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Journal of Clinical Endocrinology & Metabolism , doi:10.1210/jc.2007-1756
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The Journal of Clinical Endocrinology & Metabolism Vol. 93, No. 2 470-476
Copyright © 2008 by The Endocrine Society

A More Atherogenic Serum Lipoprotein Profile Is Present in Women with Polycystic Ovary Syndrome: A Case-Control Study

Olivier Valkenburg, Regine P. M. Steegers-Theunissen, Huberdina P. M. Smedts, Geesje M. Dallinga-Thie, Bart C. J. M. Fauser, Egbertine H. Westerveld and Joop S. E. Laven

Department of Gynecology, Divisions of Reproductive Medicine (O.V., J.S.E.L.) and Obstetrics and Prenatal Medicine (R.P.M.S-T., H.P.M.S.), and Departments of Epidemiology and Biostatistics (R.P.M.S.-T.), Clinical Genetics (R.P.M.S.-T.), and Pediatrics/Division of Pediatric Cardiology (R.P.M.S.-T.), Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands; Laboratory of Experimental Vascular Medicine (G.M.D.-T.), Academic Medical Center, 1100 DD Amsterdam, The Netherlands; and Departments of Reproductive Medicine (B.C.J.M.F.) and Internal Medicine (E.H.W.), University Medical Center, 85500 3508 GA Utrecht, The Netherlands

Address all correspondence and requests for reprints to: O. Valkenburg, M.D., Division of Reproductive Medicine, Department of Gynecology and Obstetrics, Room HS 508, Erasmus Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. E-mail: o.valkenburg{at}erasmusmc.nl.


   Abstract
Top
 Abstract
Introduction
 Subjects and Methods
 Results
 Discussion
 References
 
Context: Polycystic ovary syndrome (PCOS) is associated with a higher frequency of cardiovascular risk factors. Apolipoprotein (apo) A-I and apoB are potent markers for cardiovascular risk. Data on apo levels in women with PCOS are scarce and contradictory.

Objective: Our objective was to identify changes in lipid metabolism in women with PCOS, and the relative impact of obesity, insulin resistance, and hyperandrogenism on lipid parameters.

Design: This was a case-control study.

Setting: The study was performed at a single referral center.

Subjects: PCOS was diagnosed according to the 2003 Rotterdam criteria. Healthy mothers with regular menstrual cycles served as controls.

Main Outcome Parameters: Fasting insulin, triglycerides (TGs), cholesterol, high-density lipoprotein (HDL)-cholesterol, apoA-I, and apoB were determined. Low-density lipoprotein (LDL)-cholesterol was calculated using the Friedewald formula.

Results: We included 557 women with PCOS and 295 controls. After correction for age and body mass index, PCOS women had higher median levels of insulin (10.1 vs. 6.9 mU/liter), TGs (95 vs. 81 mg/dl), cholesterol (196 vs. 178 mg/dl), and LDL-cholesterol (125 vs. 106 mg/dl) in combination with lower levels of HDL-cholesterol (46 vs. 55 mg/dl) and apoA-I (118 vs. 146 mg/dl) compared with controls (all P values ≤ 0.01). apoB levels were similar in cases and controls. Free androgen index, body mass index, SHBG, and estradiol were independent predictors of apoA-I levels in women with PCOS.

Conclusions: PCOS is associated with a more pronounced atherogenic lipid profile. Furthermore, obesity and hyperandrogenism contribute to an adverse lipid profile. Finally, PCOS seems to constitute an additional risk factor for an atherogenic lipid profile.


   Introduction
Top
 Abstract
 Introduction
Subjects and Methods
 Results
 Discussion
 References
 
Polycystic ovary syndrome (PCOS) is a syndrome of ovarian dysfunction that is characterized by anovulation, hyperandrogenism, and/or the presence of polycystic ovary (PCO) morphology (1). Obesity and insulin resistance occur frequently in association with this syndrome. Cardiovascular risk factors seem to cluster in women with PCOS compared with the general population (2). A wide variety of risk factors have been studied in association with PCOS, including obesity, insulin resistance, dyslipidemia, endothelial dysfunction, and the presence of the metabolic syndrome (3, 4, 5, 6). In view of the high frequency of cardiovascular risk factors in women with PCOS, it is rather surprising that excess coronary heart disease was not found in a retrospective cohort study of women with PCOS (7). However, data on prospective long-term follow-up are not yet available. It has been speculated that women with PCOS may be exposed to a protective factor, such as prolonged exposure to estrogens.

