Higher Testosterone Levels Research Articles

Digit ratio (2D:4D) and performance in non-elite male badminton players

Background: The second to fourth digit ratio (2D:4D ratio) is derived by dividing the length of the index finger (2D) by the length of the ring finger (4D). It has been considered as an index of how much the fetus is exposed to testosterone in utero. Research has suggested that high levels of testosterone are associated with low 2D:4D ratio. The relationship between 2D:4D ratio and physical performance is still an unexplored field in badminton players. Aims and Objectives: This study intends to assess the digit ratio 2D:4D in non-elite male badminton players in comparison to their sedentary controls. Materials and Methods: The study included 30 male badminton players in the age group of 19–23 years who were practicing badminton for more than 3 years and 30 age, body mass index-matched sedentary controls. The second and fourth finger measurements were taken from scanned printouts using Vernier calipers. Results: The 2D:4D ratio was significantly lower in the left hand of badminton players when compared to their controls (P = 0.0001). There was no significant difference in 2D:4D ratios of the right hand and 2D:4D (Δ r–l) between badminton players and controls. Conclusion: The findings in our study partly support the concept that 2D:4D ratio in an important parameter in selection of athletes. The reason for no difference in 2D:4D ratio and controls in the right hand could be due to the fact that badminton is a moderate intensity sport, and also, the study participants were non-elite players.

Testosterone is positively associated with coronary artery calcium in a low cardiovascular disease risk population.

In industrialized populations, low male testosterone is associated with higher rates of cardiovascular mortality. However, coronary risk factors like obesity impact both testosterone and cardiovascular outcomes. Here, we assess the role of endogenous testosterone on coronary artery calcium in an active subsistence population with relatively low testosterone levels, low cardiovascular risk and low coronary artery calcium scores. In this cross-sectional community-based study, 719 Tsimane forager-horticulturalists in the Bolivian Amazon aged 40+ years underwent computed tomography (49.8% male, mean age 57.6 years). Coronary artery calcium levels were low; 84.5% had no coronary artery calcium. Zero-inflated negative binomial models found testosterone was positively associated with coronary artery calcium for the full sample (Incidence Rate Ratio [IRR] = 1.477, 95% Confidence Interval [CI] 1.001-2.170, P = 0.031), and in a male-only subset (IRR = 1.532, 95% CI 0.993-2.360, P = 0.053). Testosterone was also positively associated with clinically relevant coronary atherosclerosis (calcium >100 Agatston units) in the full sample (Odds Ratio [OR] = 1.984, 95% CI 1.202-3.275, P = 0.007) and when limited to male-only sample (OR = 2.032, 95% CI 1.118-4.816, P = 0.024). Individuals with coronary artery calcium >100 had 20% higher levels of testosterone than those with calcium <100 (t = -3.201, P = 0.007). Among Tsimane, testosterone is positively associated with coronary artery calcium despite generally low normal testosterone levels, minimal atherosclerosis and rare cardiovascular disease (CVD) events. Associations between low testosterone and CVD events in industrialized populations are likely confounded by obesity and other lifestyle factors.

The Complex Interplay between Serum Testosterone and the Clinical Course of Coronavirus Disease 19 Pandemic: A Systematic Review of Clinical and Preclinical Evidence.

Since the beginning of the coronavirus disease 19 (COVID-19) pandemic, efforts in defining risk factors and associations between the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), clinical, and molecular features have initiated. After three years of pandemic, it became evident that men have higher risk of adverse outcomes. Such evidence provided the impetus for defining the biological fundaments of such a gender disparity. Our objective was to analyze the most recent literature with the aim of defining the relationship between COVID-19 and fertility, in particular, we assessed the interplay between SARS-CoV-2 and testosterone in a systematic review of literature from December 2019 (first evidence of a novel coronavirus in the Hubei province) until March 2022. As a fundamental basis for understanding, articles pertaining preclinical aspects explaining the gender disparity (n=9) were included. The main review categories analyzed the risk of being infected with SARS-CoV-2 according to testosterone levels (n=5), the impact of serum testosterone on outcomes of COVID-19 (n=23), and the impact SARS-CoV-2 on testosterone levels after infection (n=19). Preclinical studies mainly evaluated the relation between angiotensin-converting enzyme 2 (ACE2) and its androgen-mediated regulation, articles exploring the risk of COVID-19 according to testosterone levels were few. Although most publications evaluating the effect of COVID-19 on fertility found low testosterone levels after the infection, follow-up was short, with some also suggesting no alterations during recovery. More conclusive findings were observed in men with low testosterone levels, that were generally at higher risk of experiencing worse outcomes (i.e., admission to intensive care units, longer hospitalization, and death). Interestingly, an inverse relationship was observed in women, where higher levels of testosterone were associated to worse outcomes. Our finding may provide meaningful insights to better patient counselling and individualization of care pathways in men with testosterone levels suggesting hypogonadism.

