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1.
Evolutionary determinants of polycystic ovary syndrome: part 2.
Fessler, DMT, Natterson-Horowitz, B, Azziz, R
Fertility and sterility. 2016;(1):42-47
Abstract
Polycystic ovary syndrome (PCOS) is a prehistoric complex genetic trait, perhaps dating back at least 50,000 years. The disorder also represents an evolutionary paradox, demonstrating clear reproductive disadvantages (i.e., lack of evolutionary fitness), albeit persisting tens of thousands of years. Here we examine possible explanations for this paradox. We evaluate a variety of possible benefits accruing to women in ancestral populations who possessed this trait, including considerations of whether dramatic changes in environment and lifestyle from the ancestral past to the contemporary present have altered the selection dynamics operating on the trait. Putative benefits include metabolic functioning, immune system dynamics, patterns of child-rearing and mothering, reproductive longevity, in utero or childhood survival, and musculoskeletal advantages. However, there is limited evidence that the persistence and relative homogeneity in the prevalence of PCOS can be accounted for by direct positive selection. Rather, PCOS evolution has likely been driven by nonadaptive evolutionary mechanisms, including genetic drift due to a serial founder effect and population balance due to sexually antagonistic selection. Ultimately, insights into the evolutionary origins of PCOS will emerge through the study not only of unique characteristics of affected individuals and their environments butalso through a broad consideration of the potential adaptive and beneficial aspects of vulnerability to the disorder, importantly including examination of populations whose fertility, disease load, and diet resemble those of ancestral humans.
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2.
Selenium Supplementation and the Effects on Reproductive Outcomes, Biomarkers of Inflammation, and Oxidative Stress in Women with Polycystic Ovary Syndrome.
Razavi, M, Jamilian, M, Kashan, ZF, Heidar, Z, Mohseni, M, Ghandi, Y, Bagherian, T, Asemi, Z
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 2016;(3):185-90
Abstract
Selenium supplementation could be effective on reproductive outcomes, biomarkers of inflammation, and oxidative stress among women with polycystic ovary syndrome (PCOS). The aim of the study was to determine the effects of selenium supplementation on reproductive outcomes, biomarkers of inflammation, and oxidative stress in PCOS patients. The present randomized double-blind, placebo-controlled trial was conducted on 64 women aged 18-40 years old with PCOS at the clinic affiliated to Ardabil University of Medical Sciences, Ardabil, Iran. The participants were randomly assigned to 2 groups receiving either 200 μg selenium daily (n=32) or placebo (n=32) for 8 weeks. Hormonal profiles, biomarkers of inflammation, and oxidative stress were measured and compared both before and after the treatment. After 8 weeks of intervention, pregnancy rate in the selenium group was higher than in the placebo group: 18.8 (6/32) vs. 3.1% (1/32), p=0.04. In addition, alopecia (40.6 vs. 9.4%, p=0.004) and acne (46.9 vs. 12.5 %, p=0.003) decreased following the consumption of selenium supplements compared with placebo. Additionally, patients who received selenium supplements had significantly decreased serum dehydroepiandrosterone (DHEA) levels (p=0.02), hirsutism (modified Ferriman-Gallwey scores) (p<0.001), serum high sensitivity C-reactive protein (hs-CRP) (p=0.02), and plasma malondialdehyde (MDA) levels (p=0.01) compared with placebo. We did not observe any significant effects of taking selenium supplements on other hormonal profiles, nitric oxide (NO), and other biomarkers of oxidative stress. Taken together, selenium supplementation for 8 weeks among PCOS women had beneficial effects on reproductive outcomes, DHEA, hs-CRP, and MDA levels. Supporting Information for this article is available online at http://www.thieme-connect.de/products.
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3.
Physiological Aspects of Female Fertility: Role of the Environment, Modern Lifestyle, and Genetics.