Most studies of dyslipidemia and PCOS have reported on cholesterol levels and triglycerides (TGs). The lipid profile that is found in women with PCOS consists of elevated TG levels, together with low levels of high-density lipoprotein-cholesterol (HDL-C) (8). These changes are consistent with the lipid profile that is typically found in association with insulin resistance. The effects of insulin resistance on lipid metabolism are well known. Increased secretion of very low-density lipoprotein (VLDL) particles by the liver results in elevated plasma TG concentrations. Subsequently, TGs are exchanged for cholesteryl ester (CE) by the activity of CE transfer protein. This process results in TG-enriched high-density lipoprotein (HDL) particles that are catabolized more rapidly, and CE-enriched VLDL particles that are converted into small dense low-density lipoprotein (LDL) particles (9). As a consequence, insulin resistance contributes to decreased plasma levels of HDL-C and apolipoprotein (apo) A-I, and higher levels of apoB (10, 11, 12).

In addition to insulin resistance, lipid metabolism in women with PCOS may also be affected by ovarian and/or adrenal secretion of sex steroids. The effects of sex steroids on lipid metabolism are complex and involve the actions of both androgens and estrogens. Hyperandrogenism has been associated with increased hepatic lipase (HL) activity. This enzyme, which has a role in the catabolism of HDL particles, exhibits strong sexual dimorphism, with exogenous androgens up-regulating and estrogens down-regulating its activity (13, 14). A study of 17 female-to-male transsexuals who were exposed to treatment with exogenous testosterone (T) showed a significant increase in HL activity in association with decreased plasma HDL-C levels (15). Endogenous estrogens may affect LDL metabolism through up-regulation of the LDL receptor, resulting in enhanced hepatic clearance of LDL particles from plasma (16, 17).

Apolipoprotein B and apoA-I are the main structural proteins of atherogenic lipoproteins and HDL particles, respectively. Population-based longitudinal follow-up studies have indicated that apoA-I and apoB levels are potent markers for cardiovascular risk (18, 19, 20, 21). apoB levels reflect the entire spectrum of pro-atherogenic particles, whereas apoA-I contributes to the antiatherogenic properties of HDL particles. At present, only a limited number of studies have investigated apolipoprotein levels in women with PCOS. Typically, these studies are limited by small sample sizes (3, 22, 23, 24). Macut et al. (25) reported similar apoB and apoA-I levels in women with PCOS and controls. However, the control group was limited to 56 women. Reports with regard to apoA-I levels show either unchanged (3, 22, 25) or lower (23, 24, 26) levels in women with PCOS. Therefore, data on plasma apoA-I and apoB levels in women with PCOS remain inconclusive.

It is expected that women with PCOS have a more atherogenic lipid profile than healthy controls. To test this hypothesis, we performed a case-control study in a large cohort of women who were uniformly phenotyped according to the 2003 Rotterdam criteria (1). Plasma lipids, apoA-I and apoB levels were measured in all PCOS cases and controls. Furthermore, this study aims to assess the relative impact of obesity, insulin resistance, and hyperandrogenism on the lipid profile of women with PCOS.


   Subjects and Methods
Top
 Abstract
 Introduction
 Subjects and Methods
Results
 Discussion
 References
 
Subjects

Patients attended our fertility clinic between 1996 and 2005, with oligomenorrhea (interval between menstrual periods ≥ 35 d) or amenorrhea (absence of vaginal bleeding for at least 6 months) and serum FSH concentrations within normal limits (1–10 IU/liter), i.e. normogonadotropic anovulation (classification according to the World Health Organization) (27). The diagnosis of PCOS was established on the basis of the 2003 revised Rotterdam criteria (1). In agreement with the Rotterdam criteria, hyperandrogenism was defined as having either biochemical or clinical signs of androgen excess. For the purpose of this study, clinical hyperandrogenism was assessed by the Ferriman-Gallwey score and was defined as a Ferriman-Gallwey score of more than or equal to 8. Biochemical hyperandrogenism was determined by calculation of the free androgen index (FAI) as: 100 x T (nmol/liter)/SHBG (nmol/liter); to convert into Systeme International units, multiply T (ng/dl) and SHBG (µg/dl) by 0.0347 and 34.72, respectively. A cutoff level of 4.5 was used for the definition of hyperandrogenism (27). The presence of polycystic ovaries (PCOs) was detected by vaginal ultrasound examination. PCO was defined as the presence of 12 follicles or more in one or both ovaries, and/or increased ovarian volume (>10 ml). Exclusion criteria were diabetes mellitus with a fasting glucose level of 126 mg/dl or higher, nonfasting state at investigation, and the presence of related disorders with similar clinical presentation, such as congenital adrenal hyperplasia and Cushing’s syndrome.