Polycystic ovary syndrome in a patient with type B insulin resistance syndrome can improve with glucocorticoid treatment: a case report and literature review.

Polycystic ovary syndrome (PCOS) frequently exhibits hyperinsulinemia due to insulin resistance, but there are many unknown aspects of this disease. This report presents the case of a 31-year-old woman with PCOS and type B insulin resistance syndrome (TBIRS). The patient had repeated hyperglycemia and hypoglycemia, and prominent hyperinsulinemia. The insulin receptor antibody was positive, leading to a diagnosis of TBIRS. She also had amenorrhea during the previous 3 months, high blood testosterone levels, and enlarged polycystic ovaries, leading to a diagnosis of PCOS at the same time. The patient was treated with glucocorticoid for TBIRS. The insulin receptor antibody eliminated at 8 weeks after initiation of glucocorticoid treatment, and the blood glucose levels and hyperinsulinemia improved at 9 weeks. Then, the enlargement of both ovaries diminished at 32 weeks, and the menstruation had normalized since 36 weeks. The blood testosterone level normalized at 41 weeks. To the best of our knowledge, this is the first report to demonstrate that enlarged polycystic ovaries and a menstrual disorder in TBIRS improved after glucocorticoid treatment. It is possible that elimination of insulin receptor antibodies by glucocorticoid treatment attenuated insulin resistance and subsequently improved PCOS in TBIRS.

Elevated level of testosterone in amniotic fluid during prenatal stress and its association with development of Attention-Deficit/Hyperactivity Disorder (ADHD) like symptoms in toddlers.

To investigate the "prenatal testosterone hypothesis", according to which, high level of testosterone associated with the development of ADHD like symptoms in younger children, and to investigate whether maternal stress during pregnancy in-creases the risk of developing ADHD like symptoms in early childhood. This was a prospective study with three measurement periods: the first one during pregnancy (12 to 25 weeks of gestation); the second period involved the assessment of infants of this pregnancy at the age of 6 months and the third one the assessment of the same infants at the age of 18 months. The research plan is approved by "David Tvildiani Medical University" Research Ethics Committee. The study does not contain serious predictable risks as the expected benefit overweighs them. The study group is presented by 40 pregnant women and 40 infants of these pregnancies. Pregnant women were asked about their perceived stress levels, critical life events of the past year and pregnancy-specific stress levels using standardized questionnaires. Child's temperament and behavioral regulation were assessed using the questionnaires. Amniotic fluid was collected undergoing amniocentesis. Total testosterone in amniotic fluid was measured by radioimmunoassay. Although statistically significant relationship was identified between hyperactivity, also impulsiveness symptoms and pre-natal stress, no statistically significant relationship was identified between testosterone level and hyperactivity, also impulsivity symptoms, as well as between testosterone level and prenatal stress level. The performed study did not support the "hypothesis about prenatal testosterone", because there was a significant negative correlation between the frequency of hyperactivity symptoms and testosterone level.

The close proximity between the human rectum and prostate: a functional-anatomic arrangement favoring prostate health

Prostate health is related to the frequency of ejaculation and prostate drainage. Frequent, repetitive ejaculations theoretically may pose a prostate cancer risk due to ensuing high testosterone levels and loss of zinc. In line with this, the proximity of the human rectum and prostate is of diagnostic and therapeutic importance. We provide evidence to support the view that the proximity of the rectum and prostate in men enables lower bowel distention to compress the prostate’s lateral side to facilitate drainage, which might lower cancer risk. This drainage mechanism is likely on-going and gradual, compared to rapid drainage following ejaculation. The physiological context suggests that these mechanisms of prostate drainage are complementary. Dietary content containing polyphenol- and fiber-rich meals, along with voluminous stool formation and increased gastrointestinal transit may all help improve prostate drainage. This may be important in voluntary abstinent men or other categories of sexually limited men. Recognizing that the anatomic relationship between the rectal area and prostate may facilitate prostate drainage, because of diet and gastro-intestinal activity, could be important to prostate health maintenance.

