Low Free Testosterone Research Articles

P–666 Validating the hypo-androgenic PCOS-like phenotype (H-PCOS), derived from the “lean” PCOS phenotype at younger ages

Abstract Study question Is the resistance to standard infertility treatments of the H-PCOS-like phenotype reversed through reconstitution of androgen levels and can principle diagnostic markers of H-PCOS be validated? Summary answer Pre-supplementation with dehydroepiandrosterone (DHEA) eliminated treatment resistance of H-PCOS in comparison to matched infertile controls, also validating previously reported diagnostic features of this condition. What is known already H-PCOS evolves at older ages from a hyper-androgenic “lean” PCOS phenotype at young ages. Its ontogeny diverts from other PCOS phenotype between 20s and mid–30s by going from being hyper- to being hypo-androgenic due to insufficiency in adrenal androgen production, believed to represent an autoimmune process. In contrast to other PCOS phenotypes, the “lean” PCOS phenotype appears highly treatment resistant to standard fertility treatments. Study design, size, duration Retrospective case control study. Participants/materials, setting, methods We investigated 54 H-PCOS patients with qualifying diagnostic criteria1,2 and 50 matched infertility patients without diagnostic H-PCOS criteria as controls. Both study groups underwent routine in vitro fertilization (IVF) cycles, including androgen pre-supplementation in both groups via dehydroepiandrosterone (DHEA) for women diagnosed as hypo-androgenic. Main outcome measures were clinical pregnancy and live birth rates. 1Gleicher et al., J Sterodi Biochem Mol Biol 2017;167:144–152; 2Gleicher N, et al., Endocrine 2018;59(3):661–676 Main results and the role of chance Study groups were similar in age, number of prior IVF cycles and previous live births. H-PCOS patients in contrast to controls, however, demonstrated previously reported characteristics of H-PCOS diagnosis, including a significantly higher DHEA/DHEAS ratio, significantly higher AMH, confirming higher functional ovarian reserve, significantly lower free testosterone and significantly higher sex hormone binding globulin (SHBG), further confirming lower androgens. Finally, H-PCOS patients also demonstrated significantly increased evidence for immune system hyperactivity. Clinical pregnancy and live birth rates were separately assessed in first IVF cycles and cumulatively. Both analyses demonstrated, even after age-adjustments, absolutely no outcome differences in cycle cancellations, numbers of oocytes retrieved, first and cumulative pregnancy and live birth rates. At least one pregnancy was achieved in 12 women in both groups (22.2% and 24.0%) and at least one live birth in 11 (20.4%) vs. 8 (14.8%), respectively. Limitations, reasons for caution As a retrospective case control study, here presented data must be interpreted with caution. The close match between H-PCOS and control patients and the very clear differentiation in patient characteristics between the two groups, however, support the credibility of this study. Wider implications of the findings: This study demonstrated that androgen reconstitution in H-PCOS patients completely reversed treatment resistance compared to well-matched infertile control patients. It also validated previously defined diagnostic criteria of H-PCOS, hopefully facilitating a timelier diagnosis of a, still, widely overlooked condition in female infertility. Trial registration number NA

Obstructive Sleep Apnea Is Associated With Low Testosterone Levels in Severely Obese Men.

BackgroundDisrupted sleep affects cardio-metabolic and reproductive health. Obstructive sleep apnea syndrome represents a major complication of obesity and has been associated with gonadal axis activity changes and lower serum testosterone concentration in men. However, there is no consistent opinion on the effect of obstructive sleep apnea on testosterone levels in men.ObjectiveThe aim of this study was to determine the influence of obstructive sleep apnea on total and free testosterone levels in severely obese men.Materials and methodsThe study included 104 severely obese (Body Mass Index (BMI) ≥ 35 kg/m2) men, aged 20 to 60, who underwent anthropometric, blood pressure, fasting plasma glucose, lipid profile, and sex hormone measurements. All participants were subjected to polysomnography. According to apnea-hypopnea index (AHI) patients were divided into 3 groups: <15 (n = 20), 15 - 29.9 (n = 17) and ≥ 30 (n = 67).ResultsThere was a significant difference between AHI groups in age (29.1 ± 7.2, 43.2 ± 13.2, 45.2 ± 10.2 years; p < 0.001), BMI (42.8 ± 5.9, 43.2 ± 5.9, 47.1 ± 7.8 kg/m2; p = 0.023), the prevalence of metabolic syndrome (MetS) (55%, 82.4%, 83.6%, p = 0.017), continuous metabolic syndrome score (siMS) (4.01 ± 1.21, 3.42 ± 0.80, 3.94 ± 1.81, 4.20 ± 1.07; p = 0.038), total testosterone (TT) (16.6 ± 6.1, 15.2 ± 5.3, 11.3 ± 4.44 nmol/l; p < 0.001) and free testosterone (FT) levels (440.4 ± 160.8, 389.6 ± 162.5, 294.5 ± 107.0 pmol/l; p < 0.001). TT level was in a significant negative correlation with AHI, oxygen desaturation index (ODI), BMI, MetS and siMS. Also, FT was in a significant negative correlation with AHI, ODI, BMI, age, MetS and siMS. The multiple regression analysis revealed that both AHI and ODI were in significant correlation with TT and FT after adjustment for age, BMI, siMS score and MetS components.ConclusionObstructive sleep apnea is associated with low TT and FT levels in severely obese men.