Controls were recruited at child health centers in the same geographic area as the study population. The control group consisted of fertile mothers of healthy children who visited the hospital at a standardized study moment of around 17 months after pregnancy. Controls have been described previously (28, 29). Exclusion criteria for controls were irregular menstrual cycle at investigation, breastfeeding, diabetes mellitus, and nonfasting state. Information on general health and cycle history was gathered by questionnaire. This study was approved by the Central Committee on Research Involving Human Subjects (the Hague, The Netherlands) and the institutional review board at the Erasmus Medical Center. Informed consent was obtained from all participants.

Clinical and endocrine examination

Anovulatory patients underwent a standardized initial examination that was performed after an overnight fast on a random day between 0900 and 1100 h. Clinical examination included menstrual history and anthropometric measurements (height and weight). Transvaginal ultrasonography was performed to assess ovarian volume and follicle count for both ovaries. Blood samples were obtained by venipuncture and processed within 2 h. Serum was isolated after centrifugation at 3000 rpm for 10 min at 20 C and stored at –20 C until assayed. Endocrine evaluation included serum levels of gonadotropic hormones (LH, FSH) and estradiol (E2), androgens [T, androstenedione (AD), dehydroepiandrosterone (DHEA), and dehydroepiandrosterone sulfate (DHEAS)], progesterone and 17-hydroxyprogesterone (17-OH-Pg), SHBG, fasting glucose and insulin, TSH, and prolactin. Hormone assays have been described in detail elsewhere (30). LH, FSH, TSH, prolactin, and insulin were measured by immunoradiometric assay. T, AD, E2, SHBG, progesterone, 17-OH-Pg, DHEA, and DHEAS were determined by RIAs. Intraassay and interassay coefficients of variation were less than 5% and less than 15% for LH, less than 3% and less than 8% for FSH, less than 3% and less than 5% for T, less than 8% and less than 11% for AD, less than 5% and less than 7% for E2, and less than 4% and less than 5% for SHBG, respectively. Controls underwent a standardized clinical examination that included maternal height and weight. Data on general health, cycle history, and the presence of diabetes were collected by questionnaire.

Lipid assays

Venous blood samples were drawn at examination and stored at –80 C after centrifugation at 3000 rpm for 10 min at 20 C. Lipid assays were performed in both cases and controls. Total cholesterol and TGs were analyzed using commercially available assays (Wako Diagnostics, Osaka, Japan). HDL-C was analyzed using the direct HDL assay from Wako Diagnostics. Serum apoA-I and apoB were analyzed with a commercially available immunoturbidimetric assay (Wako Diagnostics). All assays were analyzed on a Cobas Mira autoanalyzer (Roche Diagnostics, Indianapolis, IN). LDL-C was calculated with the Friedewald formula: LDL-C = cholesterol – HDL-C – (TG/5).

Statistical analysis

Distributions of the characteristics in the study groups are presented as the mean and SD when distributed normally or as the median and interquartile range (P25-P75) when not normally distributed. A nonparametric test (Mann-Whitney U) was used for exploratory comparison of continuous variables between groups. Variables were checked for normal distributions with the one-sample Kolmogorov-Smirnov test and log transformed when not distributed normally. Analysis of covariance (ANCOVA) was applied to adjust for differences in age and body mass index (BMI). Between-group differences of categorical variables were evaluated by Pearson’s {chi}2 test. Statistical significance for all analyses was defined as a two-tailed P value of less than or equal to 0.05. Multiple linear regression analysis was used to identify the best predictors of apo levels in women with PCOS. To assess the univariable relation between the initial screening variables and apolipoproteins, Spearman’s correlation coefficients were computed. Initial screening variables that were significant in univariate analysis were entered into the multiple regression models in a forward stepwise fashion. Data analysis was performed using SPSS, version 12.0 (SPSS, Inc., Chicago, IL).