Hart, RJ
Physiological reviews. 2016;(3):873-909
Abstract
Across the Western World there is an increasing trend to postpone childbearing. Consequently, the negative influence of age on oocyte quality may lead to a difficulty in conceiving for many couples. Furthermore, lifestyle factors may exacerbate a couple's difficulty in conceiving due mainly to the metabolic influence of obesity; however, the negative impacts of low peripheral body fat, excessive exercise, the increasing prevalence of sexually transmitted diseases, and smoking all have significant negative effects on fertility. Other factors that impede conception are the perceived increasing prevalence of the polycystic ovary syndrome, which is further exacerbated by obesity, and the presence of uterine fibroids and endometriosis (a progressive pelvic inflammatory disorder) which are more prevalent in older women. A tendency for an earlier sexual debut and to have more sexual partners has led to an increase in sexually transmitted diseases. In addition, there are several genetic influences that may limit the number of oocytes within the ovary; consequently, by postponing attempts at childbearing, a limitation of oocyte number may become evident, whereas in previous generations with earlier conception this potentially reduced reproductive life span did not manifest in infertility. Environmental influences on reproduction are under increasing scrutiny. Although firm evidence is lacking however, dioxin exposure may be linked to endometriosis, phthalate exposure may influence ovarian reserve, and bisphenol A may interfere with oocyte development and maturation. However, chemotherapy or radiotherapy is recognized to lead to ovarian damage and predispose the woman to ovarian failure.
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4.
Evolutionary determinants of polycystic ovary syndrome: part 1.
Ünlütürk, U, Sezgin, E, Yildiz, BO
Fertility and sterility. 2016;(1):33-41
Abstract
Polycystic ovary syndrome (PCOS) is a common and complex genetic disorder that develops under varying degrees of hyperandrogenemic and hyperinsulinemic conditions that cause phenotypic variability ranging from mild hirsutism to anovulation and infertility. In addition to increased risk of reproductive disability, PCOS is associated with metabolic diseases including type 2 diabetes, dyslipidemia, and cardiovascular disease. Similar prevalence rates and shared genetic susceptibility of PCOS among different populations suggest that genetic risk factors were already present in the ancestors of humans. Contemporary human genetic studies inform us that the origin of human ancestors is from Africa. Sharing common susceptibility loci between Chinese and European ancestry suggests that PCOS may have persisted for more than 50,000 years, before the migration of humans out of Africa. Although PCOS is the most common cause of anovulatory infertility, its high prevalence is still a paradox. From an evolutionary perspective, the pathogenic mechanisms underlying PCOS might be candidate factors for survival advantage of the human being. Former compensatory advantageous factors may become pathogenic mechanisms underlying complex metabolic disease with prolonged life expectancy and transition to sedentary lifestyle.
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5.
The effect of obesity on polycystic ovary syndrome: a systematic review and meta-analysis.
Lim, SS, Norman, RJ, Davies, MJ, Moran, LJ
Obesity reviews : an official journal of the International Association for the Study of Obesity. 2013;(2):95-109
Abstract
While many women with polycystic ovary syndrome (PCOS) are overweight, obese or centrally obese, the effect of excess weight on the outcomes of PCOS is inconsistent. The review aimed to assess the effects of overweight, obesity and central obesity on the reproductive, metabolic and psychological features of PCOS. MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials (CENTRAL) and PSYCINFO were searched for studies reporting outcomes according to body mass index categories or body fat distribution. Data were presented as mean difference or risk ratio (95% confidence interval). This review included 30 eligible studies. Overweight or obese women with PCOS had decreased sex hormone-binding globulin (SHBG), increased total testosterone, free androgen index, hirsutism, fasting glucose, fasting insulin, homeostatic model assessment-insulin resistance index and worsened lipid profile. Obesity significantly worsened all metabolic and reproductive outcomes measured except for hirsutism when compared to normal weight women with PCOS. Overweight women had no differences in total testosterone, hirsutism, total-cholesterol and low-density lipoprotein-cholesterol compared to normal weight women and no differences in SHBG and total testosterone compared to obese women. Central obesity was associated with higher fasting insulin levels. These results suggest that prevention and treatment of obesity is important for the management of PCOS.
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6.
The complex interaction between obesity, metabolic syndrome and reproductive axis: a narrative review.
