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PubMed1998

Phenotype and genotype in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a common disorder in premenopausal women and is characterized by hyperandrogenic chronic anovulation. The cause is unknown. PCOS is associated with significant insulin resistance as well as with defects in insulin secretion. These abnormalities place these women at substantial risk for developing type 2 diabetes mellitus. A defect in insulin-mediated receptor autophosphorylation has been found in a substantial proportion of PCOS women. Both PCOS and the insulin resistance that accompanies it appear to have major genetic components. Family studies of PCOS have supported this, although they suffer from incomplete phenotyping of probands and first-degree relatives. The phenotype in males and nonreproductive age females is uncertain. Despite the shortcomings of the family studies of PCOS, they have consistently indicated familial clustering and suggested that the mode of inheritance is dominant. Our initial studies of 50 families of PCOS probands indicate that 24% of sisters are affected with PCOS. There also appears to be an intermediate phenotype of sisters with regular menstrual cycles who are hyperandrogenic per se (22% of sisters). Additionally, there appears to be a major familial defect, with 50% of first-degree relatives having glucose intolerance (impaired glucose tolerance by oral glucose tolerance test or type 2 diabetes mellitus). These findings suggest that hyperandrogenism in females and glucose intolerance may be genetic traits in PCOS kindreds. Systematic phenotyping will allow assignment of affected status for eventual linkage analysis.

Female↗

PubMed2025

Gut microbiota: a hidden player in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is an endocrine disorder that affects reproductive-aged women worldwide, causing hormonal imbalances and ovarian dysfunction. PCOS affects metabolic health and increases the risk of obesity, insulin resistance, and cardiovascular disease, in addition to infertility. This review delves deeper into the connections of gut microbiota with PCOS pathophysiology, particularly into its impact on hormone metabolism, obesity, inflammation, and insulin resistance by way of short-chain fatty acids, lipopolysaccharides, and gut-brain axis. Studies also show that changes in the metabolic processes and immune responses are seen in changes in the gut microbiota in PCOS subjects, such as changes in the Bacteroidetes and Firmicutes groups. Some bacteria, like Escherichia and Shigella, have been associated with dysbiosis in patients with PCOS, leading to systemic inflammation and changed hormone levels, which further worsen the clinical symptoms. Therapeutic interventions targeting the gut microbiota comprise probiotics, prebiotics, and fecal microbiota transplantation; these have potential to alleviate the symptoms of PCOS. Other precision microbiome-based therapies include postbiotics, and CRISPR-Cas9 genome editing, which are relatively new avenues toward precision treatment. This complex interlink of gut microbiota and PCOS pathophysiology will open the avenues for possible treatments for hormonal imbalances and metabolic problems that characterize these complex disorders. The review here focuses on the requirement of further studies to be able to elucidate the specific pathways relating gut microbiota dysregulation to PCOS and, thus, improve microbiome-based therapies for better clinical outcomes in affected individuals.

Humans↗

PubMed2025

Polycystic ovary syndrome and idiopathic central precocious puberty: two sides of the same coin?

