European Journal of Obstetrics & Gynecology and Reproductive Biology 176 (2014) 168–172
Contents lists available at ScienceDirect
European Journal of Obstetrics & Gynecology and Reproductive Biology journal homepage: www.elsevier.com/locate/ejogrb
Apelin levels in relation with hormonal and metabolic profile in patients with polycystic ovary syndrome ¨ zlem Altinkaya a,*, Su¨meyra Nergiz a, Mert Ku¨c¸u¨k b, Hasan Yu¨ksel a Su¨ndu¨z O a b
Department of Gynecology & Obstetrics, Adnan Menderes University, Faculty of Medicine, Aydin, Turkey Department of Gynecology & Obstetrics, Sıtkı Koc¸man University, Faculty of Medicine, Mugla, Turkey
A R T I C L E I N F O
A B S T R A C T
Article history: Received 26 September 2013 Received in revised form 20 January 2014 Accepted 10 February 2014
Objective: To evaluate serum concentrations of apelin in relation to the hormonal and metabolic profile in patients with and without polycystic ovary syndrome (PCOS). Study design: A total of 45 women with PCOS and 45 age-matched controls were eligible for the study. Hirsutism scores, hormonal and metabolic profile as well as apelin levels were evaluated in each subject. Results: Women with PCOS exhibited lower serum concentrations of apelin than controls (194.1 50.7 pg/ml versus 292.1 85.6 pg/ml, p < 0.001). Apelin levels were significantly correlated positively with body mass index (BMI), insulin, triglyceride (TG), free testosterone (fT) levels, modified Ferriman Gallwey scores and Homeostasis Model Assessment (HOMA) index; but negatively correlated with high density lipoprotein (HDL) levels in patients with PCOS (p < 0.05). When overweight or obese (BMI 25) and normal weight (BMI < 25) women with PCOS were compared to BMI-matched controls, lower apelin levels were found in the PCOS group (226.7 45.4 pg/ml versus 378.6 80.9 pg/ml and 165.5 36.1 versus 249.0 46.6 pg/ml, p < 0.001, respectively). Conclusion: The data suggest that serum apelin levels are lower in women with PCOS than in controls. Furthermore, apelin can be used as a specific marker for insulin sensitivity and lipid profile and this adipokine might play a role in the pathogenesis of PCOS. ß 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: Polycystic ovary syndrome Apelin Adipokine
1. Introduction Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders affecting women, with a prevalence of 6–12% in women of reproductive age [1]. It is characterized by androgen excess, chronic oligoanovulation and polycystic ovaries (PCO) on ultrasound. Clinically, the androgen excess presents as hirsutism and acne, whereas anovulation presents as subfertility and menstrual irregularity. In addition, symptoms and complications such as insulin resistance, inflammation, visceral fat, cardiovascular disease, and infertility are common among women with PCOS [2]. Apelin is a bioactive peptide originally identified from bovine stomach extracts as the endogenous ligand of the G proteincoupled receptor APJ [3]. Recently, it has been identified as a new adipokine linked to obesity and insulin resistance. Collected data from both the clinical and basic research settings show that apelin (1) correlates with states of insulin resistance and obesity, (2) stimulates glucose utilization, (3) decreases insulin secretion, and (4) negatively regulates catecholamine-mediated lipolysis [4].
¨ niversitesi Tıp Faku¨ltesi Kadın * Corresponding author at: Adnan Menderes U Hastalıkları ve Dog˘um Anabilim Dali, Aydin, Turkey. Tel.: +90 505 3904529. ¨ . Altinkaya). E-mail address: [email protected] (S.O http://dx.doi.org/10.1016/j.ejogrb.2014.02.022 0301-2115/ß 2014 Elsevier Ireland Ltd. All rights reserved.
Apelin synthesis in adipocytes is stimulated by insulin, and plasma apelin level markedly increases in obesity associated with insulin resistance and hyperinsulinemia [5]. The apelinergic system has been demonstrated to be involved in the pathogenesis of a number of conditions, such as hypertension, heart failure, glucose intolerance and diabetes mellitus [6–8]. Since apelin seems to be a key regulator in glucose and lipid metabolism and may be associated with insulin resistance, and PCOS is known to be associated with increased insulin resistance and other metabolic disorders such as dyslipidemia, hypertension, endothelial dysfunction and reduced vascular compliance and atherosclerosis; the present study aimed toinvestigate whetherthere was adifference in serum apelin levels between women with and without PCOS. This study also set out to correlate serum apelin levels with the hormonal and metabolic profile to investigate the associations between several markers related to cardiovascular disease. 2. Materials and methods The design of the present study was approved by the Ethical Committee and Institutional Review Board of Adnan Menderes University Faculty of Medicine, where the study was conducted. Written informed consent was obtained from all participants.