Evaluation of Serum Testosterone Level in Patients with Psoriasis and Its Correlation to Severity of the Disease

Background: Psoriasis is a chronic inflammatory, immune-mediated systemic disease with skin manifestations that typically follow a relapsing and remitting course. The most common form, plaque psoriasis, occurs in ∼80–90% of psoriatic patients. Objective: The aim of the current work was to evaluate level of serum testosterone in psoriasis male patients and its relation to severity of the disease. Patients and methods: This cohort study included a total of 35 psoriatic patients, attending At Outpatient Clinic, Dermatology and Venereology Department, Zagazig University Hospital, Egypt. This study was conducted between January 2020 to October 2020. Serum free and total testosterone and total cholesterol were measured. Result: About two thirds of the studied group (71.4 %) had normal testosterone level and (28.6 %) had low testosterone level. Conclusion: Low serum total and free testosterone levels in male psoriasis patients are present and they correlate with disease severity.

Combined Oral Contraceptive Treatment Does Not Alter the Gut Microbiome or Serum Metabolomic Profile in Obese Girls with Polycystic Ovary Syndrome

Abstract Title: Combined Oral Contraceptive Treatment Does Not Alter the Gut Microbiome or Serum Metabolomic Profile in Obese Girls with Polycystic Ovary Syndrome Background: The gut microbiome is altered in obese adolescents with polycystic ovary syndrome (PCOS), and is associated with free testosterone, metabolic markers and insulin resistance. Combined oral contraceptives (OCP) are a primary treatment for PCOS and lower testosterone, but it was unknown if they changed the gut microbiome in obese adolescents with PCOS. Objective: Assess the gut microbiome profile, targeted serum metabolomics, hormonal and metabolic measures in adolescents with PCOS and obesity with and without OCP treatment. Methods: Adolescent girls with PCOS and obesity with and without PCOS were recruited from a tertiary referral hospital and underwent stool and fasting blood collection, an oral glucose tolerance test and MRI for hepatic fat fraction. Fecal bacterial were profiled by high throughput 16S rRNA gene sequencing and fasting serum metabolomics performed with mass spectroscopy. Groups were compared with t-tests and correlations performed. Results: Twenty-nine obese adolescents with PCOS [Untreated N=21, 16±1.2 years, BMI%ile 36.5± 3.0; OCP N=8, 15.5±0.9, BMI%ile 32.5±3.9] participated. OCP therapy had lower free testosterone and higher SHBG (p&amp;lt;0.001). Platelets were significantly higher (p=0.01), along with a trend in elevated CRP (p=0.09) in the OCP group. There was no difference in measures of fasting glucose, insulin or lipids. Measures of insulin resistance including HOMA-IR and Matsuda were also similar. Principle components analysis of the serum metabolome was not different between the groups. Girls treated with OCP had similar stool microbiome α-diversity measures of bacterial evenness (p=0.28), bacterial diversity (p=0.15), and global microbial composition (β-diversity, p=0.56). Further, the percent relative abundance (%RA) of the Firmicutes: Bacteroidetes ratio was similar, as well as the %RA at the phyla, family and genus level. Bacterial α-diversity was negatively associated with serum bile acids and branched chain amino acids. A higher %RA of family Ruminococcaceae was significantly associated with serum conjugated bile acids and HOMA-IR. Conclusion: Despite changes in free testosterone and SHBG, adolescent girls with PCOS treated with OCP had similar clinical and gut microbiome profile compared to the untreated PCOS group. The significant association between bacterial α-diversity, Ruminococcaceae, clinical markers and bile acids suggests a potential role of the gut microbiome in the pathogenesis of metabolic syndrome and PCOS.

Prolactinoma in Two Brothers - Unidentified Genetic Cause Versus Co-Incidence?

