Cardiovascular Disease, Metabolic Syndrome, Polycystic Ovary Syndrome
Conditions
Keywords
PCOS, DM, Hypertension, CVD
Brief summary
Polycystic ovary syndrome (PCOS) is an extremely common disorder in women of reproductive age. Diagnosis of PCOS is principally based on clinical and physical findings. Diagnostic criteria and PCOS definitions used by clinicians and researchers are almost as heterogeneous as the syndrome. Of those diagnosed with PCOS using the 2003 Rotterdam criteria, 61% fulfilled 1990 NIH criteria for unexplained hyperandrogenic chronic anovulation. The patient populations with the new phenotypes had less severe ovulatory dysfunction and less androgen excess than patients diagnosed using the 1990 NIH criteria. These findings might be common across all female populations with PCOS, whether in Oriental or Occidental countries. Data for clinical hyperandrogenism indicated that the prevalence of hirsutism in Taiwanese PCOS women is lower than that for Caucasians/Western women. The extent of metabolic abnormalities in women with PCOS may vary with phenotype, age and ethnicity. Obesity represents a major risk factor for metabolic syndrome and insulin resistance. Approximately 40-50% of all women with PCOS are overweight or obese. Obese subjects with PCOS had a higher risk of developing oligomenorrhea, amenorrhea and biochemical hyperandrogenemia than non-obese women with PCOS. Moreover, obese women with PCOS had significantly more severe insulin resistance, lower serum LH levels, and lower LH-to-FSH ratios than non-obese women with PCOS. PCOS women in Taiwan presented with higher LH-to-FSH ratio and lower insulin resistance than PCOS women in Western Countries. However, the average body mass index (BMI) was significantly lower in Taiwanese PCOS women than Western women, which might partially explain the difference between these two populations in terms of clinical and biochemical presentations. To further document the ethnic variation between women with PCOS in Taiwan and Western, the effect of obesity on the diagnosis and clinical presentations of PCOS-related syndromes should not be neglected in future studies. Therefore, the investigators plan to do this prospective study for evaluation the clinical and biochemical presentation of Taiwanese women with PCOS.
Detailed description
1\. Method 1. This study was approved by the Institutional Review Board of the Wan Fang Medical Center at Taipei Medical University (WF99041, approved August 2010) and performed at the Reproductive Endocrinology Clinic at the Wan Fang Medical Center from 31 August 2010 to 31 August 2011. The following women were excluded: (i) women who had been diagnosed with hyperprolactinemia, hypogonadotropic hypogonadism, premature ovarian failure, congenital adrenal hyperplasia, androgen-secreting tumor,Cushing's syndrome, disorders of the uterus and chromosomal anomalies; (ii) women who were less than three years past menarche or who were older than 45 years; (iii) women who received hormones or medication for major medical diseases (diabetes or cardiovascular disease); and (iv) women who had had ovarian cysts or ovarian tumors identified by ultrasonographic examination. 2. Statistical analysis: We used chi-squared and Fisher's exact tests to perform categorical comparisons and ANOVA to compare the continuous variables. The means of more than two groups were compared using one-way ANOVA and post hoc Dunnett's t-test with equal variances not assumed.
Interventions
None listed
Sponsors
Taipei Medical University WanFang Hospital
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Age
15 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* women at reproductive age * women with PCOS and women without PCOS.
