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PubMed2003

Laparoscopy-assisted intrapelvic sonography with a high-frequency, real-time miniature transducer to assess the ovary: a preliminary report.

OBJECTIVE: Our purpose was to evaluate the normal and pathologic internal textures of the ovary using laparoscopy-assisted intrapelvic sonography (LAIPS) with a specially developed 20-MHz flexible catheter-based high-resolution real-time miniature (2.4 mm in outer diameter) ultrasound transducer in patients with gynecologic disorders and infertile women. METHODS: 30 women (19 patients with gynecologic disorders and normal menstrual cycles (2 adenomyoses, 1 cervical cancer, 5 fibromyomas, 5 simple ovarian cysts, 1 endometriosis, 3 benign cystic teratomas, and 2 endometriomas), and 11 patients with infertility including 4 with polycystic ovarian syndrome, PCOS) were studied by intrapelvic sonography using a high-frequency real-time miniature transducer with pelvic saline effusion and laparoscopy. RESULTS: In the normal ovary in the mid-follicular phase, follicles were depicted more distinctly than with transvaginal sonography (TVS). In the late-follicular phase, cumulus oophorus formations were visualized in 6 of 9 patients (54.5%), but were not clear using TVS. In the luteal phase, the corpus luteum was noted in 9 of 12 patients (75%) by both TVS and LAIPS. In patients with PCOS, the thickened capsule of the ovary was distinguished clearly especially in the peripheral type, in which numerous small cysts were aligned in the subcapsular region of the ovary, whereas it could not be detected by TVS. In all 4 cases with PCOS (8 ovaries), the ovarian capsular thickness could be measured by means of LAIPS. In subjects with benign cystic teratoma, minimal high echoic lesions were depicted. In subjects with endometrioma, a diffuse coarse-granular internal texture was visualized. However, depiction of internal structures in large pathologic ovarian lesions was markedly limited because of the shallow scanning range of the high-frequency transducer. CONCLUSION: LAIPS with a high-frequency real-time miniature transducer might be a useful diagnostic modality to evaluate the normal physiologic textures of the ovary, as well as those with PCOS.

Adult↗

PubMed2004

Prevalence of polycystic ovary syndrome in girls aged 14-18 years in Isfahan, Iran.

OBJECTIVE: To determine the prevalence of clinical polycystic ovary syndrome (PCOS) in 14- to 18-year-old high school girls in Isfahan, Iran. METHODS: In this cross-sectional study, 1,000 high school girls (14-18 years old) were selected by multi-stage random sampling from different high schools in Isfahan. Following physical examination, a single physician recorded the presence of hirsutism, severe acne, androgenic alopecia, menstrual dysfunction and obesity using a validated questionnaire. Clinical PCOS was diagnosed if menstrual dysfunction and clinical hyperandrogenism were detected. RESULTS: Clinical PCOS was present in 30 (3%), hirsutism in 60 (6%), menstrual dysfunction in 74 (7.4%) and severe acne in 47 (4.7%) of the population studied. CONCLUSION: The prevalence of clinical PCOS in our study population was similar to those of other studies; however, the prevalence could have been higher with hormonal assessment.

Acne Vulgaris↗

PubMed2004

Pregnancy loss, polycystic ovary syndrome, thrombophilia, hypofibrinolysis, enoxaparin, metformin.

Thrombophilia, hypofibrinolysis, and polycystic ovary syndrome (PCOS) are associated with recurrent pregnancy loss (RPL) and spontaneous abortion (SAB) alone and concurrently. The efficacy and safety of combined enoxaparin-metformin was prospectively assessed in women with PCOS with one or more previous SAB, thrombophilia, and/or hypofibrinolysis. Twenty-four white women with PCOS were studied; 23 with previous pregnancies, seven with RPL of unknown etiology (>/=three consecutive pregnancy losses <20 weeks' gestation), two with two consecutive SABs, 13 with one SAB, and one with one live birth (HELLP syndrome). Prospectively, metformin (1.5 to 2.55 g/day) was administered before and throughout gestation, with concurrent enoxaparin (60 mg/day) throughout gestation. The 24 cases differed from 93 normal white female controls for the factor V Leiden mutation, 17% vs. 2%, Fisher's p [p(f)] = .016, and for the 4G4G mutation of the plasminogen activator inhibitor-1 (PAI-1) gene (46% vs. 24%, Chi-square 4.63, p =. 031). The patients also differed from 44 normal white female controls for high levels (> 21.1 U/mL) of the PAI-1 gene product, plasminogen activator inhibitor activity (PAI-Fx) (33% vs. 8%, p(f) =. 018), and for high factor VIII (>150%) (22% vs. 0%, p(f) = .037). Of the 24 women, 23 had 65 previous pregnancies without metformin or enoxaparin, with 18 live births, 46 SAB (71%), and one elective abortion. On metforminenoxaparin, the same 23 women had 26 current pregnancies (28 fetuses), with 20 live births, two normal pregnancies 13 weeks or longer, and six SAB (21%), 3.4-fold lower than previous gestations (McNemar's S = 33.6, p <. 0001). There were no adverse maternal or fetal therapy effects. Enoxaparin-metformin reduces pregnancy loss in women with PCOS with one or more previous SAB, who also have thrombophilia and/or hypofibrinolysis.

