-
1.
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.
-
2.
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.
-
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.
-
4.
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
-
-
Free full text
-
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.
-
5.
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.
-
6.
Testosterone concentrations and risk of cardiovascular events in androgen-deficient men with atherosclerotic cardiovascular disease.
Boden, WE, Miller, MG, McBride, R, Harvey, C, Snabes, MC, Schmidt, J, McGovern, ME, Fleg, JL, Desvigne-Nickens, P, Anderson, T, et al
American heart journal. 2020;:65-76
Abstract
BACKGROUND Whether androgen deficiency among men increases the risk of cardiovascular (CV) events or is merely a disease marker remains a subject of intense scientific interest. OBJECTIVES Among male subjects in the AIM-HIGH Trial with metabolic syndrome and low baseline levels of high-density lipoprotein (HDL)-cholesterol who were randomized to niacin or placebo plus simvastatin, we examined the relationship between low baseline testosterone (T) concentrations and subsequent CV outcomes during a mean 3-year follow-up. METHODS In this post hoc analysis of men with available baseline plasma T concentrations, we examined the relationship between clinical/demographic characteristics and T concentrations both as a continuous and dichotomous variable (<300 ng/dL ["low T"] vs. ≥300 ng/dL ["normal T"]) on rates of pre-specified CV outcomes, using Cox proportional hazards models. RESULTS Among 2118 male participants in whom T concentrations were measured, 643 (30%) had low T and 1475 had normal T concentrations at baseline. The low T group had higher rates of diabetes mellitus, hypertension, elevated body mass index, metabolic syndrome, higher blood glucose, hemoglobin A1c, and triglyceride levels, but lower levels of both low-density lipoprotein and HDL-cholesterol, and a lower rate of prior myocardial infarction (MI). Men with low T had a higher risk of the primary composite outcome of coronary heart disease (CHD) death, MI, stroke, hospitalization for acute coronary syndrome, or coronary or cerebral revascularization (20.1%) compared with the normal T group (15.2%); final adjusted HR 1.23, P = .07, and a higher risk of the CHD death, MI, and stroke composite endpoint (11.8% vs. 8.2%; final adjusted HR 1.37, P = .04), respectively. CONCLUSIONS In this post hoc analysis, there was an association between low baseline testosterone concentrations and increased risk of subsequent CV events in androgen-deficient men with established CV disease and metabolic syndrome, particularly for the composite secondary endpoint of CHD death, MI, and stroke. CONDENSED ABSTRACT In this AIM-HIGH Trial post hoc analysis of 2118 men with metabolic syndrome and low HDL-cholesterol with available baseline plasma testosterone (T) samples, 643 males (30%) had low T (mean: 229 ng/dL) and 1475 (70%) had normal T (mean: 444 ng/dL) concentrations. The "low T" group had a 24% higher risk of the primary 5-component endpoint (20.1%) compared with the normal T group (15.2%); final adjusted HR 1.23, P = .07). There was also a 31% higher risk of the secondary composite endpoint: coronary heart disease death, myocardial infarction, and stroke (11.8% vs. 8.2%, final adjusted HR 1.37, P = .04) in the low vs. normal T group, respectively.
-
7.
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.
-
8.
The effects of age and obesity on postprandial dynamics of serum testosterone levels in men.
Van de Velde, F, Reyns, T, Toye, K, Fiers, T, Kaufman, JM, T'Sjoen, G, Lapauw, B
Clinical endocrinology. 2020;(3):214-221
Abstract
OBJECTIVE Guidelines recommend using fasting samples to evaluate testosterone (T) levels in men, as free and total T levels decrease postprandially. However, it is not clear whether these dynamics are affected by age or obesity. This could be relevant given the obesity epidemic, ageing population and the barrier for screening which fasting could impose. DESIGN/PARTICIPANTS A total of 43 men underwent a solid mixed meal tolerance test. Serum samples were taken fasting, and at 30, 60 and 120 minutes postprandially. A commercial immunoassay was used to determine sex hormone-binding globulin (SHBG) levels, liquid chromatography coupled to tandem mass spectroscopy for total T concentrations and free T levels were calculated. RESULTS Postprandially, both total and free T were lower at all-time points compared with fasting (all, P < .005). At 60 minutes, maximum mean decreases of 15 ± 15% and 17 ± 16% were seen for total and free T levels, respectively. Younger men had greater decreases in both total and free T levels compared with men older than 40 years (all, P < .05). A greater decrease at 30 and 60 minutes postprandially was observed for both total and free T levels in nonobese vs obese men (all, P < .05). CONCLUSIONS After a mixed meal, total and free T serum levels decreased whereas SHBG levels did not change. Interestingly, postprandial decreases were less pronounced in men older than 40 years and/or with obesity. Although this study indicates less pronounced decreases in certain men, fasting samples remain a prerequisite for establishing correct diagnosis of male hypogonadism.
-
9.
Long-Term Effect of Combination of Creatine Monohydrate Plus β-Hydroxy β-Methylbutyrate (HMB) on Exercise-Induced Muscle Damage and Anabolic/Catabolic Hormones in Elite Male Endurance Athletes.
