Insights into Manipulating Postprandial Energy Expenditure to Manage Weight Gain in Polycystic Ovary Syndrome

This study was designed to differentiate the contributions of hyperandrogenism, insulin resistance (IR), and body weight to the development of endothelial dysfunction in polycystic ovary syndrome and determine the effectiveness of insulin sensitization and antiandrogenic therapy after the establishment of vascular and metabolic dysfunction using a rat model of polycystic ovary syndrome. We hypothesized that the observed endothelial dysfunction was a direct steroidal effect, as opposed to changes in insulin sensitivity or body weight. Prepubertal female rats were randomized to the implantation of a pellet containing DHT or sham procedure. In phase 1, DHT-exposed animals were randomized to pair feeding to prevent weight gain or metformin, an insulin-sensitizing agent, from 5 to 14 weeks. In phase 2, DHT-exposed animals were randomized to treatment with metformin or flutamide, a nonsteroidal androgen receptor blocker from 12 to 16 weeks. Endothelial function was assessed by the vasodilatory response of preconstricted arteries to acetylcholine. Serum steroid levels were analyzed in phase 1 animals. Fasting blood glucose and plasma insulin were analyzed and homeostasis model assessment index calculated in all animals. Our data confirm the presence of endothelial dysfunction as well as increased body weight, hypertension, hyperinsulinemia, and greater IR among DHT-treated animals. Even when normal weight was maintained through pair feeding, endothelial dysfunction, hyperinsulinemia, and IR still developed. Furthermore, despite weight gain, treatment with metformin and flutamide improved insulin sensitivity and blood pressure and restored normal endothelial function. Therefore, the observed endothelial dysfunction is most likely a direct result of hyperandrogenism-induced reductions in insulin sensitivity, as opposed to weight gain.

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607Longitudinal weight gain and lifestyle factors in women with and without polycystic ovary syndrome

International Journal of Epidemiology ◽

10.1093/ije/dyab168.046 ◽

2021 ◽

Vol 50 (Supplement_1) ◽

Author(s):

Mamaru Ayenew Awoke ◽

Arul Earnest ◽

Anju Joham ◽

Allison Hodge ◽

Wendy Brown ◽

...

Keyword(s):

Physical Activity ◽

Weight Gain ◽

Polycystic Ovary Syndrome ◽

Energy Intake ◽

Glycemic Index ◽

Weight Change ◽

Polycystic Ovary ◽

Lifestyle Factors ◽

Sitting Time ◽

Ovary Syndrome

Abstract Background Women with polycystic ovary syndrome (PCOS) have a higher prevalence of overweight/obesity and greater weight gain than women without PCOS. The association of lifestyle factors with weight change in PCOS is not known. Methods We used data from the 1973-78 birth cohort of the Australian Longitudinal Study on Women’s Health collected from seven surveys over 19 years (N = 14127 survey 1). Linear mixed-effects models were used to examine associations between diet, physical activity, and sitting time with weight change, after adjustment for socio-demographics, psychological factors, and health care utilisation. Results Women with PCOS gained more weight annually (0·26 kg/year, 95% CI 0·13, 0·39; P < 0·0001) and over 19 years (4·75 kg; 95% CI 3·17, 6·34; P < 0·0001) than women without PCOS (adjusted analyses). For all women, there were positive associations between weight gain and energy intake, sitting time, and stress; inverse associations with fibre intake and physical activity; and no associations with diet quality, glycemic index, healthcare utilization, depression, or anxiety. There were interactions between lifestyle factors (energy intake P = 0·006, glycemic index P = 0·007, sitting time P = 0·029, and physical activity P = 0·022), PCOS status and time (age) such that weight gain varied between women with and without PCOS according to these factors. Conclusions Women with PCOS had a higher rate of weight gain than women without PCOS. This was most marked in those with indicators of unhealthy lifestyles. Increased stress, energy intake and sitting time and lower physical activity contributed to weight gain in women with and without PCOS. Key messages The findings reinforce the importance of early and ongoing lifestyle intervention and the potential use of specific lifestyle factors for weight gain prevention and management in PCOS.

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Androgen excess increases food intake in a rat polycystic ovary syndrome model by down-regulating hypothalamus insulin and leptin signaling pathways preceding weight gain

Neuroendocrinology ◽

10.1159/000521236 ◽

2021 ◽

Author(s):

Ying Liu ◽

Yu-chen Xu ◽

Yu-gui Cui ◽

Shi-wen Jiang ◽

Fei-yang Diao ◽

...