Abortion, Habitual↗

PubMed2005

The effects of a low-carbohydrate, ketogenic diet on the polycystic ovary syndrome: a pilot study.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder affecting women of reproductive age and is associated with obesity, hyperinsulinemia, and insulin resistance. Because low carbohydrate diets have been shown to reduce insulin resistance, this pilot study investigated the six-month metabolic and endocrine effects of a low-carbohydrate, ketogenic diet (LCKD) on overweight and obese women with PCOS. RESULTS: Eleven women with a body mass index >27 kg/m2 and a clinical diagnosis of PCOS were recruited from the community. They were instructed to limit their carbohydrate intake to 20 grams or less per day for 24 weeks. Participants returned every two weeks to an outpatient research clinic for measurements and reinforcement of dietary instruction. In the 5 women who completed the study, there were significant reductions from baseline to 24 weeks in body weight (-12%), percent free testosterone (-22%), LH/FSH ratio (-36%), and fasting insulin (-54%). There were non-significant decreases in insulin, glucose, testosterone, HgbA1c, triglyceride, and perceived body hair. Two women became pregnant despite previous infertility problems. CONCLUSION: In this pilot study, a LCKD led to significant improvement in weight, percent free testosterone, LH/FSH ratio, and fasting insulin in women with obesity and PCOS over a 24 week period.

Journal Article↗

PubMed2006

Stress in women: metabolic syndrome and polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a heterogeneous syndrome that is characterized from oligo- or anovulation, clinical and/or biochemical signs of hyperandrogenism, and polycystic ovaries. Clinical expression is determined by genetic as well as environmental factors. Women with PCOS are a specific group of women which have several aspects of metabolic syndrome (MBS). Concomitantly MBS could be part of metabolic abnormalities present in PCOS. Stress has been linked to aggravate the metabolic abnormalities present in MBS. An interaction seems to exist between stress, environmental, as well as genetic factors, starting from the prenatal age and continuing to the adult life. This results in specific endocrinological and metabolic disorders which are shared by women with PCOS and women with MBS.

Atherosclerosis↗

PubMed2002

Plasminogen activator inhibitor-1 in girls with precocious pubarche: a premenarcheal marker for polycystic ovary syndrome?

In both obese and nonobese women, polycystic ovary syndrome (PCOS) is essentially a disorder of hyperinsulinemic insulin resistance, and it may be heralded by precocious pubarche (PP; appearance of pubic hair in girls aged <8 y). The risk of progression from PP to PCOS is related to low birth weight, but there are no early biochemical markers of this risk. As increased plasminogen activator-inhibitor type 1 (PAI-1) activity (act) is an early marker of cardiovascular risk in PCOS, we have sought abnormalities in young girls with PP. In 33 young PP girls (age range 6-11 y), PAI-1-act was increased (mean + SEM: 15.6 +/- 1.5 IU/mL) compared with age-, sex-, and pubertal stage-matched controls (n = 13, 10.7 +/- 1.9, p < 0.05). PAI-1-act levels were inversely related to birth weight SD score (r = -0.33, p < 0.05), and PAI-1-act levels were therefore higher in PP girls with low birth weights (n = 14, 19.5 +/- 2.5 IU/mL) than normal birth weights (n = 19, 12.8 +/- 1.5, p < 0.01). During longitudinal observation in 10 PP girls (mean time interval 2.7 y), PAI-1-act levels in early puberty were positively related to postmenarcheal insulin levels (mean serum insulin SDS postoral glucose, r = 0.65, p < 0.05), and showed a similar relationship to postmenarcheal testosterone levels (r = 0.61, p = 0.06). Together with low birth weight, increased plasma PAI-1-act levels in early pubertal PP girls may indicate those girls with greater risk of developing hyperinsulinemic-hyperandrogenism features of PCOS.