PURPOSE: Several studies have reported an association between central precocious puberty (CPP) and a higher prevalence of polycystic ovary syndrome (PCOS), raising the hypothesis that CPP may act as an early-life indicator of increased PCOS risk. This review investigates the shared genetic, epigenetic, and environmental factors potentially underlying CPP and PCOS, with the aim of clarifying their connection and supporting advances in early detection and management. METHODS: A comprehensive literature review was conducted using the PubMed/MEDLINE database, prioritizing research from the past two decades, supplemented by key studies from earlier years. This research included studies on genetic and epigenetic factors, endocrine-disrupting chemicals (EDCs), and metabolic influences related to CPP and PCOS. Both original research and review articles were selected, focusing on the identification of pathophysiological mechanisms and risk factors linking these disorders. RESULTS: Genome-wide association studies (GWAS) have linked genetic variants in the kisspeptin and neurokinin B signaling pathways to increased gonadotropin-releasing hormone (GnRH) secretion, triggering early puberty. Moreover, increased GnRH pulsatility contributes to elevated luteinizing hormone (LH) levels, altered LH/follicle-stimulating hormone (FSH) ratios, and ovarian hyperandrogenism—key pathophysiological features of PCOS. Additionally, epigenetic modifications, particularly changes in DNA methylation at CpG sites, have been observed in both CPP and PCOS. A hyperandrogenic intrauterine environment and inadequate fetal growth contribute to prenatal epigenetic alterations, while postnatal factors such as obesity, insulin resistance, and exposure to EDCs further influence epigenetic modifications. Although insulin resistance and hyperandrogenism are central features linking CPP to PCOS, the precise mechanisms underlying these associations remain complex and not yet fully elucidated. CONCLUSIONS: Identifying shared genetic and environmental factors influencing early puberty onset and PCOS highlights the importance of close clinical monitoring in early life, though preventive interventions remain unproven. Further research is needed to clarify these mechanisms, which will support the development of more precise prevention and treatment strategies in clinical practice.

Humans↗

PubMed2006

Mild androgen phenotypes.

Mild androgen phenotypes are found in 30-40% of patients referred to an endocrine clinic because of suspected hyperandrogenic syndrome. These disorders are characterized by clinical or biological signs of hyperandrogenism in women with normal ovulatory menstrual cycles. Three main mild androgen disorders may be distinguished: ovulatory polycystic ovarian syndrome (PCOS), idiopathic hyperandrogenism, and idiopathic hirsutism. Ovulatory PCOS includes ovulatory hyperandrogenic patients presenting with polycystic ovaries. Using ESHRE/ASRM criteria for diagnosis of PCOS, this disorder is now part of PCOS spectrum. While in vivo and in vitro studies have confirmed the similarities between the two forms of PCOS, ovulatory PCOS presents clinicians with some unique problems. In fact, fertility is not a problem, but insulin resistance is present, and although milder than in classic PCOS it may be associated with an increased cardiovascular and metabolic risk. Because of this, an ovarian sonography should be performed in all ovulatory hyperandrogenic patients, and when polycystic ovaries are found cardiovascular and metabolic risk should be carefully evaluated. Ovulatory PCOS patients with altered glucose tolerance and/or with dyslipidaemia may need treatment with insulin-sensitizing agents. Idiopathic hyperandrogenism regroups ovulatory patients with increased androgen levels and normal ovaries, while idiopathic hirsutism includes ovulatory patients presenting with hirsutism but normal circulating androgens and normal ovaries. The differentiation between these two disorders may be difficult because commercial assays of androgen levels are generally unreliable. While idiopathic hyperandrogenism may be associated with insulin resistance, neither disorder is associated with an increased cardiovascular risk. The main clinical problem is hirsutism, and this may be approached by aesthetic or pharmacological therapies.

Adult↗

PubMed2005

Anatomical evidence for in utero androgen exposure in women with polycystic ovary syndrome.

OBJECTIVE: To determine whether women with polycystic ovary syndrome (PCOS) have masculinized finger length patterns compared to women without PCOS. DESIGN: A case control study. SETTING: University teaching hospital and in vitro fertilization unit. PATIENT(S): Seventy women aged between 18 and 40 years with PCOS were compared to 70 women without PCOS. INTERVENTION(S): Measurement of the second to fourth finger length ratio on the ventral surface of the left and right hand from the basal crease of the digit to the tip was made using Vernier calipers. MAIN OUTCOME MEASURE(S): The second to fourth finger length ratio. RESULT(S): We found a significantly reduced ratio in the right hand of the women with PCOS compared to the controls. The geometric mean right finger length ratio in the PCOS group was 98.3% that of the controls (95% confidence interval, 99.3%-97.3%). CONCLUSION(S): Here we show a subtle difference in the finger length pattern of women with PCOS. This may constitute anatomical evidence of in utero androgen exposure in PCOS.