Background: Most prolactinomas occur sporadically. Familial prolactinomas are uncommon. Clinical Case(s): A 35 YO male with no significant past medical history presented to endocrine clinic with c/o fatigue, decreased libido, and erectile dysfunction. Labs showed low total testosterone of 177 ng/dl (normal range 250-1100 ng/dl), low free testosterone of 19.9 pg/ml (normal range 46-224), low LH 1.1 (normal range 1.5-9.3 mIU/ml) with elevated prolactin of 47 ng/ml (normal range 2-18). MRI pituitary showed a 4.2x4x6 mm pituitary microadenoma. Physical exam was unremarkable except for obese body habitus. No known family history of MEN syndromes or parathyroid /calcium disorders. Dopamine agonist therapy resulted in significant improvement in testosterone levels, fatigue, and libido. One year after patient’s diagnosis his 32 YO younger brother was evaluated for c/o fatigue, inability to lose weight, left breast enlargement, galactorrhea, and decreased libido. Work up showed markedly elevated prolactin levels of 2405 ng/ml (normal range 4-15), decreased total testosterone of 70 ng/dl (normal range 249-836), low free testosterone of 4.8 pg/ml (normal range 8.7 to 25.1), FSH <0.1 mIU/ml (normal range 1.4-15.4), LH < 0.1 mIU/ml (normal range 1.7-8.6). MRI Pituitary showed a 25x28x20 mm pituitary macroadenoma invading the right cavernous sinus, encasing the right internal carotid artery, and abutting the optic chiasma. Our patient had genetic testing done for sequencing and deletion/duplication analysis of MEN1 and AIP (Aryl hydrocarbon receptor interacting protein) genes—two well identified causes of familial pituitary adenomas—and tested negative for both. His brother was treated with dopamine agonists with marked improvement in Prolactin to undetectable levels within a few weeks. His energy levels, headaches, and sexual function improved and galactorrhea resolved. However, testosterone levels remained below normal range even after 11 months, despite normal prolactin levels. Discussion: Prolactinomas are the most common functional pituitary adenomas, majority of them sporadic. Familial pituitary adenomas in non-syndromic form are rare. Familial isolated pituitary adenoma (FIPA) and Multiple endocrine neoplasia type 1(MEN 1) are two main causes of familial pituitary adenomas. In FIPA, pituitary adenomas occur as a result of mutations or deletions in aryl hydrocarbon receptor interacting protein gene (AIP). Identifying these mutations is important as pituitary adenomas in FIPA tend to be more aggressive, present at a younger age and are resistant to treatment. Our patient tested negative for both MEN 1 and AIP gene mutations. Whether our patient has an unidentified genetic cause or whether it was a coincidence that two brothers have prolactinomas is unclear.

Клініко-діагностичні аспекти дефіциту тестостерону в жінок фертильного віку

Актуальність. До сьогодні роль андрогенів в організмі жінки не отримала належної оцінки. Поки не існує чіткого і загальноприйнятого визначення поняття «андрогенний дефіцит у жінок» за аналогією з таким у чоловіків. Мета дослідження: вивчити клініко-діагностичні аспекти дефіциту тестостерону в жінок репродуктивного віку. Матеріали та методи. Під наглядом перебувало 60 жінок із дефіцитом тестостерону без супутньої патології. Середній вік пацієнток становив 28,3 року. Контрольну групу становили 20 здорових жінок. Пацієнтки були розподілені за показником індексу маси тіла (ІМТ) на три групи. Першу групу становили 20 жінок із надмірною масою тіла (ІМТ 25–29,9 кг/м2), другу групу— 20 жінок з ожирінням I ступеня і третю групу— 20 жінок з ожирінням II ступеня. Результати. Для пацієнток із групи з ожирінням I ступеня була характерна на 14-й день оваріально-менструального циклу тенденція до зниження базальних рівнів лютеїнізуючого гормона (ЛГ), фолікулостимулюючого гормона (ФСГ), естрадіолу і прогестерону на тлі вірогідної гіпоандрогенемії. У пацієнток із групи з ожирінням II ступеня відзначалося вірогідне зниження базальних рівнів ЛГ, ФСГ, естрадіолу, прогестерону на тлі вірогідної гіпоандрогенемії. При проведенні кореляційного аналізу виявлений прямий зв’язок дефіциту тестостерону зі ступенем ожиріння. Так, найнижчі значення тестостерону виявлені в пацієнток третьої групи (&lt;0,05нмоль/л). Водночас у пацієнток першої і другої груп рівень тестостерону також був значно знижений— від 0,02 до 0,05 нмоль/л відповідно. Вірогідно зниженими виявилися рівні дегідроепіандростерону и 17-оксипрогестерону, особливо в третій групі— 0,3 мкг/мл і 0,1 нмоль/л відповідно. Висновки. У більшості жінок репродуктивного віку з дефіцитом тестостерону спостерігається гіпоменорея з низьким вмістом вільного тестостерону. Встановлено пряму кореляційну залежність дефіциту тестостерону від ступеня ожиріння в жінок з андрогенною недостатністю.