   Results
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
Discussion
 References
 
Baseline characteristics of women with PCOS and controls

The case group consisted of 638 women who were diagnosed with normogonadotropic anovulation. Eight women were excluded for having diabetes mellitus, and seven women had not fasted on the day of venipuncture. Applying the 2003 Rotterdam criteria, 66 women did not meet the criteria for PCOS. All PCOS women reported cycle disorders. The control group consisted of 408 women, of whom 61 individuals were excluded for reasons of being pregnant (n = 32), breastfeeding (n = 14), not having fasted at the day of investigation (n = 14), or the presence of diabetes mellitus (n = 1). Of the remaining 347 women, 52 (15%) reported various abnormalities regarding their menstrual cycle. The final group of 295 women all reported regular menstrual cycles.

Oligomenorrhea occurred in 74% (n = 412) of women with PCOS. All remaining women had amenorrhea. PCO, as evidenced by vaginal ultrasound, was found in 89% (n = 493) of women with PCOS. Hyperandrogenism was present in 64% (n = 358) of women with PCOS. There was a small, but significant, difference in age between the case group (median age 28.8 yr) and controls (32.4 yr; P ≤ 0.01). Obesity (BMI ≥ 30 kg/m2) occurred more frequently in PCOS cases (n = 183, 33%) compared with the control group (n = 36, 12.2%). The differences in age and BMI between the case group and controls were statistically significant. Therefore, further analyses were adjusted for these two parameters. ANCOVA showed that women with PCOS had slightly higher fasting insulin levels than controls (medians adjusted for age and BMI: 9.4 and 7.8 mU/liter, respectively). Although small, this difference was statistically significant.

Lipid profile

Table 1Go summarizes baseline characteristics and lipid profiles in PCOS patients and controls. Women with PCOS had higher levels of cholesterol (adjusted medians: 197 vs. 182 mg/dl; P ≤ 0.01), TGs (98 vs. 88 mg/dl; P ≤ 0.01), and LDL-C (123 vs. 106 mg/dl; P ≤ 0.01) compared with controls. On the contrary, serum levels of HDL-C (adjusted medians: 46 vs. 55 mg/dl; P ≤ 0.01) and apoA-I (117 vs. 136 mg/dl; P ≤ 0.01) were significantly lower in women with PCOS. Figure 1Go illustrates apoA-I levels in PCOS cases and controls. Across the entire range of BMI values, apoA-I levels were significantly lower in women with PCOS. No differences in apoB levels were observed among PCOS cases and controls.


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  		TABLE 1. Baseline characteristics and lipid profiles of women with PCOS and healthy controls

 

Figure 1
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  		FIG. 1. apoA-I levels in women with PCOS and healthy controls. Note medians and box (P25-P75) and whisker (p5-p95) plots of apoA-I levels in women with PCOS (gray) and controls (white). Patients and controls were stratified by BMI (tertiles calculated for PCOS cases: P33 = 23.5 kg/m2 and P66 = 29.8 kg/m2). *, P ≤ 0.01.

 
Stratification for BMI

Table 2Go shows the result of a comparison of lipid parameters and fasting insulin levels in lean (20 ≤ BMI < 25 kg/m2), overweight (25 ≤ BMI < 30), and obese (BMI ≥ 30 kg/m2) women with PCOS and controls. First, lean women with PCOS were compared with lean controls. Plasma insulin levels were similar in both groups. Lean PCOS women had significantly higher plasma levels of cholesterol, LDL-C, and apoB to apoA-I ratio in combination with lower apoA-I levels. Plasma levels of apoB and HDL-C were equal in both groups. Next, we compared plasma lipids and insulin levels in overweight PCOS women and overweight controls. Women with PCOS had higher plasma levels of TGs, cholesterol, and LDL-C, together with lower HDL-C and apoA-I levels and a higher apoB to apoA-I ratio. However, overweight PCOS cases had significantly higher BMI and fasting insulin levels than overweight controls (Table 2Go). Finally, a comparison of obese women with PCOS and obese controls showed higher serum levels of TGs, cholesterol, LDL-C, and apoB in combination with lower levels of HDL-C and apoA-I in obese PCOS cases, whereas we did not observe significant differences in BMI or fasting insulin levels.


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  		TABLE 2. Insulin and lipid profiles, stratification according to BMI subgroups

 
To study the effect of BMI on fasting insulin levels and lipid parameters, P values for linear trend were calculated in both the case group as well as controls. Highly significant trends were observed for fasting insulin levels, TGs, HDL, and apoA-I in both PCOS cases and controls (all parameters: P < 0.01). Trends for cholesterol, LDL-C, and apoB were significant in PCOS cases (P ≤ 0.01), but not in controls (P > 0.05). However, the obese control group was limited to 36 individuals.

