肥胖对女性生殖和代谢的影响

肥胖与女性生殖功能改变之间的关系已得到公认。肥胖，尤其是腹型肥胖，与一系列的代谢紊乱相关，特别是伴胰岛素抵抗的高胰岛素血症以及雄激素过多症。所有这些因素可能直接或间接地损害卵巢功能，导致女性生殖能力的下降。肥胖与多囊卵巢综合征（PCOS）之间存在强烈关联。胰岛素抵抗和高胰岛素血症是PCOS妇女的关键特征，对PCOS的病理生理有重要的影响，特别是伴有肥胖的患者，很大程度上导致了PCOS妇女的生育障碍。肥胖对PCOS的表现型有着深远的影响．其与更严重的雄激素过多症、胰岛素抵抗状态和生育障碍有关。     

瘦素（leptin）与生殖

肥胖基因编码的蛋白质瘦素（ｌｅｐｔｉｎ）,由脂肪组织分泌,作为抑脂信号作用于中枢,调节摄食中枢和能量平衡,从而降低食物摄取和体重。瘦素缺乏的动物模型中,瘦素浓度极低可削弱下丘脑功能,引起低促性腺性性腺功能低下。而高浓度的瘦素可损害卵泡细胞对ＦＳＨ刺激的敏感性。在下丘脑,瘦素与受体结合后抑制神经肽Ｙ的合成与释放,从而激活ＧｎＲＨ神经元活动使未成熟雌性小鼠青春期出现并加速其进展。瘦素不足尚可引起胰岛素     

关注影响女性健康的重要生殖内分泌疾病多囊卵巢综合征

多囊卵巢综合征（polycystic ovary syndrome,PCOS）是一种病因不明的异质性疾病,是育龄女性最常见的生殖内分泌疾病,是引起女性排卵障碍性不孕、月经失调和高雄激素的重要原因。 浏览更多请关注本刊微信公众号及当期杂志。     

关注影响女性健康的重要生殖内分泌疾病多囊卵巢综合征

        多囊卵巢综合征（polycystic ovary syndrome,PCOS）是一种病因不明的异质性疾病,是育龄女性最常见的生殖内分泌疾病,是引起女性排卵障碍性不孕、月经失调和高雄激素的重要原因。浏览更多请关注本刊微信公众号及当期杂志。     

甲福明治疗多囊卵巢综合征：内分泌、代谢与生殖结局

多囊卵巢综合征(PCOS)是影响育龄妇女常见的内分泌疾病之一,卵巢出现多囊性改变是其必备的特征,但据报道卵巢的这种形态学改变占成人女性20％左右。最近的观察发现,胰岛素抵抗和血中胰岛素过高是引起PCOS出现其它内分泌改变的两个主要因素,这一发现促进了特殊治疗方法的发展,即降低胰岛素水平的治疗方法。 甲福明是一种水溶性口服制剂,由于它的抗糖尿病作用而广泛用于非胰岛素依赖型糖尿病(2型糖尿病)。甲福明增强胰岛素在肝和周围组织的敏感性,抑制肝脏葡萄糖的产     

多囊卵巢综合征和肥胖及其治疗的研究进展

多囊卵巢综合征(PCOS)是一种异质性的内分泌紊乱疾病,在育龄妇女中高发.临床上发现PCOS和肥胖密切相关,PCOS患者中肥胖者居多,而肥胖的PCOS患者与非肥胖患者相比,有更加严重的内分泌代谢紊乱,肥胖在PCOS中可能起一定的病因作用.因此,需要更加重视肥胖PCOS患者的治疗,除常规PCOS的治疗外,肥胖患者还需纠正长期代谢紊乱导致的远期并发症.     