Keyword(s):

Weight Gain ◽

Food Intake ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Androgen Excess ◽

Ovary Syndrome ◽

Leptin Signaling ◽

Leptin Sensitivity ◽

Androgen Levels ◽

Restricted Food Intake

Background Polycystic ovary syndrome (PCOS) is a common reproductive and metabolic disorder characterized by high androgen levels. The aim of this study was to evaluate the effects of hyperandrogenism on the hypothalamus, and subsequently on the food intake and obesity in females. Methods A dihydroxy testosterone (DHT)-induced rat model was established to recapitulate the hyperandrogenism features of PCOS patients. Body weight and food intake of the rats were recorded. The food intake of DHT-induced rats was restricted by pair feeding to exclude possible effects of weight gain on the hypothalamus. The expression levels of relevant proteins and mRNAs in the hypothalamus, primary hypothalamic neurons exposed to DHT were analyzed by Western blotting and RT-PCR respectively. The leptin levels in serum and cerebrospinal fluid (CSF) were measured, and leptin was injected via the intracerebroventricular (ICV) route to test the leptin sensitivity of hypothalamus. Results The excessive pre-puberty androgen levels in the DHT-induced rats markedly elevated food intake prior to weight gain. Consistent with this, the expression of NPY and Agouti-related peptide (Agrp) mRNAs were up-regulated, which occurred prior to obesity and even with restricted food intake. In addition, the hypothalamic sensitivity to insulin and leptin was also impaired in the DHT-induced rats before obesity and with restricted food intake. DHT significantly reduced the leptin levels in the CSF, and ICV injection of leptin inhibited the DHT-induced increase in food intake. Conclusions Androgen excess increased food intake in rats and promoted obesity by down-regulating insulin and leptin signaling in the hypothalamus, most likely by suppressing leptin levels in the CSF.

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The Use of SenseWear Armband for Assessment of Daily Energy Expenditure and the Relation to Body Fat Distribution and Nutritional Intake in Lean Women with Polycystic Ovary Syndrome

Journal of Nutrition and Metabolism ◽

10.1155/2020/9191505 ◽

2020 ◽

Vol 2020 ◽

pp. 1-7

Author(s):

Gulcan Arusoglu

Keyword(s):

Physical Activity ◽

Body Composition ◽

Energy Expenditure ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Nutritional Intake ◽

Control Group ◽

Ovary Syndrome ◽

Sensewear Armband ◽

Segmental Body Composition

Objective. To evaluate nutritional intake, energy expenditure, and segmental body composition in lean women with polycystic ovary syndrome (PCOS) and compare them with age- and body mass index- (BMI-) matched control women. Methods. 32 nonobese patients with PCOS and 31 age- and BMI-matched healthy women were included in the study. Energy expenditure and physical activity level were assessed by metabolic Holter equipment (SenseWear Armband, SWA) which was never previously used in lean PCOS population. Food intake is recorded with 24 hours of food record. Segmental body composition analysis was assessed by bioelectrical impedance analyses (BIA). Results. Mean BMI was 22.64 ± 3.64 and 21.55 ± 2.77 kg/m2 (p=0.185) in PCOS and control groups, respectively. Mean age was 22.03 ± 4.21 and 21.71 ± 2.67 year (p=0.720), respectively. No significant differences were found in total energy intake and percentage of carbohydrates, fats, and other micronutrients (p>0.05). Energy percentage of proteins (%12.73 ± 1.98, p=0.008) was statistically lower in subjects versus the control group. The measurements of physical activity duration (PAD) (1.40 ± 0.87/2.18 ± 0.99 hours, p=0.002), active energy expenditure (372.35 ± 198.32/494.10 ± 186.50 kcal, p=0.018), and step counting (9370.03 ± 3587.49/11730.90 ± 3564.31 steps, p=0.013) measurement of the PCOS group were lower than the control group, respectively. Conclusions. New diagnosed women with PCOS had similar distribution and quantity of body fat parameters and nutritional status when compared to healthy women. Control subjects were found more active in energy expenditure.

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Weight Gain and Dyslipidemia in Early Adulthood Associate With Polycystic Ovary Syndrome: Prospective Cohort Study

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2015-3543 ◽

2016 ◽

Vol 101 (2) ◽

pp. 739-747 ◽

Cited By ~ 45

Author(s):

Meri-Maija E. Ollila ◽

Terhi Piltonen ◽

Katri Puukka ◽

Aimo Ruokonen ◽

Marjo-Riitta Järvelin ◽

...