Fernández-Landa, J, Fernández-Lázaro, D, Calleja-González, J, Caballero-García, A, Córdova, A, León-Guereño, P, Mielgo-Ayuso, J
Biomolecules. 2020;(1)
Abstract
Creatine monohydrate (CrM) and β-hydroxy β-methylbutyrate (HMB) are widely studied ergogenic aids. However, both supplements are usually studied in an isolated manner. The few studies that have investigated the effect of combining both supplements on exercise-induced muscle damage (EIMD) and hormone status have reported controversial results. Therefore, the main purpose of this study was to determine the effect and degree of potentiation of 10 weeks of CrM plus HMB supplementation on EIMD and anabolic/catabolic hormones. This study was a double-blind, placebo-controlled trial where participants (n = 28) were randomized into four different groups: placebo group (PLG; n = 7), CrM group (CrMG; 0.04 g/kg/day of CrM; n = 7), HMB group (HMBG; 3 g/day of HMB; n = 7), and CrM-HMB group (CrM-HMBG; 0.04 g/kg/day of CrM plus 3 g/day of HMB; n = 7). Before (baseline, T1) and after 10 weeks of supplementation (T2), blood samples were collected from all rowers. There were no significant differences in the EIMD markers (aspartate aminotransferase, lactate dehydrogenase, and creatine kinase) among groups. However, we observed significant differences in CrM-HMBG with respect to PLG, CrMG, and HMBG on testosterone (p = 0.006; η2p = 0.454) and the testosterone/cortisol ratio (T/C; p = 0.032; η2p = 0.349). Moreover, we found a synergistic effect of combined supplementation on testosterone (CrM-HMBG = -63.85% vs. CrMG + HMBG = -37.89%) and T/C (CrM-HMBG = 680% vs. CrMG + HMBG = 57.68%) and an antagonistic effect on cortisol (CrM-HMBG = 131.55% vs. CrMG + HMBG = 389.99%). In summary, the combination of CrM plus HMB showed an increase in testosterone and T/C compared with the other groups after 10 weeks of supplementation. Moreover, this combination presented a synergistic effect on testosterone and T/C and an antagonistic effect on cortisol compared with the sum of individual or isolated supplementation.
-
10.
Effects of natural polyphenol-rich pomegranate juice on the acute and delayed response of Homocysteine and steroidal hormones following weightlifting exercises: a double-blind, placebo-controlled trial.
Ammar, A, MounaTurki, , Trabelsi, K, Bragazzi, NL, Boukhris, O, Bouaziz, M, Ayadi, F, El Abed, K, Driss, T, Souissi, N, et al
Journal of the International Society of Sports Nutrition. 2020;(1):15
Abstract
BACKGROUND Maximal strength-speed exercise is a powerful stimulus to acutely increase concentrations of circulating steroid hormones and homocysteine [Hcy]. There is some evidence that antioxidant beverages rich in polyphenols can attenuate [Hcy] levels and modulate endocrine responses in favor of an anabolic environment. Polyphenols-rich pomegranate (POM) have been reported to possess one of the highest antioxidant capacities compared to other purported nutraceuticals and other food stuffs. Studies focused on proving the beneficial effect of POM consumption during maximal strength exercises have only measured physical performance, muscle damage, oxidative stress and inflammatory responses, while POM effects on [Hcy] and hormonal adaptations are lacking. The aim of the present study was to investigate the effect of consuming natural polyphenol-rich pomegranate juice (POMj) on the acute and delayed [Hcy] and steroidal hormonal responses to a weightlifting exercises session. METHODS Nine elite weightlifters (21.0 ± 1 years) performed two Olympic-weightlifting sessions after ingesting either the placebo (PLA) or POMj supplements. Venous blood samples were collected at rest and 3 min and 48 h after each session. RESULTS Compared to baseline values, circulating cortisol [C] decreased (p < 0.01) and testosterone/cortisol [T/C] ratio increased immediately following the training session in both PLA and POMj conditions (p = 0.003 for PLA and p = 0.02 for POM). During the 48 h recovery period, all tested parameters were shown to recover to baseline values in both conditions with significant increases in [C] and decreases in [T/C] (p < 0.01 for PLA and p < 0.05 for POMj) from 3 min to 48 h post-exercises. Compared to PLA, a lower level of plasma testosterone [T] was registered 3 min post exercise using POMj supplementation (p = 0.012) and a significant decrease (p = 0.04, %change = - 14%) in plasma [Hcy] was registered during the 48 h recovery period only using POMj. A moderate correlation was observed between [Hcy] and [T] responses (p = 0.002, r = - 0.50). CONCLUSION In conclusion, supplementation with POMj has the potential to attenuate the acute plasma [T] response, but did not effect 48 h recovery kinetics of [Hcy] following weightlifting exercise. Further studies investigating androgen levels in both plasma and muscular tissue are needed to resolve the functional consequences of the observed acute POMj effect on plasma [T]. TRIAL REGISTRATION Clinical Trials.gov, ID: NCT02697903. Registered 03 March 2016.