http://informahealthcare.com/gye ISSN: 0951-3590 (print), 1473-0766 (electronic) Gynecol Endocrinol, Early Online: 1–5 ! 2014 Informa UK Ltd. DOI: 10.3109/09513590.2014.984676
ORIGINAL ARTICLE
Adiponectin and leptin in overweight/obese and lean women with polycystic ovary syndrome Chin-I Chen1, Ming-I Hsu2*, Shyh-Hsiang Lin3*, Yuan-Chin I. Chang4, Chun-Sen Hsu2, and Chii-Ruey Tzeng5 Department of Neurology and 2Department of Obstetrics and Gynaecology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan, 3School of Nutrition and Health Science, Taipei Medical University, Taipei, Taiwan, 4Institute of Statistical Science, Academia Sinica, Taipei, Taiwan, and 5 Department of Obstetrics and Gynaecology, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan Gynecol Endocrinol Downloaded from informahealthcare.com by Nyu Medical Center on 06/08/15 For personal use only.
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Abstract
Keywords
Aim: The objective of this study was to evaluate the adiponectin and leptin levels in overweight/obese and lean women with polycystic ovary syndrome (PCOS). Design: This was a retrospective study. Patients: Of the 422 studied patients, 224 women with PCOS and 198 women without PCOS were evaluated. Main outcome measure(s): Insulin resistance and the metabolic components were assessed. The adiponectin and leptin levels were also evaluated. Results: Adiponectin was negatively correlated with insulin resistance, body mass index (BMI), and total testosterone, triglyceride, and low-density lipoprotein (LDL) levels; conversely, leptin reversed the aforementioned reaction and was negatively correlated with adiponectin levels. The adiponectin to leptin ratios were significantly lower in PCOS women than in those without PCOS. Compared to women with non-PCOS, overweight/obese women with PCOS had lower serum adiponectin levels than women without PCOS, which was not the case for lean women. Conversely, lean women with PCOS had higher serum leptin levels than those without PCOS, which was not the case for overweight/obese women. Conclusions: Adipose tissue might play an important role in the metabolic complications in women with PCOS. To study the impact of obesity biomarkers in women with PCOS, overweight/obese and lean women should be considered separately.
Adiponectin, insulin resistance, leptin, obesity, PCOS
Introduction Polycystic ovary syndrome (PCOS) is the most frequent endocrinopathy in reproductive-aged women, which is mainly characterized by oligo-anovulation and hyperandrogenism (HA). PCOS is associated with an adverse cardio-metabolic profile, which consists of increased total or central adiposity and abnormal glucose metabolism [1]. Obesity is characterized by adipocyte hypertrophy. Adipose tissue participates in the regulation of energy homeostasis as an important endocrine organ that secretes a number of biologically active adipokines [2]. Dysregulated production or the secretion of these adipokines from adipose tissue dysfunction can contribute to obesity-linked complications [3]. Adiponectin and leptin are among the most commonly investigated factors that may impact overweight/obese women. Adiponectin is a recently identified adipocyte-derived collagen-like protein. It is exclusively expressed in adipose tissue, and it is released into the circulation [4]. Adiponectin levels hold *Ming-I Hsu and Shyh-Hsiang Lin contributed equally to this work. Address for correspondence: Ming-I Hsu, Department of Obstetrics and Gynaecology, Wan Fang Hospital, Taipei Medical University, No.111, Sec. 3, Xinglong Rd., Taipei 11696, Taiwan. Tel: +886-2-29307930 ext. 2501. Fax: +886-2-29300036. E-mail: [email protected]
History Received 21 January 2014 Revised 29 October 2014 Accepted 3 November 2014 Published online 25 November 2014
great promise for use in clinical applications as a potent indicator of underlying metabolic complications [5]. Leptin, an adipocytederived hormone encoded by the ‘‘ob’’ gene, relays metabolic signals to the neuronal networks in the brain to modulate the hypothalamo–pituitary–ovarian axis [6]. The leptin- neuropeptide Y axis has been suggested for its implications in reproductive disturbance [7]. Adiponectin and leptin could be useful for identifying metabolic complications in overweight/obese women. Studies on an adipose-related factor in women with PCOS have reported controversial findings. Olszanecka-Glinianowicz suggested that obese but not normal-weight women with PCOS have lower adiponectin levels, whereas the resistin concentrations did not differ in normal-weight and obese PCOS subjects compared with control subjects [8]. Several studies have suggested that adiponectin and leptin contribute to insulin resistance in women with PCOS. Wang suggested that low serum adiponectin and high serum resistin levels might play important roles in the pathogenesis of insulin resistance in PCOS patients [9]. Pehlivanov reported a positive correlation between the serum leptin levels and the clinical and hormonal indices of insulin resistance. Pehlivanov suggested that hyperleptinemia is due to leptin resistance and may be a characteristic of PCOS [10]. Isolated adipocytes from women with PCOS express higher mRNA concentrations of some adipokines involved in cardiovascular
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risk and insulin resistance [11]. All of the above studies provide evidence that adiponectin and leptin play important roles in insulin resistance in women with PCOS. Obesity is associated with increased adipose and plasma leptin levels and lower adiponectin expression [12]. Obesity might affect the pathogenesis of adipose tissue hormones. Studies on an adipose-related factor in women with PCOS have reported controversial findings. Adipose tissue is a key endocrine organ [13], and any correlation between adipokines and insulin resistance in women with PCOS should be considered in lean and overweight/obese women separately. Therefore, we evaluated the adiponectin and leptinin overweight/obese and lean women with and without PCOS.