Adolescent↗

PubMed2005

Müllerian-inhibiting substance reflects ovarian findings in women with polycystic ovary syndrome better than does inhibin B.

OBJECTIVE: To investigate Müllerian-inhibiting substance (MIS) levels in women with polycystic ovary syndrome (PCOS), as well as relationships to ovarian morphology, levels of inhibin B, and other reproductive hormones. DESIGN: Prospective clinical study. SETTING: Academic endocrinology centers in Palermo, Italy and New York. PATIENT(S): Forty-six women with PCOS, recruited on the basis of the classic criteria of chronic anovulation and hyperandrogenism, and 25 age-matched ovulatory controls. INTERVENTION(S): Fasting blood was obtained in all subjects in the early follicular phase (days 5-6) after spontaneous or induced menses (in PCOS), and transvaginal ultrasounds were performed. MAIN OUTCOME MEASURE(S): Assessment of values for luteinizing hormone (LH), testosterone (T), androstenedione (A), estradiol (E2), inhibin B, MIS, fasting insulin, and the calculated quantitative sensitivity check index (QUICKI), as well as assessments of ovarian volume and blood flow. RESULT(S): Women with PCOS had higher LH, T, and A; higher insulin and lower QUICKI; and higher ovarian volume and lower pulsatility index. Inhibin B concentrations were statistically significantly higher in PCOS patients (70 +/- 8.0 vs. 40 +/- 3.4 pg/mL), as was MIS (6.7 +/- 0.9 vs. 4.6 +/- 0.5 ng/mL). Inhibin B had a statistically significant direct correlation with levels of MIS (r = 0.351). However, MIS, but not inhibin B, had a statistically significant positive correlation with ovarian size (r = 0.350); the reproductive hormones LH, T, A, and E2; and insulin (r = 0.249), independent of body mass index. Women with PCOS with the highest levels of MIS had higher ovarian volumes and values of LH, T, A, and insulin. CONCLUSION(S): Measurements of MIS reflect ovarian findings in PCOS better than levels of inhibin B and are more frequently elevated. However, MIS lacks sensitivity for use as a diagnostic tool in PCOS.

Anovulation↗

PubMed2006

Obesity and insulin resistance but not hyperandrogenism mediates vascular dysfunction in women with polycystic ovary syndrome.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is associated with biochemical evidence of early atherosclerosis; however, data regarding vascular function are controversial. We hypothesized that resistance vessel function (mediated by the endothelium or smooth muscle) would be impaired in women with PCOS and aimed to determine the contribution of hyperandrogenism, obesity, or insulin resistance to vascular dysfunction. DESIGN: Prospective study. SETTING: University practice. PATIENT(S): Women with PCOS (n = 24) and age/weight-matched controls (n = 22). INTERVENTION(S): Vascular function was assessed by measuring forearm vasodilatation in response to both endothelium-dependent (acetylcholine/bradykinin) and endothelium-independent dilators (nitroprusside/verapamil). MAIN OUTCOME MEASURE(S): Resistance vessel function. RESULT(S): Forearm vasodilatation to all four drugs was reduced (>50%) in obese PCOS compared to lean PCOS subjects. There was no significant difference in vascular function between obese or lean women with PCOS compared to corresponding controls. Androgen levels did not correlate with vascular function. Stepwise regression analysis showed that body mass index (BMI) contributed maximally to vascular dysfunction (R(2) = 0.47). CONCLUSION(S): This comprehensive study demonstrates for the first time that obese women with PCOS have markedly reduced vascular smooth muscle function compared to lean subjects with PCOS. In our study obesity and insulin resistance, but not hyperandrogenism, appeared to be significant modulators of vascular function.

Adolescent↗

PubMed2006

Screening for bipolar disorder in women with polycystic ovary syndrome: a pilot study.

