Assessment the Levels of Leptin, Adiponectin, and Insulin Resistance in Iraqi Women with Polycystic Ovary Syndrome (PCOS)

Afrah N Faris^1*, Khalid G Al-Fartosi¹ and Wassan R Al-Khafaji²

^*Correspondence: Afrah N Faris, Department of Biology, College of Science, University of Thi-Qar, Iraq, Email:

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Introduction

PCOS, or polycystic ovary syndrome, is a widely known endocrine disorder in women distinguished by hyperandrogenism during reproductive age [1]. Women with PCOS often have menstrual problems and infertility issues. Moreover, it may contribute to longterm health problems like diabetes and heart disease, cancer of the uterus and mood disorders [2] The exact causes of PCOS are very complex and still not clear. There are many suggested etiologies for PCOS. But it is not fully supported, in general, this hormonal imbalance consists of a combination of excess androgen and insulin resistance. In addition to environmental and genetic factors that contribute to this hormonal imbalance, all of these causes the development of PCOS [3]. Symptoms and signs vary among women with PCOS, it includes a combination of hyperandrogenism (hirsutism, alopecia, acne, high blood testosterone), obesity and severe menstrual irregularity (oligomenorrhea or amenorrhea) [4]. Adipose tissue is a major source of energy for the human body. It is also secreting adipocytokines adiponectin and leptin [5]. Leptin is a hormone that regulates body weight, discovered in 1991, 167 amino acids, secreted by adipose tissue and hypothalamus, stomach, placenta, skeletal muscle, and mammary epithelial cells [6,7]. Polycystic ovary syndrome is associated with metabolic disorders such as obesity and resistance Insulin [8], as obesity occurs in about half of women with polycystic ovary syndrome 70% of patients with – cysts [9], while there is insulin resistance in about 50 Independently of obesity [10]. Given the well-known link between leptin and PCOS obesity and insulin action, it is possible to hypothesize that leptin plays a role in its pathogenesis of PCOS [11]. Adiponectin (a protein with 244 amino acids and a molecular weight of 28 kDa) is secreted by adipose tissues that has anti-inflammatory properties and can positively modulate the endocrine system by increasing insulin sensitivity in obese animals and humans [12,13]. Adiponectin might be responsible for the metabolic and neuroendocrine (hormonal) issues that are associated with obesity and obesityrelated diseases, such as polycystic ovary syndrome [14]. The purpose of this study was to focus on leptin and adiponectin levels in women with PCOS, as well as their relationship to insulin resistance.

Subjects and Methods

Subjects

This is a case control study that lasted from 1 March 2021 to 30 September 2021 and included 100 married infertile PCOS patients and 80 married healthy controls from private health institutions in Thi-Qar governorate, Iraq. The following two groups were investigated: 1- patients, infertile women with PCOS, their age ranged from (18 – 41) years. All of them were diagnosed and selected by gynecologists using the Rotterdam criteria [15]. This study excluded PCOS patients with the following criteria: thyroid problems, acanthosis nigricans, hyperprolactinemia, Cushing's disease, Congenital adrenal hyperplasia with late onset, using oral contraceptives and ovulation stimulants. 2-The control group, 80 healthy women, have matching age to patients, there were normovulatory women.

Methods

All study participants underwent clinical evaluation and anthropometrics (weight, Height). Venous blood was sampled from fasting participants in luteal phase for determination of parameters in this study. Elisa technology used to assay the levels of leptin ( by kit of Mediagnost, Germany), adeponectin (by kits of sunlong, Chine) Also Enzymatic colorimetric test used to assay the level of fasting blood sugar (FBS) by Cobas integra 400 plus (Kits and instrument Roche- Germany) and insulin level were determined by using Cobas 411 immunoassay analysis (Kits and instrument Roche-Germany). Subgroups: control and patients groups were classified into two groups based on the BMI value, the first group being normal weight (BMI<24) and the second group being overweight and obese (BMI>24) [16].

insulin resistance (HOMA-IR) was calculated as: glucose (mg/dL) × insulin (μU/mL)/405.

Statistical analysis

All results are shown as the mean ± standard deviation (SE). Individual hormone levels were examined to see whether there were any variations in mean levels. using the student t-test.

Results

Study's parameters in general for patients and control groups

Table 1 explain a significant elevation in the levels of BMI, leptin, FBS, insulin and HOMA-IR while there was a significant decline in the level of adeponectin in the patients with PCOS group compared to the control group (p<0.05).

Table 1: BMI, leptin, adeponectin and insulin resistance (with related factors) of the control and patients with PCOS groups.

Levels of leptin, adeponectin and insulin resistance according BMI categories

The results of this study also recorded a significant increase in the level of leptin in the first and second BMI group of patients compared to the first and second BMI group of the control group respectively. There was nonsignificant difference in the level of leptin in two BMI groups for each control and patients’ groups (p<0.05) as shown in Table 2.

Table 2: Leptin levels in control and patients’ groups According to BMI categories.

Adeponectin

Table 3 explain a significant decline in the levels of adeponectin in the first and second BMI group of patients compared to matching BMI group of the control group. There was non-significant difference in the level of adeponectin in two BMI groups for each control and patients’ groups (p<0.05).

Table 3: Adeponectin levels in control and patients’ groups according to BMI categories.

HOMA-IR

The results of the current study also showed a significant increase in HOMA-IR in the first and second BMI group of patients compared to the first and second BMI group of the control group respectively. There was nonsignificant difference in HOMA-IR in two BMI groups for each control and patients’ groups (p<0.05) as shown in Table 4.