Analysis of high risk factors for chronic atrophic gastritis.

Screening for chronic atrophic gastritis (CAG) is crucial for the prevention and early detection of gastric cancer. Endoscopy is the main method of CAG diagnosis, with high training requirements and limited accuracy, making it difficult to popularize. The study attempts to improve the positive rate and accuracy of CAG screening through non-invasive testing. A total of 2564 patients who underwent gastroscopy were included in this study. The results of gastroscopic evaluation, histological biopsy results (including H. pylori biopsy), urea breath test (UBT) results, serum pepsinogen, and testosterone were statistically analyzed. We found significant differences in the diagnosis of CAG between endoscopy and histological biopsy. Pepsinogen II and pepsinogen I/II ratio were more useful for the diagnosis of CAG compared with pepsinogen I. The risk of CAG was increased when pepsinogen II exceeded 11.05 μg/L, and the pepsinogen I/II ratio was less than 3.75. CAG positivity was higher in patients with positive H. pylori infection on UBT screening. In addition, higher levels of testosterone, SHBG and HSD17B2, and lower level of GNRH1 were found in CAG mucosa. Patients with high serum testosterone had a higher risk of CAG. CAG screening should be combined with endoscopic evaluation, biopsy, and other non-invasive tests. Non-invasive tests include the combination of serum pepsinogen II protein and pepsinogen I/II ratio and high level of serum testosterone. UBT combined with serum pepsinogen testing may improve the positive rate of CAG and reduce gastric mucosal damage from multiple biopsies.

Otizm Spektrum Bozukluğunda El 2D:4D Parmak Oranı ve Yüz Simetrisi

There are many theories about the etiology of autism, and the most striking is the theory of testosterone exposure in the womb. In this study, it was investigated whether the second and fourth finger and face measurements were symmetrical in boys with autism spectrum disorder (ASD) and children with normal development. For the study, 30 boys diagnosed with ASD were compared with 30 normally developing boys. Photographs of each individual's face were taken digitally and measurements were made at eight different reference lengths on the face halves. Half-face measurements in children diagnosed with autism were compared among themselves and with the control group with normal healthy development. In addition, the symmetry level was analyzed by photographing the right and left hands and measuring the lengths of the second (2D) and fourth (4D) fingers for symmetry detection. As a result of the face and finger analysis, it was determined that the faces of the individuals with ASD were more symmetrical than the individuals with normal development, and the 2D-4B finger lengths were closer to each other than the children with normal development. In addition, it was determined that as the severity of autism increased, the tendency for symmetry increased in both the face and fingers. The tendency to symmetry detected in the face and hand is compatible with the high testosterone level exposed in the womb of individuals with autism and, accordingly, the excessive male brain theory.

Rare virilizing tumor: ovarian steroid cell tumor, not otherwise specified: a case report

BackgroundOvarian steroid cell tumors, not otherwise specified is a rare sex cord-stromal tumor. Almost 60% of all steroid cell tumors are categorized as not otherwise specified and represent less than 0.1% of all ovarian neoplasm. Some of them are endocrinologically active, producing virilization signs in young women. The recommended treatment is primarily surgical.Case presentationWe present the case of a 20-year-old Mexican woman with secondary amenorrhea and virilization signs. She was treated with combined oral contraceptives from 13 years old, due to a misdiagnosis of polycystic ovarian syndrome. However, 4 months after stopping medication, amenorrhea and virilization signs worsened. Biochemically, she had high serum total testosterone and free testosterone levels, and a pelvic and transvaginal ultrasound followed by a pelvic tomography scan demonstrated a right adnexal tumor. She underwent right salpingo-oophorectomy and the histopathological and immunochemistry exams confirmed the diagnosis. The patient was followed for a year after surgery and until then, her menses were regular and she had no recurrence of virilization signs. ConclusionThe purpose of this case report is to alert physicians to rule out ovarian steroid cell tumor, not otherwise specified diagnosis in young women with increased testosterone after discarding common causes such as polycystic ovarian syndrome. A multidisciplinary team including a gynecologist, endocrinologist, radiologist, and pathologist should be involved for correct diagnosis at the proper time.