Determinants of dyslipidemia in women with PCOS

The PCOS group was stratified into four subgroups, based on the presence or absence of hyperandrogenism and BMI ≥ 25 kg/m2. Table 3Go shows fasting insulin levels and lipid parameters in the four subgroups and lean controls (20 ≤ BMI < 25 kg/m2). First, the subgroup of lean PCOS women who did not have signs of hyperandrogenism (n = 102) were compared with lean controls. Notwithstanding the absence of hyperandrogenism and obesity, PCOS cases had significantly higher plasma levels of cholesterol, LDL-C, and apoB to apoA-I ratio in combination with lower apoA-I levels. Next, the influence of hyperandrogenism was examined in lean women with PCOS in a comparison of hyperandrogenic (n = 76) and nonhyperandrogenic (n = 102) subjects. We observed that hyperandrogenism in lean women with PCOS was associated with higher insulin levels (P = 0.01, adjusted for BMI) and apoB to apoA-I ratio (P = 0.03) in combination with lower HDL-C (P ≤ 0.01) and apoA-I (P ≤ 0.01). In a similar fashion, the independent influence of body weight on lipid parameters was investigated in nonhyperandrogenic PCOS cases in the absence (n = 102) or presence of BMI ≥ 25 kg/m2 (n = 61). The latter group showed significantly higher insulin levels, TGs, apoB, and apoB to apoA-I ratio in combination with lower levels of HDL-C and apoA-I (all parameters: P ≤ 0.01). Insulin levels and lipid profiles were most severely affected in the subgroup of PCOS cases that had both hyperandrogenism and BMI ≥ 25 kg/m2.


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  		TABLE 3. Insulin and lipid profiles in women with PCOS and controls, stratified by the presence of hyperandrogenism (HA) and/or increased body mass (BMI ≥ 25 kg/m2)

 
To test the hypothesis that hyperandrogenism and obesity were independent predictors for the presence of a more atherogenic lipid profile in women with PCOS, multiple linear regression analysis was performed. Table 4Go shows the clinical and endocrine parameters of all women with PCOS. The results of the univariate and multivariate analyses showed that the most important independent determinants for serum apoA-I levels in women with PCOS were FAI, BMI, SHBG, and E2. The final model that included all four parameters explained 17% of the variability in apoA-I levels. Likewise, independent determinants for apoB were calculated as BMI, age, and FAI (multiple R2 0.14; data not shown).


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  		TABLE 4. Clinical and endocrine parameters of 557 women with PCOS, forward stepwise multivariate analyses of initial screening parameters for the prediction of apoA-I levels

 

   Discussion
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
References
 
The present study confirms the presence of a more atherogenic lipid profile in women with PCOS. We found higher levels of TGs, cholesterol, and LDL-C in combination with decreased HDL-C in women with PCOS. Additional information on cardiovascular risk factors in women with PCOS was gained by measuring apo levels (21). Interestingly, apoA-I levels were significantly lower in women with PCOS without any difference in apoB levels. Atherogenic changes in lipid profile were most pronounced in a subgroup of obese PCOS women with hyperandrogenism. Furthermore, univariate and multivariate analyses revealed that FAI, BMI, SHBG, and E2 were independent determinants of apoA-I levels in women with PCOS. Although these factors accounted for no more than 17% of the variance, this supports the hypothesis that ovarian sex steroids are involved in the pathogenesis of dyslipidemia in women with PCOS.

The data on TGs, cholesterol, HDL-C, and LDL-C are consistent with prior studies of dyslipidemia in women with PCOS (31). The strength of the present study lies in the number of patients that were uniformly phenotyped. Moreover, both patients and controls were derived from the same geographic area in The Netherlands. Evidently, studies of dyslipidemia in women with PCOS are hampered by the fact that obesity frequently accompanies this syndrome. It is well known that obesity influences the lipid profile, independently of the presence or absence of PCOS. The stratified analysis shows that PCOS is associated with changes in plasma levels of cholesterol, LDL-C, and apoA-I, and a higher apoB to apoA-I ratio, even when signs of hyperandrogenism or obesity are absent.

Multivariable analysis showed that, after adjustment for age and BMI, women with PCOS had slightly higher fasting insulin levels than controls. The stratified analysis confirms a small difference in insulin levels in the same direction, although this finding was not statistically significant. In contrast, both cases and controls showed that fasting insulin levels more than doubled in the presence of obesity. Therefore, it is suggested that, although PCOS may contribute to insulin resistance, the influence of BMI is much more pronounced. Likewise, lean PCOS cases did not show higher levels of TGs when compared with lean controls.