Biomarkers↗

PubMed2004

The molecular-genetic basis of functional hyperandrogenism and the polycystic ovary syndrome.

The genetic mechanisms underlying functional hyperandrogenism and the polycystic ovary syndrome (PCOS) remain largely unknown. Given the large number of genetic variants found in association with these disorders, the emerging picture is that of a complex multigenic trait in which environmental influences play an important role in the expression of the hyperandrogenic phenotype. Among others, genomic variants in genes related to the regulation of androgen biosynthesis and function, insulin resistance, and the metabolic syndrome, and proinflammatory genotypes may be involved in the genetic predisposition to functional hyperandrogenism and PCOS. The elucidation of the molecular genetic basis of these disorders has been burdened by the heterogeneity in the diagnostic criteria used to define PCOS, the limited sample size of the studies conducted to date, and the lack of precision in the identification of ethnic and environmental factors that trigger the development of hyperandrogenic disorders. Progress in this area requires adequately sized multicenter collaborative studies after standardization of the diagnostic criteria used to classify hyperandrogenic patients, in whom modifying environmental factors such as ethnicity, diet, and lifestyle are identified with precision. In addition to classic molecular genetic techniques such as linkage analysis in the form of a whole-genome scan and large case-control studies, promising genomic and proteomic approaches will be paramount to our understanding of the pathogenesis of functional hyperandrogenism and PCOS, allowing a more precise prevention, diagnosis, and treatment of these prevalent disorders.

Androgens↗

PubMed2002

Exercise decreases plasma total homocysteine in overweight young women with polycystic ovary syndrome.

Women with polycystic ovary syndrome (PCOS) have a clustering of cardiovascular risk factors, such as obesity, lipid abnormalities, impaired glucose tolerance, insulin resistance, and hypertension. Exercise is reported to lower the incidence of cardiac events. The effect of exercise on plasma homocysteine concentrations, an independent cardiovascular risk factor, has not been previously reported in women with PCOS. We examined the effects of exercise on plasma total homocysteine concentrations in young overweight or obese PCOS women [age (mean +/- SD), 30.6 +/- 6.6 yr; body mass index, 35.49 +/- 7.57 kg/m(2)]. Twenty-one women consented to a 6-month exercise program; 12 women (exercisers) adhered to the program, whereas 9 (nonexercisers) did not. In both groups of women, the following parameters were recorded at baseline and 6 months: body mass index, waist-to-hip ratio, and aerobic capacity (maximal oxygen consumption); blood samples were taken after an overnight fast for plasma total homocysteine, insulin, and other biochemical parameters. A significant decrease in plasma total homocysteine concentrations (P < 0.001) and waist-to-hip ratio (P = 0.041) and a significant increase in maximal oxygen consumption (P = 0.019) were recorded at 6 months, compared with baseline in the exercise group. This decrease in homocysteine was not explained by changes in anthropometric or biochemical parameters. In contrast, no significant changes in any of the variables were observed in the nonexercise group. Our study has provided the first evidence that regular exercise significantly lowers plasma homocysteine in young overweight or obese women with PCOS, a group at increased risk of premature atherosclerosis. The precise mechanism by which exercise is associated with a reduction in homocysteine remains to be elucidated.

Adult↗

PubMed2003

Hormonal profile of women with self-reported symptoms of oligomenorrhea and/or hirsutism: Northern Finland birth cohort 1966 study.