Relationship between thyroid hormone and sex hormone levels and non-suicidal self-injury in male adolescents with depression.

Non-suicidal self-injury (NSSI) is the intentional and repeated direct injury to one's bodily tissues or organs without the intent to die, which is not socially sanctioned and does not result in death. This study will be the first to explore the relationship between NSSI behavior and thyroid hormone and sex hormone levels in male adolescents with depression. Among the inpatients in the children's ward of Shandong Mental Health Center, eighty male patients with first-episode depressive disorder were randomly selected. Forty male adolescent depressed patients with NSSI behaviors were set as the NSSI group, and forty male adolescent depressed patients without NSSI behaviors were set as the No-NSSI group. Their thyroid hormones (free triiodothyronine, free thyroxine, and thyroid stimulating hormone) and sex hormones (estradiol, progesterone, and testosterone) were measured, and the severity of self-injury in the NSSI group was assessed using the Adolescent Self-Injury Questionnaire. The NSSI group was tested again after 6 weeks of sertraline treatment for biological indicators and assessed by the Self-Injury Questionnaire to compare the hormonal differences between the NSSI group and the No-NSSI group and compare the differences of each index before and after treatment in the NSSI group. T3/T4 (p = 0.001) and FT3 (p = 0.023), TSH levels (p < 0.001) were lower in the NSSI group than in the No-NSSI group before treatment, and FT4 (p = 0.036) and T (p < 0.001) levels were higher than in the No-NSSI group. T3/T4 levels were higher in the NSSI group after treatment (p < 0.001). FT4 (p < 0.001) and T (p = 0.001) levels and self-injury questionnaire scores (p < 0.001) decreased after treatment in the NSSI group. In the NSSI group at baseline, FT4 levels were negatively correlated with self-injury questionnaire scores (r = -0.459, p = 0.003) and testosterone levels were positively correlated with self-injury questionnaire scores (r = 0.383, p = 0.015), and in the NSSI group after treatment, FT4 difference was negatively correlated with self-injury questionnaire score reduction rate (r = -0.037, p = 0.019), and testosterone difference was positively correlated with self-injury questionnaire score reduction rate (r = 0.424, p = 0.006). Logistic regression analysis showed that low TSH and high testosterone levels were independent risk factors for the development of non-suicidal self-harming behaviors in male adolescent depressed patients. Changes in thyroid hormone and sex hormone levels may be associated with non-suicidal self-injurious behavior in male adolescent depressed patients.

Higher Serum Testosterone Level Was Associated with a Lower Risk of Prediabetes in US Adults: Findings from Nationally Representative Data.

Low testosterone may be a novel risk factor for prediabetes. We assessed the associations between prediabetes and total serum testosterone (TT), and whether the associations were modified by population characteristics. The data from 5330 adults aged ≥ 20 years, who participated in the 2011−2016 National Health and Nutrition Examination Survey in the United States, were used. Prediabetes was based on fasting plasma glucose, HbA1c, or OGTT. Sociodemographic, obesity, co-morbidities, and lifestyle factors were included in logistic regression models. A dose-response relationship was found between prediabetes and the testosterone quartiles. The odds ratio (OR and 95% CI) for prediabetes across the quartiles of TT were: 1.00, 0.68 (0.50−0.92), 0.51 (0.36−0.72), and 0.48 (0.34−0.70) in men; and 1.00, 1.06 (0.81−1.40), 0.81 (0.61−1.06), and 0.68 (0.49−0.93) in women. The results changed marginally if the models were adjusted for additional variables such as BMI. The subgroup analyses showed differences in the association, which was stronger in some groups (for men: age < 50, white and black, overweight/obese, adequate physical activity, never-smoking; and for women: age ≥ 50, black). A higher testosterone level was associated with a lower risk of prediabetes among US adults. The strength of the association varied by population characteristics, weight status, gender, and lifestyle factors.

The effects of melatonin and metformin on histological characteristics of the ovary and uterus in letrozole-induced polycystic ovarian syndrome mice: A stereological study.