Keyword(s):

Cohort Study ◽

Weight Gain ◽

Polycystic Ovary Syndrome ◽

Prospective Cohort Study ◽

Prospective Cohort ◽

Polycystic Ovary ◽

Early Adulthood ◽

Ovary Syndrome

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Polycystic Ovaries and Polycystic Ovary Syndrome in Epilepsy: Evidence for Neurogonadal Disease

Epilepsy Currents ◽

10.1111/j.1535-7511.2005.00039.x ◽

2005 ◽

Vol 5 (4) ◽

pp. 142-146 ◽

Cited By ~ 13

Author(s):

Cynthia L. Harden

Keyword(s):

Weight Gain ◽

Adverse Effects ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Moving Target ◽

Polycystic Ovaries ◽

Ovary Syndrome ◽

Reproductive Disorder ◽

Underlying Causes ◽

Androgen Levels

Polycystic ovary syndrome (PCOS) is a mysterious reproductive disorder that results in subfertility. The underlying causes are not known, and even the definition is a moving target. Women with epilepsy have features of PCOS at a higher than expected rate, and polycystic ovaries (PCO) also are present at high rates in this population. Valproate is associated with weight gain and increased androgen levels, two features of PCOS. This review proposes that epilepsy, with its known adverse effects on luteinizing hormone pulsatility, could be a cause of PCOS and that valproate could be an imitator, if not also a cause of the syndrome.

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Low validity of predictive equations for calculating resting energy expenditure in overweight and obese women with polycystic ovary syndrome

Journal of Human Nutrition and Dietetics ◽

10.1111/jhn.12498 ◽

2017 ◽

Vol 31 (2) ◽

pp. 266-275 ◽

Cited By ~ 2

Author(s):

A. M. dos S. Rodrigues ◽

A. B. P. Costa ◽

D. L. Campos ◽

M. P. S. Silva ◽

A. L. Cândido ◽

...

Keyword(s):

Energy Expenditure ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Resting Energy Expenditure ◽

Obese Women ◽

Ovary Syndrome ◽

Predictive Equations ◽

Resting Energy

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Polycystic Ovary Syndrome, Obesity and Melatonin: An Etiological Perspective

Journal of Nutrition and Dietetics ◽

10.33076/2021.bdd.1518 ◽

2021 ◽

pp. 1-8

Author(s):

Büşra Başar Gökcen ◽

Makbule Gezmen Karadağ

Keyword(s):

Circadian Rhythm ◽

Energy Expenditure ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Ovary Syndrome ◽

Mitochondrial Functions ◽

Metabolic Dysfunctions ◽

The Relationship ◽

Shed Light ◽

Circadian Rhythm Disorders

Although the reproductive and metabolic dysfunctions associated with polycystic ovary syndrome are clearly known, the mechanisms between these dysfunctions are still unclear. One of the hypotheses put forward for these mechanisms is related to circadian rhythm. To date, many reproductive and metabolic dysfunctions have been associated with circadian rhythm disorders. Especially in women with polycystic ovary syndrome, the relationship between melatonin rhythm, which lasts until late in the morning and starts early at night, and metabolic dysfunctions has been revealed by recent studies. When the relationship between obesity and melatonin is examined, it is clearly seen that melatonin exhibits its effect on energy expenditure rather than energy intake. This hormone affects energy expenditure through adipogenesis, thermogenesis, mitochondrial functions and adipocytokines release, and shows anti-obesity effect. It is thought that this review will shed light on further studies on the therapeutic use of melatonin in obesity associated with polycystic ovary syndrome and contribute to the development of strategies for the prevention of obesity.

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Associations between pre-pregnancy body mass index and gestational weight gain with pregnancy outcomes in women with polycystic ovary syndrome

Diabetology & Metabolic Syndrome ◽

10.1186/s13098-020-00595-3 ◽

2020 ◽

Vol 12 (1) ◽

Author(s):

Lirui Zhang ◽

Wei Zheng ◽

Cheng Liu ◽

Xin Liang ◽

Li Zhang ◽

...