OBJECTIVE: Previous reports have attributed polycystic ovary syndrome (PCOS) to valproate treatment in women with bipolar disorder and with epilepsy. However, since high rates of mood disorders have been identified in women with PCOS, we sought to investigate the hypothesis that an intrinsic association may exist between PCOS and bipolar disorder, independent of pharmacotherapy. METHOD: Seventy-eight women identified with PCOS were screened for the presence of bipolar illness using the Mood Disorders Questionnaire (MDQ), a validated self-assessment screen for bipolar disorder. RESULTS: Twenty-eight percent of subjects had either a previous bipolar diagnosis or met MDQ threshold criteria for bipolar screen positivity. Ninety seven percent of previously diagnosed or MDQ screen-positive subjects had no valproate exposure before PCOS diagnosis. LIMITATIONS: Possible selection bias, lack of direct comparison with a control group, and lack of knowledge of specific diagnostic work up for PCOS, should all be considered in interpretation of these results. The MDQ as a self-report screen may be less sensitive to detect bipolar II or NOS than bipolar I disorder, and was not corroborated by a diagnostic interview. CONCLUSION: These preliminary findings suggest a higher rate of bipolar screen positivity among women with PCOS than is expected in the general population, independent of an association with valproate. This observed link between PCOS and bipolar screen-positivity is consistent with a possible shared hypothalamic-pituitary-gonadal axis abnormality.

Adolescent↗

PubMed2006

Interleukin-1 alpha but not interleukin-1 beta gene polymorphism is associated with polycystic ovary syndrome.

Interleukin-1 (IL1) is a multifunctional cytokine and IL1-mediated inflammatory processes have been proposed to influence the processes of ovulation, fertilization and implantation. All these parameters are also affected in women with polycystic ovary syndrome (PCOS). This study investigated the association of common polymorphisms of the interleukin-1 genes (IL1A and IL1B) with the occurrence and clinical characteristics of PCOS. We evaluated one polymorphism of the IL1alpha gene (IL1A C[-889]T) and two of the IL1beta gene (IL1B promoter C[-511]T and IL1B exon 5 position +3953) in 105 Caucasian women with PCOS and 102 healthy Caucasian controls by polymerase chain reaction. For the mutated IL1A allele, allele frequencies in women with PCOS and controls were 60% and 46%, respectively, versus 40% and 54%, respectively, for the wild type allele. Allele frequencies in women with PCOS and controls were 59% (54%) and 61% (41%), respectively, for the mutated IL1B promoter (mutated IL1B exon 5) and 41% (46%) and 39% (59%), respectively, for the wild type alleles. Presence of a polymorphism in the interleukin-1alpha but not the interleukin-1beta gene was found to correlate with the occurrence of PCOS (p=0.04; odds ratio 1.8). The serum level of FSH and subsequent LH/FSH ratio correlated with the polymorphism of IL1A within the PCOS group (p=0.005 and 0.01, respectively). We have shown that a common polymorphism of the interleukin-1alpha but not interleukin-1beta gene is associated with the presence of PCOS and with clinical parameters of women affected by this condition.

Adult↗

PubMed2006

Plasma interleukin 6 levels are elevated in polycystic ovary syndrome independently of obesity or sleep apnea.

