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PubMed2002

Insulin resistance is attenuated in women with polycystic ovary syndrome with the Pro(12)Ala polymorphism in the PPARgamma gene.

Polycystic ovary syndrome (PCOS) is common in women of reproductive age and is associated with a high risk for development of type 2 diabetes. Insulin resistance, a key component in the pathogenesis of PCOS and glucose intolerance, is ameliorated by the thiazolidinediones, synthetic ligands for the PPARgamma. In the present study we have examined the relationship of the Pro(12)Ala polymorphism in the PPARgamma gene (PPARG) to clinical and hormonal features of PCOS. Two hundred and eighteen women with PCOS had a 75-g oral glucose tolerance test, and blood was obtained for measurement of serum androgen levels. Sixty percent of the subjects were Caucasian, 26% were African-American, 6% were Hispanic, 6% were South Asian, and 2% were Middle-Eastern. Compared with Caucasians, the African-American group had a higher prevalence of diabetes (19% vs. 5%, respectively), were more obese (body mass index, 40.9 +/- 1.8 vs. 36.3 +/- 0.8 kg/m(2); P < 0.05), and were more insulin resistant. Twenty-eight of 218 subjects had the Ala allele, all in the heterozygous state. The frequency of the Ala allele varied among the groups: 0.01 in African-Americans, 0.08 in Caucasians, and 0.15 in Hispanics. Nondiabetic Caucasians with an Ala allele (Pro/Ala group) were more insulin sensitive than those in the Pro/Pro group, as evidenced by a lower homeostasis model assessment index (5.18 +/- 1.33 vs. 6.54 +/- 0.54; P < 0.05) and lower levels of insulin at both the fasting (132 +/- 27 vs. 165 +/- 12 pmol/liter; P = 0.03) and 2 h (688 +/- 103 vs. 10190 +/- 99 pmol/liter; P = 0.04) time points during the oral glucose tolerance test. We conclude that Pro(12)Ala in PPARG is a modifier of insulin resistance in Caucasian women with PCOS.

Adult↗

PubMed2002

Steroid receptor coactivator expression throughout the menstrual cycle in normal and abnormal endometrium.

The endometrium of reproductive aged women undergoes cyclic developmental changes in preparation for implantation in response to estrogen and progesterone. These steroids and their receptors are tightly regulated throughout the menstrual cycle, and their actions are facilitated by the presence of steroid receptor coactivators of the p160 family. In this study using immunohistochemistry and Western blot analysis, we characterize the expression patterns of three coactivators, steroid receptor coactivator-1, amplified in breast cancer-1 (AIB1), and transcriptional intermediary factor-2 in human endometrium obtained prospectively from normal fertile women throughout the menstrual cycle. With the exception of glandular AIB1, which increased in the late secretory phase, none of the coactivators changed significantly during the menstrual cycle. We compared coactivator expression patterns in fertile endometrium to the endometrium of anovulatory (proliferative; n = 3) and clomiphene-induced ovulatory (secretory; n = 13) women with polycystic ovarian syndrome (PCOS), a group that have a higher likelihood of developing estrogen-induced endometrial hyperplasia and cancer. To control for the effect of clomiphene citrate, an additional group was included consisting of ovulatory women treated with clomiphene citrate for "male factor" infertility. Compared with both fertile and infertile controls, PCOS women exhibited elevated levels of AIB1 and transcriptional intermediary factor-2 expression in both epithelial and stromal cells. We postulate that increased coactivator expression may render the endometrium more sensitive to estrogen. In support of this, we describe an increased expression of ERalpha (an estrogen-induced gene product) during the menstrual cycle in PCOS endometrium compared with fertile controls. In summary, we demonstrate that the expression of p160 coactivators are regulated in endometrium during the menstrual cycle in normal fertile women but are overexpressed in the endometrium of women with PCOS. Based on these findings, we suggest a possible mechanism to explain the poor reproductive performance observed in PCOS and the increased incidence of endometrial hyperplasia and cancer noted in this group of women.

Anovulation↗

PubMed2004

Influencing prescribing in English primary care: the views of primary care organisations.