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Methods This study was approved by the Institutional Review Board of Taipei Medical University – Wan Fang Hospital, Taipei, Taiwan with the identifier Hsu2013-TMU-JIRB201307021 and registered at ClinicalTrials.gov with the identifier NCT01989039. We retrospectively reviewed the medical records of female patients who visited our Reproductive Endocrinology Clinic from 1 January 2009 to 31 December 2012. The study population Study data Women who had a complete set of anthropometric measurements as well as clinical and biochemical data regarding insulin resistance parameters and obesity biomarkers were initially included. The subjects’ medical histories included a detailed menstrual and medical/surgical history, anthropometric measurements (weight, height, waist, and hip), and blood pressure. The dates and assays performed for blood sampling have been described previously [14]. The following data were collected and calculated: (1) the obesity hormone levels: adiponectin, leptin, ghrelin, and resistin; (2) the serum androgen levels, including total testosterone, androstenedione, dehydroepiandrosterone sulfate (DHEA-S), and the free androgen index (FAI), which was calculated as follows: FAI ¼ total testosterone (nmol/ L) 100/sex hormone binding globulin (SHBG) (nmol/L); (3) the insulin sensitivity and glucose tolerance assessments, including fasting insulin and glucose levels, 2-h glucose levels and the homeostasis model assessment insulin resistance index (HOMA); and (4) lipid profiles including total cholesterol, triglyceride, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) levels. Furthermore, the risk of metabolic syndrome (MBS), impaired glucose tolerance and diabetes were evaluated in every subject. The waist-to-hip ratio (WHR) was defined as the waist circumference/hip circumference. The body mass index (BMI) was defined as the body weight in kilograms divided by the body height in meters squared (kg/m2). Overweight/obesity was defined as BMI 5 kg/m2and lean was defined as BMI 525 kg/ m2. An ovarian pelvic ultrasonograph, preferably transvaginal, was performed to detect polycystic ovaries. The adiponectin and leptin levels were measured by RIA (LINCO Research, Inc. St. Charles, Missouri, MO). PCOS was diagnosed according to the Androgen Excess and PCOS Society criteria [15]), which requires HA (hirsutism and/or biochemical) and ovarian dysfunction (oligo-anovulation and/or polycystic ovaries). The definitions of oligo-anovulation and polycystic ovaries have previously been described in detail. HA was defined as hirsutism and/or biochemical hyperandrogenemia (BioHA). Biochemical hyperandrogenemia was defined as a total serum testosterone value 2.78 nmol/L (0.8 ng/mL, the normal range for female adults is 0.1–0.8 ng/mL) and/or FAI 6.53.
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Hirsutism was defined as a modified Ferriman–Gallwey (mF-G) score 6. The insulin sensitivity index was evaluated by the homeostasis model assessment insulin resistance index (HOMA) using the following formula: HOMA ¼
½fasting insulinðmU=mLÞ fasting glucoseðmg=dLÞ 405
The World Health Organization 2006 diagnostic criteria for diabetes were used (fasting plasma glucose [FPG] 7 nmol/L (126 mg/dL) or 2-h plasma glucose 11.1 nmol/L (200 mg/dL)). Impaired glucose tolerance (IGT) was defined as 2-h glucose levels of 7.77–11.1 nmol/L (140–199 mg/dL) in the 75-g oral glucose tolerance test. In women with IGT, the FPG levels should be lower than 7 nmol/L. MBS was defined (2005 National Cholesterol Education Program – Adult Treatment Panel III) as the presence of at least three of the following criteria: abdominal obesity (waist circumference480 cm in women), serum triglyceride levels 1.7 nmol/L (150 mg/dL), serum HDL levels 51.3 nmol/L (50 mg/dL), systolic blood pressure 130 mmHg and/or diastolic blood pressure 85 mmHg, and fasting plasma glucose levels 5.6 nmol/L (100 mg/dL). A total of 543 women were primarily included for evaluation in the study. Of these, 121 cases were excluded due to premature ovarian failure (N ¼ 23) and hyperprolactinemia (N ¼ 98). Finally, 422 cases were analyzed in this study. Statistical analysis Statistical analysis was performed using SPSS 13.0 for Windows (SPSS, Inc., Chicago, IL). We evaluated the correlation between the serum HOMA IR, total testosterone, adiponectin, and leptin using Pearson’s correlation coefficients with the two-tailed method (Table 2). The data are represented as the mean ± standard deviation in Table 1. We used the chi-square and Fisher’s exact tests to compare categorical variables and ANOVA to compare continuous variables in Tables 1 and 3. Differences between the groups were considered significant if the corresponding p value was less than 0.05.
Results Among the 422 studied patients, 224 women had PCOS and 198 women did not. There were 182 overweight/obese women (BMI 425); 121 of these had PCOS and 61 did not. The remaining patients included 240 lean women (BMI 25); 103 of these women had PCOS, and 137 did not. Table 1 presents a separate comparison between overweight/obese and lean PCOS and nonPCOS women. The adiponectin to leptin ratios were significantly lower in women with PCOS than in women without PCOS. Compared to women without PCOS, overweight/obese women with PCOS had lower serum adiponectin levels, which was not the case for lean women. Conversely, lean women with PCOS had higher serum leptin levels than those without PCOS, which was not the case for overweight/obese women. The insulin resistance prevalence was similar between women with and without PCOS. Table 2 demonstrates the correlation between insulin resistance (HOMA), the total testosterone levels, and BMI with various obesity biomarkers. Adiponectin was negatively correlated with HOMA, BMI, and the total testosterone, triglyceride, LDL and leptin levels (all p50.001); conversely, the leptin levels were significantly positively correlated with HOMA; BMI; and the total testosterone, triglyceride, and LDL levels (all p50.001).
