Original article http://dx.doi.org/10.6065/apem.2015.20.3.136 Ann Pediatr Endocrinol Metab 2015;20:136-142
Metabolic effects of polycystic ovary syndrome in adolescents Yejin Han, MD1, Hae Soon Kim, MD, PhD1, Hye-Jin Lee, MD, PhD2, Jee-Young Oh, MD, PhD2, Yeon-Ah Sung, MD, PhD2 Departments of 1Pediatrics and 2 Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea
Purpose: Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenic anovulation in women of reproductive age. We investigated the metabolic effects of lean and overweight adolescents with PCOS. Methods: Anthropometric measurements and biochemical parameters were evaluated in 49 adolescents with PCOS and 40 age- and body mass index (BMI)matched controls. We further divided both PCOS and control groups into those having BMI within the normal range of less than 85th percentile and those being overweight and obese with a BMI greater than 85th percentile. Results: Hemoglobin, gamma-glutamyl transferase (r-GT), total cholesterol, lowdensity lipoprotein-cholesterol and 2-hour postglucose load plasma insulin levels were significantly elevated in the lean PCOS group than in the lean control group. In the overweight/obese PCOS group, hemoglobin and r-GT levels were significantly elevated than in the overweight/obese control group. In the normal weight group, none of the subjects had metabolic syndrome according to the Adult Treatment Panel III criteria, but the incidence of metabolic syndrome in the overweight/obese PCOS group was 8.3% and that in the overweight/obese control group was 6.7%. Conclusion: PCOS in adolescents causes metabolic abnormalities, underscoring the importance of early diagnosis of PCOS in oligomenorrheic adolescents. Keywords: Polycystic ovary syndrome, Metabolic syndrome, Insulin resistance
Introduction
Received: 7 July, 2015 Revised: 19 August, 2015 Accepted: 21 September, 2015 Address for correspondence: Hae Soon Kim, MD, PhD Department of Pediatrics, Ewha Womans University Mokdong Hospital, Ewha Womans University School of Medicine, 1071 Anyangcheon-ro, Yangcheon-gu, Seoul 07985, Korea Tel: +82-2-2650-5569 Fax: +82-2-2653-3718 E-mail: [email protected]
Polycystic ovarian syndrome (PCOS) is one of the common endocrine disorders amongst women of reproductive age, with a prevalence of 5%–10%1). The prevalence of PCOS in college students from Seoul, Korea was 4.9%2). PCOS is diagnosed in women in whom 2 years have passed since menarche and if she meets the criteria of the 1990 National Institute of Child Health and Human Development (NICHD) conference guideline for hyperandrogenemia with oligo-ovulation (less than 9 menstrual cycles per year) and exclusion of other known disorders such as congenital adrenal hyperplasia or Cushing's syndrome3). The 2003 Rotterdam European Society for Human Reproduction and Embryology diagnostic criteria of PCOS consist of the occurrence of two of the following three features: (1) chronic anovulation, (2) clinical or biochemical signs of hyperandrogenism, and (3) ultrasound results indicating polycystic ovaries4). Insulin resistance, elevated luteinizing hormone-follicle-stimulating hormone ratio, abdomi nal obesity, and infertility are also common in women diagnosed with PCOS. Insulin resistance plays a key role in the occurrence of metabolic syndrome, and hyperandrogenemia is an important risk factor for metabolic syndrome in PCOS patients5). Glueck et al.6) reported that 46% of the women with PCOS had metabolic syndrome. PCOS shares many clinical features with metabolic syndrome, including insulin resistance, obesity, type 2 diabetes mellitus (DM), hyperlipidemia, and hypertension. Among these characteristics, obesity is one of the most
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http:// creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
©2015 Annals of Pediatric Endocrinology & Metabolism
ISSN: 2287-1012(Print) ISSN: 2287-1292(Online)
Han Y, et al. • Clinical and metabolic characteristics in adolescents with PCOS
common features in women with PCOS. Approximately 50% of women with PCOS are overweight or obese7). Obesity is thought to be an independent risk factor of impaired glucose tolerance or type 2 DM8). However, Manco et al.9) reported that women with PCOS had high levels of insulin resistance in both normal and overweight/obese PCOS patients. There are few studies on the metabolic abnormalities in adolescents with PCOS. The aim of our study was to investigate metabolic abnor malities among adolescents with PCOS.