The hormonal profiles of nested female patients (n = 500) with self-reported symptoms typical of polycystic ovary syndrome (PCOS), oligomenorrhea, and/or hirsutism and their randomly selected controls (n = 1026) at the age of 31 yr were analyzed in a general population-based Northern Finland birth cohort 1966 to find out whether the symptomatic women also have the endocrine characteristics of PCOS and could be detected in a general population using simple questions. Higher medians of serum testosterone (T) (2.10 vs. 1.90 nmol/liter, P < 0.001), LH (5.40 vs. 4.85 U/liter, P = 0.005), insulin (53.8 vs. 51.66 pmol/liter, P = 0.040), and free androgen index (FAI) (4.01 vs. 3.03, P < 0.001) and lower glucose/insulin ratio (91.1 x 10(8) vs. 94.9 x 10(8), P = 0.048) and SHBG (52.4 vs. 60.7 nmol/liter, P < 0.001) were observed among the cases, but no difference was observed in cortisol and glucose levels between the cases and controls. Of all the women in the cohort, 10.2% reported only oligomenorrhea and had biochemical findings similar to the whole case group. Those who reported only hirsutism (10.4%) were in between the case and control groups according to biochemical findings. The subjects who reported both oligomenorrhea and hirsutism (3.4%) had the highest T, LH, FAI, insulin, and glucose and the lowest SHBG and glucose/insulin ratio, compared with the case group and the groups with either symptom only indicating a dose-response manner in typical endocrine profile of PCOS by adding up symptoms. The levels of T and FAI were higher and SHBG lower in groups with overweight or obesity both at 14 and 31 yr, compared with groups with normal weight at 14 yr and overweight or obesity at 31 yr. In the group with normal weight at 14 and 31 yr and the group with overweight or obesity at 14 yr but normal weight at 31 yr, the levels of T and FAI were lowest and SHBG highest. T and FAI were higher and SHBG lower among the cases than the controls in groups stratified by weight development from adolescence to adulthood. In conclusion, this longitudinal study of a large, stable population indicates that women with self-reported symptoms of hirsutism and/or oligomenorrhea show endocrine characteristics of PCOS and can be detected in a general population using simple questions. These symptoms are markers of the underlying metabolic alterations possibly associated with increased health risks in later life.

Adult↗

PubMed2003

Regulation of HOXA-10 expression by testosterone in vitro and in the endometrium of patients with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) affects approximately 5% of reproductive-age women and is characterized by anovulation and increased androgen production. Despite the ability to correct ovulatory disorders, pregnancy rates remain paradoxically low, and spontaneous pregnancy loss rates are high. To determine whether uterine dysfunction contributed to the adverse reproductive outcomes in PCOS, we assessed the effect of the increased ovarian androgens on a well-characterized gene essential to endometrial receptivity. Up-regulation of HOXA10 in the endometrium is necessary for receptivity to embryo implantation. In vitro, HOXA10 expression was repressed by testosterone but not by dehydroepiandrosterone, dehydroepiandrosterone sulfate, or insulin. Testosterone also prevented the increased expression of HOXA10 previously reported with estradiol or progesterone. Dihydrotestosterone produced an effect similar to that of testosterone, whereas flutamide blocked the testosterone effect. Endometrial biopsies, obtained from women with PCOS, demonstrated decreased HOXA10 mRNA. Testosterone is a novel regulator of HOXA10. Diminished uterine HOXA10 expression may contribute to the diminished reproduction potential of women with PCOS.

Adult↗

PubMed2003

Platelet dysfunction in lean women with polycystic ovary syndrome and association with insulin sensitivity.

Platelet dysfunction and its association with insulin resistance and/or hyperandrogenemia were evaluated in 50 women with polycystic ovary syndrome (PCOS), 50 women with non-classic congenital adrenal hyperplasia (NC-CAH), and 30 women in the control group. Agonist-induced platelet aggregation was measured. Women with PCOS had significantly higher levels of platelet aggregations induced by ADP (77.4 +/- 3.3 vs. 67.3 +/- 2.8), collagen (79.7 +/- 1.8 vs. 69.1 +/- 3.9), and epinephrine (84.7 +/- 2.6 vs. 67.8 +/- 3.8), compared with controls. However platelet aggregations of women with NC-CAH because of ADP (68.2 +/- 4.22), collagen (69.5 +/- 5.4), or epinephrine (68.6 +/- 4.3) were similar to those in the control group. There were negative correlations between aggregations induced by agonists and the insulin sensitivity in women with PCOS. These correlations also appeared significant after androgen levels with covariance analysis were excluded. These covariance analyses were performed because serum androgen levels might affect platelet function. Any significant correlations were not found between androgen levels and agonist-induced platelet aggregation in women with NC-CAH. We conclude that platelet dysfunction may be an important reason for the possible cardiovascular heart diseases in women with PCOS.