Table 4: HOMA-IR levels in control and patients’ groups According to BMI categories.

Discussion

The current study focuses on the role of adipose tissue hormones in PCOS, also taking the body's metabolic condition into account. Adipokines with potential effects on reproductive function are secreted by white adipose tissue. Leptin and adiponectin are the two most researched adipokines in this issue; their effects on fertility have been attributed to either central effects on the hypothalamus or peripheral effects on the ovary, reproductive tract, endometrial development, or embryo implantation [17].

Obese and non-obese women with PCOS had low adiponectin levels and high leptin levels [18,19]. This is consistent with the results of our study. Also, the results of this study showed a significant increase in insulin resistance in PCOS patients, and these results are consistent with other study which showed that polycystic ovary syndrome is associated with metabolic disorders such as obesity and Insulin resistance [8]. Leptin functions as a metabolic regulator of reproductive capability by informing GnRH neurons about the amount of energy stored in the body [20]. It is suggested that increased leptin levels are linked to the risk of insulin resistance, metabolic problems, infertility, and cardiovascular disease in PCOS, and may even contribute to the development of PCOS [21]. It has been demonstrated that leptin secretion is related to sex hormones [21]. High leptin levels also have a role in the pathogenesis of PCOS by enhancing GnRH release, activating pituitary gonadotrophs, or stimulating the ovaries [22]. Intraneuronal pathways including neuropeptide-Y, proopiomelanocortin, and kisspeptin modulate leptin's effects on GnRH [23].

Leptin resistance is a common feature in obese people, and it has been linked to ovulatory failure and infertility (frequently associated with PCOS) [24]. Hyperleptinemia can directly impair mature oocyte development as well as ovarian and adrenal steroidogenesis [25].

At a physiological level, leptin has been shown to increase oocyte maturation via activating the STAT signal transduction system [26]. High amounts of circulating leptin inhibited folliculogenesis in mice, but low levels of circulating leptin aided the transition from primary to secondary follicle [27]. Leptin may have a role in preovulatory follicular development, oocyte fertilization ability, and eventual embryo implantation potential [28]. Leptin hormone Ineffective in PCOS, we suggest, this due to a rise in leptin hormone levels to the stage of leptin resistance, which is causally due to high insulin and the state of insulin resistance in PCOS patients. Obese and non-obese women, since leptin is affected by the volume and distribution of body fat rather than body mass, as previously stated. The adipokines are the link between PCOS, obesity, and insulin resistance [29,30]. Adiponectin levels are decreased in both PCOS and prediabetic individuals. Li et al. [31] underlined that adiponectin levels were reduced in women with PCOS, which linked with PCOS independent of weight or insulin resistance.

Adiponectin activates fatty acid oxidation and glucose absorption in vitro [32]. Thiazolidinediones' pharmacological impact on insulin sensitivity entails a rise in both total and HMW adiponectin [33]. Adiponectin lowers tissue triglyceride levels while increasing insulin signaling [34]. Adiponectin inhibits gluconeogenesis in the liver, which may explain for its acute glucose-lowering effects [35]. Insulin lowers adiponectin levels [36], and adiponectin levels are higher in type 1 diabetics than in healthy controls [37]. Hyperinsulinemia may reduce circulating adiponectin levels, resulting in insulin resistance [38]. Adiponectin has been shown to inhibit LH and GnRH release [39], implying a function in the control of the hypothalamopituitary- gonadal axis [40]. Obese people had lower circulating Adiponectin levels, which are inversely connected to testosterone levels [41]. Testosterone has an inhibitory impact on adipocytes' production of HMW Adiponectin [42]. Women with PCOS have a decrease in HMW Adiponectin that is independent of BMI and insulin receptor (IR) [43]. It influences ovulation and steroidogenesis in a pleiotropic manner [44]. However, we considered in this study that the high level of leptin in PCOS patients had progressed to the stage of leptin resistance, especially given the ongoing increase in body mass index and the lack of weight reduction, which is one of the most significant roles of the hormone leptin. Furthermore, as with obesity, leptin resistance in pregnancy may be caused by impaired transport across the blood–brain barrier or by the sequestration of bioactive leptin in the circulation by a soluble receptor [45]. Frisch hypothesized in 1974 that the capacity to reproduce required a minimum level of body fat to serve as the minimal reserve of energy required for ovulation, menstruation, and intended pregnancy [46]. Body mass index had no effect on the outcomes of this study since the parameter's decline or elevation was constant in obese and non-obese women. To explain this case, we propose that PCOS occurs in response to a metabolic disorder that occurs when the fat mass in a woman's body reaches a certain threshold, particularly around the organs in the abdominal area, serving as the minimal fat amount to cause a metabolic disorder so that the body reaches the stage of insulin resistance and leptin resistance (taking into account other non-metabolic disorders that cause insulin resistance and leptin resistance such as genetics, environment and food) which lead to onset of PCOS, and the issue develops with an increase in body mass index.

Conclusion

According to the results of this study, the levels of leptin and adiponectin can be considered effective biomarkers in the early diagnosis of PCOS, especially in non-obese women, and can be used to predict the risk of developing PCOS in women without obvious symptoms, With the possibility of considering these indicators as therapeutic targets for PCOS. it appears to be a positive relationship between insulin resistance and leptin and a negative relationship with adiponectin in PCOS patients. It was also showed that parameters abnormalities in this study are not related to BMI in PCOS, while BMI enhances PCOS complications.

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