Hypogonadism in opioid using males in an inner-city cohort: A cross-sectional study.

The link between male hypogonadism and opioids is well-established, but whether there is a difference in the frequency of hypogonadism between heroin and methadone for treatment of opioid use disorder (OUD) has not been -determined. Cross-sectional. Setting, patients, and participants: Male drug users and nonusers matched for socioeconomic status between 18 and 65 years, recruited in Baltimore as part of the study of HIV, injection drug use, nutrition, and endocrinology (SHINE). Hypogonadism was defined as low free testosterone <50 pg/mL. Participants were categorized into three groups based on opioid use: (1) NONE, (2) methadone use as treatment of OUD (METHADONE), and (3) Heroin use (HEROIN). This third group was further divided to mild (MH), and heavy (HH) heroin use. We used multiple logistic regression to examine the association between hypogonadism and different groups. The cohort consisted of 189 men, 94 percent black, average age 43 years, with high HIV (56 percent) and HCV (38 percent) prevalence. 24 percent had hypogonadism. Compared to NONE, there were higher odds of hypogonadism in METHADONE (aOR 3.46; 95 percent CI [1.34,8.93]; p = 0.01) but not in HEROIN. After dividing HEROIN into MH and HH, there were higher odds of hypogonadism in HH compared to NONE (aOR 3.27; 95 percent CI [1.12,9.53]; p = 0.03) but not in MH. Methadone used for treatment of OUD was associated with male hypogonadism similar to heavy heroin use. Targeted hypogonadism screening and treatment may be warranted in this population to reduce its health consequences such as sexual dysfunction, osteoporosis, and abdominal adiposity.

Metabolism of testosterone during weight loss in men with obesity

ObjectiveMen with obesity often have low total and, with increasing adiposity, also low free testosterone (T) levels, which can partially restore during weight loss. Although this is partly explained by lower sex hormone binding globulin (SHBG) production and hypothalamic-pituitary downregulation, it is still not unravelled whether changes in androgen metabolism contribute to this phenomenon. Therefore, early changes in urinary excretion of T and its metabolites, during weight loss, in men with obesity are investigated. DesignLongitudinal study. MethodsFourteen men with obesity (age 52(45–60)years, BMI 42.6(41.8–44.8)kg/m²) underwent gastric bypass surgery (GBS). Before surgery and 3 weeks, 6 weeks, 6 months and 1 year thereafter, 24 h urine and fasting serum samples were collected. Serum T and estradiol (E2) levels were analyzed using LC-MS/MS and urinary metabolites of T with GC-MS/MS. ResultsAlready three weeks after GBS, serum SHBG and total T levels increased and remained increased as compared to baseline (all,p < 0.0125). Gonadotropins and (free) E2 levels were unchanged, serum E2/T ratio decreased (p < 0.0125). Total amount of urinary T increased non-significantly with mean increases of 53 % one year after GBS (p = 0.026). Urinary E2/T, estrone/T, 3α-androstanediol/T and androsterone/T ratios decreased after GBS (p < 0.0125). ConclusionsRestoration of circulating T levels during weight loss in this population is not only brought about by normalization of circulating SHBG levels, but increased production of and alterations in T metabolism also contribute. More specifically, relative decreases in aromatization and lower 5α-reductase activity might also be involved in restoring T levels in men with obesity.

Low Serum-Free Testosterone Concentration in Chinese Male Patients with Uncomplicated Acute Type B Aortic Dissection

Although aortic dissection occurs predominantly in men, its association with androgens is unknown. The aim of this study was to evaluate the androgen levels in Chinese male patients with uncomplicated, acute type B aortic dissection. Cross-sectional study. A total of 192 age-matched male patients with uncomplicated, acute type B aortic dissection or essential hypertension were recruited between 2016 and 2018. The demographic and clinical data were analyzed. Male patients with uncomplicated, acute type B aortic dissection had lower serum total testosterone and free testosterone than male patients with essential hypertension (7.6 ± 3.7 nmol/L vs. 10.9 ± 3.8 nmol/L, P < 0.001; 36.0 ± 19.8 pmol/L vs. 56.4 ± 19.2 pmol/L, P < 0.001). Lower free testosterone level was significantly associated with uncomplicated, acute type B aortic dissection (univariate odds ratio 0.948, P < 0.001; multivariate odds ratio = 0.966, P = 0.002). No statistical difference was observed for free testosterone between younger patient groups (aged < 51 years; aged 51-60 years) and older patient groups (aged 61-70 years; aged >70 years) with uncomplicated, acute type B aortic dissection (33.7 ± 19.8 pmol/L vs. 38.5 ± 19.8 pmol/L, P = 0.239). Lower free testosterone was independently associated with uncomplicated, acute type B aortic dissection in the Chinese male population with hypertension. Additional studies are needed to clarify whether earlier onset in Chinese patients with aortic dissection is associated with androgen deficiency.