Polycystic ovarian syndrome (PCOS) with anovulation, hyperandrogenism, ovarian and uterine histological changes, menstrual irregularities, etc. signs is an infertility type. It seems that melatonin and metformin can improve these abnormalities. To evaluate the effects of melatonin and metformin on the ovary and uterus in PCOS-induced mice using stereological methods. Seventy-two adult female BALB/c mice (8-wk-old, 20-30 gr) were randomly divided into control (distilled water, gavage), PCOS (90 µg/kg letrozole, gavage), PCOS+metformin (500 mg/kg, gavage), PCOS+melatonin (10 mg/kg, intraperitoneal injection), and PCOS+melatonin control (0.5% ethanol saline) groups (n = 12/each). Another PCOS group was kept for a month to ensure that PCOS features remained. Finally, a stereological evaluation of the uterus and ovary was carried out, and vaginal cytology and serum testosterone levels were assessed. PCOS mice treated with metformin and melatonin had lower testosterone levels, body weight, and more regular estrus cycles than the PCOS group (p 0.001). A significant decrease in conglomerate and daughter gland numbers, and primary, secondary, atretic, and cystic follicles numbers with a significant increase in primordial and Graafian follicles, and corpus luteum numbers (p 0.001) was seen in these treated mice. Also, endometrial vessels' volume and length significantly increased, but ovarian, endometrial, myometrial, stromal, and glands volume, and endometrial and myometrial thickness dramatically declined (p 0.001). It appears that metformin and melatonin could restore the PCOS phenotype including estrus cycle irregularity, high testosterone level, and ovarian and uterine micromorphology to the control levels. However, the 2 treatments had similar effects on the examined parameters.

Lungworm parasite intensity and its association with the endocrine and immune systems and energy reserves in male cane toads

Host-parasite interactions can be harmful or harmless depending on the fitness and stress levels of the organisms. Interactions between the endocrine system, the immune system and energy expenditure are critical in the maintenance of homeostasis during stressful periods in vertebrates. We examined whether lungworm loads (Rhabdias spp.) of male cane toad (Rhinella marina) sampled during the wet season from three different populations, are associated with hormone levels, immune competence, and metabolic status. We found evidence of direct and strong associations between parasite burdens and variables related to hormonal levels, metabolic status and immune competence. We also found that interrelationships among independent variables can change the strength of the association with lungworm loads. These findings suggest that high levels of corticosterone affect immune competence against parasites, both directly and by inducing changes in the metabolic status of the animals. Additionally, high testosterone levels during the reproductive season, influenced variables related to metabolic status, which will also lead to higher parasite loads. Overall, we conclude that the endocrine system and metabolic status in male cane toads are critical to the immune competence against parasites during the reproductive season.

Evening chronotype is associated with hormonal and metabolic disorders in polycystic ovary syndrome.

Despite current treatments for polycystic ovary syndrome (PCOS), a considerable number of women with this syndrome do not reach the treatment goal, suggesting the presence of other probable misdiagnosed features of this syndrome that are not taken into account in the assessment and therefore in the therapeutical approach. The aim of this study was to investigate the prevalence of chronotype categories in women with PCOS and their role in determining hormonal and metabolic aspects of PCOS.This observational case-control study was conducted on 112 women with PCOS and 112 healthy women matched for age and body mass index (BMI). At baseline anthropometric parameters such as weight, height, BMI and waist circumference, clinical parameters such as Ferriman-Gallwey (FG) score, biochemical parameters such as fasting plasma glucose, insulin levels and assessment of the homeostasis model of insulin resistance (HoMA-IR), inflammatory parameters such as C-reactive protein (CRP) and hormonal parameters such as testosterone levels were evaluated.Women with PCOS had a lower chronotype score (p < .001) which indicates a higher prevalence of evening chronotype (EC) category (p = .037) compared to controls. After adjustment for BMI, chronotype score was significantly negatively correlated with CRP levels (r = -0.418, p < .001), testosterone levels (r = -0.543, p < .001) and FG score (r = -0.514, p < .001). Linear regression analysis showed that high testosterone levels were among the factors most associated with a lower chronotype score (p < .001), followed by BMI (p < .001) and HoMA-IR (p < .05).In conclusion, there is a higher prevalence of EC in women with PCOS than in women without the condition, which in turn was associated with a worse hormonal and metabolic profile. These findings provide support for the relevance of including chronotype assessment in the treatment of women with PCOS.

