Ultrasound examination of polycystic ovaries: is it worth counting the follicles?

BACKGROUND: This study revisited the ultrasonographic diagnostic criteria of polycystic ovary syndrome (PCOS) and studied the relationship between the major hormonal and metabolic features of PCOS and the follicle number per ovary (FNPO). METHODS: This prospective study included 214 women with PCOS compared with 112 women with normal ovaries. Main clinical, biological and ultrasonographic markers of PCOS were assessed during the early follicular phase. RESULTS: The mean FNPO of follicles 2-5 mm in size was significantly higher in polycystic ovaries than in controls, while it was similar within the 6-9 mm range. Setting the threshold at 12 for the 2-9 mm FNPO offered the best compromise between specificity (99%) and sensitivity (75%). Within the 2-5 mm follicular range, we found significant positive relationships between the FNPO and androgens. The FNPO within the 6-9 mm range was significantly and negatively related to body mass index and fasting insulin serum level. CONCLUSIONS: We propose to modify the definition of polycystic ovaries by adding the presence of > or =12 follicles measuring 2-9 mm in diameter (mean of both ovaries). Also, our findings strengthen the hypothesis that the intra-ovarian hyperandrogenism promotes excessive early follicular growth and that further progression cannot proceed normally because of hyperinsulinism and/or other metabolic influence linked to obesity.     

异常月经周期与多囊卵巢综合征的相关性分析

目的分析异常月经周期与多囊卵巢综合征的相关性。方法调查2009年10月-2010年1月期间,在北京妇产医院和北医三院生殖中心的门诊病人810例并采用2003年鹿特丹标准诊断多囊卵巢综合征,分析两者间的关系。结果 1.810名妇女中月经周期异常占68.9%(558/810)。月经稀发和闭经占异常月经周期的99.1%(553/558),月经稀发所占比例最高(65.6%,366/558),月经频发比例最小(0.9%,5/558)。2.随着年龄的增加,月经稀发与闭经的发生率呈逐渐降低的趋势,而正常月经周期所占的比例则逐渐增加(P=0.000)。3.多囊卵巢综合征有523例。在月经稀发患者中多囊卵巢(PCO)占83.3%(305/366);高雄激素血症(HA)占52.7%(193/366)。闭经患者中多囊卵巢占90.4%(169/187);高雄激素血症占61.5%(115/187)。月经稀发和闭经PCOS患者中,均以月经稀发/闭经(O)+多囊卵巢(P)+高雄(H)最多见。O+H亚型与O+P+H比较,O+H主要以月经稀发为主,而O+P+H的闭经率则显著高于经典型O+H。结论月经稀发与PCOS关系密切,可以作为PCOS的第一步筛查指标。要重视月经周期超过35天的妇女。     

Androgen excess fetal programming of female reproduction: a developmental aetiology for polycystic ovary syndrome?

The aetiology of polycystic ovary syndrome (PCOS) remains unknown. This familial syndrome is prevalent among reproductive-aged women and its inheritance indicates a dominant regulatory gene with incomplete penetrance. However, promising candidate genes have proven unreliable as markers for the PCOS phenotype. This lack of genetic linkage may represent both extreme heterogeneity of PCOS and difficulty in establishing a universally accepted PCOS diagnosis. Nevertheless, hyperandrogenism is one of the most consistently expressed PCOS traits. Animal models that mimic fetal androgen excess may thus provide unique insight into the origins of the PCOS syndrome. Many female mammals exposed to androgen excess in utero or during early post-natal life typically show masculinized and defeminized behaviour, ovulatory dysfunction and virilized genitalia, although behavioural and ovulatory dysfunction can coexist without virilized genitalia based upon the timing of androgen excess. One animal model shows particular relevance to PCOS: the prenatally androgenized female rhesus monkey. Females exposed to androgen excess early in gestation exhibit hyperandrogenism, oligomenorrhoea and enlarged, polyfollicular ovaries, in addition to LH hypersecretion, impaired embryo development, insulin resistance accompanying abdominal obesity, impaired insulin response to glucose and hyperlipidaemia. Female monkeys exposed to androgen excess late in gestation mimic these programmed changes, except for LH and insulin secretion defects. In utero androgen excess may thus variably perturb multiple organ system programming and thereby provide a single, fetal origin for a heterogeneous adult syndrome.     