Adenosine Diphosphate↗

PubMed2004

Influence of SHBG gene pentanucleotide TAAAA repeat and D327N polymorphism on serum sex hormone-binding globulin concentration in hirsute women.

SHBG is the specific plasma transport protein for sex steroid hormones in humans. Plasma SHBG concentration follows a gender dimorphism but varies with nutritional and hormonal status in both sexes. In addition, a genetic influence on SHBG in humans has recently been suggested by family studies. We investigated the relationship between a point mutation (D327N) in SHBG gene exon 8 that delays human SHBG half-life and a pentanucleotide repeat polymorphism [PNRP (TAAAA)(n)] in the SHBG gene 5' untranslated region that influences transcription in vitro, on the one hand, and SHBG levels on the other, in a population of 303 women referred for hirsutism. Of these patients, 154 (51%) met the criteria for polycystic ovary syndrome (PCOS) and 124 (41%) were overweight [body mass index (BMI) > or = 25 kg/m(2)]. The two SHBG gene alleles for D327N substitution, wild-type (W) and variant (v), were identified by restriction fragment length polymorphism in the whole population, and the GeneScan method was used to identify PNRP alleles in 245 subjects. Six alleles of the pentanucleotide motif with six to 11 repeats were present in our population. Plasma SHBG concentration was related to PCOS status, non-SHBG-bound testosterone, BMI, fasting blood glucose level, fasting insulinemia, and D327N allele v. The v allele was associated with higher SHBG levels [36.9 +/- 15.9 nmol/liter for W/v (n = 52) and 43.5 +/- 3.5 nmol/liter for v/v (n = 2)] than was the wild-type W allele [31.1 +/- 16.1 nmol/liter (n = 249); P = 0.039]. Multivariate analysis showed that BMI, PCOS status, and D327N polymorphism influenced plasma SHBG concentrations, each of these parameters contributing independently of the others. Investigating the role of each allele of the TAAAA repeat polymorphism on SHBG levels was more complex because of the number of different genotypes (as many as 18 in our population) and the low frequency of some of them. Moreover, a strong disequilibrium linkage was found between D327N allele v and the eight-TAAAA repeat allele (P < 0.0001). This could mask the effect of the TAAAA repeat polymorphism on SHBG concentration in vivo. Nevertheless, SHBG levels in patients who were homozygous for six repeats (34.9 +/- 16.2 nmol/liter; n = 21) were significantly (P = 0.043) higher than in nine-repeat homozygous patients (21.5 +/- 13.0 nmol/liter; n = 8), and lay between the two for eight-repeat homozygous patients (28.5 +/- 15.8 nmol/liter; n = 44). Delineating the precise role of this PNRP polymorphism will need further investigation in a large healthy population. In summary, although BMI and PCOS status have a major influence on circulating SHBG levels in hirsute women, the present results support the notion that polymorphism(s) within the coding sequence and, potentially, in the regulatory sequence of the SHBG gene are associated with circulating SHBG levels and may represent part of the genetic background of sex steroid hormone activity in humans.

Adult↗

PubMed2003

Specific CAPN10 gene haplotypes influence the clinical profile of polycystic ovary patients.

Recently, several research groups have evaluated CAPN10 gene in polycystic ovarian syndrome (PCOS) patients and other phenotypes, including hirsutism or intermediate phenotypes of PCOS. Molecular genetic analysis of CAPN10 gene indicates that different alleles may play a role in PCOS susceptibility and could be associated with idiopathic hirsutism. However, these observations are not exempt from controversy, because independent studies cannot replicate these preliminary findings. We present a haplotype-phenotype correlation study of CAPN10 haplotypes in 148 women showing ecographically detected polycystic ovaries (PCO) combined with one or more of these clinical symptoms: amenorrhea or severe oligomenorrhea, hyperandrogenism, and anovulatory infertility, as well as 93 unrelated controls. We have reconstructed and analyzed 482 CAPN10 haplotypes in patients and controls. We detected the association of UCSNP-44 allele with PCO phenotype in the Spanish population (P = 0.02). In addition, we identified several CAPN10 alleles associated to phenotypic differences observed between PCO patients, such as the presence of hypercholesterolemia (haplotype 1121, P = 0.005), presence of hyperandrogenic features (P = 0.05), and familial cancer incidence (haplotype 1111, P = 0.0005). Our results confirm the association of UCSNP-44 allele with PCO phenotype in the Spanish population. Moreover, we have identified novel candidate risk alleles and genotypes, within CAPN10 gene, that could be associated with important phenotypic and prognosis differences observed in PCOS patients.