Serum testosterone measured by liquid chromatography-tandem mass spectrometry is an independent predictor of response to castration in metastatic hormone-sensitive prostate cancer

BackgroundAlthough testosterone levels have been associated with progression-free survival (PFS) in metastatic hormone-sensitive prostate cancer (mHSPC) patients, this has primarily been investigated using inaccurate immunoassays (IA). Here, we investigated whether castrate testosterone levels determined by a liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay is an independent risk factor for treatment response in mHSPC. MethodsIn total, 106 mHSPC patients treated with luteinizing-hormone releasing-hormone (LHRH) agonists were retrospectively analyzed between March 2018 and August 2021. Testosterone levels in serum samples were quantitated using an LC-MS/MS assay. In a subset of patients, IA (Roche Cobas Pro) values were compared with LC-MS/MS results. Survival analysis was performed using Kaplan-Meier curves and Cox proportional hazard models. ResultsMedian PFS was shorter for high testosterone levels (>0.231 nmol/L, 18.4 v. 42.6 months, HR 1.7, p = 0.018). Low testosterone levels and a PSA response below 4 ng/mL was associated with longer median PFS (46.2 months) than the remaining combinations (13.8–19.3 months, 3.4–5.8, overall p < 0.01). In 67 patients, testosterone levels below the median remained associated with longer PFS, whereas IA measurements did not show a similar difference. ConclusionOur results suggest that high castration testosterone levels measured by LC-MS/MS is an independent response predictor for mHSPC patients.

Sex-specific differences in atherosclerosis, thrombospondin-1, and smooth muscle cell differentiation in metabolic syndrome versus non-metabolic syndrome mice.

Metabolic syndrome (MetS) amplifies the risks of atherosclerosis. Despite well-known sexual dimorphism in atherosclerosis, underlying mechanisms are poorly understood. Our previous findings highlight a proatherogenic protein, thrombospondin-1 (TSP-1), in hyperglycemia- or hyperleptinemia (mimicking obesity)-induced atherosclerosis. However, the role of TSP-1 in the development of atherosclerosis prompted by co-existing hyperglycemia and obesity, characteristic of MetS, is unknown. The goal of this study was to examine sex-specific differences in lesion progression in a model of combined MetS and atherosclerosis (KKAyApoE) and interrogate how these differences relate to TSP-1 expression. Male and female KKAy+/-ApoE-/- (with ectopic agouti gene expression) and age-matched non-agouti KKAy-/-ApoE-/- littermates were placed on a standard laboratory diet from 4 to 24 weeks age followed by blood and tissue harvests for biochemical, molecular, and aortic root morphometric studies. Metabolic profiling confirmed MetS phenotype of KKAy+/-ApoE-/-; however, only male genotypes were glucose intolerant with elevated VLDL-cholesterol and VLDL-triglyceride levels. Aortic root morphometry demonstrated profound lipid-filled lesions, increased plaque area, and augmented inflammatory and SMC abundance in MetS vs non-MetS males. This increase in lesion burden was accompanied with elevated TSP-1 and attenuated LMOD-1 (SM contractile marker) and SRF (transcriptional activator of SM differentiation) expression in male MetS aortic vessels. In contrast, while lipid burden, plaque area, and TSP-1 expression increased in MetS and non-MetS female mice, there was no significant difference between these genotypes. Increased collagen content was noted in MetS and non-MetS genotypes, specific to female mice. Measurement of plasma testosterone revealed a link between the atherogenic phenotype and abnormally high or low testosterone levels. To interrogate whether TSP-1 plays a direct role in SMC de-differentiation in MetS, we generated KKAy+/- mice with and without global TSP-1 deletion. Immunoblotting showed increased SM contractile markers in male KKAy+/-TSP-1-/- aortic vessels vs male KKAy+/-TSP-1+/ +. In contrast, TSP-1 deletion had no effect on SM contractile marker expression in female genotypes. Together, the current study implicates a role of plasma testosterone in sex-specific differences in atherosclerosis and TSP-1 expression in MetS vs non-MetS mice. Our data suggest a sex-dependent differential role of TSP-1 on SMC de-differentiation in MetS. Collectively, these findings underscore a fundamental link between TSP-1 and VSMC phenotypic transformation in MetS.