Exclusion criteria
* young women who had their menarche less than 3 years * women older than 45 years old, Amenorrhea of menopause, hyperglycemia, hyperthyroidism, hypothyroidism, heart failure, lung failure, renal failure, anemia, dystrophy, gonitis.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Fasting Insulin | 1 year | A fasting serum insulin level of greater than the upper limit of normal for the assay used (approximately 60 pmol/L) is considered evidence of insulin resistance. |
| Total Testosterone | 1 year | Using serum total testosterone to represent the severity of hyperandrogenism. |
| BMI | 1 year | BMI categorization was based on the WHO Asia-Pacific classification for obesity, which was defined as BMI ≧ 25 kg/m2(WHO: Obesity: preventing and managing the global epidemic. Geneva: WHO; 2000). |
| Fasting Glucose | 1 year | Fasting blood sugar (FBS) measures blood glucose after you have not eaten for at least 8 hours. It is often the first test done to check for prediabetes and diabetes. World Health Organization 2006 diagnostic criteria for diabetes were employed (fasting plasma glucose ≥7.0 mmol/L or two hour plasma glucose ≥11.1 mmol/L). |
| Two Hour Glucose | 1 year | 2-hour postprandial blood sugar measures blood glucose exactly 2 hours after you start eating a meal. This is not a test used to diagnose diabetes. World Health Organization 2006 diagnostic criteria for diabetes were employed (fasting plasma glucose ≥7.0 mmol/L or two hour plasma glucose ≥11.1 mmol/L). |
| Homeostasis Model Assessment Insulin Resistance Index (HOMA-IR) | 1 year | HOMA-IR = \[fasting insulin (in μIU/mL) × fasting glucose (in mg/dL)\]/405. |
| Cholesterol | 1 year | Hypercholesterolemia was defined as \>6 mmol / L. |
| Triglycerides | 1 year | Abnormal serum triglycerides defined as ≥ 1.7 mmol/L |
| HDL | 1 year | Metabolic syndrome 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 circumference \>80 cm in women); serumtriglycerides≥1.7 mmol/L; serumHDL\<1.3 mmol/L; systolic blood pressure ≥130 mmHg and/or diastolic blood pressure ≥85 mmHg; and fasting plasma glucose ≥7.0 mmol/L. |
| LDL | 1 year | Lipid profiles, including total cholesterol, triglycerides, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and sex hormone binding globulin (SHBG). Abnormal LDL was ≧4.14mmol/L. |
| Impaired Glucose Tolerance | 1 years | Impaired glucose tolerance was defined as two hour glucose levels of 7.8-11.1 mmol/L in the 75 g oral glucose tolerance test. In women with impaired glucose tolerance, the fasting plasma glucose level should be \<7 mmol/L. |
Countries
Taiwan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Control The normal women | 70 |
| PCOS Women who met the 2003 Rotterdam criteria, which require a minimum of two of the following three criteria:
1. Oligo- or anovulation
2. Clinical and/or biochemical signs of hyperandrogenism
3. Polycystic ovaries and exclusion of other etiologies (congenital adrenal hyperplasia, androgen-secreting tumors, Cushing's syndrome) | 220 |
| Total | 290 |
Baseline characteristics
| Characteristic | Control | PCOS | Total |
|---|---|---|---|
| Age, Continuous | 28.3 years old STANDARD_DEVIATION 4.4 | 26.9 years old STANDARD_DEVIATION 5.8 | 27.68 years old STANDARD_DEVIATION 7.1 |
| Region of Enrollment Taiwan | 70 participants | 220 participants | 290 participants |
| Sex: Female, Male Female | 70 Participants | 220 Participants | 290 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 70 | 0 / 220 |
| serious Total, serious adverse events | 0 / 70 | 0 / 220 |
Outcome results
Primary
BMI
BMI categorization was based on the WHO Asia-Pacific classification for obesity, which was defined as BMI ≧ 25 kg/m2(WHO: Obesity: preventing and managing the global epidemic. Geneva: WHO; 2000).
Time frame: 1 year
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control | BMI | 23.4 kg/m2 | Standard Deviation 5.2 |
| PCOS | BMI | 25.9 kg/m2 | Standard Deviation 6.1 |
p-value: <0.05ANOVA
Primary
Cholesterol
Hypercholesterolemia was defined as \>6 mmol / L.
Time frame: 1 year
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control | Cholesterol | 4.5 mmol/L | Standard Deviation 0.8 |
| PCOS | Cholesterol | 4.9 mmol/L | Standard Deviation 0.9 |
p-value: <0.05ANOVA
Primary
Fasting Glucose
Fasting blood sugar (FBS) measures blood glucose after you have not eaten for at least 8 hours. It is often the first test done to check for prediabetes and diabetes. World Health Organization 2006 diagnostic criteria for diabetes were employed (fasting plasma glucose ≥7.0 mmol/L or two hour plasma glucose ≥11.1 mmol/L).