Michalakis, K, Mintziori, G, Kaprara, A, Tarlatzis, BC, Goulis, DG
Metabolism: clinical and experimental. 2013;(4):457-78
Abstract
The aim of this narrative review is to provide current evidence for the interaction between obesity, metabolic syndrome (MS) and reproductive axis. Gonadotropin-releasing hormone (GnRH) pulses and, consequently, normal function of reproductive (hypothalamus-pituitary-gonadal) axis depend on normal energy balance, which presupposes sufficient food intake, reasonable energy consumption and average thermoregulatory costs. In case of an energy imbalance, reproductive dysfunction may occur. In young women, excessive leanness is accompanied by puberty delay, whereas premature puberty might be a manifestation of obesity. In a similar way, obesity in men affects fertility. Excess adipose tissue results in increased conversion of testosterone to estradiol, which may lead to secondary hypogonadism through reproductive axis suppression. Moreover, oxidative stress at the level of the testicular micro-environment may result in decreased spermatogenesis and sperm damage. Products of the adipocyte, such as leptin, adiponectin and resistin, and gut peptides, such as ghrelin, are considered to be crucial in the interaction between energy balance and reproduction. Finally, an indirect evidence for the interplay between MS and reproductive axis is the fact that when treating components of one, parameters of the other can be improved as well. These therapeutic interventions include lifestyle modifications, pharmacological agents, such as sex hormone replacement therapy, and surgical procedures. Although many issues remain unclear, the elucidation of the complex interaction between MS and reproductive axis will have obvious clinical implications in the therapeutic approach of both entities.
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7.
The effect of a hypocaloric diet with and without exercise training on body composition, cardiometabolic risk profile, and reproductive function in overweight and obese women with polycystic ovary syndrome.
Thomson, RL, Buckley, JD, Noakes, M, Clifton, PM, Norman, RJ, Brinkworth, GD
The Journal of clinical endocrinology and metabolism. 2008;(9):3373-80
Abstract
CONTEXT In overweight women with polycystic ovary syndrome (PCOS), the benefits of the addition of exercise to an energy-restricted diet in further improving cardiometabolic risk factors and reproductive function has not been extensively studied. OBJECTIVE The objective was to evaluate the effects of aerobic and aerobic-resistance exercise when combined with an energy-restricted high protein diet (5000-6000 kJ/d) on metabolic risk factors and reproductive function in women with PCOS. DESIGN AND SETTING A 20-wk outpatient, randomized, parallel study was conducted in a metropolitan research clinic. PATIENTS AND INTERVENTION Ninety-four overweight and obese women with PCOS (age 29.3 +/- 0.7 yr; body mass index 36.1 +/- 0.5 kg/m2) were randomized to diet only (DO; n = 30), diet and aerobic exercise (DA; n = 31), or diet and combined aerobic-resistance exercise (DC; n = 33). MAIN OUTCOME MEASURES Weight, body composition, cardiometabolic risk factors, hormonal status, menstrual cyclicity, and ovulatory function were assessed. RESULTS All interventions reduced weight (DO 8.9 +/- 1.6%, DA 10.6 +/- 1.7%, and DC 8.7 +/- 1.7%; P < 0.001) with no difference between treatments (P = 0.7, time x treatment). Fat mass decreased more (3 kg) and fat-free mass decreased less (2 kg) in DA and DC compared with DO (P < or = 0.03). Reductions in blood pressure (5.6/2.7 mm Hg), triglycerides (0.4 mmol/liter), total cholesterol (0.5 mmol/liter), low-density lipoprotein cholesterol (0.1 mmol/liter), glucose (0.2 mmol/liter), fasting insulin (4.3 mIU/liter), testosterone (0.4 nmol/liter), and free androgen index (2.8) (P < 0.001) and improvements in SHBG (7.0 nmol/liter) and reproductive function occurred in all groups, with no difference between treatments. CONCLUSION In overweight and obese women with PCOS, the addition of aerobic or combined aerobic-resistance exercise to an energy-restricted diet improved body composition but had no additional effect on improvements in cardiometabolic, hormonal, and reproductive outcomes relative to diet alone.
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8.
Genetic and environmental origins of obesity relevant to reproduction.
