In overweight women with polycystic ovary syndrome (PCOS), increased insulin resistance has been observed. Since abdominal obesity is associated with impaired fibrinolytic capacity and elevated levels of plasminogen activator inhibitor (PAI-1) and since PAI-1 seems to be related to insulin resistance, we investigated the possible effects of dietary intervention on lipids, fibrinolysis, coagulation, and insulin sensitivity in obese PCOS women. Nine women aged 22 to 39 years (median weight, 97 kg) ate a protein-rich very-low-calorie diet (VLCD) (Nutrilett, Nycomed Pharma, Oslo, Norway; 421 kcal/d) for 4 weeks (part 1). After significant reductions of body fat (13%, P < .01), two of nine women achieved regular menstruation and became pregnant. Six of the remaining women continued on a conventional low-calorie diet (1,000 to 1,500 kcal/d) for the next 20 weeks (part 2), during which time they were generally able to preserve the body fat loss obtained in part 1 of the study. During part 1, significant reductions of total serum cholesterol (29%, P = .001) and fasting triglyceride ([TG] 31%, P < .05) levels were observed, as well as significant reductions of fasting glucose (6%, P < .05) and insulin (20%, P < .05). Insulin sensitivity (glucose disposal rate [GDR]) was increased by 93% (P < .05). After finishing part 2, insulin sensitivity was still significantly increased (86%, P < .05) and PAI-1 activity was significantly reduced (54%, P < .05). Moreover, overall fibrinolytic activity was significantly improved (serum D-dimer concentration increased by 75%, P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)
"Short-term low calorie diets (4 weeks) with 6.6-9.0% weight loss have been shown to decrease IR (Hamilton-Fairley et al., 1993; Andersen et al., 1995). Studies of moderate caloric restriction for 2-15 months also gave positive outcomes (Pasquali et al., 1989). "
[Show abstract][Hide abstract] ABSTRACT: Insulin resistance (IR) is a consequence of obesity, and in women it is often inextricably linked with ovarian function leading to clinical reproductive manifestations such as early menarche onset, subfertility and polycystic ovary syndrome (PCOS). Likewise, the dramatic fall in oestrogen production after menopause may contribute to weight gain and changes in adipose tissue distribution. Overall, women who are obese, especially those with reproductive complications including PCOS, have been identified as specific high risk subgroups for further progression through to prediabetes, type 2 diabetes mellitus (T2DM) and potentially cardiovascular disease (CVD). This review focuses on the interrelationship between the ovarian function and obesity as well as its treatment strategies.
"Hyperinsulinemia contributes to the prothrombotic state by reducing fibrinolysis and raising the level of plasminogen activator inhibitor (PAI-1) (Potter van Loon et al 1993). In patients with PCOS, the level of PAI-1 was found to be elevated (Atiomo et al 1998; Sampson et al 1996; Yildiz et al 2002), and it decreased with improvement in insulin sensitivity, either through weight loss (Andersen et al 1995) or the use of insulin sensitizing agents (Ehrmann et al 1997; Velazquez et al 1997). The increase in PAI-1 activity in PCOS was thought to be independent of body mass index since elevated levels were also observed in lean PCOS women. "
[Show abstract][Hide abstract] ABSTRACT: It is estimated that 60%-7% of women of reproductive age have polycystic ovarian syndrome (PCOS). Women with this condition exhibit an adverse cardiovascular risk profile, characteristic of the cardiometabolic syndrome and given the high prevalence of PCOS in the female population, this condition may contribute towards the acceleration of cardiovascular disease among young women. This article summarizes the recent development and findings in the cardiometabolic abnormalities in patients with PCOS. Patients with PCOS have the clinical features of oligomenorrhoea, hirsutism and infertility; however, they also exhibit hyperinsulinemia, obesity, hypertension, dyslipidemia, and an increased pro-thrombotic state. They have an increased risk of type 2 diabetes and impaired glucose tolerance, and sleep apnea is also found more commonly in this population. However, despite the presence of cardiovascular risk factors and increased surrogate markers of cardiovascular disease it is unclear if they have accelerated atherosclerosis. End point studies are currently lacking and the available evidence are conflicting. Adipose tissue has emerged as an important endocrine organ over the last decade and gained recognition in having an important role in the cardiometabolic syndrome. Adiponectin that is secreted exclusively by adipocytes has recently been recognized as an important marker of cardiometabolic syndrome, obesity, type 2 diabetes, and coronary artery disease. Other adipocytokines like leptin and resistin have also recently been recognized. This article will address the current evidence for the adverse cardiovascular risk in PCOS and the other factors that may be implicated. Finally the therapeutic options for treatment will be discussed.
Vascular Health and Risk Management 02/2007; 3(1):55-63.
"Lowering PAI-1 activity has been theorized to improve the ongoing pregnancy rate in these individuals. Plasma PAI-1 decreases with hypocaloric weight loss (Andersen et al., 1995; Mavri et al., 1999; Bastard et al., 2000c; Arvidsson et al., 2004) and after gastric bypass and gastric restrictive bariatric surgery procedures (van Dielen et al., 2004; Uzun et al., 2004; Vazquez et al., 2004). van Dielen et al. (2004) reported a rapid drop at 3 months post-operatively, followed by stabilization of PAI-1 concentrations up to 2 years after surgery. "
[Show abstract][Hide abstract] ABSTRACT: Reproductive function declines at both extremes of human energy balance. The relationship between obesity and reproductive function is complex and incompletely understood. The literature has established the negative impact of excess energy stores on ovulatory function and investigated the mechanisms whereby this occurs. Furthermore, weight loss in obese anovulatory women increases ovulation and conception. Obesity and anti-obesity therapy effects on the endometrium, implantation and early fetal development have received less attention. The discovery of adipokines and enterokines greatly expands the ability to investigate the relationship between obesity, therapies to produce weight loss and reproductive function. In this review, we discuss select adipose and enteric signals. We focus on in vitro, animal and human data that lend biological plausibility to adipokines and enterokines as mediators of obesity and reproduction. Very little published work exists that directly addresses adipocyte and enteric signals in this specific role; therefore, much of this review is on the basis of a synthesis of the literature in three areas: (i) in vitro and in vivo evidence regarding the reproductive effects of these signals; (ii) adipokine and enterokine changes that occur with weight-loss therapies, focusing on hypocaloric diets, bariatric surgery and drugs that target adipocyte or enteric signals and (iii) reproductive changes produced by these weight-loss therapies.
Human Reproduction Update 09/2006; 12(5):585-601. DOI:10.1093/humupd/dml024 · 10.17 Impact Factor
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