Adiponectin & leptin in PCOS
DOI: 10.3109/09513590.2014.984676
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Table 1. Clinical and biochemical characteristics in overweight/obese and lean women with and without PCOS. Overweight/obese
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Total Case number 422 Age (y/o) 27.5 ± 6.4 Menarche (y/o) 12.6 ± 1.5 Anthropometric measurements Weight (kg) 63.6 ± 15.7 Height (cm) 160.6 ± 5.2 BMI (kg/m2) 24.6 ± 5.8 Waist (cm) 82.9 ± 14.2 Hip (cm) 98.8 ± 10.5 Waist-to-hip ratio 0.84 ± 0.08 Adipose tissue components Adiponectin (ng/mL) 9306 ± 6155 Leptin (ng/mL) 14.35 ± 10.63 Adiponectin/Leptin 1380.1 ± 2058.7 Androgens Total testosterone (nmol/L) 2.13 ± 1.05 Androstenedione (nmol/L) 9.28 ± 4.41 Free Androgen Index 8.26 ± 8.25 DHEAS (nmol/L) 5230 ± 2783 Insulin sensitivity and glucose tolerance Fasting Insulin (pmol/L) 92.90 ± 86.15 Fasting glucose (mmol/L) 5.13 ± 1.00 2-h glucose (mmol/L) 6.34 ± 2.66 3.19 ± 3.22 HOMAa Impaired glucose tolerance 12% Diabetes mellitus 5% Hormonal components LH (mIU/mL) 10.09 ± 10.80 FSH (mIU/mL) 6.38 ± 2.14 LH/FSH 1.65 ± 2.23 Lipid profiles and blood pressure Cholesterol(mmol/L) 4.87 ± 0.90 Triglycerides (mmol/L) 1.07 ± 1.00 HDL (mmol/L) 1.39 ± 0.41 LDL (mmol/L) 2.91 ± 0.80 Metabolism Metabolic syndrome 29% Hypertension 32% HDL 51.3 mmol/L 47% Triglycerides 1.7 mmol/L 13% Waist 480 cm 50% FPG 5.6 mmol/L 15%
Lean
PCOS
Non-PCOS
121 27.0 ± 5.8 12.4 ± 1.4
61 30.1 ± 7.3 12.2 ± 1.2
79.0 ± 10.8 161.1 ± 4.9 30.4 ± 3.6 96.4 ± 9.1 108.5 ± 7.6 0.89 ± 0.07
p Value
PCOS
Non-PCOS
p Value
0.002* 0.182
103 25.1 ± 5.7 12.7 ± 1.5
137 28.5 ± 6.4 13.0 ± 1.6
50.001* 0.185
78.0 ± 12.6 161.1 ± 5.9 30.1 ± 4.6 94.2 ± 13.4 107.7 ± 8.0 0.87 ± 0.09
0.588 0.985 0.608 0.180 0.510 0.171
52.8 ± 5.7 160.1 ± 5.0 20.4 ± 1.7 73.4 ± 6.4 92.0 ± 4.6 0.80 ± 0.05
51.9 ± 6.2 160.2 ± 5.2 20.2 ± 2.1 72.9 ± 7.1 91.3 ± 5.9 0.80 ± 0.08
0.246 0.859 0.301 0.585 0.318 0.790
6117 ± 3166 22.43 ± 11.31 365.5 ± 302.7
7328 ± 4445 20.05 ± 11.70 677.4 ± 1536.0
0.036* 0.188 0.032*
11 267 ± 7698 9.71 ± 5.78 1648.3 ± 1517.1
11 531 ± 6048 8.16 ± 4.89 2387.5 ± 2838.6
0.764 0.026* 0.017*
2.80 ± 1.09 10.78 ± 4.45 15.81 ± 9.88 5447 ± 2656
1.89 ± 0.84 7.66 ± 4.76 8.52 ± 8.11 5377 ± 3079
50.001* 50.001* 50.001* 0.874
2.35 ± 0.95 10.52 ± 4.28 6.91 ± 4.30 5678 ± 2504
1.48 ± 0.68 7.76 ± 3.51 3.02 ± 1.97 4635 ± 2883
50.001* 50.001* 50.001* 0.004*
152.81 ± 116.02 5.38 ± 0.88 7.29 ± 2.60 5.36 ± 4.16 25% 9%
110.69 ± 66.73 5.73 ± 1.93 7.89 ± 4.28 4.22 ± 3.41 17% 15%
0.009* 0.078 0.247 0.067 0.304 0.251
56.64 ± 28.83 4.90 ± 0.62 5.48 ± 1.89 1.81 ± 1.04 4% 1%
59.32 ± 55.13 4.83 ± 0.39 5.47 ± 1.39 1.85 ± 1.72 6% 1%
0.653 0.256 0.940 0.822 0.496 0.840
10.15 ± 8.64 5.96 ± 1.64 1.90 ± 3.22
6.85 ± 6.16 5.59 ± 2.24 1.33 ± 1.04
0.004* 0.192 0.139
13.97 ± 11.86 6.57 ± 1.84 2.09 ± 1.57
8.36 ± 10.73 6.85 ± 2.52 1.29 ± 1.22
0.005* 0.620 0.001*
5.09 ± 0.90 1.61 ± 1.51 1.12 ± 0.27 3.31 ± 0.75
4.99 ± 0.99 1.27 ± 0.69 1.21 ± 0.40 3.20 ± 0.76
0.528 0.094 0.083 0.322
4.90 ± 0.88 0.84 ± 0.66 1.57 ± 0.36 2.80 ± 0.79
4.59 ± 0.79 0.69 ± 0.34 1.58 ± 0.40 2.51 ± 0.65
0.004* 0.030* 0.877 0.002*
64% 56% 83% 29% 98% 28%
52% 59% 66% 18% 87% 28%
0.119 0.719 0.010* 0.112 0.001* 0.974
6% 13% 24% 4% 16% 6%
4% 12% 25% 3% 18% 4%
0.613 0.804 0.923 0.682 0.582 0.427
Data are either mean ± SD or are percentage; *p50.05. The homeostasis model assessment insulin resistance index (HOMA), dehydroepiandrosterone sulfate (DHEA-S), the free androgen index (FAI), highdensity lipoprotein (HDL), low-density lipoprotein (LDL).
a
Table 2. Pearson correlation between insulin resistance, total testosterone, and body mass index with adiponectin and leptin. HOMAa: a
HOMA : BMIa: a
Testosterone : Adiponectin Leptin Insulin Triglycerides HDL LDL
1 0.536* p50.001 0.185* p50.001 0.314* p50.001 0.372* p50.001 0.958* p50.001 0.349* p50.001 0.361* p50.001 0.214* p50.001
BMIa:
Testosteronea:
Adiponectin
Leptin
Insulin
Triglycerides
HDL
LDL
1 0.283* p50.001 0.459* p50.001 0.669* p50.001 0.497* p50.001 0.368* p50.001 0.582* p50.001 0.351* p50.001
1 0.210* p50.001 0.334* p50.001 0.198* p50.001 0.169* p50.001 0.155* p50.001 0.216* p50.001
1 0.290* p50.001 0.290* p50.001 0.315* p50.001 0.525* p50.001 0.223* p50.001
1 0.379* p50.001 0.191* p50.001 0.369* p50.001 0.252* p50.001
1 0.299* p50.001 0.343* p50.001 0.186* p50.001
1 0.366* p50.001 0.248* p50.001
1 0.207* p50.001
1
*p50.05. a The homeostasis model assessment insulin resistance index (HOMA), body mass index (BMI), high-density lipoprotein (HDL), low-density lipoprotein (LDL).