肥胖与女性生殖内分泌

肥胖(obesity)指人体因各种原因引起的脂肪组织过多，是一种由遗传和环境因素，包括激素内环境异常，共同作用引起的体内脂肪积聚过多。随着生活水平的提高及生活方式的改变，全球肥胖症发生率迅速增加，并呈年轻化趋势。肥胖对全身各系统都可能产生不良的影响。在女性，肥胖可导致月经失调、不孕、流产及乳腺癌、子宫内膜癌等；此与肥胖引起生殖内分泌紊乱有关。     

肥胖与青少年多囊卵巢综合征

多囊卵巢综合征（PCOS）是育龄妇女常见生殖内分泌疾病。近年发现,随着儿童肥胖患病率增加,青少年PCOS发病率也逐年提高。肥胖可通过增加外周循环胰岛素水平影响PCOS发病机制,PCOS患者高雄激素血症也会增加内脏脂肪沉积。肥胖会增加与PCOS相关的代谢和心血管方面的并发症的患病风险,如胰岛素抵抗（IR）、高脂血症、高血压以及临床症状不明显的动脉粥样硬化等。早期识别青春期PCOS,有利于及时纠正、阻断其内分泌紊乱,防止近期及远期并发症发生。     

肥胖与青少年多囊卵巢综合征

多囊卵巢综合征（PCOS）是育龄妇女常见生殖内分泌疾病。近年发现,随着儿童肥胖患病率增加,青少年PCOS发病率也逐年提高。肥胖可通过增加外周循环胰岛素水平影响PCOS发病机制,PCOS患者高雄激素血症也会增加内脏脂肪沉积。肥胖会增加与PCOS相关的代谢和心血管方面的并发症的患病风险,如胰岛素抵抗（IR）、高脂血症、高血压以及临床症状不明显的动脉粥样硬化等。早期识别青春期PCOS,有利于及时纠正、阻断其内分泌紊乱,防止近期及远期并发症发生。     

多囊卵巢综合征和肥胖及其治疗的研究进展

多囊卵巢综合征(PCOS)是一种异质性的内分泌紊乱疾病，在育龄妇女中高发。临床上发现PCOS和肥胖密切相关，PCOS患者中肥胖者居多，而肥胖的PCOS患者与非肥胖患者相比，有更加严重的内分泌代谢紊乱，肥胖在PCOS中可能起一定的病因作用。因此，需要更加重视肥胖PCOS患者的治疗，除常规PCOS的治疗外，肥胖患者还需纠正长期代谢紊乱导致的远期并发症。     

The epidemiology of obesity in reproduction

Over the last decades, overweight and obesity rates have been rising exponentially and have now reached epidemic proportions. These are significantly higher in women than men, and indeed, data from 2022 show rates varying from the lowest (12%) in the South East Asian Region to the highest (82.8%) in the Western Pacific Region. This rise is mirrored by the increasing health cost of obesity and overweight. Recent estimates put the percentage of medical spending in various countries to vary from 3 to 21%. Obesity is associated with noncommunicable diseases, such as hypertension, diabetes mellitus, and cardiovascular disorders. It is associated with 13 cancers, among which are breast, endometrial, and ovarian. The reproductive consequences of obesity are variable and include but not exclusively menstrual disorders; fertility difficulties; recurrent miscarriages; gestational diabetes, hypertension, and pre-eclampsia; postpartum hemorrhage; and fetal macrosomia. Various factors are responsible for these increasing rates (which are more marked in middle- and low-income countries). These include genetic, epigenetic, environmental, physiologic, cultural, political, and socioeconomic factors that interact in most cases, making it challenging to develop effective interventions on both a local and global scale. In this article, we review the epidemiology of obesity and the factors which modify rates, as well as an overview of the reproductive consequences of obesity. We discuss approaches to reduce the rates and that these should be at three levels: individual, national, and international.     

