, 175. Self-reported (Pre/Post Therapy) estrogen deficiency symptoms such as hot flashes, night sweats, vaginal dryness, joint pain, and sleep disturbances were significantly improved post T+AI therapy. In addition, the intramammary tumor decreased in size > 95% by month 5. Summary: These results show that low-dose SC AI therapy (4-6 mg/2-3 months = 0.1 mg/day) with T (120 mg/2-3 months = 1-2 mg/day) increases T to supra-physiological levels, prevents T metabolism to estrogens E2 and E1, reduces estrogen deficiency symptoms, and has beneficial effects on tumor growth inhibition. Simultaneous testing of sex-steroids E2, E1, T, and aromatase inhibitors LET and ANZ by LC-MS/MS provides a convenient means to monitor the bioavailable levels of these analytes and adjust them as necessary to optimize therapeutic efficacy and reduce adverse side effects.

Effect of different doses of 17α-methyl testosterone (17-α MT) hormone on male broodstock of tiger shrimp Penaeus monodon sperm quality

This study aimed to determine the optimum dose of 17α-MT hormone to improve male shrimp P. monodon sperm quality. Male tiger shrimp P. monodon originated from pond with an average weight (57.56 ± 12.79) g were transferred to hatchery and acclimated for 1 week prior treatments. Shrimps were set up in controlled tanks in 5 shrimps/tank density. Treatments were 17α-MT hormone induction in different doses, i.e. A = control (ablation); B = 200 ng/100 g of broodstock body weight (BW); C = 300 ng/100 g BW; and D = 400 ng/100 g BW. The 17-α MT hormone was given using injection method every 7 days in 3 times frequency. Research was completely randomized designed with 4 treatments and 2 replications. Observed variables were: the amount of shrimps which carried spermatophores, weight of spermatophores, quantity of spermatozoa, spermatophores histology and water quality. Data of the amount of shrimps which carried spermatophores, weight of spermatophores and the quantity of spermatozoa were analyzed using analysis of variance (ANOVA), while data of spermatophores histology and water quality were analyzed descriptively. The amount of shrimps which carried spermatophores and weight of spermatophores were not significantly different (P>0.05), but spermatozoa quantity was significantly different (P<0.05). The highest spermatozoa quantity was obtained at 300 ng/100 g BW dose in fourth gonad maturity stage. The 17α-MT in 300 ng/100 g BW was the optimum dose for P. monodon sperm quality improvement and it could be applied to replace ablation method.

Virilizing doses of testosterone decrease circulating insulin levels and differentially regulate insulin signaling in liver and adipose tissue of females.

Transgender men undergoing hormone therapy are at risk for insulin resistance. However, how virilizing testosterone therapy affects serum insulin and peripheral insulin sensitivity in transgender men is unknown. This study assessed the effect of acute, virilizing testosterone on serum insulin concentrations and insulin signaling in liver, skeletal muscle, and white adipose tissue (WAT) of female pigs as a translational model for transgender men. Females received three doses of intramuscular testosterone cypionate (TEST females; 50 mg/day/pig) or corn oil (control) spaced 6 days apart starting on the day of estrus (D0). Fasting blood was collected on D0, D3, D5, D11, and D13, and females were euthanized on D13. On D13, TEST females had virilizing concentrations of serum testosterone with normal concentrations of serum estradiol. Virilizing serum testosterone concentrations (D13) were associated with decreased serum insulin and C-peptide concentrations. Blood glucose and serum glycerol concentrations were not altered by testosterone. Virilizing concentrations of testosterone downregulated AR and ESR1 in subcutaneous (sc) WAT and upregulated transcript levels of insulin-signaling pathway components in WAT and liver. At the protein level, virilizing testosterone concentrations were associated with increased PI3K 110α in liver and increased insulin receptor (INSR) and phospho(Ser256)-FOXO1 in visceral (v) WAT but decreased phospho(Ser473)-AKT in vWAT and scWAT. These results suggest that acute exposure to virilizing concentrations of testosterone suppresses circulating insulin levels and results in increased abundance of proteins in the insulin-signaling pathway in liver and altered phosphorylation of key proteins in control of insulin sensitivity in WAT.NEW & NOTEWORTHY Acute virilizing doses of testosterone administered to females suppress circulating insulin levels, upregulate components of the insulin-signaling pathway in liver, and suppress insulin signaling in white adipose tissue. These results suggest that insulin resistance in transgender men may be due to suppression of the insulin-signaling pathway and decreased insulin sensitivity in white adipose tissue.

Not giving up: Testosterone promotes persistence against a stronger opponent

Recent research suggests that when we lack a sense of control, we are prone to motivational failures and early quitting in competitions. Testosterone, on the other hand, is thought to boost competitiveness. Here we investigate the interaction between these factors, testing the testosterone’s potential to enhance persistence in a competition against a stronger opponent, depending on experimentally manipulated perceived control. Healthy participants were administered a single dose of testosterone or placebo. They first underwent a task designed to either induce low or high perceived control and then entered a costly competition against a progressively stronger opponent that they could quit at any time. In the placebo group, men with low perceived control quitted twice as early as those with high perceived control. Testosterone countered this effect, making individuals with low control persist in the competition for as long as those with high perceived control, and did so also despite raising participants’ explicit awareness of the opponents’ advantage. This psychoendocrinological effect was not modulated by basal cortisol levels, CAG repeat polymorphism of the androgen receptor gene, or trait dominance. Our results provide the first causal evidence that testosterone promotes competitive persistence in humans and demonstrate that this effect depends on the psychological state elicited prior to the competition, broadening our understanding of the complex relationships between testosterone and social behaviors.