Materials and methods The volunteers included healthy adolescents, who were high school students, having irregular menstruation and were recruited via a survey between December 2008 and October 2010. This study was performed at the Endocrinology and Gynecology Clinics at Ewha Womans University Hospital in Seoul, Korea. A trained nurse contacted eligible candidates by telephone to determine whether they were both capable and willing to participate in the study. After excluding those who did not meet the eligibility criteria, we invited volunteers to visit our hospital in the morning of the third day of their menstrual period following an overnight fast for at least 8 hours. We conducted physical examinations of 49 PCOS students and 40 control students between the ages of 16 and 18 years. Students were diagnosed with PCOS if it had been 2 years since their menarche and if they met the criteria of the 1990 NICHD conference guideline, i.e., hyperandrogenemia with oligo-ovulation (less than 9 menstrual cycles per year), and exclusion of other known disorders, such as congenital adrenal hyperplasia or Cushing's syndrome. Women with abnormal thyroid-stimulating hormone (5.0 mIU/ L) or prolactin levels (>25 μg/L) were excluded. Biochemical hyperandrogenemia is defined as a total testosterone level above the 95th percentile (total testosterone≥67 ng/dL) based on the testosterone levels in 1,120 healthy women with regular menstrual cycles10). Clinical hyperandrogenism is defined as hirsutism with a modified Ferriman-Gallwey (mFG) score11). After overnight fasting at least for 8 hours, fasting blood test, hormonal profiling and ovarian ultrasonography were performed in the early follicular phase. Testosterone levels were measured by a chemiluminescent immunoassay using a commercial kit (Siemens, New York, NY, USA). Fasting plasma glucose (FPG) level was analyzed using the glucose oxidase method (Beckman Instruments, Fullerton, CA, USA), and 2-hour postglucose load plasma glucose (2h-PG) levels were obtained using a standard 75-g oral glucose tolerance test. Fasting plasma insulin (FPI) and 2-hour postglucose load plasma insulin (2h-PI) concentrations were measured by radioimmunoassay using a commercial kit (Diagnostic Products Corp., Los Angeles, CA, USA). Anthropometric measurements and body composition analyses were performed, and both systolic and diastolic blood pressures were measured twice using a sphygmomanometry, following a 10-minute rest, and mean values were recorded.
The control group consisted of students who had normal menstrual cycles as well as similar body mass indexes (BMIs) and age as the PCOS group. Then, we further divided the two groups into those having within normal BMI of less than 85th percentile for sex and age and those being overweight and obese with a BMI greater than 85th percentile for sex and age. The diagnosis of metabolic syndrome was made when more than 3 of the following risk factors were present: waist circumference, >80 cm; systolic blood pressure, 130 mmHg; or diastolic blood pressure, 85 mmHg; and levels of fasting glucose, 110 mg/dL; fasting triglycerides, 150 mg/dL; and high-density lipoprotein (HDL)-cholesterol,
Metabolic effects of polycystic ovary syndrome in adolescents Yejin Han, MD1, Hae Soon Kim, MD, PhD1, Hye-Jin Lee, MD, PhD2, Jee-Young Oh, MD, PhD2, Yeon-Ah Sung, MD, PhD2 Departments of 1Pediatrics and 2 Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea
Purpose: Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenic anovulation in women of reproductive age. We investigated the metabolic effects of lean and overweight adolescents with PCOS. Methods: Anthropometric measurements and biochemical parameters were evaluated in 49 adolescents with PCOS and 40 age- and body mass index (BMI)matched controls. We further divided both PCOS and control groups into those having BMI within the normal range of less than 85th percentile and those being overweight and obese with a BMI greater than 85th percentile. Results: Hemoglobin, gamma-glutamyl transferase (r-GT), total cholesterol, lowdensity lipoprotein-cholesterol and 2-hour postglucose load plasma insulin levels were significantly elevated in the lean PCOS group than in the lean control group. In the overweight/obese PCOS group, hemoglobin and r-GT levels were significantly elevated than in the overweight/obese control group. In the normal weight group, none of the subjects had metabolic syndrome according to the Adult Treatment Panel III criteria, but the incidence of metabolic syndrome in the overweight/obese PCOS group was 8.3% and that in the overweight/obese control group was 6.7%. Conclusion: PCOS in adolescents causes metabolic abnormalities, underscoring the importance of early diagnosis of PCOS in oligomenorrheic adolescents. Keywords: Polycystic ovary syndrome, Metabolic syndrome, Insulin resistance
Introduction
Received: 7 July, 2015 Revised: 19 August, 2015 Accepted: 21 September, 2015 Address for correspondence: Hae Soon Kim, MD, PhD Department of Pediatrics, Ewha Womans University Mokdong Hospital, Ewha Womans University School of Medicine, 1071 Anyangcheon-ro, Yangcheon-gu, Seoul 07985, Korea Tel: +82-2-2650-5569 Fax: +82-2-2653-3718 E-mail: [email protected]