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Table 3. A comparison of adiponectin and leptin among overweight/obese with lean women with or without PCOS. PCOS
Case number BMIa (kg/m2) Adiponectin (ng/mL) Leptin (ng/mL) Adiponectin/leptin HOMAa HOMA-IRa
Non-PCOS
Overweight/obese
Lean
p Value
Overweight/obese
Lean
p Value
121 30.4 ± 3.6 6117 ± 3166 22.43 ± 11.31 365.5 ± 302.7 5.36 ± 4.16 76%
103 20.4 ± 1.7 11 264 ± 7698 9.71 ± 5.78 1648.3 ± 1517.1 1.81 ± 1.04 37%
50.001* 50.001* 50.001* 50.001* 50.001* 50.001*
61 30.1 ± 4.6 7328 ± 4445 20.05 ± 11.70 677.4 ± 1513.5 4.22 ± 3.41 74%
137 20.2 ± 2.1 11 531 ± 6048 8.16 ± 4.89 2387.5 ± 2838.6 1.85 ± 1.72 27%
50.001* 50.001* 50.001* 50.001* 50.001* 50.001*
Data are either mean ± SD or are percentage; *p50.05. Body mass index (BMI), The homeostasis model assessment insulin resistance index (HOMA), HOMA-IR: 42.14.
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a
After adjusting for BMI, the adiponectin levels were negatively correlated with the triglyceride ( ¼ 0.176, p50.001) and HDL ( ¼ 0.358, p50.001) levels. The leptin levels were positively correlated with the total testosterone levels ( ¼ 0.207, p50.001). To separately consider the impact of obesity on women with and without PCOS, Table 3 summarizes the adiponectin and leptin levels in overweight/obese and lean women with or without PCOS. The results demonstrate that the adiponectin and leptin levels, as well as the adiponectin/leptin ratio, were significantly different in the overweight/obese and lean women in the PCOS and non-PCOS groups.
Discussion The status of the cardiovascular system in women with PCOS might contribute to different health factors, including insulin resistance, androgen status and BMI [16]. Excess androgen should be the most important component of PCOS [17]. The total serum testosterone levels could be considered to be indicative of the HA severity. HOMA was also considered to be an indicator of insulin resistance, and BMI was an indicator of obesity. The first part of this study was to evaluate the correlation between the adiponectin, leptin, HOMA, BMI and total testosterone levels. The adiponectin and leptin levels were strongly BMI-dependent. The adiponectin- and leptin-mediated reversal of insulin resistance and lipid profiles was very clear. Adipocytes are considered to be endocrine cells that synthesize and release molecules (adipokines) that play an endocrine/paracrine role. Our results demonstrate that the adiponectin levels were negatively associated with BMI, insulin resistance, and the total testosterone. Conversely, leptin reversed the aforementioned reaction and was negatively correlated with the adiponectin levels. Svendsen suggested that PCOS does not have an independent effect on the adipose tissue expression of leptin, adiponectin, IL-6 or circulating adipocytokine levels [12]. We found that overweight/ obese women with or without PCOS had lower adiponectin and higher leptin levels than lean women. Our study also confirmed the findings in a previous report that the adiponectin/leptin ratio is a marker of PCOS [18]. Furthermore, our results were the first to suggest opposing roles of adiponectin and leptin in overweight/ obese and lean women with PCOS. Compared with normal controls, lean but not overweight/obese women with PCOS presented with significantly higher serum leptin levels. Conversely, overweight/obese, but not lean women, with PCOS presented with lower serum adiponectin levels than normal controls. Our results also demonstrated a negative correlation between the total testosterone and adiponectin levels; therefore, overweight/obese women with PCOS had significantly lower adiponectin levels than overweight/obese controls. Our study also confirmed that the adiponectin levels and insulin resistance are significantly correlated and that low adiponectin levels may be
involved in insulin resistance in PCOS patients, as was previously reported [19]. The fasting insulin levels in obese women with PCOS were significantly higher than those of the obese controls. Obesity-linked adiponectin down-regulation might be a mechanism through which obesity can cause insulin resistance and diabetes [2]; furthermore, PCOS might enhance this condition. The findings in this study also indicate that circulating adiponectin levels could be treated as a biomarker of insulin resistance [5] and that the adipocytokine and metabolic biomarker levels are significantly correlated [19]. Furthermore, we observed a strong positive correlation between the adiponectin and HDL levels, even after adjusting for BMI, which might indicate that adiponectin has a favorable effect on the lipid profile. Adipose tissue might play an important role in the metabolic complications in women with PCOS. However, when studying the impact of obesity biomarkers in women with PCOS, overweight/obese and lean women should be considered separately. The major weakness of this study is that the women evaluated in the present study were recruited from the outpatient clinic of a tertiary care center and do not reflect the true distribution of the general population. Therefore, these results should be applied to the general population with caution. Finally, we conclude the following: Women with PCOS presented with a decreased adiponectin-toleptin ratio. Compared with normal controls, women with PCOS display increased serum leptin levels, which were only observed in lean subjects. Conversely, decreased serum adiponectin levels were observed in overweight/obese but not lean subjects. When studying the impact of obesity biomarkers in women with PCOS, overweight/obese and lean women should be considered separately.
Declaration of interest The authors report that they have no conflicts of interest to disclose. This work was supported by the Taiwan National Science Council Grant NSC102-2629-B-038-001 and Taipei Medical University – Wan Fang Hospital Grant 100-TMU-WFH-02-4.
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6. Chakrabarti J. Serum leptin level in women with polycystic ovary syndrome: correlation with adiposity, insulin, and circulating testosterone. Ann Med Health Sci Res 2013;3:191–6. 7. Jacobs HS, Conway GS. Leptin, polycystic ovaries and polycystic ovary syndrome. Hum Reprod Update 1999;5:166–71. 8. Olszanecka-Glinianowicz M, Kuglin D, Da˛bkowska-Huc´ A, Skałba P. Serum adiponectin and resistin in relation to insulin resistance and markers of hyperandrogenism in lean and obese women with polycystic ovary syndrome. Eur J Obstet Gynecol Reprod Biol 2011;154:51–6. 9. Wang Y, Xie X, Zhu W. Serum adiponectin and resistin levels in patients with polycystic ovarian syndrome and their clinical implications. J Huazhong Univ Sci Technolog Med Sci 2010;30: 638–42. 10. Pehlivanov B, Mitkov M. Serum leptin levels correlate with clinical and biochemical indices of insulin resistance in women with polycystic ovary syndrome. Eur J Contracept Reprod Health Care 2009;14:153–9. 11. Garruti G, Depalo R, Vita MG, et al. Adipose tissue, metabolic syndrome and polycystic ovary syndrome: from pathophysiology to treatment. Reprod Biomed Online 2009;19:552–63. 12. Svendsen PF, Christiansen M, Hedley PL, et al. Adipose expression of adipocytokines in women with polycystic ovary syndrome. Fertil Steril 2012;98:235–41. 13. Galic S, Oakhill JS, Steinberg GR. Adipose tissue as an endocrine organ. Mol Cell Endocrinol 2010;316:129–39.