High levels of follicular fluid testosterone could impair oocyte developmental competency via affecting aryl hydrocarbon receptor pathway in PCOS patients

BackgroundAlthough hormonal and metabolic dysfunction have been recognized as a possible cause of polycystic ovarian syndrome (PCOS), the associations between hyperandrogenism and aryl hydrocarbon receptor (Ahr) signaling pathway remains controversial. The current study aimed to investigate the effect of hyperandrogenism on oocyte developmental competency via regarding Ahr signaling downstream pathway in granulosa cells.Materials and methodsGranulosa cells were collected from 45 PCOS patients under assisted reproductive technique (ART). Gene expression of Ahr downstream pathway was evaluated based on Reverse Transcription Q-PCR assay. Moreover the correlation was investigated between gene expression and hyperandrogenism, and oocyte developmental competency in PCOS.ResultsFrom the 45 PCOS patients, 26 (64.44%) had a high level of follicular fluid testosterone (FFT). Based on the FFT level, two groups of PCOS: HFT (high level of FFT) and non-HFT, were shown significant differences in oocyte and embryo quality, and fertilization and cleavage rates. Moreover, the mean relative expressions of Ahr and Arnt genes were significantly higher in HFT –PCOS group (p < 0.01 and p < 0.01) respectively. Also, the significant positive correlations were obtained for Ahr, Arnt, Cyp1A1, and Cyp1B1 with incidence of clinical hyperandrogenism and FFT level. Besides, our results showed that Ahr, Cyp1A1, and Cyp1B1 gene expression was correlated significantly with fertilization rate.ConclusionThe present study suggested that hyperandrogenism could impair oocyte developmental competency via affecting Ahr signaling downstream pathway.

Severe intrahepatic cholestasis of pregnancy due to a Sertoli-Leydig cell tumour in a woman with polycystic ovary syndrome: a case report

BackgroundIntrahepatic cholestasis of pregnancy (ICP) is a common gestational complication characterized by pruritus and elevated bile acids, usually occurring in the third trimester when the serum estrogen and progesterone levels are highest. Hyperandrogenism during pregnancy is a pathological state that is mostly induced by polycystic ovary syndrome (PCOS) but rarely by concomitant androgen-secreting ovarian tumours. To date, no correlation has been drawn between ICP and hyperandrogenism.Case presentationHere, we present a rare case of early-onset severe ICP in a PCOS patient conceived via in vitro fertilization-embryo transfer, with worsening hirsutism and acne due to high levels of testosterone and dehydroepiandrosterone sulphate, both of which were produced by a fast-growing ovarian Sertoli–Leydig cell tumour. Her serum estradiol was also very high, which was speculated to be converted from the circulating androgens by the placenta. She had preterm premature rupture of membranes and delivered at 30 weeks, followed by a rapid remission of ICP as her serum estradiol dropped. However, the excessive androgens did not retreat until the large ovarian tumour was surgically removed.ConclusionThis unusual case highlights the concurrence of original hyperandrogenism and subsequent hyperestrogenism during pregnancy and the resultant confounding manifestations. Obstetricians should be aware of the potential association between androgen excess and ICP via placental aromatization.

RF01 | PMON77 Low Libido Despite High Testosterone Levels in a Man With FSH-Secreting Pituitary Macroadenoma

Abstract Background Up to 60% of non-functioning pituitary adenomas stain for gonadotrophins on immunocytochemistry but do not secrete excess gonadotrophins. Functioning gonadotroph adenomas with clinical manifestations are extremely rare and majority of these are FSH secreting macroadenomas. Diagnosis may be difficult in pre-menopausal women with high oestrogen and variable FSH levels but in men, the unusually high gonadotrophins give the clues for diagnosis. Clinical Case We present the case of a 37-year-old Caucasian male with clinical manifestations of an FSH-secreting pituitary macroadenoma. He had sexual dysfunction with loss of libido for a year followed by bilateral testicular pain and enlargement (right &amp;gt;left). He was initially investigated under urology and had repeated treatment for suspected epididymitis. The diagnosis came to light many months later when he presented to emergency department with headaches and visual disturbance. Brain imaging confirmed a pituitary macroadenoma (3×2.5×3cm) with optic chiasm compression. He had bilateral superior temporal visual field defects. Pituitary profile showed unusually high FSH 200 IU/L (0.7-11.1), normal LH 7.6 IU/L (0.8-7.6) and a high normal testosterone 27 nmol/L (8.5-29). Prolactin was slightly elevated at 474mIU/L (0-350), cortisol and TSH were in normal range. He had polycythaemia (Haemoglobin 181g/l and HCT 0.51 L/L) and old blood results indicate his haemoglobin was above the upper limit of normal for previous 10 years. This gentleman had a successful transsphenoidal hypophysectomy with near complete resection of pituitary adenoma. His vison improved immediately after surgery. Histology of the resected adenoma showed gonadotroph differentiation and immunoreactivity predominantly with FSH and also with LH and prolactin stains. A day after surgery, his FSH levels dropped to 18 IU/L and LH was undetectable. Symptoms of hypogonadism had gradually worsened post-surgery and 2 months later, his pituitary profile showed severe hypogonadotrophic hypogonadism (FSH 3.6 IU/L, undetectable LH and testosterone 0.9 nmol/L). He was started on testosterone replacement which he continues till date. He remains asymptomatic with no testicular pain and the last MR imaging, a year after his surgery showed no recurrence in the pituitary adenoma. Conclusion Testicular enlargement and hypogonadal symptoms with low testosterone levels are recognised features in FSH secreting pituitary adenomas. Our patient had testicular enlargement but consistently high testosterone levels prior to surgery and polycythaemia for many years prior to presentation. This may be due concomitant hypersecretion of both FSH and LH from his pituitary adenoma. The reason for low libido despite high androgen levels was not entirely clear. Symptoms of hypogonadism overlap with many non-gonadal illnesses. A normal testosterone level in most cases would not lead to further endocrine investigations. Our case highlights the need to suspect such rare underlying pituitary pathology when dealing with unusual combination of hypogonadal symptoms, testicular enlargement and normal or high normal testosterone levels. Presentation: Saturday, June 11, 2022 1:30 p.m. - 1:35 p.m., Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