OBJECTIVE: The rapid rise of prescribing expenditure is a concern in many industrialised countries and methods to manage medicines are widely employed. The purpose of this study was to identify the approaches to improve primary care prescribing by primary care organisations (PCOs) in the National Health Service (NHS) in England. METHODS: A questionnaire (Management of Medicines, MANMED) was mailed to prescribing advisers and prescribing leads in 332 PCOs. RESULTS: A response rate of 66% (220/332) was achieved. Most PCOs report the improvement of the quality of prescribing as their top priority, followed by budget adherence at both practice and PCO levels. Prescribing advisers typically offer several forms of support: practice visits, prescribing reviews, indicators of prescribing, prescribing newsletters, hands-on support, seminars and local formularies. PCOs are pursuing a wide range of prescribing initiatives, covering, on average, seven different therapeutic areas. National targets are the main driver for prescribing initiatives but other key influences include inappropriate prescribing and clinical governance. Although cost considerations are important, improving the quality of prescribing is perceived as the overriding principle on which PCO prescribing strategy is based. Multifaceted prescribing support is widespread and national targets are the largest single factor influencing choice of therapeutic area for prescribing initiatives. CONCLUSIONS: Diversity in approaches presents the opportunity to improve the evidence base for medicines management. Not only could such research inform PCOs in their central aim of improving the quality of prescribing within the NHS, but it may also offer insights of relevance to other countries if the influence of process and context upon the effectiveness of medicines management is systematically explored.

Budgets↗

PubMedDate not supplied

Polycystic ovary syndrome: the influence of environmental and genetic factors.

Polycystic ovary syndrome (PCOS) is a complex and heterogeneous disorder characterized by hyperandrogenemia, hyperinsulinemia, insulin resistance, and chronic anovulation. It is the most common endocrine disorder in women of reproductive age with an enigmatic pathophysiologic and molecular basis. The high prevalence of affected individuals and the wide range of phenotypic expression can be explained by the interaction of a number of key genes with environmental factors. Heritability of PCOS has been inferred from studies of the syndrome in various population groups (ethnic groups, twins, and PCOS families). Although evidence of familial segregation and clustering of the disease in first-degree relatives of women diagnosed with PCOS has been presented, no particular pattern of inheritance has emerged. Some of the problems in genetic studies have been the lack of uniform criteria for diagnosis, heterogeneity of phenotypic features, and the fact that the disorder is only expressed clinically in women during their reproductive years. Even within affected families and between sisters with polycystic ovaries, there is heterogeneity in presentation. However, regardless of diagnostic criteria used to identify the propositus and to determine affected status in the kindred, the genetic studies available suggest a strong familial component. Currently, PCOS is considered a polygenic trait that might result from the interaction of susceptible and protective genomic variants and environmental factors, during either prenatal or postnatal life.

Collagen↗

PubMed2004

The plasminogen activator system in young and lean women with polycystic ovary syndrome.

The purpose of the study was to evaluate the plasminogen activator inhibitor-1 (PAI-1) levels and PAI-1 activity in young and lean women with PCOS and to compare with controls matched for age and weight. Thirty two women with PCOS and 25 weight and age-matched healthy controls participated in this study. Patients were evaluated clinically and by pelvic ultrasound and fasting blood samples were taken for hematological and biochemical tests. Fasting insulin, glucose, lipid profile, FSH, LH, PRL, testosterone, SHBG, 17-hydroxyprogesterone, androstenedione, PAI-1 antigen; PAI-1 activity, insulin sensitivity indices (HOMA and QUICKI) were measured. PAI-1 Ag and activity were significantly higher in PCOS women than healthy control group. PAI-1 levels were directly correlated with BMI, insulin levels and insulin sensitivity indices. PAI-1 activity was also correlated with insulin levels and insulin resistance. As a conclusion PAI-1 Ag levels and activity were increased in lean PCOS women and these were directly correlated with insulin resistance. The finding may contribute to evidence of increase risk of cardiovascular disease and anovulatory infertility in PCOS women.

Adult↗

PubMed2002

Treatment of polycystic ovary syndrome with insulin-lowering agents.