Amenorrhea↗

PubMed2003

Enhanced granulosa cell responsiveness to follicle-stimulating hormone during insulin infusion in women with polycystic ovary syndrome treated with pioglitazone.

Women with polycystic ovary syndrome (PCOS) are known to exhibit insulin resistance with compensatory hyperinsulinemia. To determine the role of hyperinsulinemia on follicle function in PCOS, we examined 24-h estradiol (E(2)) responses to recombinant human FSH (r-hFSH), 75 IU, before and during insulin infusion both before and after administration of pioglitazone (30 mg/d) in seven PCOS women. Each subject underwent two 10-h hyperinsulinemic-euglycemic clamps at rates of 30 (low dose) and 200 (high dose) mU/m(2).min, respectively. During both low- and high-dose insulin infusions, E(2) responses to r-hFSH were unaltered compared with that observed in the absence of insulin. Pioglitazone administration for 5 months improved insulin sensitivity as indicated by significantly (P < 0.05) increased glucose infusion rates during the clamp studies. At 3 months of treatment, r-hFSH-stimulated E(2) responses were not different from those observed before treatment. With pioglitazone treatment, E(2) responses to r-hFSH remained unchanged during low-dose insulin infusion, whereas a highly significant (P < 0.02) increased response was noted with the high-dose hyperinsulinemic-euglycemic clamp. In addition to a greater magnitude of response, peak levels of E(2) were sustained longer compared with that seen before treatment. The data indicate that granulosa cell responsiveness to FSH was enhanced by insulin after improved insulin sensitivity induced by pioglitazone. These findings are consistent with the possibility that PCOS granulosa cells are insulin resistant.

Adult↗

PubMed2004

Association of the polycystic ovary syndrome with genomic variants related to insulin resistance, type 2 diabetes mellitus, and obesity.

We have evaluated the possible association of polycystic ovary syndrome (PCOS) with 15 genomic variants previously described to influence insulin resistance, obesity, and/or type 2 diabetes mellitus. Seventy-two PCOS patients and 42 healthy controls were genotyped for 15 variants in the genes encoding for paraoxonase (three variants), plasma cell differentiation antigen glycoprotein, human sorbin and SH3 domain containing 1, plasminogen activator inhibitor-1, peroxisome proliferator-activated receptor-gamma2, protein tyrosine phosphatase 1B (two variants), adiponectin (two variants), IGF1, IGF2, IGF1 receptor, and IGF2 receptor. Compared with controls, PCOS patients were more frequently homozygous for the -108T variant in paraoxonase (36.6% vs. 9.5%; P = 0.002) and homozygous for G alleles of the ApaI variant in IGF2 (62.9% vs. 38.1%; P = 0.018). Paraoxonase is a serum antioxidant enzyme and, because -108T alleles result in decreased paraoxonase expression, this increase in oxidative stress might result in insulin resistance. G alleles of the ApaI variant in IGF2 may increase IGF2 expression, and IGF2 stimulates adrenal and ovarian androgen secretion. In conclusion, the paraoxonase -108 C-->T variant and the ApaI polymorphism in the IGF2 gene are associated with PCOS and might contribute to increased oxidative stress, insulin resistance, and hyperandrogenism in this prevalent disorder.

Adiponectin↗

PubMed2004

Metabolic cardiovascular disease risk factors in women with self-reported symptoms of oligomenorrhea and/or hirsutism: Northern Finland Birth Cohort 1966 Study.