Clinical Characteristics of Low Androgen Status in Males with Type 2 Diabetes Mellitus.

To determine the clinical characteristics of low androgen status in adult males with diabetes, we retrospectively analyzed the medical records of patients with type 2 diabetes mellitus in whom serum free testosterone (FT) levels were examined for 1 year. Among the 46 patients (56 ± 1.5 years old), decreases in serum FT levels to < 8.5 pg/ml (indicating the occurrence of late-onset hypogonadism [LOH]) were detected in 18 (39%). The per-centages of patients with low FT levels were high in the ≥ 50 years age group (83%), the HbA1c < 7% group (67%), and the 25 ≤ BMI < 30 kg/m2 group (56%). The serum FT levels tended to decrease age-dependently. The level of HbA1c was significantly correlated with the Heinemann Aging Male Symptoms (AMS) score (R = 0.47). The low-FT group had decreased levels of hemoglobin. Of note, the serum FSH level (R = -0.32) was negatively correlated with the serum FT level, whereas the serum TSH level (R = 0.36) was positively correlated with the serum FT level. Collectively, these results revealed that many diabetic males may have low FT levels and that the AMS score is related to the HbA1c level. A slightly anemic condition, thyroid dysfunction, and obesity (class 1) might be involved in LOH in middle-aged diabetic males.

Serum testosterone in Nigerian men with type 2 diabetes mellitus and its relationship with insulin sensitivity and glycemic control

BackgroundThere is increasing evidence that testosterone deficiency has key associations with insulin sensitivity and glycemic control. Its presence may therefore contribute to and/or exacerbate clinical disease in men with type 2 diabetes mellitus (T2DM). This study sought to determine the frequency of low free testosterone and explore its relationship with, insulin sensitivity and glycemic control among Nigerian men with T2DM. MethodsOne hundred and four men with type 2 DM and one hundred and one apparently healthy non-diabetic men matched for age, were recruited into the study Socio-demographic data, anthropometric measurements and blood samples were obtained for measurement of serum total testosterone (TT), sex hormone binding globulin (SHBG), fasting plasma insulin, fasting plasma glucose (FPG), glycated hemoglobin (HbA1c) and fasting lipid profile in all the subjects. Insulin sensitivity (%IS) and free testosterone (CFT) were then calculated. ResultsThe median CFT for men with T2DM was significantly lower than that of non-diabetic controls (0.17 nmol/L vs 0.58 nmol/L respectively; P < 0.001). 52.9% of men with T2DM had low CFT, as compared with 21.4% amongst the non-diabetic controls; P < 0.001.Among men with T2DM, those with lower CFT had significantly lower median % S and higher mean HbA1c than those with normal CFT (37.0% versus 63.0%; P = 0.021 and 7.79 (2.03) % versus 7.02 (1.94) %; P = 0.038 respectively]. HbA1c had significant negative correlations with both CFT (correlation coefficient: −0.239 (P < 0.05) and TT (correlation coefficient: 0.354; P < 0.01.There was no significant difference in serum lipids when T2DM men with low serum CFT were compared with T2DM men with normal serum CFT levels. ConclusionWe conclude that low serum testosterone is common among men with T2DM and has a significant association with glycemic control (HbA1c) and insulin sensitivity.

Risk factors for decreased bone mineral density in men with type 2 diabetes.

BACKGROUND: Type 2 diabetes and osteoporosis are widespread diseases in the middle-aged and elderly people. Most studies of osteoporosis in patients with type 2 diabetes have been performed in women; meantime risk factors for lowering bone mineral density (BMD) in men have been little studied.AIMS: to identify risk factors for decreased BMD at the lumbar spine, femoral neck and forearm in men with type 2 diabetes.METHODS: Eighty two men from 50 to 75 years old, with duration of diabetes for at least one year, were included in the study. Individuals with known risk factors for secondary osteoporosis were not included. Twenty-three men with normal BMD having no diabetes or obesity were acted as control. The T-score at the lumbar spine, femoral neck and forearm of a non-dominant arm, as well as body composition parameters, were evaluated by dual-energy X-ray absorptiometry. The levels of hormones that affect bone metabolism (parathyroid hormone, free testosterone, 25-OH vitamin D) were measured in blood serum by ELISA. Risk factors for reducing BMD were identified using multivariate regression analysis and receiver operating characteristic (ROC) curves.RESULTS: Among patients with diabetes, 49 individuals had normal BMD and 33 showed decreased T-score values (&lt;-1 SD). Free testosterone &lt;5.92 pg/ml was predictor for decreased BMD at the lumbar spine (OR=4.4, p=0.04). For femoral neck, the risk factors were body weight &lt;95.5 kg (OR=2.8, p=0.04), total fat mass &lt;27 kg (OR=3.3, p=0.03), truncal fat mass&lt;17.5 kg(OR=4.5, p=0.006), android (central abdominal) fat mass &lt;3.2 kg(OR=4.0, p=0.01), gynoid (hip) fat mass &lt;3.5 kg(OR=3.3, p=0.02), and lean mass &lt;59 kg(OR=3.0, p=0.04). Risk factors for reduced BMD at the forearm were diabetes duration&gt;15.5 years (OR=3.7, p=0.03) and HbA1c &lt;8.15% (OR=3.8, p=0.03). Parathyroid hormone and 25-OH-vitamin D did not predict BMD independently.CONCLUSIONS: In men with type 2 diabetes, low free testosterone is a risk factor for decreased BMD in the lumbar spine, and diabetes duration is a risk factor for decreased BMD in the forearm. The presence of obesity is associated with an increase in BMD in the femoral neck; a high HbA1c is associated with an increase in BMD in the forearm.