Metabolic effects of obesity on reproduction

Obese women are characterized by similar comorbidities to men, particularly type 2 diabetes mellitus and cardiovascular diseases. Moreover, they also develop some specific problems, including fertility-related disorders and some hormone-dependent forms of cancer. The relationship between excess body fat and reproductive disturbances appears to be stronger for early-onset obesity. Early onset of obesity, particularly during adolescence, favours the development of menses irregularities, chronic oligo-anovulation and infertility in adulthood. Moreover, obesity in women can increase the risk of miscarriage and impair the outcome of assisted reproductive technologies. The main factor implicated in the association between obesity and fertility-related disorders is insulin excess, which accompanies insulin resistance. Hyperinsulinaemia may be directly responsible for the development of androgen excess, through its effects in reducing sex hormone-binding globulin synthesis and circulating concentrations, and in stimulating ovarian androgen production rates. Androgen excess, in turn, represents one of the major factors leading to altered ovarian physiology and associated ovulatory disturbances. Obesity-associated hyperleptinaemia may represent an additional factor involved in anovulation, not only through the induction of insulin resistance, but also through a direct impairment of ovarian function.     

Toxicity of chemotherapy and radiation on female reproduction

One of the most devastating consequences of cancer treatment in the young female population is ovarian damage, resulting in diminished fertility potential. The extent of damage is related to age, chemotherapeutic regimen, and dose of pelvic radiation received. It is crucial that physicians know the impact each of these factors has on future fertility to advice patients on fertility preservation options. Anticancer drugs injure the female reproductive system through ovarian follicular and stromal damage. Although the exact mechanisms of damage remain unclear, it is essential to better understand these mechanisms to develop methods to diminish ovarian injury.     

Thyroid disease and female reproduction

Objective: To review the menstrual function and fertility in thyroid disease, mainly in hyperthyroidism and hypothyroidism. Also to register the consequences of ¹³¹I therapy, which is used widely in the treatment of Graves’ disease and thyroid cancer, on subsequent pregnancies and on fertility in these patients.

Design: A MEDLINE computer search was used to identify relevant studies. The type of menstrual disturbances and the status of fertility were recorded from all the studies found. Also, the fertility and genetic hazard of female patients with Graves’ disease and thyroid cancer who were treated with ¹³¹I were registered.

Result(s): Both hyperthyroidism and hypothyroidism may result in menstrual disturbances. Menstrual abnormalities are less common now than in previous series. In a recent study, we found that only 21.5% of 214 thyrotoxic patients had some type of menstrual disturbance, compared to 50 to 60% in some older series. The most common manifestations are hypomenorrhea and oligomenorrhea. According to the results of endometrial biopsies, most thyrotoxic women remain ovulatory. Moreover, the genetic hazard incident to radioiodine therapy in Graves’ disease and thyroid carcinoma is very small; exposure to ¹³¹I does not cause reduced fecundity, and the risk of loss of fertility is not a contraindication for its use in these patients. mIn hypothyroidism, the frequency of menstrual irregularities has very recently been reported to be 23.4% among 171 hypothyroid patients studied. This is much less than that reported in previous studies, which showed that 50 to 70% of hypothyroid female patients had menstrual abnormalities. The most common manifestation is oligomenorrhea. Severe hypothyroidism is commonly associated with failure of ovulation. Ovulation and conception can occur in mild hypothyroidism. These pregnancies are, however, often associated with abortions, stillbirths, or prematurity. The latter may be of greater clinical importance in infertile women with unexplained infertility.

Conclusion(s): These new data, mainly concerning menstrual abnormalities in hyperthyroidism and hypothyroidism, are inconsistent with what is generally believed and written in the classic thyroid textbooks and indicate that such opinions should be revised.     

Extracellular vesicles and female reproduction

Extracellular vesicles (EVs) are nano-sized membrane bound complexes that have been identified as a mean for intercellular communication between cells and tissues both in physiological and pathological conditions. These vesicles contain numerous molecules involved in signal transduction including microRNAs, mRNAs, DNA, proteins, lipids, and cytokines and can affect the behavior of recipient cells. Female reproduction is dependent on extremely fine-tuned endocrine regulation, and EVs may represent an added layer that contributes to this regulation. This narrative review article provides an update on the research of the role of EVs in female reproduction including folliculogenesis, fertilization, embryo quality, and implantation. We also highlight potential pitfalls in typical EV studies and discuss gaps in the current literature.     