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14. Liang SJ, Hsu CS, Tzeng CR, et al. Clinical and biochemical presentation of polycystic ovary syndrome in women between the ages of 20 and 40. Hum Reprod 2011; 26:3443–9. 15. Azziz R, Carmina E, Dewailly D, et al; Task Force on the Phenotype of the Polycystic Ovary Syndrome of The Androgen Excess and PCOS Society. The Androgen Excess and PCOS Society criteria for the polycystic ovary syndrome: the complete task force report. Fertil Steril 2009;91:456–88. 16. Samy N, Hashim M, Sayed M, Said M. Clinical significance of inflammatory markers in polycystic ovary syndrome: their relationship to insulin resistance and body mass index. Dis Markers 2009; 26:163–70. 17. Azziz R, Carmina E, Dewailly D, et al; Androgen Excess Society. Positions statement: criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: an Androgen Excess Society guideline. J Clin Endocrinol Metab 2006;91:4237–45. 18. Golbahar J, Das NM, Al-Ayadhi MA, Gumaa K. Leptin-toadiponectin, adiponectin-to-leptin ratios, and insulin are specific and sensitive markers associated with polycystic ovary syndrome: a case-control study from Bahrain. Metab Syndr Relat Disord 2012; 10:98–102. 19. Wang Q, Guo T, Tao Y, et al. Association between serum adipocyte factor level and insulin resistance in polycystic ovarian syndrome. Gynecol Endocrinol 2011;27:931–4.
ORIGINAL ARTICLE
Adiponectin and leptin in overweight/obese and lean women with polycystic ovary syndrome Chin-I Chen1, Ming-I Hsu2*, Shyh-Hsiang Lin3*, Yuan-Chin I. Chang4, Chun-Sen Hsu2, and Chii-Ruey Tzeng5 Department of Neurology and 2Department of Obstetrics and Gynaecology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan, 3School of Nutrition and Health Science, Taipei Medical University, Taipei, Taiwan, 4Institute of Statistical Science, Academia Sinica, Taipei, Taiwan, and 5 Department of Obstetrics and Gynaecology, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan Gynecol Endocrinol Downloaded from informahealthcare.com by Nyu Medical Center on 06/08/15 For personal use only.
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Abstract
Keywords
Aim: The objective of this study was to evaluate the adiponectin and leptin levels in overweight/obese and lean women with polycystic ovary syndrome (PCOS). Design: This was a retrospective study. Patients: Of the 422 studied patients, 224 women with PCOS and 198 women without PCOS were evaluated. Main outcome measure(s): Insulin resistance and the metabolic components were assessed. The adiponectin and leptin levels were also evaluated. Results: Adiponectin was negatively correlated with insulin resistance, body mass index (BMI), and total testosterone, triglyceride, and low-density lipoprotein (LDL) levels; conversely, leptin reversed the aforementioned reaction and was negatively correlated with adiponectin levels. The adiponectin to leptin ratios were significantly lower in PCOS women than in those without PCOS. Compared to women with non-PCOS, overweight/obese women with PCOS had lower serum adiponectin levels than women without PCOS, which was not the case for lean women. Conversely, lean women with PCOS had higher serum leptin levels than those without PCOS, which was not the case for overweight/obese women. Conclusions: Adipose tissue might play an important role in the metabolic complications in women with PCOS. To study the impact of obesity biomarkers in women with PCOS, overweight/obese and lean women should be considered separately.
Adiponectin, insulin resistance, leptin, obesity, PCOS
Introduction Polycystic ovary syndrome (PCOS) is the most frequent endocrinopathy in reproductive-aged women, which is mainly characterized by oligo-anovulation and hyperandrogenism (HA). PCOS is associated with an adverse cardio-metabolic profile, which consists of increased total or central adiposity and abnormal glucose metabolism [1]. Obesity is characterized by adipocyte hypertrophy. Adipose tissue participates in the regulation of energy homeostasis as an important endocrine organ that secretes a number of biologically active adipokines [2]. Dysregulated production or the secretion of these adipokines from adipose tissue dysfunction can contribute to obesity-linked complications [3]. Adiponectin and leptin are among the most commonly investigated factors that may impact overweight/obese women. Adiponectin is a recently identified adipocyte-derived collagen-like protein. It is exclusively expressed in adipose tissue, and it is released into the circulation [4]. Adiponectin levels hold *Ming-I Hsu and Shyh-Hsiang Lin contributed equally to this work. Address for correspondence: Ming-I Hsu, Department of Obstetrics and Gynaecology, Wan Fang Hospital, Taipei Medical University, No.111, Sec. 3, Xinglong Rd., Taipei 11696, Taiwan. Tel: +886-2-29307930 ext. 2501. Fax: +886-2-29300036. E-mail: [email protected]
History Received 21 January 2014 Revised 29 October 2014 Accepted 3 November 2014 Published online 25 November 2014
great promise for use in clinical applications as a potent indicator of underlying metabolic complications [5]. Leptin, an adipocytederived hormone encoded by the ‘‘ob’’ gene, relays metabolic signals to the neuronal networks in the brain to modulate the hypothalamo–pituitary–ovarian axis [6]. The leptin- neuropeptide Y axis has been suggested for its implications in reproductive disturbance [7]. Adiponectin and leptin could be useful for identifying metabolic complications in overweight/obese women. Studies on an adipose-related factor in women with PCOS have reported controversial findings. Olszanecka-Glinianowicz suggested that obese but not normal-weight women with PCOS have lower adiponectin levels, whereas the resistin concentrations did not differ in normal-weight and obese PCOS subjects compared with control subjects [8]. Several studies have suggested that adiponectin and leptin contribute to insulin resistance in women with PCOS. Wang suggested that low serum adiponectin and high serum resistin levels might play important roles in the pathogenesis of insulin resistance in PCOS patients [9]. Pehlivanov reported a positive correlation between the serum leptin levels and the clinical and hormonal indices of insulin resistance. Pehlivanov suggested that hyperleptinemia is due to leptin resistance and may be a characteristic of PCOS [10]. Isolated adipocytes from women with PCOS express higher mRNA concentrations of some adipokines involved in cardiovascular
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risk and insulin resistance [11]. All of the above studies provide evidence that adiponectin and leptin play important roles in insulin resistance in women with PCOS. Obesity is associated with increased adipose and plasma leptin levels and lower adiponectin expression [12]. Obesity might affect the pathogenesis of adipose tissue hormones. Studies on an adipose-related factor in women with PCOS have reported controversial findings. Adipose tissue is a key endocrine organ [13], and any correlation between adipokines and insulin resistance in women with PCOS should be considered in lean and overweight/obese women separately. Therefore, we evaluated the adiponectin and leptinin overweight/obese and lean women with and without PCOS.
