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1.
Vitamin D and Polycystic Ovary Syndrome: a Narrative Review.
Mu, Y, Cheng, D, Yin, TL, Yang, J
Reproductive sciences (Thousand Oaks, Calif.). 2021;(8):2110-2117
Abstract
Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders of reproductive age women and contributes to metabolic dysfunctions including insulin resistance (IR) and dyslipidemia. Vitamin D is a steroid hormone, which is involved in calcium metabolism and bone structure and has a potential role in the prevention of many illnesses, including cancers, autoimmune disorders, hypertension, diabetes, and obesity. Recently, it has been reported that vitamin D deficiency was a common complication of PCOS and vitamin D status was associated with reproductive ability, metabolic alterations, and mental health of PCOS patients. This review summarizes the advances between vitamin D status and the pathophysiological process of PCOS. Vitamin D level was negatively associated with serum androgen level. Vitamin D treatment could reduce serum androgen and anti-MüllerianHormone (AMH) levels, and decrease endometrial thickness, which resulted in improvement of menstrual cycle and folliculogenesis of PCOS patients. Moreover, vitamin D concentrations were negatively correlated with parameters of IR and body fat mass. Vitamin D supplementation has beneficial effects on IR and lipid metabolism. In addition, a positive of vitamin D on mental health of PCOS patients was proposed. Understanding the relationship between vitamin D status and the symptoms of PCOS patients is of great clinical significance to treat and prevent the progression of PCOS.
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2.
The effect of resistant dextrin as a prebiotic on metabolic parameters and androgen level in women with polycystic ovarian syndrome: a randomized, triple-blind, controlled, clinical trial.
Gholizadeh Shamasbi, S, Dehgan, P, Mohammad-Alizadeh Charandabi, S, Aliasgarzadeh, A, Mirghafourvand, M
European journal of nutrition. 2019;(2):629-640
Abstract
INTRODUCTION Polycystic ovary syndrome (PCOS) is one of the most common abnormalities in women of reproductive age that can lead to a variety of metabolic and reproductive disorders. Studies reveal that a healthy diet is the most effective way for treating the risk factors associated with metabolic disorders and place greater emphasis on the consumption of prebiotic foods. The present study aims to determine the effect of resistant Dextrin on metabolic parameters, including lipid profile, fasting blood glucose (FBS) and high sensitivity C-reactive protein (hsCRP), and androgen levels, including serum levels of dehydroepiandrosterone sulfate (DHEA-S) and free testosterone, as the primary outcomes, and manifestations of PCOS including menstrual cycle irregularity and hirsutism, as the secondary outcomes. METHODS This randomized, controlled, triple-blind, clinical trial was conducted on 62 women aged 18-45 in Tabriz, Iran, in 2016-2017. The participants were divided into a prebiotic group and a placebo group using block randomization. The prebiotic group consumed 20 g of resistant dextrin dissolved in a glass of water and the placebo group 20 g of maltodextrin also dissolved in a glass of water on a daily basis for 3 months. To measure the serum lipid profile, FBS, hsCRP, DHEA-S and free testosterone before and 3 months after the intervention, 5-ml blood samples were collected from the participants and analyzed using the ELISA method. The Ferriman-Gallwey scale for assessing hirsutism and a checklist for assessing menstrual cycle characteristics were completed before and 3 months after the intervention. A general linear model was used to analyze the data. RESULTS No statistically significant differences were observed between the two groups in terms of sociodemographic characteristics and baseline values. 3 months after the intervention, based on the ANCOVA and after adjusting for the baseline values, the mean serum levels of LDL-C (adjusted mean difference = - 29.79; 95% CI = - 43.37 to - 16.21; P < 0.001), triglyceride (AMD = - 38.50; 95% CI = - 59.73 to - 17.28; P = 0.001), total cholesterol (AMD = - 29.98; 95% CI = - 40.14 to - 19.82; P < 0.001), FBS (AMD = - 11.24; 95% CI = - 15.43 to - 7.06; P < 0.001), hsCRP (AMD = - 1.75; 95% CI = - 2.92 to - 0.57; P = 0.004), DHEA-S (AMD = - 0.7; 95% CI = - 1.34 to - 0.13; P = 0.017) and free testosterone (AMD = - 0.32; 95% CI = - 0.56 to - 0.08; P = 0.010) revealed a statistically significant decrease in the intervention group compared to the placebo group, while the mean serum HDL-C showed a statistically significant increase in this group compared to the placebo group (AMD = 5.82; 95% CI = 2.27-9.37; P = 0.002). 3 months after the intervention, there was a significant difference between the two groups in terms of menstrual cycle intervals and hirsutism (P < 0.001). CONCLUSION Resistant dextrin consumption can regulate metabolic parameters and androgen levels and manifestations including hirsutism and menstrual cycle irregularity in women with PCOS.