Early diagnosis and therapy of the underlying insulin resistance of heritable polycystic ovary syndrome (PCOS), often manifested at menarche, facilitate the reduction and/or reversal of the reproductive and metabolic morbidity of PCOS, as well as reduce the risk factors for cardiovascular disease. PCOS is characterised by oligoamenorrhoea, clinical and biochemical hyperandrogenism, infertility, recurrent miscarriage, insulin resistance, hyperinsulinaemia, gestational diabetes, impaired glucose tolerance, Type 2 diabetes, morbid obesity, hypertension, hypofibrinolysis, hypertriglyceridaemia, low levels of high density lipoprotein-cholesterol and a sevenfold risk increase in cardiovascular disease. Insulin sensitising-lowering agents reduce insulin resistance and hyperinsulinaemia, reverse PCOS endocrinopathy and ameliorate the reproductive, metabolic and cardiovascular morbidity of the disorder. The largest literature on the subject discusses metformin. Improved pregnancy outcomes in women with PCOS receiving metformin may be attributed to its ability to reduce insulin resistance, hyperinsulinaemia and hypofibrinolytic plasminogen activator inhibitor activity by the enhancement of folliculogenesis and improvement of oocyte quality.

Female↗

PubMed2001

Receiver operating characteristic analysis of the performance of basal serum hormone profiles for the diagnosis of polycystic ovary syndrome in epidemiological studies.

OBJECTIVE: We have used receiver operating characteristic (ROC) analysis to determine the diagnostic performance of several serum parameters, in order to evaluate their potential usefulness in establishing the diagnosis of polycystic ovary syndrome (PCOS) in epidemiological studies. DESIGN: Prospective study. METHODS: One hundred and fourteen women reporting spontaneously for blood donation were included in the study. Menopausal and oral contraceptive-treated women were excluded. Serum samples were obtained at the moment of donation, independently of fasting, time of day or day of menstrual cycle. Measurements included total testosterone, sex hormone-binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEAS), LH, FSH and estradiol. The free testosterone (FT) concentration and the free androgen index (FAI) were calculated from testosterone and SHBG levels. ROC curves were calculated for all these serum determinations. RESULTS: Eight patients were diagnosed with PCOS, according to the presence of oligomenorrhea, hirsutism, acne and/or hyperandrogenemia, and exclusion of non-classic congenital adrenal hyperplasia, hypothyroidism and hyperprolactinemia. Of the parameters studied SHBG, FAI, FT and DHEAS were considered adequate measures for the diagnosis of PCOS. For example, serum SHBG levels showed an area under the ROC curve of 0.875+/-(S.E.(w))0.045 (95% confidence interval 0.800-0.929). A SHBG decision threshold <37 nmol/l had a sensitivity of 87.5%, a specificity of 86.8%, a positive likelihood ratio of 6.63, and a negative likelihood ratio of 0.14, for the diagnosis of PCOS. CONCLUSIONS: Our present results strongly suggest that decreased SHBG levels, and increased FAI, free testosterone concentration and DHEAS concentrations, are highly effective as single analytical procedures in epidemiological studies for the detection of PCOS in women of reproductive age.

Adult↗

PubMed2002

The genetic basis of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of reproductive age. The disorder is characterized by clinical features of hyperandrogenism, menstrual irregularities and often central obesity and hyperinsulinaemia. PCOS may increase the risk for infertility, type 2 diabetes mellitus, dyslipidaemia, cardiovascular disease and endometrial cancer, emphasizing the need for early diagnosis of the syndrome. The genetic basis of PCOS is unknown. There is a strong familial component but the mode of inheritance is uncertain and several candidate genes have been proposed to contribute to susceptibility. Not only genes involved in steroid hormone biosynthesis have been studied but also genes associated with the regulation of insulin secretion and action since hyperinsulinaemia is a characteristic of PCOS. So far there is evidence that INS VNTR (insulin variable number of tandem repeats) or CYP11alpha (cholesterol side chain cleavage) genes are associated with this syndrome. PCOS appears, however, to be an oligogenic disorder and more studies are necessary to define the genetic basis.

Cholesterol Side-Chain Cleavage Enzyme↗

PubMed2006

Increased micronucleus frequencies in peripheral blood lymphocytes in women with polycystic ovary syndrome.