Polycystic ovarian syndrome (PCOS) is one of the common endocrine disorders amongst women of reproductive age, with a prevalence of 5%–10%1). The prevalence of PCOS in college students from Seoul, Korea was 4.9%2). PCOS is diagnosed in women in whom 2 years have passed since menarche and if she meets the criteria of the 1990 National Institute of Child Health and Human Development (NICHD) conference guideline for hyperandrogenemia with oligo-ovulation (less than 9 menstrual cycles per year) and exclusion of other known disorders such as congenital adrenal hyperplasia or Cushing's syndrome3). The 2003 Rotterdam European Society for Human Reproduction and Embryology diagnostic criteria of PCOS consist of the occurrence of two of the following three features: (1) chronic anovulation, (2) clinical or biochemical signs of hyperandrogenism, and (3) ultrasound results indicating polycystic ovaries4). Insulin resistance, elevated luteinizing hormone-follicle-stimulating hormone ratio, abdomi nal obesity, and infertility are also common in women diagnosed with PCOS. Insulin resistance plays a key role in the occurrence of metabolic syndrome, and hyperandrogenemia is an important risk factor for metabolic syndrome in PCOS patients5). Glueck et al.6) reported that 46% of the women with PCOS had metabolic syndrome. PCOS shares many clinical features with metabolic syndrome, including insulin resistance, obesity, type 2 diabetes mellitus (DM), hyperlipidemia, and hypertension. Among these characteristics, obesity is one of the most
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http:// creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
©2015 Annals of Pediatric Endocrinology & Metabolism
ISSN: 2287-1012(Print) ISSN: 2287-1292(Online)
Han Y, et al. • Clinical and metabolic characteristics in adolescents with PCOS
common features in women with PCOS. Approximately 50% of women with PCOS are overweight or obese7). Obesity is thought to be an independent risk factor of impaired glucose tolerance or type 2 DM8). However, Manco et al.9) reported that women with PCOS had high levels of insulin resistance in both normal and overweight/obese PCOS patients. There are few studies on the metabolic abnormalities in adolescents with PCOS. The aim of our study was to investigate metabolic abnor malities among adolescents with PCOS.
Materials and methods The volunteers included healthy adolescents, who were high school students, having irregular menstruation and were recruited via a survey between December 2008 and October 2010. This study was performed at the Endocrinology and Gynecology Clinics at Ewha Womans University Hospital in Seoul, Korea. A trained nurse contacted eligible candidates by telephone to determine whether they were both capable and willing to participate in the study. After excluding those who did not meet the eligibility criteria, we invited volunteers to visit our hospital in the morning of the third day of their menstrual period following an overnight fast for at least 8 hours. We conducted physical examinations of 49 PCOS students and 40 control students between the ages of 16 and 18 years. Students were diagnosed with PCOS if it had been 2 years since their menarche and if they met the criteria of the 1990 NICHD conference guideline, i.e., hyperandrogenemia with oligo-ovulation (less than 9 menstrual cycles per year), and exclusion of other known disorders, such as congenital adrenal hyperplasia or Cushing's syndrome. Women with abnormal thyroid-stimulating hormone (5.0 mIU/ L) or prolactin levels (>25 μg/L) were excluded. Biochemical hyperandrogenemia is defined as a total testosterone level above the 95th percentile (total testosterone≥67 ng/dL) based on the testosterone levels in 1,120 healthy women with regular menstrual cycles10). Clinical hyperandrogenism is defined as hirsutism with a modified Ferriman-Gallwey (mFG) score11). After overnight fasting at least for 8 hours, fasting blood test, hormonal profiling and ovarian ultrasonography were performed in the early follicular phase. Testosterone levels were measured by a chemiluminescent immunoassay using a commercial kit (Siemens, New York, NY, USA). Fasting plasma glucose (FPG) level was analyzed using the glucose oxidase method (Beckman Instruments, Fullerton, CA, USA), and 2-hour postglucose load plasma glucose (2h-PG) levels were obtained using a standard 75-g oral glucose tolerance test. Fasting plasma insulin (FPI) and 2-hour postglucose load plasma insulin (2h-PI) concentrations were measured by radioimmunoassay using a commercial kit (Diagnostic Products Corp., Los Angeles, CA, USA). Anthropometric measurements and body composition analyses were performed, and both systolic and diastolic blood pressures were measured twice using a sphygmomanometry, following a 10-minute rest, and mean values were recorded.
The control group consisted of students who had normal menstrual cycles as well as similar body mass indexes (BMIs) and age as the PCOS group. Then, we further divided the two groups into those having within normal BMI of less than 85th percentile for sex and age and those being overweight and obese with a BMI greater than 85th percentile for sex and age. The diagnosis of metabolic syndrome was made when more than 3 of the following risk factors were present: waist circumference, >80 cm; systolic blood pressure, 130 mmHg; or diastolic blood pressure, 85 mmHg; and levels of fasting glucose, 110 mg/dL; fasting triglycerides, 150 mg/dL; and high-density lipoprotein (HDL)-cholesterol,