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3.
Understanding the Role of Androgen Action in Female Adipose Tissue.
Schiffer, L, Arlt, W, O'Reilly, MW
Frontiers of hormone research. 2019;:33-49
Abstract
Adipose tissue is an important target of androgen action in humans. Androgens exert important effects on adipose tissue biology, including fat mass expansion and distribution, insulin signalling and lipid metabolism. In conditions of female androgen excess such as polycystic ovary syndrome (PCOS), androgens exert metabolically deleterious effects on adipose tissue function in a depot-specific manner. Androgen excess in women is metabolically deleterious, and adverse metabolic effects may be mediated by effects on preadipocyte differentiation and adipocyte hypertrophy. Circulating androgen burden correlates with adiposity in women, and drives visceral fat mass accumulation. Adipose tissue is also an important organ of pre-receptor androgen metabolism, and is host to a complex network of androgen activating and inactivating enzymes. Adipose androgen generation is increased in subcutaneous (SC) adipose tissue in women with PCOS, and intra-adipose concentrations of potent androgens may exceed those measured in peripheral circulation. Increased expression of the key androgen-activating enzyme aldo-ketoreductase type 1C3 in PCOS SC adipose tissue leads to high concentrations of testosterone and dihydrotestosterone. Enhanced local androgen generation may further contribute to the adverse metabolic profile of women with PCOS by exerting lipotoxic effects on local adipose biology.
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4.
Source and amount of carbohydrate in the diet and inflammation in women with polycystic ovary syndrome.
Barrea, L, Marzullo, P, Muscogiuri, G, Di Somma, C, Scacchi, M, Orio, F, Aimaretti, G, Colao, A, Savastano, S
Nutrition research reviews. 2018;(2):291-301
Abstract
High carbohydrate intake and low-grade inflammation cooperate with insulin resistance and hyperandrogenism to constitute an interactive continuum acting on the pathophysiology of polycystic ovary syndrome (PCOS), the most common endocrine disorder in women of reproductive age characterised by oligo-anovulatory infertility and cardiometabolic disorders. The role of insulin in PCOS is pivotal both in regulating the activity of ovarian and liver enzymes, respectively involved in androgen production and in triggering low-grade inflammation usually reported to be associated with an insulin resistance, dyslipidaemia and cardiometabolic diseases. Although an acute hyperglycaemia induced by oral glucose loading may increase inflammation and oxidative stress by generating reactive oxygen species through different mechanisms, the postprandial glucose increment, commonly associated with the Western diet, represents the major contributor of chronic sustained hyperglycaemia and pro-inflammatory state. Together with hyperinsulinaemia, hyperandrogenism and low-grade inflammation, unhealthy diet should be viewed as a key component of the 'deadly quartet' of metabolic risk factors associated with PCOS pathophysiology. The identification of a tight diet-inflammation-health association makes the adoption of healthy nutritional approaches a primary preventive and therapeutic tool in women with PCOS, weakening insulin resistance and eventually promoting improvements of reproductive life and endocrine outcomes. The intriguing nutritional-endocrine connections operating in PCOS underline the role of expert nutritionists in the management of this syndrome. The aim of the present review is to provide an at-a-glance overview of the possible bi-directional mechanisms linking inflammation, androgen excess and carbohydrate intake in women with PCOS.
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5.
Testosterone a key factor in gender related metabolic syndrome.
Bianchi, VE, Locatelli, V
Obesity reviews : an official journal of the International Association for the Study of Obesity. 2018;(4):557-575
Abstract
Metabolic syndrome (MetS) is highly correlated with cardiovascular diseases. Although an excess of body fat is a determinant factor for MetS development, a reduced level of testosterone plays a fundamental role in its regulation. Low testosterone level is highly related to insulin resistance, visceral obesity and MetS. We have searched in Pubmed clinical trial with the password: testosterone and insulin resistance, and testosterone and MetS. We found 19 studies on the correlation between testosterone level with insulin resistance and 18 on the effect of testosterone therapy on MetS. A high correlation between low testosterone and insulin resistance has been found in men, but not in women. Testosterone administration in hypogonadal men improved MetS and reduced the mortality risk. Androgen and oestrogen receptors are expressed in adipocytes, muscle and liver tissue, and their activation is necessary to improve metabolic control. Normalization of testosterone level should be the primary treatment in men, along with caloric restriction and physical exercise. These findings come mainly from correlative data, and there remains a need for randomized trials to strengthen this evidence. This review will consider the effects of testosterone on the regulation and development of MetS in men and women.