Premenopausal women with polycystic ovary syndrome (PCOS) are at a much higher risk for excessive daytime sleepiness, fatigue, and insulin resistance than control women. Elevated levels of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) are presumably part of the pathogenesis of these clinical manifestations. Forty-two obese women with PCOS, 17 body mass index-comparable obese controls, and 15 normal-weight controls free from apnea participated in the study that included one 8-hour nighttime polysomnography, single morning cytokine plasma concentrations, and insulin resistance indices. Women with PCOS exhibited higher plasma concentrations of IL-6 than obese controls, who had intermediate values, or normal-weight controls, who had the lowest values (4.75 +/- 0.5 vs 3.65 +/- 0.4 vs 1.84 +/- 0.3 pg/mL, P < .01). Tumor necrosis factor alpha values were higher in PCOS and obese controls compared with normal-weight controls, but the difference was not statistically significant (4.05 +/- 0.3 vs 3.79 +/- 0.2 vs 3.14 +/- 0.2 pg/mL, P = .103). Based on backward regression analysis, IL-6 levels had a stronger association with the PCOS group than with the obese group, and the sleep or hypoxia variables did not make a significant contribution to either IL-6 or TNF-alpha. Both IL-6 and TNF-alpha correlated positively with body mass index (P < .01) in obese controls but not in women with PCOS. Furthermore, within the PCOS group, IL-6 and TNF-alpha correlated more strongly with indices of insulin resistance than obesity. We conclude that IL-6 levels are elevated in obese women with PCOS independently of obesity or sleep apnea and may represent a pathophysiologic link to insulin resistance.

Adult↗

PubMed2026

Integrative machine learning models to unravel gut microbial dysbiosis and functional disruption in polycystic ovary syndrome.

OBJECTIVE: To study gut microbial diversity and metabolic pathway disruptions in women with PolyCystic Ovary Syndrome (PCOS) compared with healthy controls, and to evaluate the diagnostic potential of microbiome-driven machine learning models. DESIGN: Case-controlled metagenomic data analysis SUBJECTS: Gut metagenomic data from women diagnosed with PCOS and age-matched healthy female controls EXPOSURE: Presence of PCOS MAIN OUTCOME MEASURES: The primary outcome measures will include gut microbial alpha and beta diversity indices, microbial taxon abundance, functional pathway profiles, predicted metabolite levels, microbe-functional pathway-metabolite interaction networks, and the diagnostic accuracy of microbiome-based machine learning models. RESULTS: Alpha and beta diversity analyses revealed marked gut microbial dysbiosis in women with PCOS, despite comparable species richness to healthy controls. Differential abundance analysis identified 41 significantly altered microbial species, including enrichment of proinflammatory taxa, such as Bacteroides vulgatus and Ruminococcus gnavus, and depletion of beneficial commensals, including Roseburia hominis and Prevotella copri. These compositional shifts indicate a proinflammatory microbial community structure in PCOS. Functional profiling demonstrated the upregulation of pathways involved in nucleotide turnover, lipid and carbohydrate metabolism, and neurotransmitter synthesis, potentially contributing to metabolic and neuroendocrine disruption. Network analysis revealed fragmented and unstable microbial-metabolite associations in PCOS compared with cohesive networks in controls. Microbiome-based machine learning models achieved a diagnostic accuracy of 84.25% (area under the curve 0.93), underscoring their predictive potential. CONCLUSION: The gut microbiome in PCOS is characterized by a proinflammatory community structure and disrupted metabolic pathways. These findings demonstrate the diagnostic potential of microbiome-based models and underscore the gut microbiome as a promising target for therapeutic interventions in the management of PCOS.

Polycystic Ovary Syndrome↗

PubMed2000

Serum levels of inhibins are differentially altered in patients with polycystic ovary syndrome: effects of being overweight and relevance to hyperandrogenism.

