-
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.
-
2.
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.
-
3.
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.
-
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.
-
5.
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.
-
6.
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.
-
7.
The polycystic ovary syndrome: a position statement from the European Society of Endocrinology.
Conway, G, Dewailly, D, Diamanti-Kandarakis, E, Escobar-Morreale, HF, Franks, S, Gambineri, A, Kelestimur, F, Macut, D, Micic, D, Pasquali, R, et al
European journal of endocrinology. 2014;(4):P1-29
Abstract
Polycystic ovary syndrome (PCOS) is the most common ovarian disorder associated with androgen excess in women, which justifies the growing interest of endocrinologists. Great efforts have been made in the last 2 decades to define the syndrome. The presence of three different definitions for the diagnosis of PCOS reflects the phenotypic heterogeneity of the syndrome. Major criteria are required for the diagnosis, which in turn identifies different phenotypes according to the combination of different criteria. In addition, the relevant impact of metabolic issues, specifically insulin resistance and obesity, on the pathogenesis of PCOS, and the susceptibility to develop earlier than expected glucose intolerance states, including type 2 diabetes, has supported the notion that these aspects should be considered when defining the PCOS phenotype and planning potential therapeutic strategies in an affected subject. This paper offers a critical endocrine and European perspective on the debate on the definition of PCOS and summarises all major aspects related to aetiological factors, including early life events, potentially involved in the development of the disorder. Diagnostic tools of PCOS are also discussed, with emphasis on the laboratory evaluation of androgens and other potential biomarkers of ovarian and metabolic dysfunctions. We have also paid specific attention to the role of obesity, sleep disorders and neuropsychological aspects of PCOS and on the relevant pathogenetic aspects of cardiovascular risk factors. In addition, we have discussed how to target treatment choices based according to the phenotype and individual patient's needs. Finally, we have suggested potential areas of translational and clinical research for the future with specific emphasis on hormonal and metabolic aspects of PCOS.
-
8.
Phytoandrogenic properties of Eurycoma longifolia as natural alternative to testosterone replacement therapy.
George, A, Henkel, R
Andrologia. 2014;(7):708-21
Abstract
The testosterone deficiency syndrome (TDS) is characterised by numerous symptoms, including low libido, increased fat mass, fatigue, erectile dysfunction or osteoporosis, and up to 80% of men will experience some kind of ageing males' symptoms. This is caused by the age-depending decline in serum testosterone levels with concentrations being about 40-50% lower in men older than 60 years compared with young men. This significant decline in testosterone levels is further closely linked with medical conditions such as obesity, metabolic syndrome, diabetes or hypertension. The conventional way of treating TDS is the testosterone replacement therapy (TRT), for which preparations are on the market. Apart from the beneficial effects of TRT, significant adverse side effects have been described, and prostate cancer (PCa) as absolute contraindication is debated. Eurycoma longifolia (Tongkat Ali; TA) is natural alternative to TRT and has been shown to restore serum testosterone levels, thus significantly improving sexual health. This includes significant positive effects on bone health and physical condition of patients. In addition, a significant antihyperglycaemic effect and cytotoxicity against PCas cells has been shown. Thus far, at therapeutic concentrations, no significant side effects of the treatment were obvious. Therefore, TA might be a safe alternative to TRT.
-
9.
Testosterone supplementation therapy in the treatment of patients with metabolic syndrome.
Kovac, JR, Pastuszak, AW, Lamb, DJ, Lipshultz, LI
Postgraduate medicine. 2014;(7):149-56
-
-
Free full text
-
Abstract
Metabolic syndrome (MetS) comprises a clinical complex of patient risk factors, including increased waist circumference, high triglyceride levels, low high-density lipoprotein cholesterol level, high blood pressure, and insulin resistance, the presence of which increases the likelihood of developing diabetes and cardiovascular disease. With a quarter of the American adult population affected, MetS and type 2 diabetes mellitus have been referred to as the most significant public health threats of the 21st century. Lifestyle modification and weight loss are recommended, however, no specific pharmacologic treatment is known. Given that low levels of testosterone have been implicated in the pathogenesis of MetS and an inverse relationship exists between circulating testosterone levels and the development of MetS, it is tempting to speculate that men with MetS may benefit from testosterone supplementation therapy. As such, our review examines the role of testosterone and the use of testosterone supplementation therapy as a treatment in men with MetS.
-
10.
[Role of androgen in the elderly. Problems of androgen deprivation therapy].
Tsujimura, A
Clinical calcium. 2013;(8):1185-90
Abstract
Androgen deprivation therapy has been considered as one of useful treatment options for prostate cancer. However, it presents several symptoms of "castration syndrome" as side effects, based on low serum testosterone concentration. The symptoms includes loss of libido and sexual interest, erectile dysfunction, general fatigue, decreased intellectual ability, depression, loss of muscle strength, increased abdominal fat mass, and loss of vigor. They are almost similar to the representative symptoms of late onset hypogonadism. Furthermore, side effects such as increased risk of fracture and metabolic syndrome caused by androgen deprivation therapy should be taken care, even though subjective complaints do not appear.