The results of this study show that there is an additional influence on the lipid profile of women with PCOS that is independent of BMI and seems to be centered on HDL metabolism, i.e. apoA-I levels. One possible explanation may be that hyperandrogenism affects lipid metabolism by the induction of HL activity. This enzyme, which has a role in the catabolism of HDL particles, was significantly up-regulated by exogenous androgens in a study of female-to-male transsexuals (15) and women using androgenic anabolic steroids (13). Moreover, increased HL activity was found in a study of 52 PCOS cases and 14 controls that were matched for BMI (32). The present data support this hypothesis by the fact that the FAI, which is a measure of free circulating androgens, had a strong negative correlation with apoA-I levels that was independent of BMI, serum levels of SHBG and E2 in the multiple linear regression analysis.

Apolipoprotein B levels were not affected by the presence of PCOS, contrary to what was expected. However, this finding is in line with reports that may have lacked sufficient statistical power (22, 23, 25). Subgroup analysis only showed significantly higher apoB levels in obese hyperandrogenic women with PCOS. Multivariate analysis confirmed that BMI, age, and FAI were independent determinants of apoB levels in women with PCOS. However, the combined model could account for no more than 14% of the total variance.

Considering that women with PCOS generally showed a more atherogenic lipid profile than controls, it may be possible to identify subgroups of PCOS patients who have a more adverse cardiovascular risk profile than others. It was observed that both hyperandrogenism and obesity were independently associated with a more atherogenic lipid profile in women with PCOS. Accordingly, insulin levels and lipid parameters were most affected in a subgroup of PCOS patients who presented with BMI ≥ 25 kg/m2 and hyperandrogenism.

It is tempting to speculate that the lack of changes in apoB levels may partly explain the fact that excessive cardiovascular morbidity and mortality were not found in a retrospective follow-up study of women with PCOS (7). However, it should be considered that low apoA-I levels in combination with higher LDL-C and apoB to apoA-I ratio still constitute increased cardiovascular risk. The apoB to apoA-I ratio is an important risk factor for acute myocardial infarction (33). In our population, an increased apoB to apoA-I ratio resulted primarily from decreased apoA-I levels. Although apoA-I is not usually regarded as a risk factor by itself, evidence has mounted for a role of low apoA-I levels in the pathogenesis of coronary heart disease (34). Moreover, apoA-I levels were strong predictors for the risk of fatal myocardial death in a study of 76,831 women who were followed up for a mean of 64.4 months (Apolipoprotein-Related Mortality Risk study) (21).

Results from the Framingham offspring study suggest that increased exposure to exogenous estrogens in premenopausal women is associated with decreased levels of apoB and LDL-C (35). The present study shows that E2 is an independent determinant of apoA-I, but not apoB. The question whether changes in the exposure to estrogens do indeed exert a protective influence on cardiovascular risk in women with PCOS is beyond the scope and design of this study. It is possible that other, currently unknown, factors are involved in the regulation of lipid metabolism and cardiovascular risk in women with PCOS.

In summary, a more atherogenic lipid profile, in particular related to HDL metabolism, was found in women with PCOS. We hypothesize that both obesity and hyperandrogenism contribute to these changes. Furthermore, there was evidence for an additional influence of PCOS on lipid metabolism that was independent of obesity. The results of this study may indicate increased risk for cardiovascular disease in women with PCOS. However, this hypothesis still remains to be proven in prospective long-term follow-up studies of women with PCOS.


   Footnotes
 
Disclosure Statement: The authors have nothing to disclose.

First Published Online December 4, 2007

Abbreviations: AD, Androstenedione; ANCOVA, analysis of covariance; apo, apolipoprotein; BMI, body mass index; CE, cholesteryl ester; DHEA, dehydroepiandrosterone; DHEAS, DHEA sulfate; E2, estradiol; FAI, free androgen index; HDL, high-density lipoprotein; HDL-C, HDL-cholesterol; HL, hepatic lipase; LDL, low-density lipoprotein; LDL-C, LDL-cholesterol; 17-OH-Pg, 17-hydroxyprogesterone; PCO, polycystic ovary; PCOS, PCO syndrome; T, testosterone; TG, triglyceride.

Received August 6, 2007.

Accepted November 21, 2007.


   References
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
 References
 

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Update in Female Reproduction: A Life-Cycle Approach
J. Clin. Endocrinol. Metab., July 1, 2008; 93(7): 2439 - 2446.
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