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1.
The causes of adverse changes of testosterone levels in men.
Wrzosek, M, Woźniak, J, Włodarek, D
Expert review of endocrinology & metabolism. 2020;(5):355-362
Abstract
INTRODUCTION As men age, progressive testosterone deficiency syndrome becomes an increasingly common problem. However, the decreased testosterone levels are not only the result of advanced age. AREAS COVERED PubMed search of published data on testosterone, nutritional deficiency, stress, sleep, and obesity. Many factors impact the male HPG axis (the hypothalamic-pituitary-adrenal), including body weight, calorific and nutritional value of a diet, the amount and quality of sleep, as well as the level of stress. In the case of persons of healthy weight, a below-average calorific value of a diet may decrease the levels of testosterone in men. On the other hand, the same caloric deficiency in obese persons may result in a neutral or positive impact on testosterone levels. EXPERT OPINION Many factors, including external, environmental and internal factors, influence testosterone levels. Undoubtedly, nutritional deficiency, and particularly of such nutrients as zinc, magnesium, vitamin D, together with low polyphenols intake, affects the HPG axis. The levels of mental and oxidative stress can also adversely impact the axis. Hence, a diagnosis of the cause of disturbance in testosterone levels depends on many factors and requires a broad range of research, as well as a change of patients' lifestyle.
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2.
Associations of SRD5A1 gene variants and testosterone with dysglycemia: Henan Rural Cohort study.
Liu, X, Wei, D, Jiang, J, Liu, X, Tu, R, Luo, Z, Wang, Y, Dong, X, Qiao, D, Shen, F, et al
Nutrition, metabolism, and cardiovascular diseases : NMCD. 2020;(4):599-607
Abstract
BACKGROUND AND AIM Multiple studies support a complex relationship between testosterone and type 2 diabetes mellitus (T2DM) and the transformation of testosterone is affected by several reductases. Thus, we aimed to explore the associations of steroid-5α-reductase type 1 (SRD5A1) gene polymorphism with impaired fasting glucose (IFG) and T2DM and the interactive effects of testosterone and genotypes on glycometabolism. METHODS AND RESULTS A case-control study including 2365 participants was performed. Genomic DNA was extracted from the whole blood and genotyped for the SRD5A1 single nucleotide polymorphisms (SNP) rs1691053. Multivariable logistic regression and linear regression were performed to estimate the associations of SRD5A1 rs1691053 alleles and genotypes with glycometabolism. Generalized linear models were used to investigate the modulatory effects of serum testosterone on glycometabolism indexes in males. After multivariable adjustment, the odds ratio (OR) of homozygous CC genotypes in male carriers was 2.62 (95%CI: 1.11-6.18) for IFG. Furthermore, significant associations of SRD5A1 rs1691053 polymorphisms with adverse indices of glycometabolism were observed in males. Interestingly, the opposite associations in females were observed. The interactive associations of SNP and testosterone were found and mutations were more likely to lead unfavorable metabolic phenotypes. CONCLUSION These results showed that SRD5A1 rs1691053 gene polymorphism was independently associated with glycometabolism. The interaction between a genetic polymorphism from SRD5A1 and testosterone involved glycometabolism was identified in males. Although this preliminary data should be replicated with other rigorous researches, it highlighted the importance of the SNP-testosterone interaction over the present of glycometabolism.
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3.
Effect of clomiphene citrate treatment on the Sertoli cells of dysmetabolic obese men with low testosterone levels.
Pelusi, C, Fanelli, F, Baccini, M, Triggiani, V, Bartolomeo, N, Carbone, MD, De Pergola, G, Di Dalmazi, G, Pagotto, U, Pasquali, R, et al
Clinical endocrinology. 2020;(1):38-45
Abstract
BACKGROUND Clomiphene citrate (CC) has been shown to restore the hypothalamic-pituitary-gonadal (HPG) axis by increasing testosterone (T) levels to physiological levels in patients with dysmetabolic conditions such as obesity, metabolic syndrome and type 2 diabetes mellitus (T2DM). However, the data are unclear regarding the effects on Sertoli cell (SC) function. AIM: To study SC function by assessing Inhibin B (IB) and anti-Mullerian hormone (AMH) levels at baseline and after 3 months of CC treatment. MATERIALS AND METHODS This is an ancillary study of a cross-over, randomised, double-blind, placebo-controlled trial performed to evaluate androgen response to CC treatment in dysmetabolic obese subjects with low T levels treated with metformin. We evaluated SC function by assessing IB and AMH levels at baseline and after 3 months of each treatment in ten dysmetabolic obese subjects with low T levels. In all subjects, the influence of the clinical characteristics, metabolic and hormonal baseline parameters on SC and Leydig (LC) function, evaluated respectively with AMH, IB, follicle-stimulating hormone (FSH) and T levels, was tested. RESULTS No significant changes were observed for IB and AMH concentrations after each treatment period. Whereas T and oestradiol (E2) levels were shown to be significantly higher in the CC plus metformin phase (CC/Met) only. No clinical, metabolic or hormonal parameters showed significant effects on serum AMH at baseline or after treatments. However, baseline T, dihydrotestosterone (DHT) and E2 positively affected IB levels during CC/Met therapy (P = .003, P = .038 and P = .049, respectively). Baseline leptin and FSH had a negative (P = 031) and positive (P = .048) respectively role on T levels during CC/Met, as they were statistically significant compared to the placebo period (Plac/Met). CONCLUSION Unlike the LC activity, CC was unable to influence SC function, as shown by the lack of IB and AMH serum modifications, thus suggesting an intrinsic nonreversible defect of SC cells in patients with dysmetabolic conditions.