Low free testosterone level as a predictor of cardiovascular events in Japanese men with coronary risk factors

Aim: We investigated whether low plasma free testosterone (FT) levels could predict cardiovascular events (CVE) in Japanese men with coronary risk factors. Methods: Male patients with classical coronary risk factors who had undergone serum FT testing were enrolled. New incidences of CVE were retrospectively investigated among all eligible participants based on their medical records. Results: Overall, 466 male outpatients with coronary risk factors without a previous history of CVE were identified. Throughout the follow-up period (median = 92 months), 126 CVE occurred. The Kaplan–Meier survival analysis according to the tertiles of plasma FT levels revealed that patients with the lowest FT tertile (<6.5 pg/mL) had a higher likelihood of developing CVE than those with the highest tertile (>9.3 pg/mL) (p<.01). Multivariate analysis showed that increased frequency of CVE was observed with lower FT tertiles, independent of other coronary risk factors, with hazard ratios of 0.617 (95% CI, 0.389–0.976; p=.030) and 0.524 (95% CI, 0.309–0.887; p=.016) for the second and highest tertile relative to the lowest FT tertile, respectively. Conclusion: Among Japanese men with coronary risk factors, a lower FT level was a predictor for the development of cardiovascular diseases independent of other coronary risk factors and age.

The prevalence of and risk factors for low free testosterone levels in japanese men with well-controlled human immunodeficiency virus infection

The prevalence of and risk factors for low free testosterone levels in japanese men with well-controlled human immunodeficiency virus infection

Sexual dysfunction and mining-related jobs: A cross-sectional study in the former Katanga Province, DR Congo

Aim: Based on a preliminary case-control study of erectile dysfunction among mineworkers in the former Katanga province of the DR Congo (Musa et al. Occ Environ Med 2020), we investigated the association between sexual dysfunction and metal exposure in mining-related-jobs. Methods: In a cross-sectional study, we included 138 miners and 140 bakers from Lubumbashi, Likasi, Kipushi and Kolwezi. Using questionnaires administered face-to-face, we obtained socio-demographic and occupational data and determined the International Index of Erectile Function (IIEF-15), a validated tool to evaluate five sexual domains (maximum score 75). We measured trace metals in blood and urine, and total + free testosterone and sex hormone binding globulin (SHBG) in serum. Results: Miners and bakers had similar median (IQR) age [35.6 y (30.6-40.0)]. For several trace metals, concentrations were higher in blood or urine among miners than bakers, this being most pronounced for lead. Thus, median blood lead (µg/dl) was higher (p=0.002) in miners [6.7 (4.5-16.7)] than in bakers [5.4 (4.1-7.5)]. Blood lead and free testosterone were inversely correlated (Spearman R=-0.25, p=0.002). The median IIEF-15 score was lower (p&lt;0.001) among miners [66 (49-73)] than among bakers [73 (66-74)]. Total testosterone (ng/dl) did not differ between miners [505 (453-651)] and bakers [541 (447-709)], but free testosterone (ng/dl) was lower among miners [8.1 (6.8-10.1)] than among bakers [9.3 (8.7-12.5)]; conversely, SBGH (nmol/l) was higher (p&lt;0.001) among miners [55 (44-65)] than among bakers [47 (33-52)]. Conclusion: We confirmed that miners had lower scores of erectile function than controls. Miners had lower free testosterone and higher SHBG than bakers, and evidence of higher exposure to trace metals, especially lead. The possible role of lead in sexual dysfunction needs to be clarified, especially as lead is not among the main ores mined in the region.