OBJECTIVE: We aimed to assess possible genomic instability in women with polycystic ovary syndrome (PCOS). DESIGN: The frequency of micronuclei in cultured peripheral lymphocytes was used as a biomarker of genomic instability in somatic cells. METHODS: Nineteen women, diagnosed with PCOS and 19 healthy female volunteers of corresponding ages and body-mass index (BMI) were included in the study. Micronuclei frequencies were assessed in cytokinesis-blocked lymphocytes. RESULTS: The frequency of micronucleated cells (per thousand) was 9.00 (5.00) (interquartile range in parentheses) for patient group and 3.0 (3.0) for the control group (P < 0.0001, Mann-Whitney U-test). The serum levels of follicle-stimulating hormone (FSH), estradiol, prolactin, glucose and dehydroepiandrosterone sulfate (DHEAS) and the homeostasis model of assessment of insulin resistance (HOMA-IR) were not different between the two groups (P > 0.05). Serum total testosterone, luteinizing hormone (LH) and insulin levels and hirsutism score in the PCOS group were significantly (P = 0.007, P < 0.0001, P = 0.009 and P < 0.0001 respectively) higher than those of the control group (2.3 (2.1) nmol/l vs 1.7 (0.4) nmol/l; 8.5 (5.88) mU/ml vs 4.8 (4.4) mU/ml; 6.8 (5.1) microU/ml vs 9.7 (4.2) microU/ml; 19.5 (6.5) vs 4.0 (2.5) respectively). However, the mean level of sex hormone-binding globulin (SHBG) in PCOS group was significantly (P = 0.004) lower than in control group (36.4(22.6) nmol/l vs 48.6(25.2) nmol/l respectively). CONCLUSION: These findings suggest that women with PCOS have a high incidence of genomic instability, and this condition is positively correlated with the hirsutism score, BMI, LH and serum total testosterone and insulin levels, and is negatively correlated with SHBG.

Adult↗

PubMed2002

QT dispersion in patients with polycystic ovary syndrome.

Cardiac risk factors are observed more frequently in patients with polycystic ovary syndrome (PCOS). On the other hand, increased QT dispersion, which is a risk factor for cardiac arrhythmias and sudden death, has not been investigated in this syndrome. In this study, we evaluated QT dispersion in PCOS patients without overt heart disease. Thirty-six consecutive women with PCOS (mean age 24+/-5 years) and 36 healthy women of similar ages (mean age 24+/-4 years) participated in this study. PCOS was diagnosed if there were polycystic ovaries by ultrasound (enlarged ovaries with > or =8 cysts 2-8 mm in diameter), oligoamenorrhea (intermenstrual interval >35 days), hirsutism (Ferriman-Gallwey score, > or =7) and elevated serum levels of testosterone (> or =2.7 nmol/L). Electrocardiograms were recorded at a paper speed of 50 mm/s. QT intervals were manually measured by a cardiologist. All intervals were corrected for heart rate according to Bazett's formula: QTc interval=QT interval/square root of the RR interval. Mean values of body mass index, heart rate, and blood pressure were not significantly different between the two groups (P>0.05). No significant differences in QT intervals (maximum QT, minimum QT, QT dispersion, minimum corrected QT, maximum corrected QT, and corrected QT dispersion) were observed between the two groups (P>0.05). Our results suggest that the risk of ventricular arrhythmias or sudden cardiac death is not increased in PCOS patients.

Adult↗

PubMed2005

Thiazolidinediones for treatment of polycystic ovary syndrome.

OBJECTIVE: To review the pathophysiology and treatment of polycystic ovary syndrome (PCOS) and the evidence for use of thiazolidinediones in the treatment of this syndrome. DATA SOURCES: We conducted a MEDLINE database search for English-language literature published from January 1966-July 2004. Key terms used were thiazolidinediones, troglitazone, rosiglitazone, pioglitazone, polycystic ovary syndrome, and PCOS. Bibliographies in the relevant articles were reviewed for additional references. SELECTION: All clinical trials were reviewed. DATA SYNTHESIS: Troglitazone has been evaluated in numerous clinical trials of women with PCOS. These trials provided a body of evidence supporting the efficacy of troglitazone for management of PCOS complications, such as insulin resistance, hyperandrogenism, and anovulation. Due to safety concerns, however, troglitazone is no longer marketed in the United States. Clinical data are emerging regarding the utility of newer, safer thiazolidinediones, such as pioglitazone and rosiglitazone, for this patient population. The available literature provides evidence that these newer agents improve insulin sensitivity, glycemic control, hormone responsiveness, menstrual regularity, and ovulation rates. Pioglitazone and rosiglitazone have been well tolerated in clinical studies and have an improved safety profile in terms of liver toxicity. CONCLUSION: Pioglitazone and rosiglitazone should be considered a second-line treatment alternative to metformin for management of women with PCOS who are resistant to insulin or who are obese.