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Methods This study was approved by the Institutional Review Board of Taipei Medical University – Wan Fang Hospital, Taipei, Taiwan with the identifier Hsu2013-TMU-JIRB201307021 and registered at ClinicalTrials.gov with the identifier NCT01989039. We retrospectively reviewed the medical records of female patients who visited our Reproductive Endocrinology Clinic from 1 January 2009 to 31 December 2012. The study population Study data Women who had a complete set of anthropometric measurements as well as clinical and biochemical data regarding insulin resistance parameters and obesity biomarkers were initially included. The subjects’ medical histories included a detailed menstrual and medical/surgical history, anthropometric measurements (weight, height, waist, and hip), and blood pressure. The dates and assays performed for blood sampling have been described previously [14]. The following data were collected and calculated: (1) the obesity hormone levels: adiponectin, leptin, ghrelin, and resistin; (2) the serum androgen levels, including total testosterone, androstenedione, dehydroepiandrosterone sulfate (DHEA-S), and the free androgen index (FAI), which was calculated as follows: FAI ¼ total testosterone (nmol/ L) 100/sex hormone binding globulin (SHBG) (nmol/L); (3) the insulin sensitivity and glucose tolerance assessments, including fasting insulin and glucose levels, 2-h glucose levels and the homeostasis model assessment insulin resistance index (HOMA); and (4) lipid profiles including total cholesterol, triglyceride, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) levels. Furthermore, the risk of metabolic syndrome (MBS), impaired glucose tolerance and diabetes were evaluated in every subject. The waist-to-hip ratio (WHR) was defined as the waist circumference/hip circumference. The body mass index (BMI) was defined as the body weight in kilograms divided by the body height in meters squared (kg/m2). Overweight/obesity was defined as BMI 5 kg/m2and lean was defined as BMI 525 kg/ m2. An ovarian pelvic ultrasonograph, preferably transvaginal, was performed to detect polycystic ovaries. The adiponectin and leptin levels were measured by RIA (LINCO Research, Inc. St. Charles, Missouri, MO). PCOS was diagnosed according to the Androgen Excess and PCOS Society criteria [15]), which requires HA (hirsutism and/or biochemical) and ovarian dysfunction (oligo-anovulation and/or polycystic ovaries). The definitions of oligo-anovulation and polycystic ovaries have previously been described in detail. HA was defined as hirsutism and/or biochemical hyperandrogenemia (BioHA). Biochemical hyperandrogenemia was defined as a total serum testosterone value 2.78 nmol/L (0.8 ng/mL, the normal range for female adults is 0.1–0.8 ng/mL) and/or FAI 6.53.
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Hirsutism was defined as a modified Ferriman–Gallwey (mF-G) score 6. The insulin sensitivity index was evaluated by the homeostasis model assessment insulin resistance index (HOMA) using the following formula: HOMA ¼
½fasting insulinðmU=mLÞ fasting glucoseðmg=dLÞ 405
The World Health Organization 2006 diagnostic criteria for diabetes were used (fasting plasma glucose [FPG] 7 nmol/L (126 mg/dL) or 2-h plasma glucose 11.1 nmol/L (200 mg/dL)). Impaired glucose tolerance (IGT) was defined as 2-h glucose levels of 7.77–11.1 nmol/L (140–199 mg/dL) in the 75-g oral glucose tolerance test. In women with IGT, the FPG levels should be lower than 7 nmol/L. MBS was defined (2005 National Cholesterol Education Program – Adult Treatment Panel III) as the presence of at least three of the following criteria: abdominal obesity (waist circumference480 cm in women), serum triglyceride levels 1.7 nmol/L (150 mg/dL), serum HDL levels 51.3 nmol/L (50 mg/dL), systolic blood pressure 130 mmHg and/or diastolic blood pressure 85 mmHg, and fasting plasma glucose levels 5.6 nmol/L (100 mg/dL). A total of 543 women were primarily included for evaluation in the study. Of these, 121 cases were excluded due to premature ovarian failure (N ¼ 23) and hyperprolactinemia (N ¼ 98). Finally, 422 cases were analyzed in this study. Statistical analysis Statistical analysis was performed using SPSS 13.0 for Windows (SPSS, Inc., Chicago, IL). We evaluated the correlation between the serum HOMA IR, total testosterone, adiponectin, and leptin using Pearson’s correlation coefficients with the two-tailed method (Table 2). The data are represented as the mean ± standard deviation in Table 1. We used the chi-square and Fisher’s exact tests to compare categorical variables and ANOVA to compare continuous variables in Tables 1 and 3. Differences between the groups were considered significant if the corresponding p value was less than 0.05.
Results Among the 422 studied patients, 224 women had PCOS and 198 women did not. There were 182 overweight/obese women (BMI 425); 121 of these had PCOS and 61 did not. The remaining patients included 240 lean women (BMI 25); 103 of these women had PCOS, and 137 did not. Table 1 presents a separate comparison between overweight/obese and lean PCOS and nonPCOS women. The adiponectin to leptin ratios were significantly lower in women with PCOS than in women without PCOS. Compared to women without PCOS, overweight/obese women with PCOS had lower serum adiponectin levels, which was not the case for lean women. Conversely, lean women with PCOS had higher serum leptin levels than those without PCOS, which was not the case for overweight/obese women. The insulin resistance prevalence was similar between women with and without PCOS. Table 2 demonstrates the correlation between insulin resistance (HOMA), the total testosterone levels, and BMI with various obesity biomarkers. Adiponectin was negatively correlated with HOMA, BMI, and the total testosterone, triglyceride, LDL and leptin levels (all p50.001); conversely, the leptin levels were significantly positively correlated with HOMA; BMI; and the total testosterone, triglyceride, and LDL levels (all p50.001).