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4.
Reviewing the Evidence on Vitamin D Supplementation in the Management of Testosterone Status and Its Effects on Male Reproductive System (Testis and Prostate): Mechanistically Dazzling but Clinically Disappointing.
Santos, HO, Howell, S, Nichols, K, Teixeira, FJ
Clinical therapeutics. 2020;(6):e101-e114
Abstract
PURPOSE Vitamin D supplementation has been suggested to increase testosterone levels. The primary purpose of this literature review was to critically assess the physiologic effects of vitamin D supplementation on serum testosterone concentrations in men and the secondary purpose was to evaluate the feasibility of vitamin D status toward urologic health (testis and prostate). METHODS A structured literature review was performed using the Cochrane, MEDLINE, and Web of Science databases. The literature search encompassed studies published between 2011 and 2019. FINDINGS Observational studies suggest an association between higher testosterone and serum vitamin D concentrations. Conversely, most randomized clinical trials that investigated the effect of vitamin D administration on testosterone levels have failed to detect any significant effect. Physiologically, vitamin D is engaging in spermatogenesis, but it remains unclear whether vitamin D is a determinant of fertility. With prostate support, the management of vitamin D status has been associated with a decreased prevalence of benign prostatic hyperplasia and symptoms (ie, lower urinary tract symptoms). However, with prostate cancer, there is a paucity of evidence pertaining to vitamin D supplementation. IMPLICATIONS Mechanistically, vitamin D exhibits essential roles in the testis and prostate; otherwise, there is no apparent evidence to support the use of vitamin D supplementation to increase testosterone levels and to improve clinical outcomes related to the male reproductive system.
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5.
Androgen Therapy in Women.
Vegunta, S, Kling, JM, Kapoor, E
Journal of women's health (2002). 2020;(1):57-64
Abstract
Androgens are believed to have an important biologic role in women, particularly in regulation of libido and sexual arousal, although much about their function on other systems in women is unknown. Testosterone, the primary ovarian androgen, has been used to treat carefully selected postmenopausal women with hypoactive sexual desire disorder (HSDD). However, testosterone use in women has not been approved by the United States Food and Drug Administration (FDA) because of uncertainties regarding the effectiveness and long-term safety of this strategy. An intravaginal form of the adrenal androgen, dehydroepiandrosterone (DHEA) has been approved by the FDA to treat genitourinary syndrome of menopause. In this article, we review the current knowledge regarding the role of androgens and their clinical use in women. We conducted a systematic search of PubMed for publications describing the role and clinical use of androgens in women. We used the search terms "HSDD," "DHEA in women," "testosterone in women," and "androgens in women," and reviewed most references from all relevant articles. Most randomized placebo-controlled trials show an improvement in sexual function with low-dose testosterone therapy in select postmenopausal women with HSDD. Although this strategy appears to be safe in the short term and no major safety concerns have emerged thus far, long-term effects on cardiovascular risk and breast cancer incidence are not known. A trial of low-dose testosterone therapy may be considered for carefully selected postmenopausal women with HSDD, as long as other contributors to sexual dysfunction have been adequately addressed. However, patients need careful counseling regarding the lack of long-term safety data, and close clinical and laboratory monitoring of these women is recommended to avoid supraphysiologic dosing.
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6.
The Effect of Prostate Cancer Radiotherapy on Testosterone Level: A Systematic Review and Meta-analysis.