OBJECTIVE: To explore the abnormalities of serum inhibin isoform concentrations in a large group of patients with polycystic ovary syndrome (PCOS) and to evaluate the influence of body mass index (BMI), age, LH, and androgens on serum inhibin levels. DESIGN: Prospective study. SETTING: Reproductive endocrinology unit of an academic medical center. PATIENT(S): Forty-one women with PCOS were compared with 24 healthy women. INTERVENTION(S): Blood sampling was performed in the early follicular phase in patients and in control women. MAIN OUTCOME MEASURE(S): Serum levels of inhibin A, inhibin B, alpha-inhibin, pro-alphaC (alpha-inhibin precursor proteins), LH, FSH, E(2), T, and androstenedione (A) were assessed in all subjects. RESULT(S): Serum alpha-inhibin levels together with LH, T, and A levels were significantly increased in women with PCOS. Serum inhibin A levels were lower in patients with PCOS than controls (median +/- SD: 7.35 +/- 2.9 vs. 9.4 +/- 4.7 pg/mL), pro-alphaC levels were higher (264 +/- 136.7 vs. 127 +/- 81.5 pg/mL), and inhibin B levels did not differ between the groups (110.5 +/- 51.5 vs. 108 +/- 47.5 pg/mL). Simple regression analysis showed that inhibin A and B levels were negatively correlated with BMI in patients with PCOS (r = -0.43 and r27 kg/m(2)) displayed significantly lower inhibin A and inhibin B levels and a higher pro-alphaC-inhibin A ratio than nonobese patients with PCOS (BMI </=27 kg/m(2)). In this last subgroup, the mean inhibin B level was significantly higher than in controls (median +/- SD: 144 +/- 53.5 vs. 108 +/- 47.5 pg/mL). Partial regression analysis, after controlling for age and BMI, demonstrated that in patients with PCOS, pro-alphaC levels were positively and independently correlated with LH and A levels. CONCLUSION(S): Among women with PCOS, the trend toward an excess serum inhibin B level is observed exclusively in nonobese patients. The higher pro-alphaC levels and the lower inhibin A levels might reflect a defect in the processing of inhibins specific to polycystic ovaries. In addition, our data suggest that pro-alphaC originates from the theca-interstitial cells and could participate in control of the androgen production by these cells.

Adolescent↗

PubMed2000

A variant of the glucocorticoid receptor gene is not associated with adrenal androgen excess in women with polycystic ovary syndrome.

OBJECTIVE: To determine whether the frequency of the N363S variant of the glucocorticoid receptor (GRL) was increased in women with PCOS and adrenal androgen (AA) excess. DESIGN: Prospective case-control study. SETTING: University reproductive endocrinology laboratory and outpatient clinic. PATIENT(S): Consecutive patients of non-Hispanic white race diagnosed with PCOS (n = 114) and healthy controls (n = 92). INTERVENTION(S): Blood and DNA sampling before hormonal therapy. MAIN OUTCOME MEASURE(S): PCOS patient and healthy control genotypes, with the N363S allele representing a variant of GRL. RESULT(S): Fifty-four PCOS patients with (DHEAS > or = 3000 ng/mL) and 55 without (DHEAS < or = 2,500 ng/mL) AA excess, respectively, were studied. Six of 109 (5.5%) patients studied were found to be heterozygous carriers of the A-->G base pair substitution at cDNA position 1220, resulting in the missense mutation N363S. Of these six, four had excessive AA secretion (i.e., excess DHEAS levels). There was no significant difference in the allele frequency of the GRL variant between PCOS patients with and without AA excess and controls (3.7% [95% confidence interval: 1.0%-5.7%], 1.8% [0.2%-6. 0%], and 3.3% [2.3%-6.0%]). None of the subjects were found to be homozygous for the N363S allele. CONCLUSION(S): The N363S variant of GRL was an uncommon occurrence in our population of healthy women and PCOS patients and did not appear to play a major role in the genetic predisposition to PCOS or to AA excess in PCOS.

Adrenal Glands↗

PubMed2001

In vitro maturation and fertilization of oocytes from unstimulated normal ovaries, polycystic ovaries, and women with polycystic ovary syndrome.