Bioanalytical Detection of Steroid Abuse in Sports Based on the Androgenic Activity Measurement

The anabolic androgenic steroids (AAS) are the most frequently consumed performance enhancing drugs (PED) in sports. In the anti-doping field, the detection of AAS is carried out by the analysis of the athlete’s urine using methodologies based on liquid/gas chromatography-mass spectrometry. Unfortunately, the detection of unknown compounds is not possible. BDS’s AR CALUX® bio detection technology was studied as an indirect method to detect the administration of a single dose of testosterone (T). Twelve T and placebo single dose administered men volunteers underwent a triple-blind crossover clinical trial. The UGT2B17 deletion was present among the volunteers and evenly distributed in heterozygous (ins/del), wild-type homozygous (ins/ins), and mutated homozygous (del/del) groups. A significant statistical difference in terms of bioluminescence was observed after the testosterone (T) administration for the three types of polymorphic groups. The ratio of means between the pre- and post-T administration periods, depending on the type of polymorphism, was in group ins/ins 3.31 (CI. 95%: 2.07–5.29), group ins/del 4.15 (CI 95%: 3.05–5.67), and group del/del 2.89 (CI 95%: 2.42–3.46). The results of the study are very promising, as they may offer us the possibility of designing a detection approach that, based on intra-individual monitoring of androgenic values, in the UGT2B17 deletion type.

14. Genital Bleeding in Trans Masculine Persons with Mullerian Structures on Testosterone

<h3>Background</h3> Uterine bleeding (UB) on testosterone is an emerging problem in trans masculine (TM, sex assigned female at birth who identify on the masculine spectrum) health. While most TM individuals achieve amenorrhea within a year of testosterone initiation, not all do. Little data exists on the frequency of UB following amenorrhea induction, and no guidelines exist to provide a clinical approach. The study goal was to characterize UB patterns and associated risk factors in TM adolescents on testosterone for greater than a year, and describe the diagnostic and management approaches. <h3>Methods</h3> This was an IRB approved retrospective cohort study of all TM patients seen for gender affirming testosterone therapy between 2010 and 2020. Inclusion criteria were testosterone use more than 1 year, Mullerian anatomy, and documentation of the presence or absence of UB. Variables included demographics, characteristics of testosterone therapy, serum sex steroid levels, and use of non-androgen hormones. Primary outcome was the presence of UB after 1 year on testosterone. <h3>Results</h3> Of the 232 patients who met inclusion criteria, 25% (n=58) had at least 1 episode of UB after 1 year on testosterone. No significant differences between the UB and non-UB groups were found for mean age of testosterone initiation (16.3+/-2.2 vs 16.3+/-1.8 years, p=0.86) or BMI (p=0.33). The mean duration of testosterone use was significantly longer in the UB group (37.3+/-17.0 vs 28.5+/-14.6 months, p=<0.001). There was no difference in the use of non-androgen hormones between the UB (n=31, 53.4%) and non-UB groups (n=89, 51.1%), but those who used gonadotropin releasing hormone analogs (GnRHa) were 5.8 times more likely to be in the non-UB group (95% CI 0.7-44.5, p=0.07). Testosterone and estradiol levels (taken near the bleeding episode(s)) in the UB group were not statistically different than the latest levels from the non-UB group (p=.46 and p=.052 respectively). Only 3 UB patients had imaging and 1 had thyroid testing. UB causes were idiopathic/other (40), low/missed doses (13), and changes in non-androgen hormone use (5). UB management included testosterone dose adjustment (14), progestin initiation (13), or GnRHa (2). Eight patients underwent hysterectomy for both UB and gender affirmation after testosterone use, mean duration 41.8+/-20.6 months. <h3>Conclusions</h3> This is the first long term study to describe UB patterns in TM patients. GnRHa users had the highest odds of inducing or maintaining amenorrhea following new onset UB. All menstrual suppression options should be offered, as no other method was felt to be superior for addressing new onset UB. Future studies will be needed to better stratify the success of various UB management.

Single dose testosterone administration enhances novelty responsiveness and short-term habituation in healthy males

The role of testosterone in sensory perception suggests that testosterone likely regulates adaptive responses to sensory changes, including habituation to repeated events and responsiveness to novel events. To test this hypothesis, we investigated how testosterone modulates brain responses to rapid changes in sensory inputs. Using a double-blind, placebo-controlled, within-participant design, each participant received a single dose of either testosterone or placebo, and then completed a passive auditory oddball task in which infrequent deviant tones were embedded in a series of frequent standard tones. Analysis of novelty-evoked potentials revealed smaller Mismatch Negativity (MMN) responses, but larger P3a responses in the testosterone session than in the placebo session. This suggests testosterone attenuates MMN responses that are associated with pre-attentive novelty detection and enhances P3a responses that are associated with involuntary attentional orientation toward novelty. Along with the repetition of standard tones, P2 responses on the auditory evoked potentials became significantly attenuated in the testosterone session, but not in the placebo session. This suggests testosterone enhances short-term habituation of P2 responses to recurring sensory events, which has been associated with bottom-up attention allocation. Mediation analysis further revealed that the role of testosterone in promoting attentional orientation toward novelty could be explained by the influence it exerts on short-term habituation and pre-attentive novelty detection. Overall, testosterone facilitated involuntary attention switching—withdrawal of attention from repeated sensory events and orientation toward novel sensory events—at the cost of attenuated pre-attentive novelty detection. This finding provides insight into the interplay between endocrinology and involuntary attentional processes.