Franks, S
Reproductive biomedicine online. 2006;(5):526-31
Abstract
Obesity has a negative impact on reproductive health, particularly in women with polycystic ovarian syndrome (PCOS). Obesity itself is the product of both genetic and environmental influences, although the current 'epidemic' of obesity is largely related to changes in diet and lifestyle. Single gene defects leading to obesity and disordered reproductive function are rare but can are informative about metabolic pathways involved in appetite regulation. There is good evidence that PCOS has an important genetic background, which probably involves the interaction of several genes. The phenotype of PCOS and its impact on reproductive function is profoundly affected by obesity, which, in turn has both genetic and environmental influences. Understanding the genetic basis of PCOS is important but improvements in diet and lifestyle are the best means of improving reproductive function.
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9.
Short-term meal replacements followed by dietary macronutrient restriction enhance weight loss in polycystic ovary syndrome.
Moran, LJ, Noakes, M, Clifton, PM, Wittert, GA, Williams, G, Norman, RJ
The American journal of clinical nutrition. 2006;(1):77-87
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Abstract
BACKGROUND Polycystic ovary syndrome (PCOS), a common condition in women, improves with weight loss. Meal replacements in short-term weight loss and strategies for weight maintenance have not been investigated in PCOS. OBJECTIVE We compared in overweight women with PCOS the effects of meal replacements in short-term weight-loss and longer-term carbohydrate- or fat-restriction strategies on weight maintenance and improvements in reproductive and metabolic variables. DESIGN Overweight women with PCOS (n = 43; x +/- SD age: 32.1 +/- 5.2 y; weight: 96.1 +/- 18.4 kg) followed an 8-wk weight-loss regimen (2 meal replacements/d, 4904.4 +/- 127 kJ; phase 1) and then a 6-mo weight-maintenance carbohydrate- (<120 g/d) or fat- (<50 g/d) restriction regimen (phase 2). RESULTS Thirty-four women completed phase 1, and 23 women completed phase 2; the proportion of dropouts was similar in the 2 groups. During phase 1, significant (P < 0.05) reductions in weight (5.6 +/- 2.4 kg), waist circumference (6.1 +/- 2.5 cm), body fat (4.1 +/- 2.2 kg), insulin (2.8 +/- 1.1 mU/L), total testosterone (0.3 +/- 0.7 nmol/L), and free androgen index (3.1 +/- 4.6) occurred; these changes were sustained during phase 2. No significant differences between diet groups were seen for any variables. At 6 mo, both approaches resulted in a net weight loss of 4.7 +/- 4.6 kg. Improvements in menstrual cyclicity occurred for 16 (57.1%) of 28 subjects. CONCLUSIONS Meal replacements are an effective strategy for the short-term management of PCOS. Advice on moderate fat or carbohydrate restriction was equally effective in maintaining weight reduction and improving reproductive and metabolic variables.
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10.
Leptin and reproduction: a review.
Moschos, S, Chan, JL, Mantzoros, CS
Fertility and sterility. 2002;(3):433-44
Abstract
OBJECTIVE To review recent advances in understanding the role of leptin in the physiology and pathophysiology of reproduction, with a focus on relevant clinical situations. DESIGN A MEDLINE computer search was performed to identify relevant articles. RESULT(S): Leptin, an adipocyte hormone important in regulating energy homeostasis, interacts with the reproductive axis at multiple sites, with stimulatory effects at the hypothalamus and pituitary and inhibitory actions at the gonads. More recently, leptin has been shown to play a role in other target reproductive organs, such as the endometrium, placenta, and mammary gland, with corresponding influences on important physiologic processes such as menstruation, pregnancy, and lactation. As a marker of whether nutritional stores are adequate, leptin may act in concert with gonadotropins and the growth hormone axis to initiate the complex process of puberty. Conditions in which nutritional status is suboptimal, such as eating disorders, exercise-induced amenorrhea, and functional hypothalamic amenorrhea, are associated with low serum leptin levels; and conditions with excess energy stores or metabolic disturbances, such as obesity and polycystic ovarian syndrome, often have elevated serum or follicular fluid leptin levels, raising the possibility that relative leptin deficiency or resistance may be at least partly responsible for the reproductive abnormalities that occur with these conditions. CONCLUSION(S): Leptin may act as the critical link between adipose tissue and the reproductive system, indicating whether adequate energy reserves are present for normal reproductive function. Future interventional studies involving leptin administration are expected to further clarify this role of leptin and may provide new therapeutic options for the reproductive dysfunction associated with states of relative leptin deficiency or resistance.