Adult↗

PubMed2002

Potential utility of insulin sensitizers in the treatment of patients with Polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a form of functional ovarian hyperandrogenism. It is one of the most common endocrinologic disorders in women of reproductive age. Women with PCOS may present with menstrual irregularities, chronic anovulation, infertility, obesity and hyperandrogenism. PCOS is associated with insulin resistance and hyperinsulinemia in most, if not all, patients. Besides its gynecological manifestations, PCOS is also associated with increased metabolic and cardiovascular risks. These risks are strongly linked to insulin resistance, and during recent years a novel therapeutic approach using insulin-sensitizing agents has been extensively investigated. In most studies conducted to date, metformin and the thiazolidinedione agent troglitazone have resulted in improved insulin sensitivity, resumption of regular menses and decreased serum androgen levels. Insulin-sensitizing agents may be a useful adjuvant therapy for women with PCOS.

Female↗

PubMed2003

Variation in resistin gene promoter not associated with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a leading cause of anovulatory infertility and affects approximately 4-7% of reproductive age women in the U.S. It is characterized by hyperandrogenemia and chronic anovulation and is associated with insulin resistance, obesity, and increased risk for type 2 diabetes. In a screen of candidate genes, a region on chromosome 19p13.3 was identified that shows significant evidence for both linkage and association with PCOS. A promising candidate gene for PCOS, resistin, maps to exactly this region. Resistin is a protein hormone thought to modulate glucose tolerance and insulin action. We tested for association between a single nucleotide polymorphism in the promoter region of the resistin gene and three phenotypes: PCOS, obesity, and insulin resistance. We did not find evidence for association with any of the phenotypes. It is therefore unlikely that variation in the resistin gene accounts for the strong association that we observe between chromosome 19p13.3 and PCOS. Instead, this association is most likely due to a gene or genetic element in this region that has not been identified.

Chromosomes, Human, Pair 19↗

PubMed2004

Glucose intolerance in a large cohort of mediterranean women with polycystic ovary syndrome: phenotype and associated factors.

The aim of this study was to investigate the phenotypic parameters and associated factors characterizing the development of glucose intolerance in polycystic ovary syndrome (PCOS). Among the 121 PCOS female subjects from the Mediterranean region, 15.7 and 2.5% displayed impaired glucose tolerance and type 2 diabetes, respectively. These subjects were included in a single group of overweight or obese subjects presenting with glucose intolerance (GI) states. PCOS women with normal glucose tolerance (81.8%) were subdivided into two groups: those who were overweight or obese and those of normal weight. Metabolic and hormonal characteristics of the GI group included significantly higher fasting and glucose-stimulated insulin levels, more severe insulin resistance, hyperandrogenemia, and significantly higher cortisol and androstenedione responses to 1-24 ACTH stimulation. One important finding was that lower birth weight and earlier age of menarche were associated with GI in PCOS women. Frequency of hirsutism, oligomenorrhea, acne, and acanthosis nigricans did not characterize women with GI. Our findings indicate that PCOS patients with GI represent a subgroup with specific clinical and hormonal characteristics. Our observations may have an important impact in preventative and therapeutic strategies.

Adolescent↗

PubMed1996

Elevated low-density lipoprotein-cholesterol in women with polycystic ovary syndrome.

Previous studies have indicated that women with the polycystic ovary syndrome (PCOS) are affected by hypertriglyceridemia and low high-density lipoprotein-cholesterol (HDL-C) level. However, most of these studies did not control for confounding factors such as body mass index (BMI) or differences in ethnicity. Therefore, we compared the lipid data for 26 women with PCOS with those for 1428 female control participants of the Prospective Cardiovascular Münster (PRO-CAM) study who did not use hormonal contraceptives and were of similar age. Data were adjusted for age, BMI and ethnicity. Women with PCOS had higher total cholesterol (5.55 +/- 1.24 vs. 4.99 +/- 0.88 mmol/l, p < 0.05) and low-density lipoprotein-cholesterol (LDL-C) levels (3.61 +/- 1.19 vs. 3.08 +/- 0.82 mmol/l, p < 0.05) than the control subjects. Compared with the women in the control population, those with PCOS more frequently had triglyceride levels exceeding 2.3 mmol/l (11.5 vs. 1.6%, p < 0.001), LDL-C levels exceeding 4.2 mmol/l (30.8 vs. 12.1, p < 0.01), and HDL-C levels below 1.2 mmol/l (46.2 vs. 15.3%, p < 0.001). We conclude that dyslipidemia is found more frequently in women with PCOS, independently of the excess weight that is often found in this patient group.

