Phenotypic Variation in Hyperandrogenic Women Influences the Findings of Abnormal Metabolic and Cardiovascular Risk Parameters

Abstract

In hyperandrogenic women, several phenotypes may be observed. This includes women with classic polycystic ovary syndrome (C-PCOS), those with ovulatory (OV) PCOS, and women with idiopathic hyperandrogenism (IHA), which occurs in women with normal ovaries. Where other causes have been excluded, we categorized 290 hyperandrogenic women who were seen consecutively for this complaint between 1993 and 2004 into these three subgroups. The aim was to compare the prevalence of obesity, insulin resistance, and dyslipidemia as well as increases in C-reactive protein and homocysteine in these different phenotypes with age-matched ovulatory controls of normal weight (n = 85) and others matched for body mass index (BMI) with women with C-PCOS (n = 42). Although BMI affected fasting serum insulin and the Quantitative Insulin-Sensitivity Check Index, these markers of insulin resistance were greatest in C-PCOS (n = 204), followed by OV-PCOS (n = 50) and then IHA (n = 33). Androgen levels were similar in OV-PCOS and IHA but were higher in C-PCOS, whereas gonadotropins were similar in all groups. Lipid abnormalities were highest in C-PCOS and OV-PCOS and were normal in IHA. C-reactive protein was elevated in C-PCOS and OV-PCOS but not IHA. Homocysteine was elevated only in C-PCOS. Overall, the prevalence of obesity (BMI > 30) was 29% in C-PCOS, 8% in OV-PCOS, and 15% in IHA and insulin resistance (Quantitative Insulin-Sensitivity Check Index < 0.33) was 68% in C-PCOS, 36% in OV-PCOS, and 26% in IHA. The prevalence of having at least one elevated cardiovascular risk marker was 45% in C-PCOS 38% in OV-PCOS and was not increased on IHA (6%). These results suggest that among hyperandrogenic women the prevalence of abnormal metabolic and cardiovascular risk parameters is greatest in C-PCOS, followed by OV-PCOS and then women with IHA. Moreover, in that in OV-PCOS and IHA, ages and weights were similar yet the prevalence of metabolic and cardiovascular risk was greater in OV-PCOS, the finding of polycystic ovaries may be a significant modifying factor.

Metabolic syndrome in polycystic ovary syndrome (PCOS): lower prevalence in southern Italy than in the USA and the influence of criteria for the diagnosis of PCOS

“…No patient had an androgen secreting tumor on the basis of finding very high androgen levels or abnormalities on computed tomography scan or magnetic resonance imaging. Some of these women had been included in other analyses (10). Anovulation was defined as serum progesterone , 10 nmol/l.…”

“…Patients with PCOS were divided into two subgroups according to their particular phenotype: 225 women had hyperandrogenism and chronic anovulation (classic (C)-PCOS) and 57 had hyperandrogenism and polycystic ovaries but normal ovulatory cycles (ovulatory (OV)-PCOS) (10). Eighty-five women of similar age (range 18 -35 years) were randomly selected as normal controls.…”

“…Although the prevalence of IR has been found to be similar between Italian and USA women with PCOS (10,19), the prevalence of hypertriglyceridemia is far less in Italian women (10,15). Thus the criteria used to diagnose MBS may alter the overall prevalence rate.…”

“…Using the clinical criteria of hyperandrogenism and chronic anovulation (often called National Institutes of Health (NIH) criteria (21)) a higher rate of CV risk factors may be found compared with women who were diagnosed by the ESHRE/ASRM criteria which place less emphasis on clinical findings (10).…”

High prevalence of polycystic ovary syndrome in women with mild hirsutism and no other significant clinical symptoms

“…Similarly, prevalence of classic PCOS may be higher in patients with severe hirsutism. In addition, the prevalence of the milder ovulatory form was highly increased, and also this PCOS phenotype is able to determine a higher metabolic and cardiovascular risk (18).…”