OBJECTIVE: To investigate differences in immature oocyte maturation, fertilization, and pregnancy rates among women with unstimulated normal ovaries, polycystic ovaries (PCOs), or PCOS. DESIGN: Prospective observational study. SETTING: University fertility clinic. PATIENT(S): One hundred forty-four women undergoing 180 in vitro oocyte maturation treatment cycles. INTERVENTION(S): Transvaginal immature oocyte recovery from unstimulated ovaries 36 hours after hCG priming. In vitro oocyte maturation and fertilization. Fresh embryo transfer. MAIN OUTCOME MEASURE(S): Immature oocytes collected, metaphase II oocytes, and embryos produced. Implantation and pregnancy rates. RESULT(S): The overall oocyte maturation and fertilization rates attained were 80.3% (1,222 of 1,522) and 76.5% (935 of 1,222), respectively. Significantly fewer immature oocytes were retrieved from normal ovaries (5.1 +/- 3.7) compared with the PCO (10.0 +/- 5.1) or PCOS (11.3 +/- 9.0) groups. Fertilization and cleavage rates were comparable among the three groups. The implantation, pregnancy, and live birth rates per transfer for normal ovaries were 1.5%, 4.0%, and 2.0%, respectively; for PCOs 8.9%, 23.1%, 17.3%, respectively; and for women with PCOS 9.6%, 29.9%, and 14.9%, respectively. CONCLUSION(S): Immature oocytes retrieved from normal ovaries, PCOs, or women with PCOS, when using hCG priming before oocyte retrieval, have a similarly high maturation, fertilization, and cleavage potential. In vitro maturation is a useful treatment option, particularly for women with PCOs.

Cells, Cultured↗

PubMed2002

Relationship between serum müllerian-inhibiting substance and other reproductive hormones in untreated women with polycystic ovary syndrome and normal women.

OBJECTIVE: To examine the relationship of serum müllerian-inhibiting substance (MIS), E(2), free-T, LH, and FSH in untreated women with polycystic ovary syndrome (PCOS) and in women with normal menstrual cycles. DESIGN: A prospective study. SETTING: University Departments of Obstetrics and Gynecology and Surgery. PATIENT(S): Twenty-seven women with PCOS and 20 women with normal menstrual cycles. INTERVENTION(S): Serum was collected from women with PCOS and from normal women during the early follicular phase of the menstrual cycle, stored frozen until assayed. MAIN OUTCOME MEASURE(S): Serum levels of MIS, E(2), free-T, TSH, LH, and FSH were measured. RESULT(S): Serum müllerian-inhibiting substance levels in PCOS patients were significantly higher compared with normal women (+/- SE; 5.3 +/- 0.7 and 1.4 +/- 0.2 ng/mL, respectively). An inverse correlation (r = -0.5965) was found between serum levels of MIS and E(2) in PCOS women, but not in normal women. Women with PCOS had higher serum LH levels than those of normal women (15.2 +/- 1.2 and 5.0 +/- 0.7 mIU/mL). CONCLUSION: In this study, women with PCOS have significantly higher serum MIS levels than normal women. The inverse relationship between müllerian-inhibiting substance and E(2) levels suggests that MIS may modulate ovarian E(2) synthesis and have a role in the disordered folliculogenesis characteristic of PCOS.

Adult↗

PubMed2002

Molecular progress in infertility: polycystic ovary syndrome.

OBJECTIVE: To review the evidence that polycystic ovary syndrome is a genetic disease. DESIGN: Review of published literature. RESULTS: The existing literature provides a strong basis for arguing that PCOS clusters in families. However, the mode of inheritance of the disorder is still uncertain, although the majority of studies are consistent with an autosomal dominant pattern, modified perhaps by environmental factors. In addition, studies on PCOS cells (theca, muscle, and adipocytes) in culture have documented a persistent biochemical and molecular phenotype that distinguishes them from normal cells. Although several loci have been proposed as PCOS genes including CYP11A, the insulin gene, and a region near the insulin receptor, the evidence supporting linkage is not overwhelming. The strongest case can be made for the region near the insulin receptor gene, as it has been identified in two separate studies. However, the responsible gene at chromosome 19p13.3 remains to be identified. Association studies have provided a number of potential loci with genetic variants that may create or add to a PCOS phenotype, including Calpain 10, IRS-1 and -2, and SHBG. CONCLUSIONS: Collectively, these findings are consistent with the concept that a gene or several genes are linked to PCOS susceptibility. Because the mutations/genotypes associated with PCOS are rare, and their full impact on the phenotype incompletely understood, routine screening of women with PCOS or stigmata of PCOS for these genetic variants is not indicated at this time. Currently the treatment implications for individually identified genetic variants is uncertain and must be addressed on a case by case basis.