Adult↗

PubMedDate not supplied

Serum leptin and body composition in polycystic ovarian syndrome.

BACKGROUND: The role of leptin in polycystic ovarian syndrome (PCOS) is unclear. We investigated the relationship between serum leptin levels, body composition and insulin resistance in polycystic ovarian syndrome (PCOS). METHODS: We analyzed differences between 27 patients with PCOS and 25 control subjects in serum glucose and leptin levels, insulin resistance, body fat mass, lean body mass, and water volume. RESULTS: Serum leptin was significantly correlated with basal insulin levels, BMI and IR in both groups (P<0.01). Fat mass, fat percentage, lean mass and water volumes were positively correlated and lean percentage and water percentage were negatively correlated with leptin levels (P<0.05). Leptin levels were significantly different between the groups in a multivariate regression analysis after correcting for the difference in BMI and body fat percentage (P<0.05). When the effects of fat percentage on serum leptin were eliminated, the levels were significantly different between the PCOS and control groups, and were statistically more powerful than BMI (P<0.01). CONCLUSION: These findings support the idea that factors other than excess fat mass or fat-free mass might be important in the regulation of serum leptin levels in PCOS.

Adult↗

PubMed2001

Metformin and intervention in polycystic ovary syndrome. Endocrine Society of Australia, the Australian Diabetes Society and the Australian Paediatric Endocrine Group.

Polycystic ovary syndrome (PCOS) is classically characterised by ovarian dysfunction (oligomenorrhoea, anovulation and infertility), androgen excess (hirsutism and acne), obesity, and morphological abnormalities of the ovaries (cystic enlargement and stromal expansion). More recently, insulin resistance has been found to be common in PCOS, along with an increased prevalence of other features of the "metabolic syndrome", namely glucose intolerance, type 2 diabetes mellitus, and hyperlipidaemia. Hyperinsulinaemia is likely to contribute to the disordered ovarian function and androgen excess of PCOS. Reducing insulin resistance by lifestyle modifications such as diet and exercise improves endocrine and menstrual function in PCOS. These lifestyle modifications are the best initial means of improving insulin resistance. Metformin, an oral hypoglycaemic agent that increases insulin sensitivity, has been shown to reduce serum concentrations of insulin and androgens, to reduce hirsutism, and to improve ovulation rates. The effect of metformin alone on fertility rates is unknown. Some studies suggest that metformin will reduce total body weight to a small extent, but with a predominant effect on visceral adipose reduction. The effects of metformin on lipid abnormalities, hypertension or premature vascular disease are unknown, but the relative safety, moderate cost, and efficacy in reducing insulin resistance suggest that metformin may prove to be of benefit in combating these components of the "metabolic" syndrome in PCOS. Further properly planned randomised controlled trials are required.

Diabetes Mellitus, Type 2↗

PubMed1999

[Diagnosis and treatment of polycystic ovary syndrome].

Obesity, ultrasonic ovarian morphology, serum LH levels and LH/FSH ratio are inconstant symptoms of the polycystic ovary syndrome (PCOS) and are thus no longer essential for diagnosis. PCOS is diagnosed today by the finding of chronic anovulation and hyperandrogenism characterized by a high serum level of "free" testoterone. The other causes of hyperandrogenism, as well as anovulations due to hyperprolactinemia, high levels of FSH and abnormal thyroid function have to be ruled out. PCOS is very often associated with insulin resistance (IR) and hyperinsulinemia (hyper I). From in vitro and vivo studies and treatment of hyper I, it has been shown that the hyper I of PCOS stimulates androgen production. Hyper I of PCOS increases the activity of androgens: by first provoking an important decrease of the sex hormone binding globulin (SHBG) thus increasing the "free", bioactive testosterone level. and then by activating the cytochrome P 450 c 17 alpha enzymatic system that controls androgen production. Subsequent to metformin administration, the reduction of hyper I and androgen serum levels creates a favorable condition for the resumption of ovarian function and clomiphene citrate action. This explains the high percentage of ovulations and pregnancies.

Anovulation↗