Mortezaee, K, Motallebzadeh, E, Milajerdi, A, Farhood, B, Najafi, M, Sahebkar, A
Anti-cancer agents in medicinal chemistry. 2020;(6):636-642
Abstract
INTRODUCTION In the current study, a systematic search and meta-analysis were performed to evaluate the effect of prostate cancer radiotherapy on testosterone levels of patients. METHODS To illuminate the effect of radiotherapy on the testosterone level of prostate cancer patients, a systematic search was conducted in accordance with the PRISMA guideline in electronic databases of Scopus, Embase, PubMed, Web of Science, and clinical trials up to December 2018 using relevant keywords. Based on a certain set of inclusion and exclusion criteria, 12 eligible studies that had data on the testosterone level following prostate cancer radiotherapy were included in the meta-analysis. RESULTS According to the various techniques of prostate cancer radiotherapy, the dose values scattered to the testicular tissues ranged from 0.31 to 10 Gy. Combining the findings from 12 studies, it was found that prostate cancer radiotherapy leads to a significant reduction in the testosterone level (Weighted Mean Difference [WMD]: -51.38 ng/dL, 95% CI: -75.86, -26.90, I2=0.0%, P<0.05). Furthermore, subgroup analysis by the patient number showed a significant reduction in the testosterone level at patient number < 50 (WMD: -80.32 ng/dL, 95% CI: -125.10, -35.55, I2= 0.0%) and 50 < patient number < 100 (WMD: -46.99 ng/dL, 95% CI: - 87.15, -6.82, I2= 0.0%). Subgroup analysis based on treatment technique type revealed a significant reduction in testosterone level after conventional radiotherapy (WMD: -56.67, 95% CI: -100.45,-12.88, I2= 34.3%) and IMRT/SBRT technique (WMD: -57.42, 95% CI: -99.39, -15.46, I2= 0.0%) in comparison with the proton therapy (WMD: 0.00, 95% CI: -80.24, 80.24). CONCLUSION The findings showed a significant decrease in the testosterone level of prostate cancer patients after radiotherapy compared with pre-treatment levels.
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7.
Sleeve Gastrectomy and Gastric Bypass Decrease the Carotid Intima-Media Thickness in Obese Men: Association with Weight Loss, Cardiovascular Risk Factors, and Circulating Testosterone.
Cobeta, P, Osorio, A, Cuadrado-Ayuso, M, García-Moreno, F, Pestaña, D, Galindo, J, Botella-Carretero, JI
Obesity surgery. 2020;(3):851-859
Abstract
BACKGROUND Obesity surgery has shown to decrease the carotid intima-media thickness (IMT), but studies that compare different surgical techniques are scarce, especially in men. OBJECTIVE To evaluate the changes in IMT in men after laparoscopic Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) and its association with circulating testosterone. SETTING Academic Hospital. METHODS We studied 40 men with severe obesity, of whom 20 were submitted to laparoscopic RYGB and 20 to SG. Twenty control men matched for age and degree of obesity were also included. Both patients and controls were evaluated at baseline and 6 months after surgery or conventional treatment with diet and exercise, respectively. RESULTS The mean carotid IMT decreased after surgery irrespective of the surgical technique whereas no changes were observed in the control men submitted to conventional therapy (Wilks' λ = 0.745, P < 0.001 for the interaction, P < 0.001 for RYGB vs. controls, P = 0.001 for SG vs. controls, P = 0.999 for RYGB vs. SG). The decrease in the carotid IMT correlated with the increase in total testosterone (r = 0.428, P = 0.010) and lost BMI (r = 0.486, P < 0.001). Multivariate linear regression retained only the decrease in BMI (β = 0.378, P = 0.003) after adjustment (R2 = 0.245, F = 9.229, P = 0.001). CONCLUSION Both RYGB and SG decrease carotid IMT in men with obesity compared with conventional treatment with diet and exercise.
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8.
The effects of Elaeagnus angustifolia L. whole fruit on the sex hormone profile in menopausal women: A double-blind, randomized, placebo-controlled study.