Keyword(s):

Body Mass Index ◽

Weight Gain ◽

Polycystic Ovary Syndrome ◽

Gestational Age ◽

Pregnancy Outcomes ◽

Protective Factor ◽

Polycystic Ovary ◽

Perinatal Outcomes ◽

Ovary Syndrome ◽

Gestational Weight

Abstract Background The influence of pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) on perinatal outcomes of women with polycystic ovary syndrome (PCOS) remains unclear. Therefore, we explored how the above indicators influence pregnancy outcomes in women with PCOS. Methods A retrospective study was conducted involving the baseline characteristics, laboratory data, and pregnancy outcomes of 722 pregnant women with PCOS. Subjects were grouped in a way to find out risks in their pregnancy outcomes. Multivariable logistic regression analysis was performed to investigate how BMI and GWG were associated with perinatal outcomes. Results Among women with PCOS, underweight increased the risk of small for gestational age (SGA) (OR 12.35, 95% CI 3.56–42.82), but reduced the risk of large for gestational age (LGA). Overweight but not obese women were more susceptible to developing preeclampsia (PE) than women with normal weight. In PCOS women with BMI < 25 kg/m2 before pregnancy, inadequate GWG was a protective factor for gestational hypertension (GH) and postpartum hemorrhage (PPH), excessive GWG exhibited a positive correlation with LGA. But in PCOS women with BMI ≥ 25 kg/m2, excessive GWG increased the probability of undergoing a cesarean section. Inadequate GWG did not reduce the likelihood of LGA in women with BMI ≥ 25 kg/m2, and excessive GWG did not reduce the probability of SGA in women with BMI < 25 kg/m2. Conclusion The impacts of pre-pregnancy BMI, GWG on maternal and infant outcomes among PCOS women are similar to reported results in general pregnant women. However, some unique trends were also observed in PCOS women. While the underweight factor significantly increased the risk of SGA birth, overweight but not obesity was correlated with the risk of PE. Inadequate GWG was a protective factor for GH and PPH only in women with pregestational BMI < 25 kg/m2. Inadequate GWG did not reduce the probability of LGA in women with BMI ≥ 25 kg/m2, and similarly, excessive GWG did not reduce the probability of SGA in women with BMI < 25 kg/m2. Overall, these findings indicate that women with PCOS should begin weight management before pregnancy.

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A review of maternal overweight and obesity and its impact on cardiometabolic outcomes during pregnancy and postpartum

Therapeutic Advances in Reproductive Health ◽

10.1177/2633494120986544 ◽

2021 ◽

Vol 15 ◽

pp. 263349412098654

Author(s):

Jessica A. Grieger ◽

Melinda J. Hutchesson ◽

Shamil D. Cooray ◽

Mahnaz Bahri Khomami ◽

Sarah Zaman ◽

...

Keyword(s):

Weight Gain ◽

Gestational Diabetes ◽

Polycystic Ovary Syndrome ◽

Gestational Weight Gain ◽

Polycystic Ovary ◽

Overweight And Obesity ◽

Ovary Syndrome ◽

Cardiometabolic Diseases ◽

Gestational Weight ◽

Maternal Overweight

The rates of maternal overweight and obesity, but also excess gestational weight gain, are increasing. Pregnancy complications, including gestational diabetes mellitus, gestational hypertension, pre-eclampsia and delivery of a preterm or growth restricted baby, are higher for both women with overweight and obesity and women who gain excess weight during their pregnancy. Other conditions such as polycystic ovary syndrome are also strongly linked to overweight and obesity and worsened pregnancy complications. All of these conditions place women at increased risk for future cardiometabolic diseases. If overweight and obesity, but also excess gestational weight gain, can be reduced in women of reproductive age, then multiple comorbidities associated with pregnancy complications may also be reduced in the years after childbirth. This narrative review highlights the association between maternal overweight and obesity and gestational weight gain, with gestational diabetes, pre-eclampsia, polycystic ovary syndrome and delivery of a preterm or growth restricted baby. This review also addresses how these adverse conditions are linked to cardiometabolic diseases after birth. We report that while the independent associations between obesity and gestational weight gain are evident across many of the adverse conditions assessed, whether body mass index or gestational weight gain is a stronger driving factor for many of these is currently unclear. Mechanisms linking gestational diabetes mellitus, gestational hypertension, pre-eclampsia, preterm delivery and polycystic ovary syndrome to heightened risk for cardiometabolic diseases are multifactorial but relate to cardiovascular and inflammatory pathways that are also found in overweight and obesity. The need for post-partum cardiovascular risk assessment and follow-up care remains overlooked. Such early detection and intervention for women with pregnancy-related complications will significantly attenuate risk for cardiovascular disease.

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