The role of female obesity on in vitro fertilization outcomes

The aim of this review is to analyze the role of obesity on fertility outcome in women undergoing in vitro fertilization (IVF) with respect to clinical or live birth rates and pregnancy loss rates. Despite findings from several earlier and newer studies that obesity does not adversely affect pregnancy outcome in women attempting conception, numerous reports from mostly recent studies suggest that obesity undoubtedly impairs IVF outcomes. Obesity impairs ovarian responsiveness to gonadotrophin stimulation, requiring higher doses of medication, increased risk of cycle cancelation, pre-term delivery, low birth weight or miscarriage, and decreases implantation, clinical pregnancy or live birth rates compared to women of normal weight. The mechanisms underlying the adverse effects of female obesity on IVF outcome may be primarily explained by functional alterations to the hypothalamic-pituitary-ovarian axis. Additionally, obesity appears to affect deleteriously the number and quality of oocytes or embryos, and impairs endometrial decidualization which is necessary for uterine receptivity. Nevertheless, attaining normal body weight by the use of lifestyle modifications, including a healthy diet and exercise over time of several months before and during an IVF treatment, may be successful in achievement of gradual and sustainable weight loss with improvement of IVF outcome.     

The impact of obesity on reproduction in women with polycystic ovary syndrome

The polycystic ovary syndrome (PCOS) is one of the most common causes of infertility due to anovulation in women. The clinical features of PCOS are heterogeneous and may change throughout the lifespan, starting from adolescence to postmenopausal age. This is largely dependent on the influence of obesity and metabolic alterations, including an insulin-resistant state and the metabolic syndrome, which consistently affect most women with PCOS. Obesity does in fact have profound effects on both the pathophysiology and the clinical manifestation of PCOS, by different mechanisms leading to androgen excess and increased free androgen availability and to alterations of granulosa cell function and follicle development. Notably, simple obesity per se represents a functional hyperandrogenic state. These mechanisms involve early hormonal and metabolic factors during intrauterine life, leptin, insulin and the insulin growth factor system and, potentially, the endocannabinoid system. Compared with normal weight women with PCOS, those with obesity are characterised by a worsened hyperandrogenic and metabolic state, poorer menses and ovulatory performance and, ultimately, poorer pregnancy rates. The importance of obesity in the pathogenesis of PCOS is emphasised by the efficacy of lifestyle intervention and weight loss, not only on metabolic alterations but also on hyperandrogenism, ovulation and fertility. The increasing prevalence of obesity among adolescent and young women with PCOS may partly depend on the increasing worldwide epidemic of obesity, although this hypothesis should be supported by long-term prospective epidemiological trials. This may have great relevance in preventive medicine and offer the opportunity to expand our still limited knowledge of the genetic and environmental background favouring the development of the PCOS.     

The effects of being overweight and obese on female reproduction: a review

Obesity is a major international problem related to many reproductive health problems including polycystic ovary syndrome (PCOS). This article reviews the evidence of being overweight and its effect on female reproduction. The fecundity of obese women is lower than normal weight women, but there is no absolute consensus about the effect of obesity on infertility treatment. The obese patient might have oocyte, hormone, metabolic and endometrial dysfunction affecting reproduction. Insulin and leptin may be some of the answers explaining anovulation during obesity leading to infertility. Moreover, the follicular glucose and lipids which are important for oocyte development also increase in the obese patient and these might have an effect on oocyte quality because studies in mice have revealed that the obesity affects follicular cell stress and oocyte lipids. Overall, obesity affects female reproduction by disturbing the general body metabolism, hormone metabolism and the follicular environment.