Time frame: 1 year
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control | Fasting Glucose | 5.0 mmol/L | Standard Deviation 1 |
| PCOS | Fasting Glucose | 5.1 mmol/L | Standard Deviation 0.8 |
Primary
Fasting Insulin
A fasting serum insulin level of greater than the upper limit of normal for the assay used (approximately 60 pmol/L) is considered evidence of insulin resistance.
Time frame: 1 year
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control | Fasting Insulin | 8.3 μIU/ml | Standard Deviation 5.7 |
| PCOS | Fasting Insulin | 13.5 μIU/ml | Standard Deviation 14.5 |
p-value: <0.05ANOVA
Primary
HDL
Metabolic syndrome 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 circumference \>80 cm in women); serumtriglycerides≥1.7 mmol/L; serumHDL\<1.3 mmol/L; systolic blood pressure ≥130 mmHg and/or diastolic blood pressure ≥85 mmHg; and fasting plasma glucose ≥7.0 mmol/L.
Time frame: 1 year
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control | HDL | 1.4 mmol/L | Standard Deviation 0.5 |
| PCOS | HDL | 1.3 mmol/L | Standard Deviation 0.4 |
Primary
Homeostasis Model Assessment Insulin Resistance Index (HOMA-IR)
HOMA-IR = \[fasting insulin (in μIU/mL) × fasting glucose (in mg/dL)\]/405.
Time frame: 1 year
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control | Homeostasis Model Assessment Insulin Resistance Index (HOMA-IR) | 1.9 unitless | Standard Deviation 1.3 |
| PCOS | Homeostasis Model Assessment Insulin Resistance Index (HOMA-IR) | 3.2 unitless | Standard Deviation 3.7 |
p-value: <0.05ANOVA
Primary
Impaired Glucose Tolerance
Impaired glucose tolerance was defined as two hour glucose levels of 7.8-11.1 mmol/L in the 75 g oral glucose tolerance test. In women with impaired glucose tolerance, the fasting plasma glucose level should be \<7 mmol/L.
Time frame: 1 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Control | Impaired Glucose Tolerance | 43 percentage of participants |
| PCOS | Impaired Glucose Tolerance | 25 percentage of participants |
| Non-obese With PCOS | Impaired Glucose Tolerance | 10 percentage of participants |
| Nonb-obese With Control | Impaired Glucose Tolerance | 0 percentage of participants |
p-value: <0.05ANOVA
Primary
LDL
Lipid profiles, including total cholesterol, triglycerides, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and sex hormone binding globulin (SHBG). Abnormal LDL was ≧4.14mmol/L.
Time frame: 1 year
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control | LDL | 2.6 mmol/L | Standard Deviation 0.6 |
| PCOS | LDL | 3.0 mmol/L | Standard Deviation 0.8 |
p-value: <0.05ANOVA
Primary
Total Testosterone
Using serum total testosterone to represent the severity of hyperandrogenism.
Time frame: 1 year
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control | Total Testosterone | 1.5 nmol/L | Standard Deviation 0.6 |
| PCOS | Total Testosterone | 2.9 nmol/L | Standard Deviation 1.2 |
p-value: <0.05ANOVA
Primary
Triglycerides
Abnormal serum triglycerides defined as ≥ 1.7 mmol/L
Time frame: 1 year
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control | Triglycerides | 0.8 mmol/L | Standard Deviation 0.5 |
| PCOS | Triglycerides | 1.1 mmol/L | Standard Deviation 0.9 |
p-value: <0.05ANOVA
Primary
Two Hour Glucose
2-hour postprandial blood sugar measures blood glucose exactly 2 hours after you start eating a meal. This is not a test used to diagnose diabetes. World Health Organization 2006 diagnostic criteria for diabetes were employed (fasting plasma glucose ≥7.0 mmol/L or two hour plasma glucose ≥11.1 mmol/L).
Time frame: 1 year
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control | Two Hour Glucose | 5.4 mmol/L | Standard Deviation 1.1 |
| PCOS | Two Hour Glucose | 6.4 mmol/L | Standard Deviation 2.5 |
p-value: <0.05ANOVA