S.O¨. Altinkaya et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 176 (2014) 168–172
The diagnosis of PCOS was made according to the Rotterdam criteria [9] in the presence of at least two of the following: (1) oligomenorrhea and/or anovulation, (2) biochemical and/or clinical hyperandrogenism, and (3) ultrasound appearance of polycystic ovaries (PCO) (multiple cysts >12 in number of 2–9 mm size), with the exclusion of other etiologies such as congenital adrenal hyperplasia, virilising tumor, Cushing syndrome and prolactinoma, diabetes, hypertension and other cardiovascular diseases. Over the three months preceding the study no subject had been on hormonal contraceptives, other medications or diet which could affect lipid and carbohydrate metabolism. No subject smoked or consumed alcohol. As controls 45 age-matched women who had regular menses and no clinical or biochemical hyperandrogenism or PCO were eligible. A detailed clinical history was taken and physical examination was performed for all participants. Body mass index (BMI) was also calculated. Subjects with BMI < 25 kg/m2 were accepted as normal weight, and 25–25.99 kg/m2 were overweight; whereas when BMI was 30 kg/m2 these participants were accepted as obese. Routine laboratory investigations included fasting serum glucose, fasting insulin, total cholesterol, high-density lipoprotein (HDL), lowdensity lipoprotein (LDL), triglycerides (TG), luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol (E2), thyroid stimulating hormone (TSH), free thyroxine levels (free T3 and free T4), dehydroepiandrosterone sulphate (DHEA-SO4) and free testosterone (fT) levels. Insulin resistance (IR) was determined by the Homeostasis Model Assessment (HOMA) index (fasting glucose (mg/dl) fasting insulin (mU/ml)/405) [10]. All sampling procedures were performed in the early follicular phase (day 2–5 of the menstrual cycle) in the morning after an overnight fast for 12 h. Serum apelin-36 levels were assessed by enzyme-linked immunosorbent assay (USCN Life Sciences Inc., China). The intraand inter-assay coefficients of variation were
Contents lists available at ScienceDirect
European Journal of Obstetrics & Gynecology and Reproductive Biology journal homepage: www.elsevier.com/locate/ejogrb
Apelin levels in relation with hormonal and metabolic profile in patients with polycystic ovary syndrome ¨ zlem Altinkaya a,*, Su¨meyra Nergiz a, Mert Ku¨c¸u¨k b, Hasan Yu¨ksel a Su¨ndu¨z O a b
Department of Gynecology & Obstetrics, Adnan Menderes University, Faculty of Medicine, Aydin, Turkey Department of Gynecology & Obstetrics, Sıtkı Koc¸man University, Faculty of Medicine, Mugla, Turkey
A R T I C L E I N F O
A B S T R A C T
Article history: Received 26 September 2013 Received in revised form 20 January 2014 Accepted 10 February 2014
Objective: To evaluate serum concentrations of apelin in relation to the hormonal and metabolic profile in patients with and without polycystic ovary syndrome (PCOS). Study design: A total of 45 women with PCOS and 45 age-matched controls were eligible for the study. Hirsutism scores, hormonal and metabolic profile as well as apelin levels were evaluated in each subject. Results: Women with PCOS exhibited lower serum concentrations of apelin than controls (194.1 50.7 pg/ml versus 292.1 85.6 pg/ml, p < 0.001). Apelin levels were significantly correlated positively with body mass index (BMI), insulin, triglyceride (TG), free testosterone (fT) levels, modified Ferriman Gallwey scores and Homeostasis Model Assessment (HOMA) index; but negatively correlated with high density lipoprotein (HDL) levels in patients with PCOS (p < 0.05). When overweight or obese (BMI 25) and normal weight (BMI < 25) women with PCOS were compared to BMI-matched controls, lower apelin levels were found in the PCOS group (226.7 45.4 pg/ml versus 378.6 80.9 pg/ml and 165.5 36.1 versus 249.0 46.6 pg/ml, p < 0.001, respectively). Conclusion: The data suggest that serum apelin levels are lower in women with PCOS than in controls. Furthermore, apelin can be used as a specific marker for insulin sensitivity and lipid profile and this adipokine might play a role in the pathogenesis of PCOS. ß 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: Polycystic ovary syndrome Apelin Adipokine
1. Introduction Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders affecting women, with a prevalence of 6–12% in women of reproductive age [1]. It is characterized by androgen excess, chronic oligoanovulation and polycystic ovaries (PCO) on ultrasound. Clinically, the androgen excess presents as hirsutism and acne, whereas anovulation presents as subfertility and menstrual irregularity. In addition, symptoms and complications such as insulin resistance, inflammation, visceral fat, cardiovascular disease, and infertility are common among women with PCOS [2]. Apelin is a bioactive peptide originally identified from bovine stomach extracts as the endogenous ligand of the G proteincoupled receptor APJ [3]. Recently, it has been identified as a new adipokine linked to obesity and insulin resistance. Collected data from both the clinical and basic research settings show that apelin (1) correlates with states of insulin resistance and obesity, (2) stimulates glucose utilization, (3) decreases insulin secretion, and (4) negatively regulates catecholamine-mediated lipolysis [4].