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6.
Androgens and the Regulation of Adiposity and Body Fat Distribution in Humans.
Tchernof, A, Brochu, D, Maltais-Payette, I, Mansour, MF, Marchand, GB, Carreau, AM, Kapeluto, J
Comprehensive Physiology. 2018;(4):1253-1290
Abstract
The sexual dimorphism in human body fat distribution suggests a causal role for sex hormones. This is of particular importance when considering the role of excess visceral adipose tissue accumulation as a critical determinant of obesity-related cardiometabolic alterations. Scientific literature on the modulation of body fat distribution by androgens in humans is abundant, remarkably inconsistent and difficult to summarize. We reviewed relevant literature on this topic, with a particular emphasis on androgen replacement, androgen effects on selected parameters of adipose tissue function and adipose tissue steroid-converting enzymes. In men, low androgenic status mostly reflected by reduced total testosterone is a frequent feature of visceral obesity and the metabolic syndrome. Regarding testosterone therapy, however, studies must be appreciated in the context of current controversies on their cardiovascular effects. Analyses of available studies suggest that decreases in waist circumference in response to testosterone are more likely observed in men with low levels of testosterone and high BMI at study onset. In women with androgen excess, higher testosterone and free testosterone levels are fairly consistent predictors of increased abdominal and/or visceral adipose tissue accumulation, which is not the case in nonhyperandrogenic women. Regarding mechanisms, androgens decrease adipogenesis and markers of lipid storage in vitro in men and women. Evidence also suggest that local steroid transformations by adipose tissue steroid-converting enzymes expressed in a depot-specific fashion may play a role in androgen-mediated modulation of body fat distribution. Accumulating evidence shows that androgens are critical modulators of body fat distribution in both men and women. © 2018 American Physiological Society. Compr Physiol 8:1253-1290, 2018.
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7.
The impact of testosterone replacement therapy on glycemic control, vascular function, and components of the metabolic syndrome in obese hypogonadal men with type 2 diabetes.
Groti, K, Žuran, I, Antonič, B, Foršnarič, L, Pfeifer, M
The aging male : the official journal of the International Society for the Study of the Aging Male. 2018;(3):158-169
Abstract
OBJECTIVE This study set out to assess effects of testosterone replacement therapy (TRT) on parameters of metabolic syndrome and vascular function in obese hypogonadal males with type 2 diabetes mellitus (DM2). STUDY DESIGN Fifty-five obese hypogonadal diabetic males on oral hypoglycemic treatment were enrolled into this one-year, double-blind, randomized, placebo-controlled clinical study. Group T (n = 28) was treated with testosterone undecanoate (1000 mg i.m. every 10 weeks) while group P (n = 27) received placebo. METHODS Anthropometrical and vascular measurements - flow-mediated dilatation (FMD) and intima media thickness (IMT) - biochemical and hormonal blood sample analyses were performed at the start of the study and after one year. Derived parameters (BMI, HOMA-IR, calculated free testosterone (cFT) and bioavailable testosterone (BT)) were calculated. RESULTS TRT resulted in reduction of HOMA-IR by 4.64 ± 4.25 (p < .001), HbA1c by 0.94 ± 0.88% points (p < .001), and an increase in FMD by 2.40 ± 4.16% points (p = .005). CONCLUSION TRT normalized serum testosterone levels, improved glycemic control and endothelial function while exerting no ill effects on the study population.
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8.
The Effect of n-3 Polyunsaturated Fatty Acid Supplementation on Androgen Status in Patients with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis of Clinical Trials.