Cells, Cultured↗

PubMed1993

The influence of luteinizing hormone and insulin on sex steroids and sex hormone-binding globulin in the polycystic ovarian syndrome.

OBJECTIVE: To examine the relationship between hyperinsulinemia, sex hormone-binding globulin (SHBG), and body mass index (BMI) on LH-induced hyperandrogenemia in patients with polycystic ovarian syndrome (PCOS). DESIGN: Insulin responses during an oral glucose tolerance test (OGTT) were assessed in 25 consecutive women with PCOS and 20 control women matched for BMI. Insulin responses and sensitivity (SI) were also determined using a frequently sampled intravenous glucose tolerance test (IVGTT). SETTING: The clinical research center at a university medical center. MAIN OUTCOME MEASURES: Serum LH, SI, and basal, peak, and area under the curve (AUC-insulin responses) were determined and correlated with SHBG, androstenedione (A), T, and free T concentrations. RESULTS: Compared with controls, the AUC-insulin response during OGTT was greater in PCOS, with an average increase of 44%. During IVGTT, AUC-insulin response was also significantly higher in PCOS versus controls, with an average increase of 53%. In addition, SI was reduced in PCOS versus controls with an average decrease of 53%. The average differences in oral- and intravenous-glucose-induced hyperinsulinemia and in insulin sensitivity between PCOS and controls were relatively constant across the entire physiological range of BMI. In PCOS, baseline LH showed strong positive correlations with baseline A and T. However, there were no significant correlations between either basal, peak, or AUC-insulin response during OGTT and IVGTT with basal T or A concentrations or between insulin and androgen levels measured at 30-minute intervals throughout the OGTT. However, basal, peak, and AUC-insulin responses during OGTT were strongly correlated with fasting SHBG binding capacity. CONCLUSIONS: These data are consistent with the hypothesis that hyperinsulinemia in PCOS influences the biologically active component of T by lowering SHBG concentrations while having little apparent impact on LH-induced secretion of androgens in vivo.

Administration, Oral↗

PubMed1994

Insulin sensitivity in women with polycystic ovary syndrome: relationship to hyperandrogenemia.

OBJECTIVE: To evaluate the extent of decreased insulin sensitivity in relation to body mass index and its relationship to serum androgens in women with polycystic ovarian syndrome (PCOS). DESIGN: Comparative study of endogenous glucose disposal and serum insulin responses to oral glucose load with endocrine parameters in PCOS. SETTING: Fertility and Endocrine Clinics, North Staffordshire Hospital Centre. PATIENTS: Forty-nine obese and 16 nonobese women with PCOS were compared with 18 obese and 16 nonobese control women with regular ovulatory cycles and no features of PCOS. MAIN OUTCOME MEASURES: Basal concentrations of serum LH, FSH, T, androstenedione, sex hormone-binding globulin (SHBG), and free T index. Measurements of insulin sensitivity by rate of endogenous glucose disposal after i.v. bolus injection of insulin and glucose mediated insulin responses. RESULTS: Obese women with PCOS showed decreased insulin sensitivity and hyperinsulinemia to an extent greater than can be explained by obesity alone. Serum insulin showed inverse correlation with SHBG, and therefore hyperinsulinemia increased the bioavailability of androgens in obese PCOS. In nonobese PCOS, this method of assessment failed to reveal insulin resistance. CONCLUSION: Hyperandrogenemia and insulin resistance are independent features of PCOS. Hyperinsulinemia enhances expression of hyperandrogenemia by increasing bioavailability of androgens.

17-alpha-Hydroxyprogesterone↗