¨ niversitesi Tıp Faku¨ltesi Kadın * Corresponding author at: Adnan Menderes U Hastalıkları ve Dog˘um Anabilim Dali, Aydin, Turkey. Tel.: +90 505 3904529. ¨ . Altinkaya). E-mail address: [email protected] (S.O http://dx.doi.org/10.1016/j.ejogrb.2014.02.022 0301-2115/ß 2014 Elsevier Ireland Ltd. All rights reserved.
Apelin synthesis in adipocytes is stimulated by insulin, and plasma apelin level markedly increases in obesity associated with insulin resistance and hyperinsulinemia [5]. The apelinergic system has been demonstrated to be involved in the pathogenesis of a number of conditions, such as hypertension, heart failure, glucose intolerance and diabetes mellitus [6–8]. Since apelin seems to be a key regulator in glucose and lipid metabolism and may be associated with insulin resistance, and PCOS is known to be associated with increased insulin resistance and other metabolic disorders such as dyslipidemia, hypertension, endothelial dysfunction and reduced vascular compliance and atherosclerosis; the present study aimed toinvestigate whetherthere was adifference in serum apelin levels between women with and without PCOS. This study also set out to correlate serum apelin levels with the hormonal and metabolic profile to investigate the associations between several markers related to cardiovascular disease. 2. Materials and methods The design of the present study was approved by the Ethical Committee and Institutional Review Board of Adnan Menderes University Faculty of Medicine, where the study was conducted. Written informed consent was obtained from all participants.
S.O¨. Altinkaya et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 176 (2014) 168–172
The diagnosis of PCOS was made according to the Rotterdam criteria [9] in the presence of at least two of the following: (1) oligomenorrhea and/or anovulation, (2) biochemical and/or clinical hyperandrogenism, and (3) ultrasound appearance of polycystic ovaries (PCO) (multiple cysts >12 in number of 2–9 mm size), with the exclusion of other etiologies such as congenital adrenal hyperplasia, virilising tumor, Cushing syndrome and prolactinoma, diabetes, hypertension and other cardiovascular diseases. Over the three months preceding the study no subject had been on hormonal contraceptives, other medications or diet which could affect lipid and carbohydrate metabolism. No subject smoked or consumed alcohol. As controls 45 age-matched women who had regular menses and no clinical or biochemical hyperandrogenism or PCO were eligible. A detailed clinical history was taken and physical examination was performed for all participants. Body mass index (BMI) was also calculated. Subjects with BMI < 25 kg/m2 were accepted as normal weight, and 25–25.99 kg/m2 were overweight; whereas when BMI was 30 kg/m2 these participants were accepted as obese. Routine laboratory investigations included fasting serum glucose, fasting insulin, total cholesterol, high-density lipoprotein (HDL), lowdensity lipoprotein (LDL), triglycerides (TG), luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol (E2), thyroid stimulating hormone (TSH), free thyroxine levels (free T3 and free T4), dehydroepiandrosterone sulphate (DHEA-SO4) and free testosterone (fT) levels. Insulin resistance (IR) was determined by the Homeostasis Model Assessment (HOMA) index (fasting glucose (mg/dl) fasting insulin (mU/ml)/405) [10]. All sampling procedures were performed in the early follicular phase (day 2–5 of the menstrual cycle) in the morning after an overnight fast for 12 h. Serum apelin-36 levels were assessed by enzyme-linked immunosorbent assay (USCN Life Sciences Inc., China). The intraand inter-assay coefficients of variation were