Adiponectin & leptin in PCOS
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Table 1. Clinical and biochemical characteristics in overweight/obese and lean women with and without PCOS. Overweight/obese
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Total Case number 422 Age (y/o) 27.5 ± 6.4 Menarche (y/o) 12.6 ± 1.5 Anthropometric measurements Weight (kg) 63.6 ± 15.7 Height (cm) 160.6 ± 5.2 BMI (kg/m2) 24.6 ± 5.8 Waist (cm) 82.9 ± 14.2 Hip (cm) 98.8 ± 10.5 Waist-to-hip ratio 0.84 ± 0.08 Adipose tissue components Adiponectin (ng/mL) 9306 ± 6155 Leptin (ng/mL) 14.35 ± 10.63 Adiponectin/Leptin 1380.1 ± 2058.7 Androgens Total testosterone (nmol/L) 2.13 ± 1.05 Androstenedione (nmol/L) 9.28 ± 4.41 Free Androgen Index 8.26 ± 8.25 DHEAS (nmol/L) 5230 ± 2783 Insulin sensitivity and glucose tolerance Fasting Insulin (pmol/L) 92.90 ± 86.15 Fasting glucose (mmol/L) 5.13 ± 1.00 2-h glucose (mmol/L) 6.34 ± 2.66 3.19 ± 3.22 HOMAa Impaired glucose tolerance 12% Diabetes mellitus 5% Hormonal components LH (mIU/mL) 10.09 ± 10.80 FSH (mIU/mL) 6.38 ± 2.14 LH/FSH 1.65 ± 2.23 Lipid profiles and blood pressure Cholesterol(mmol/L) 4.87 ± 0.90 Triglycerides (mmol/L) 1.07 ± 1.00 HDL (mmol/L) 1.39 ± 0.41 LDL (mmol/L) 2.91 ± 0.80 Metabolism Metabolic syndrome 29% Hypertension 32% HDL 51.3 mmol/L 47% Triglycerides 1.7 mmol/L 13% Waist 480 cm 50% FPG 5.6 mmol/L 15%
Lean
PCOS
Non-PCOS
121 27.0 ± 5.8 12.4 ± 1.4
61 30.1 ± 7.3 12.2 ± 1.2
79.0 ± 10.8 161.1 ± 4.9 30.4 ± 3.6 96.4 ± 9.1 108.5 ± 7.6 0.89 ± 0.07
p Value
PCOS
Non-PCOS
p Value
0.002* 0.182
103 25.1 ± 5.7 12.7 ± 1.5
137 28.5 ± 6.4 13.0 ± 1.6
50.001* 0.185
78.0 ± 12.6 161.1 ± 5.9 30.1 ± 4.6 94.2 ± 13.4 107.7 ± 8.0 0.87 ± 0.09
0.588 0.985 0.608 0.180 0.510 0.171
52.8 ± 5.7 160.1 ± 5.0 20.4 ± 1.7 73.4 ± 6.4 92.0 ± 4.6 0.80 ± 0.05
51.9 ± 6.2 160.2 ± 5.2 20.2 ± 2.1 72.9 ± 7.1 91.3 ± 5.9 0.80 ± 0.08
0.246 0.859 0.301 0.585 0.318 0.790
6117 ± 3166 22.43 ± 11.31 365.5 ± 302.7
7328 ± 4445 20.05 ± 11.70 677.4 ± 1536.0
0.036* 0.188 0.032*
11 267 ± 7698 9.71 ± 5.78 1648.3 ± 1517.1
11 531 ± 6048 8.16 ± 4.89 2387.5 ± 2838.6
0.764 0.026* 0.017*
2.80 ± 1.09 10.78 ± 4.45 15.81 ± 9.88 5447 ± 2656
1.89 ± 0.84 7.66 ± 4.76 8.52 ± 8.11 5377 ± 3079
50.001* 50.001* 50.001* 0.874
2.35 ± 0.95 10.52 ± 4.28 6.91 ± 4.30 5678 ± 2504
1.48 ± 0.68 7.76 ± 3.51 3.02 ± 1.97 4635 ± 2883
50.001* 50.001* 50.001* 0.004*
152.81 ± 116.02 5.38 ± 0.88 7.29 ± 2.60 5.36 ± 4.16 25% 9%
110.69 ± 66.73 5.73 ± 1.93 7.89 ± 4.28 4.22 ± 3.41 17% 15%
0.009* 0.078 0.247 0.067 0.304 0.251
56.64 ± 28.83 4.90 ± 0.62 5.48 ± 1.89 1.81 ± 1.04 4% 1%
59.32 ± 55.13 4.83 ± 0.39 5.47 ± 1.39 1.85 ± 1.72 6% 1%
0.653 0.256 0.940 0.822 0.496 0.840
10.15 ± 8.64 5.96 ± 1.64 1.90 ± 3.22
6.85 ± 6.16 5.59 ± 2.24 1.33 ± 1.04
0.004* 0.192 0.139
13.97 ± 11.86 6.57 ± 1.84 2.09 ± 1.57
8.36 ± 10.73 6.85 ± 2.52 1.29 ± 1.22
0.005* 0.620 0.001*
5.09 ± 0.90 1.61 ± 1.51 1.12 ± 0.27 3.31 ± 0.75
4.99 ± 0.99 1.27 ± 0.69 1.21 ± 0.40 3.20 ± 0.76
0.528 0.094 0.083 0.322
4.90 ± 0.88 0.84 ± 0.66 1.57 ± 0.36 2.80 ± 0.79
4.59 ± 0.79 0.69 ± 0.34 1.58 ± 0.40 2.51 ± 0.65
0.004* 0.030* 0.877 0.002*
64% 56% 83% 29% 98% 28%
52% 59% 66% 18% 87% 28%
0.119 0.719 0.010* 0.112 0.001* 0.974
6% 13% 24% 4% 16% 6%
4% 12% 25% 3% 18% 4%
0.613 0.804 0.923 0.682 0.582 0.427
Data are either mean ± SD or are percentage; *p50.05. The homeostasis model assessment insulin resistance index (HOMA), dehydroepiandrosterone sulfate (DHEA-S), the free androgen index (FAI), highdensity lipoprotein (HDL), low-density lipoprotein (LDL).