Emaminia, F, Rezaei, A, Badehnoosh, B, Ramezani, R, Shabani, M
Journal of ethnopharmacology. 2020;:112229
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Menopause is a product of interrupted ovarian activity and decrease in its estradiol production. Herbal medicines as an alternative to hormone therapy are increasingly used by menopausal women. Elaeagnus angustifolia L. (Senjed in Persian) is a well-known herbal remedy with various therapeutic effects according to Iranian traditional medicine which is recommended to relieve the menopausal side effects. The aim of present study was to evaluate the effects of oral intake of whole fruit powder of E. angustifolia on the sex hormones profile in menopausal women. MATERIALS AND METHODS In present double-blind randomized placebo-controlled trial, 58 eligible women who were referred to Kamali Women Hospital (Karaj, Iran, 2017) were randomly assigned into herbal medicine (15 g E. angustifolia) and placebo (7.5 g cornstarch +7.5 g isomalt) groups. Initially and after 10 weeks of the treatment, serum levels of estradiol, progesterone, testosterone, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) hormones were measured. RESULTS According to between-group analyses, the changes in the studied parameters were not significant between herbal medicine and placebo groups, except for joint pain that improved significantly in herbal medicine group. However, by within-group analysis the levels of FSH and FSH to testosterone showed a significant increase, whereas the level of progesterone decreased significantly after 10 weeks of E. angustifolia consumption. CONCLUSIONS The improvement of the sex hormone profile was not in a full accordance with Iranian folklore after E. angustifolia consumption in the present menopausal participants. However, considering a strong belief on the beneficial effects of E. angustifolia in Iranian folklore, a long-term studies of larger group participants are needed to evaluate the efficacy.
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9.
The effects of soy isoflavones on total testosterone and follicle-stimulating hormone levels in women with polycystic ovary syndrome: a systematic review and meta-analysis.
Zilaee, M, Mansoori, A, Ahmad, HS, Mohaghegh, SM, Asadi, M, Hormoznejad, R
The European journal of contraception & reproductive health care : the official journal of the European Society of Contraception. 2020;(4):305-310
Abstract
OBJECTIVES The aims of this systematic review and meta-analysis were to evaluate the effectiveness of soy isoflavones on serum levels of total testosterone (TT) and follicle-stimulating hormone (FSH) in women with polycystic ovary syndrome (PCOS). METHODS A meta-analysis was performed by searching for relevant randomised controlled trials (RCTs) in several databases. Of the four trials found, the eligibility criteria to evaluate the efficacy of soy isoflavones on serum levels of FSH were met by three trials and of TT by four trials. The Cochrane scale was used to evaluate the risk of bias. Fixed-effects and random-effects models were used to evaluate overall effect. The χ 2 test (Cochran's Q test) and the I 2 index were used to assess the heterogeneity of RCTs. RESULTS Our results showed that soy isoflavones significantly decreased TT (weighted mean difference [WMD] - 0.14; 95% confidence interval [CI] - 0.2, -0.02; p = 0.016; I 2 = 89%, p < 0.001) but had no significant effect on FSH levels (WMD -0.25; 95% CI -0.54, 0.02; p = 0.06; I 2 = 0%, p = 0.85). CONCLUSION Although the results of this meta-analysis showed that soy isoflavones in women with PCOS decreased TT and had no significant effect on FSH, better and more valid studies are needed to confirm these results.
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10.
Dynamic Interactions Between LH and Testosterone in Healthy Community-Dwelling Men: Impact of Age and Body Composition.
Roelfsema, F, Liu, PY, Takahashi, PY, Yang, RJ, Veldhuis, JD
The Journal of clinical endocrinology and metabolism. 2020;(3):e628-41
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Abstract
BACKGROUND Aging is associated with diminished testosterone (Te) secretion, which may be attributed to Leydig cell dysfunction, decreased pituitary stimulation, and altered Te feedback. OBJECTIVE To study all regulatory nodes-gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH) and Leydig cell-in the same cohort of healthy men. STUDY DESIGN This was a placebo-controlled, blinded, prospectively randomized cross-over study in 40 men, age range 19 to 73 years, and body mass index (BMI) range 20 to 34.3 kg/m2. A submaximal dose of the GnRH antagonist ganirelix was used to assess outflow of GnRH, by calculating the difference between LH output during the control arm and ganirelix arm. Ketoconazole (a steroidogenic inhibitor) was used to estimate feedback, by the difference in LH output during the ketoconazole and control arm. High-dose ganirelix and repeated LH infusions were used to measure testicular responsivity. Blood sampling was performed at 10-minute intervals. RESULTS There were age-related, but not body composition-related decreases in estimated GnRH secretion, the feedback strength of Te on LH, and Leydig cell responsivity to LH, accompanied by changes in approximate entropy. Bioavailable Te levels were negatively related to both age and computed tomography (CT)-estimated abdominal visceral mass (AVF), without interaction between these variables. The LH response to a submaximal dose of GnRH was independent of age and AVF. CONCLUSION Advancing age is associated with (1) attenuated bioavailable Te secretion caused by diminished GnRH outflow and not by decreased GnRH responsivity of the gonadotrope, (2) diminished testicular responsivity to infused LH pulses, and (3) partial compensation by diminished Te feedback on central gonadotropic regulation.