The metabolic cardiovascular disease (CVD) risk factors of women with self-reported oligomenorrhea and/or hirsutism, which are symptoms of polycystic ovary syndrome (PCOS), were investigated in a general population-based Northern Finland Birth Cohort 1966 Study to determine whether women with PCOS symptoms at 31 yr would be distinguishable from asymptomatic controls in terms of CVD risk factors. A total of 518 cases with oligomenorrhea and/or hirsutism and 1036 randomly selected controls were analyzed. C-Reactive protein (CRP; median, 0.70 vs. 0.60 mg/liter; P = 0.026), triglycerides (mean, 0.97 vs. 0.91 mmol/liter; P = 0.039), body mass index (BMI; mean, 25.1 vs. 24.2 kg/m(2); P < 0.001), and waist/hip ratio (mean, 0.82 vs. 0.81; P = 0.001) were significantly higher, and high-density lipoprotein cholesterol levels were lower (mean, 1.60 vs. 1.66 mmol/liter; P = 0.002) in the cases compared with the controls. Total cholesterol, low-density lipoprotein cholesterol, and blood pressure showed no statistically significant differences between the cases and the controls. In terms of metabolic CVD risk factors, women reporting hirsutism alone were indistinguishable from the control group, and those who reported both oligomenorrhea and hirsutism had the most severe changes in risk factor profiles. Because obesity is strongly related to PCOS symptoms, the analyses were stratified by BMI. After stratification into normal weight (BMI, <25 kg/m(2)), overweight (25 kg/m(2) or=30 kg/m(2)) groups, the waist/hip ratio was significantly higher among the overweight cases (mean, 0.84 vs. 0.83; P = 0.04). Among the obese women, high-density lipoprotein cholesterol was significantly lower (mean, 1.32 vs. 1.48 mmol/liter; P = 0.002) among the cases, and triglycerides tended to be higher (mean, 1.43 vs. 1.27 mmol/liter; P = 0.068) than in controls. In conclusion, these results indicate that self-reported symptoms of oligomenorrhea and/or hirsutism, particularly in the presence of both symptoms, may be helpful to identify women with metabolic cardiovascular risk factor accumulation associated with PCOS.

Adult↗

PubMed2004

Effect of the insulin sensitizer pioglitazone on insulin resistance, hyperandrogenism, and ovulatory dysfunction in women with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, chronic anovulation, and insulin resistance; long-term consequences include diabetes mellitus type 2. The aim of this randomized, double-blind, controlled trial was to investigate whether the thiazolidinedione derivative pioglitazone diminishes insulin resistance and hyperandrogenism and enhances ovulation rates in women with PCOS. Forty premenopausal women with PCOS were randomly allocated to treatment with either pioglitazone (30 mg/d) or placebo for periods of 3 months. Administration of pioglitazone resulted in a remarkable decline in both fasting serum insulin levels (P < 0.02) and the area under the insulin response curve after an oral glucose load (P < 0.02). This represented an increase in insulin sensitivity and a decrease in insulin secretion (P < 0.05). Furthermore, pioglitazone increased serum SHBG (P < 0.05), resulting in a significant decrease in the free androgen index (P < 0.05 compared with placebo). Treatment with pioglitazone was also associated with higher ovulation rates (P < 0.02). Thus, pioglitazone significantly improved insulin sensitivity, hyperandrogenism, and ovulation rates in women with PCOS, thereby providing both metabolic and reproductive benefits.

Adult↗

PubMed2004

Evidence for the presence of glucose transporter 4 in the endometrium and its regulation in polycystic ovary syndrome patients.

Glucose transporter 4 (GLUT4) seems to be involved in the mechanism of insulin resistance in polycystic ovary syndrome (PCOS) patients (PCOSs) in both muscular and adipose tissue. The observation that insulin stimulates glucose oxidation in endometrial cells led us to investigate the presence of GLUT4 in this tissue and whether a defect of GLUT4 is present at the endometrial level in PCOSs. We also investigated whether body weight influences GLUT4 expression in this syndrome. GLUT4 mRNA content was examined by real-time quantitative RT-PCR and immunostaining reaction in the endometrial tissue of nine normal subjects, nine lean and eight obese hyperinsulinemic (h-INS), and eight lean and 10 obese normoinsulinemic (n-INS) PCOSs. GLUT4 mRNA and its positive immunostaining reaction were present in epithelial cell level in the endometrium of both normal and PCOS subjects. Significantly higher levels of GLUT4 were observed in normal and lean n-INS PCOSs in comparison with other groups. In both n-INS and h-INS obese PCOSs, GLUT4 was significantly lower than in lean subjects. However, obese n-INS and lean h-INS PCOSs showed a similar low GLUT4 expression, whereas obese h-INS PCOSs showed the lowest expression when compared with other groups. In conclusion, our data demonstrate that GLUT4 is present in the endometrium of normal and PCOS subjects and that hyperinsulinism and obesity seem to have a negative effect on endometrial GLUT4 expression in PCOS.

Adult↗