a
Table 2. Pearson correlation between insulin resistance, total testosterone, and body mass index with adiponectin and leptin. HOMAa: a
HOMA : BMIa: a
Testosterone : Adiponectin Leptin Insulin Triglycerides HDL LDL
1 0.536* p50.001 0.185* p50.001 0.314* p50.001 0.372* p50.001 0.958* p50.001 0.349* p50.001 0.361* p50.001 0.214* p50.001
BMIa:
Testosteronea:
Adiponectin
Leptin
Insulin
Triglycerides
HDL
LDL
1 0.283* p50.001 0.459* p50.001 0.669* p50.001 0.497* p50.001 0.368* p50.001 0.582* p50.001 0.351* p50.001
1 0.210* p50.001 0.334* p50.001 0.198* p50.001 0.169* p50.001 0.155* p50.001 0.216* p50.001
1 0.290* p50.001 0.290* p50.001 0.315* p50.001 0.525* p50.001 0.223* p50.001
1 0.379* p50.001 0.191* p50.001 0.369* p50.001 0.252* p50.001
1 0.299* p50.001 0.343* p50.001 0.186* p50.001
1 0.366* p50.001 0.248* p50.001
1 0.207* p50.001
1
*p50.05. a The homeostasis model assessment insulin resistance index (HOMA), body mass index (BMI), high-density lipoprotein (HDL), low-density lipoprotein (LDL).
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Table 3. A comparison of adiponectin and leptin among overweight/obese with lean women with or without PCOS. PCOS
Case number BMIa (kg/m2) Adiponectin (ng/mL) Leptin (ng/mL) Adiponectin/leptin HOMAa HOMA-IRa
Non-PCOS
Overweight/obese
Lean
p Value
Overweight/obese
Lean
p Value
121 30.4 ± 3.6 6117 ± 3166 22.43 ± 11.31 365.5 ± 302.7 5.36 ± 4.16 76%
103 20.4 ± 1.7 11 264 ± 7698 9.71 ± 5.78 1648.3 ± 1517.1 1.81 ± 1.04 37%
50.001* 50.001* 50.001* 50.001* 50.001* 50.001*
61 30.1 ± 4.6 7328 ± 4445 20.05 ± 11.70 677.4 ± 1513.5 4.22 ± 3.41 74%
137 20.2 ± 2.1 11 531 ± 6048 8.16 ± 4.89 2387.5 ± 2838.6 1.85 ± 1.72 27%
50.001* 50.001* 50.001* 50.001* 50.001* 50.001*
Data are either mean ± SD or are percentage; *p50.05. Body mass index (BMI), The homeostasis model assessment insulin resistance index (HOMA), HOMA-IR: 42.14.
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a
After adjusting for BMI, the adiponectin levels were negatively correlated with the triglyceride ( ¼ 0.176, p50.001) and HDL ( ¼ 0.358, p50.001) levels. The leptin levels were positively correlated with the total testosterone levels ( ¼ 0.207, p50.001). To separately consider the impact of obesity on women with and without PCOS, Table 3 summarizes the adiponectin and leptin levels in overweight/obese and lean women with or without PCOS. The results demonstrate that the adiponectin and leptin levels, as well as the adiponectin/leptin ratio, were significantly different in the overweight/obese and lean women in the PCOS and non-PCOS groups.
Discussion The status of the cardiovascular system in women with PCOS might contribute to different health factors, including insulin resistance, androgen status and BMI [16]. Excess androgen should be the most important component of PCOS [17]. The total serum testosterone levels could be considered to be indicative of the HA severity. HOMA was also considered to be an indicator of insulin resistance, and BMI was an indicator of obesity. The first part of this study was to evaluate the correlation between the adiponectin, leptin, HOMA, BMI and total testosterone levels. The adiponectin and leptin levels were strongly BMI-dependent. The adiponectin- and leptin-mediated reversal of insulin resistance and lipid profiles was very clear. Adipocytes are considered to be endocrine cells that synthesize and release molecules (adipokines) that play an endocrine/paracrine role. Our results demonstrate that the adiponectin levels were negatively associated with BMI, insulin resistance, and the total testosterone. Conversely, leptin reversed the aforementioned reaction and was negatively correlated with the adiponectin levels. Svendsen suggested that PCOS does not have an independent effect on the adipose tissue expression of leptin, adiponectin, IL-6 or circulating adipocytokine levels [12]. We found that overweight/ obese women with or without PCOS had lower adiponectin and higher leptin levels than lean women. Our study also confirmed the findings in a previous report that the adiponectin/leptin ratio is a marker of PCOS [18]. Furthermore, our results were the first to suggest opposing roles of adiponectin and leptin in overweight/ obese and lean women with PCOS. Compared with normal controls, lean but not overweight/obese women with PCOS presented with significantly higher serum leptin levels. Conversely, overweight/obese, but not lean women, with PCOS presented with lower serum adiponectin levels than normal controls. Our results also demonstrated a negative correlation between the total testosterone and adiponectin levels; therefore, overweight/obese women with PCOS had significantly lower adiponectin levels than overweight/obese controls. Our study also confirmed that the adiponectin levels and insulin resistance are significantly correlated and that low adiponectin levels may be
involved in insulin resistance in PCOS patients, as was previously reported [19]. The fasting insulin levels in obese women with PCOS were significantly higher than those of the obese controls. Obesity-linked adiponectin down-regulation might be a mechanism through which obesity can cause insulin resistance and diabetes [2]; furthermore, PCOS might enhance this condition. The findings in this study also indicate that circulating adiponectin levels could be treated as a biomarker of insulin resistance [5] and that the adipocytokine and metabolic biomarker levels are significantly correlated [19]. Furthermore, we observed a strong positive correlation between the adiponectin and HDL levels, even after adjusting for BMI, which might indicate that adiponectin has a favorable effect on the lipid profile. Adipose tissue might play an important role in the metabolic complications in women with PCOS. However, when studying the impact of obesity biomarkers in women with PCOS, overweight/obese and lean women should be considered separately. The major weakness of this study is that the women evaluated in the present study were recruited from the outpatient clinic of a tertiary care center and do not reflect the true distribution of the general population. Therefore, these results should be applied to the general population with caution. Finally, we conclude the following: Women with PCOS presented with a decreased adiponectin-toleptin ratio. Compared with normal controls, women with PCOS display increased serum leptin levels, which were only observed in lean subjects. Conversely, decreased serum adiponectin levels were observed in overweight/obese but not lean subjects. When studying the impact of obesity biomarkers in women with PCOS, overweight/obese and lean women should be considered separately.
Declaration of interest The authors report that they have no conflicts of interest to disclose. This work was supported by the Taiwan National Science Council Grant NSC102-2629-B-038-001 and Taipei Medical University – Wan Fang Hospital Grant 100-TMU-WFH-02-4.
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