Hajishafiee, M, Askari, G, Iranj, B, Ghiasvand, R, Bellissimo, N, Totosy de Zepetnek, J, Salehi-Abargouei, A
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 2016;(5):281-9
Abstract
The anti-androgenic role of n-3 polyunsaturated fatty acids (PUFAs) among patients with polycystic ovary syndrome (PCOS) has recently been proposed. The present study aimed to systematically review clinical trials assessing the effects of n-3 PUFAs consumption on androgen status among adult females with PCOS. PubMed, ISI Web of Science, Google Scholar, and Scopus were searched up to December 2015. Clinical investigations assessing the effect of n-3 PUFAs on adult females with PCOS were included. Mean±standard deviation of change in serum total testosterone, sex hormone binding globulin (SHBG), and dehydroepiandrostrone sulfate (DHEAS) were extracted. Eight clinical trials with 298 participants were eligible. Meta-analysis showed that n-3 PUFAs supplementation marginally reduces total testosterone (mean difference [MD]: - 0.19 nmol/l; 95% CI: - 0.39 to 0.00; p=0.054), but not SHBG (MD: 1.75 nmol/l; 95% CI: -0.51 to 4.01; p=0.129) or serum DHEAS levels (Hedes' g: -0.11 nmol/l; 95% CI: -0.29 to 0.06; p=0.19) among adult females with PCOS. Subgroup analyses showed that only before-after studies (Hedges' g: 0.15; 95% CI: -0.27 to -0.04; p=0.01) and long-term interventions (>6 weeks) (Hedges' g: -0.17; 95% CI, -0.29 to -0.05; p=0.004) had reducing effects on serum DHEAS levels. The majority of long-term trials utilized a single group design (no control group). It does not appear that n-3 PUFAs supplementation significantly affects the androgenic profile of females with PCOS; however, some before-after and long-term intervention studies show reduced DHEAS levels. Future studies incorporating double blinded placebo controlled clinical trials with long follow-up periods are warranted.
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9.
Effects of selenium supplementation on glucose homeostasis and free androgen index in women with polycystic ovary syndrome: A randomized, double blinded, placebo controlled clinical trial.
Mohammad Hosseinzadeh, F, Hosseinzadeh-Attar, MJ, Yekaninejad, MS, Rashidi, B
Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS). 2016;:56-61
Abstract
BACKGROUND/OBJECTIVES Insulin resistance (IR) is a main pathophysiologic feature in polycystic ovary syndrome (PCOS) patients which is triggered by elevated oxidative stress in these patients. Selenium, an essential micronutrient, is a major constituent of antioxidant enzymes such as glutathione peroxidase. Recently, decreased plasma selenium concentrations were reported in PCOS patients. So, the present study was carried out in order to assess whether selenium consumption can improve the metabolic response to insulin and reduce the insulin resistance in these women. SUBJECTS/METHODS A total of 53 PCOS patients (diagnosed by Rotterdam criteria), 18-42 years old, participated in this randomized, double-blind and placebo controlled trial for 12 weeks (selenium, n=26; placebo, n=27). The effects of daily administration of 200 μg selenium or placebo on serum glucose, total testosterone (tT), sex hormone binding globulin (SHBG) and free androgen index (FAI) in fasting state were evaluated. RESULTS At the end of the study, insulin resistance was significantly increased in selenium recipients when compared with the placebo group (2.05 ± 0.39 when compared with 1.81 ± 0.25, p=0.017). Also, selenium supplementation resulted in marginally significant increase (p=0.056) in insulin level when compared with the placebo group. There were no statistically significant changes in other study endpoints, when comparing the two groups. CONCLUSION This study showed that selenium supplementation in PCOS patients may worsen insulin resistance in them. Until the results of larger studies become available, indiscriminate consumption of selenium supplements in PCOS patients will warrant caution.
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10.
Testosterone supplementation and body composition: results from a meta-analysis of observational studies.
Corona, G, Giagulli, VA, Maseroli, E, Vignozzi, L, Aversa, A, Zitzmann, M, Saad, F, Mannucci, E, Maggi, M
Journal of endocrinological investigation. 2016;(9):967-81
Abstract
PURPOSE The concept of testosterone (T) supplementation (TS) as a new anti-obesity medication in men with testosterone deficiency syndrome (TDS) is emerging. Data from placebo-controlled trials are more conflicting. The aim of this study is to systematically review and meta-analyze available observational and register studies reporting data on body composition in studies on TS in TDS. METHODS An extensive MEDLINE, Embase, and Cochrane search was performed including the following words: "testosterone" and "body composition." All observational studies comparing the effect of TS on body weight and other body composition and metabolic endpoints were considered. RESULTS Out of 824 retrieved articles, 32 were included in the study enrolling 4513 patients (mean age 51.7 ± 6.1 years). TS was associated with a time-dependent reduction in body weight and waist circumference (WC). The estimated weight loss and WC reduction at 24 months were -3.50 [-5.21; -1.80] kg and -6.23 [-7.94; -4.76] cm, respectively. TS was also associated with a significant reduction in fat and with an increase in lean mass as well as with a reduction in fasting glycemia and insulin resistance. In addition, an improvement of lipid profile (reduction in total cholesterol as well as of triglyceride levels and an improvement in HDL cholesterol levels) and in both systolic and diastolic blood pressure was observed. CONCLUSIONS Present data support the view of a positive effect of TS on body composition and on glucose and lipid metabolism. In addition, a significant effect on body weight loss was observed, which should be confirmed by a specifically designed RCT.