Prevalence of and Risk Factors for Low Free Testosterone Levels in Japanese Men with Well-controlled Human Immunodeficiency Virus Infection.

The change in the prevalence of hypogonadism with age in men with human immunodeficiency virus (HIV) infection is subject to debate. To address this issue, we diagnosed hypogonadism based on serum levels of free testosterone (fTST) rather than total testosterone which is thought to be an inaccurate indicator. We also determined the relationship between age and fTST levels and identified risk factors for hypogonadism in men with HIV infection. We retrospectively reviewed fTST levels and associated clinical factors in 71 wellcontrolled HIV-infected men who were treated at Teikyo University Hospital between April 2015 and March 2016 and who had data available on serum fTST levels, measured >6 months after starting antiretroviral therapy. fTST was measured using radioimmunoassay on blood samples collected in the morning. Risk factors for hypogonadism were identified using Welch's t-test and multiple regression analysis. The men had a mean (± standard deviation) age of 47.4 ± 13.6 years, and mean (± standard deviation) serum fTST level of 13.0 ± 6.1 pg/mL. Fifteen (21.1%) men had hypogonadism based on a fTST <8.5 pg/mL. Serum fTST levels significantly decreased with age (-0.216 pg/mL/year). Older age and low hemoglobin levels were identified as risk factors for hypogonadism. The men in the study experienced a more rapid decline in fTST levels with age than men in the general population (-0.161 pg/mL/year). Serum fTST levels in men with HIV infection should be monitored, especially in older men and those with low hemoglobin levels.

Free Testosterone and Prolactin Levels and Sperm Morphology and Function Among Male Patients With Tramadol Abuse

Tramadol abuse has become a crisis in Egypt and many other Middle Eastern countries. Tramadol abuse is associated with sexual dysfunction and male infertility, according to recent animal and human studies. The objective of this study was to compare tramadol abuse patients and healthy controls regarding free testosterone and prolactin levels and semen analysis. Sixty patients with opiate use disorders attributed to tramadol (OUD-T) based on Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) diagnostic criteria and 30 healthy controls were included in the study. Sociodemographic and clinical data and urine, blood, and semen samples were collected from patients and controls for assessment. Compared with controls, OUD-T patients had higher prolactin and lower free testosterone levels. Patients with OUD-T were more likely to have lower sperm count and higher abnormal motility and forms of sperms compared with controls. Patients with OUD-T were found to be more likely to have lower free testosterone levels and lower sperm counts and vitality, and higher prolactin levels and sperm abnormal forms compared with controls.

Insulin Sensitizers for Improving the Endocrine and Metabolic Profile in Overweight Women With PCOS.

ObjectiveTo evaluate the efficacy of insulin sensitizers on menstrual frequency, sex hormone, and metabolic parameters in overweight women with polycystic ovary syndrome (PCOS).MethodsWe searched multiple databases from inception to September 2019 for randomized controlled trials. Network meta-analysis was conducted using multivariate random effects method.ResultsFourteen trials reporting on 619 women were included. Compared with metformin, metformin + thiazolidinediones (TZDs) was more superior in menstrual recovery (weighted mean difference [WMD] 3.68; 95% credibility interval [CrI], 1.65 to 8.20), metformin + glucagon-like peptide-1 (GLP-1) receptor agonists was more effective in decreasing androstenedione (WMD −2.53; 95% CrI, −3.96 to −1.09), both metformin + GLP-1 receptor agonists (WMD 9.22; 95% CrI, 5.46 to 12.98) and metformin + TZDs (WMD 4.30; 95% CrI, 0.78 to 7.82) were more effective in increasing sex hormone–binding globulin (SHBG), while TZDs were less effective in decreasing body mass index (BMI) (WMD 1.69; 95% CrI, 0.72 to 2.66). Compared with GLP-1 receptor agonists, metformin + GLP-1 receptor agonists was associated with higher SHBG (WMD 7.80; 95% CrI, 4.75 to 10.85), lower free testosterone (WMD −1.77; 95% CrI, −3.25 to −0.29), lower androstenedione (WMD −2.70; 95% CrI, −3.91 to −1.50) and lower fasting blood glucose (WMD −0.41; 95% CrI, −0.73 to −0.08).ConclusionFor overweight women with PCOS, both metformin combined with GLP-1 receptor agonists and metformin combined with TZDs appear superior to monotherapy in improving hyperandrogenemia. Metformin combined with TZDs could be particularly effective in promoting the recovery of menstruation. Metformin combined with GLP-1 receptor agonists has the additional advantage of improving fasting glucose when compared with GLP-1 receptor agonists alone. TZDs are inferior to metformin in decreasing BMI.