ODP600 Is this a case of surreptitious hormonal supplements?

Abstract Background Hypogonadism in males results when there is either a failure of the testes to produce testosterone, hypothalamic or pituitary dysfunction. Although testosterone supplementation is used for documented hypogonadism, it has become widely abused, with a variety of false claims for promoting energy, virility, and muscular development, as well as enhanced athletic performance. We present a case of surreptitious abuse. Clinical Case A 63-year-old male with coronary artery disease, was initially consulted to endocrinology for evaluation of Graves’ disease with ophthalmopathy. He was treated with methimazole 5 mg daily. However, on subsequent visits, he requested measurement of testosterone levels. Laboratory tests showed FSH&amp;lt;0.2 mIU/ml (0.7-10.8); LH&amp;lt;0.2 mIU/ml; free testosterone 3050 pg/ml (35-155); total testosterone 7377 ng/DL (250-1100); prolactin 9.6 ng/ml; Hgb 14.7 g/dL (13. -17); HCT 45.5% (40-51); TSH 1.94 uIU/ml (0.358-3,74); Free T4 0.74 ng/dL (0.76-1.46); Free T3 2.60 pg/ml (2.82-3.98). When confronted with these values, he admitted that due to interest in building muscle mass and energy, for lifting weights, he was taking hormone and protein supplements ordered from an internet program. These therapies were claimed to enhance muscle mass and energy, increase testosterone and lower estrogen. He did not have blood tests for over 6 months, and it was not clear who monitored this plan. He was taking testosterone 400 mg injections of testosterone cypionate and proprionate twice weekly, as well as another form of oral testosterone, which amounted to more than double the total dose required to treat hypogonadism in 1 week. He was counseled about the risks of taking excess testosterone, for which he had no prior knowledge (including CAD, cardiomyopathy, erythrocytosis, coagulation abnormalities, major mood disorder, gynecomastia, increased risk for prostate cancer), and also that it is unclear whether he even had hypogonadism. He agreed to stop taking these supplements. Four months later, he reported slightly less energy, but he was not exercising due to back pain, and no other changes. Laboratory tests: Total testosterone 572 ng/dL, Free Testosterone 74.6, LH 3. 0 mIU/ml; FSH =3.4 mIu/ml (8-10.8). Discussion and Conclusion Although hyperthyroidism can cause an increase in total testosterone via an increase in hepatic synthesis of SHBG, the free level is normal. Abnormally high testosterone levels in men are most commonly due to anabolic steroids taken to increase muscle mass and enhance athletic performance. It is also important to evaluate for other causes, such as adrenal or testicular tumors. This case is an example of a patient innocently taking unregulated and hazardous hormonal supplements for false claims, which may result in abnormal hormonal laboratory results, and lead to unnecessary and expensive evaluations. Therefore, it is important to take a good medication history, and to query abnormal lab results at each outpatient visit. Presentation: No date and time listed