SUN-032 Digenic Inheritance of PCSK1 and CHD7 Mutations in PAX4 Homozygous Diabetic Male with Normosmic Hypogonadotropic Hypogonadism

Background: Normosmic congenital hypogonadotropic hypogonadism denotes Kallmann syndrome not associated with anosmia or hyposmia. Over the past few years, the availability of next-generation sequencing has started to unravel the complex molecular basis of congenital hypogonadotrophic hypogonadism including digenic or oligogenic pathogenecity in addition to classic monogenic causality (1). Clinical Case: A 22-year-old male patient was referred to the endocrine clinic in 2018 with recent -onset hyperglycemia. His weight was 82.2 kg with a height of 180 cm (BMI of 25.3 kg/m2). Physical examination revealed small testes, micropenis, and no axillary and pubic terminal hair. His smell sense was intact. His hormonal test reveals low testosterone (0.10 ng/mL) and low free testosterone (0.65 pg/mL) levels with inappropriately low gonadotrophins levels. Secretion of LH and FSH increased 2-fold after GnRH stimulation. His bone age was 13-years 6-months old, and brain magnetic resonance imaging showed the presence of olfactory bulbs, and unremarkable findings except for small size of the pituitary gland. There were no signs associated with CHARGE syndrome (coloboma ocular, heart defects, atresia or stenosis of the choanae, retardation of growth and/or development, genitourinary anomalies, and ear abnormalities). Biochemical investigation demonstrated high serum glucose level and high HbA1c (13.8%). To identify variants to cause the phenotype of the proband, we adopted trio-based whole exome sequencing (WES) and candidate gene approach. Candidate genes was listed from the orphanet (https://www.orpha.net). WES of the proband revealed the presence of heterozygote missense mutations of the CHD7 gene (c.6107C>T, p.Pro2036Leu, rs369543203) and PCSK1 gene (c.239G>A, p.Arg80Gln, rs1799904). The missense variants were predicted to have a damaging effect on the encoded protein, by SIFT and PolyPhen-2 analyses. Genetic analyses of his family revealed that his father had the same heterozygote missense mutations of the CHD7 gene, but wild type of PCSK1. Proband’s mother had the same heterozygote missense mutations of PCSK1, but wild type of CHD7. Furthermore, the proband had homozygote missense mutation of PAX4 (c.575G>A, p.Arg192His, rs2233580) known as maturity-onset diabetes of the young (MODY) 9 gene. Both parents have the same but heterozygous mutation of PAX4 p.Arg192His, and pre-diabetic range of hyperglycemia. Conclusion: This is the first case demonstrating digenic inheritance of mutations in PCSK1 and CHD7 as a potential cause of normosmic hypogonadotrophic hypogonadism, interestingly in PAX4 homozygous diabetic male. Reference: (1) Maione L, et al. Genetic counseling for congenital hypogonadotropic hypogonadism and Kallmann syndrome: new challenges in the era of oligogenism and next-generation sequencing. Eur J Endocrinol. 2018;178(3):R55-R80.

Regular Mindful Yoga Practice as a Method to Improve Androgen Levels in Women With Polycystic Ovary Syndrome: A Randomized, Controlled Trial.

Holistic approaches are needed to complement existing therapies for polycystic ovary syndrome (PCOS), a common disorder affecting the health of reproductive-aged females. To determine whether thrice-weekly mindful yoga practice improves endocrine, cardiometabolic, or psychological parameters in women with PCOS. Thirty-one women with PCOS between the ages of 23 and 42 years and living in Erie County, Pennsylvania, were recruited for this randomized, controlled study arm, which was part of a larger 3-part investigation. Women were randomly assigned to either a mindful yoga intervention group or no intervention (control) group. Group classes were 1 hour, thrice weekly. Initial endocrine, cardiometabolic, and psychological measurements were compared with measurements taken after the 3-month intervention period. Measurements included free testosterone, dehydroepiandrosterone, androstenedione, body mass index, waist-to-hip ratio, fasting blood glucose and insulin levels, and anxiety and depression scores. Twenty-two women completed the 3-month intervention period, 13 in the mindful yoga group and 9 in the control group. Paired comparisons of pre- and postintervention parameters indicated that women who completed the mindful yoga intervention had significantly lower free testosterone levels (5.96 vs 4.24 pg/mL; P<.05) and dehydroepiandrosterone levels that trended lower. Improved testosterone may persist for several months after completion of a 3-month, thrice-weekly mindful yoga intervention. Additionally, improvements were seen in measures of anxiety and depression. The improvements observed suggest that regular mindful yoga practice can be a useful complementary therapeutic option for women with PCOS, particularly for improving serum androgen levels, a hallmark feature of PCOS. This improvement occurred in the absence of weight loss and may persist even if there is a lapse in practice. (ClinicalTrials.gov No. NCT03383484).