The association between polycystic ovaries and endometrial cancer

BACKGROUND: Women with polycystic ovary syndrome (PCOS) are assumed to be at increased risk of endometrial cancer (EC), albeit of a more differentiated type with better prognosis than in normal women. This study was designed to test these assumptions, as evidence for them is lacking. METHODS: The prevalence of polycystic ovaries (PCO), as a marker of PCOS, was investigated in ovarian sections from 128 women with EC and 83 with benign gynaecological conditions. The expression of the prognostic markers p53, Ki67, Bcl2 and cyclin D1 was also investigated by immunohistochemistry in endometrial tumours from 11 women with PCO and 16 with normal ovaries. RESULTS: Overall, PCO were similarly prevalent in women with EC (8.6%) and benign controls (8.4%); however, in women aged <50 years, PCO were more prevalent in women with EC (62.5 versus 27.3%, P = 0.033). Cyclin D1-expressing endometrial tumours tended to be more prevalent in women with PCO compared to normal ovaries (36.4 versus 6.25%, respectively, P = 0.071). Bcl2-, p53- and Ki67-expressing tumours were similarly prevalent. CONCLUSIONS: The association between PCOS and EC appears confined to premenopausal women. The tendency for cyclin D1-expressing endometrial tumours to be more prevalent in women with PCO challenges the assumption that EC prognosis is improved in women with PCOS.     

Polycystic ovaries after precocious pubarche: relation to prenatal growth

BACKGROUND: In 1998, we revealed a sequence departing from prenatal growth restraint in girls and evolving, through precocious pubarche (PP) in mid-childhood, towards anovulatory and hyperinsulinaemic hyperandrogenism. The latter condition fulfilled the criteria for the diagnosis of polycystic ovary syndrome (PCOS), which was then defined independently of the presence of polycystic ovaries (PCOs). Since 2003, the diagnosis of PCOS has been extended by adding PCO as an alternative criterion. We verified longitudinally over 28 +or- 2 years the prevalence of PCO and its potential relationship to growth before birth in a group of post-PP women (n=14, mean age=28 years; body mass index=24.3 kg/m2) belonging to the original cohort of 35 girls in whom the PP-PCOS sequence was described. METHODS: Endocrine-metabolic variables, body composition (by dual-energy X-ray absorptiometry), carotid intima-media thickness (IMT) and ovarian morphology by transvaginal ultrasonography were assessed in all women. RESULTS: Post-PP women with a birthweight (BW) in the lowest quartile, when compared with post-PP women with a higher BW, had smaller ovaries (mean volume=4.0 versus 9.0 ml; P=0.004) and a much lower prevalence of PCO (0 versus 67%; P=0.006). The remaining variables were similar between BW subgroups. CONCLUSIONS: The presence of a PCO morphology in women with a PP history was found to relate to prenatal growth. It would be of interest to verify whether a similar relationship exists in anovulatory and/or hyperandrogenic women without PP history.     

Polycystic ovary syndrome: a simplified approach based on the evolving set of symptoms

Dear Sir, Polycystic ovary syndrome (PCOS) is the most common endocrinopathyamong women of reproductive age. It has no single accepted definition,though the most widely used indicator is the presence of typicalultrasound features of the polycystic ovaries (Adams et al.,1985) in association with hyperandrogenism and/or chronic anovulationin women     

Polycystic ovary syndrome in men: Stein-Leventhal syndrome revisited

Polycystic ovary syndrome (PCOS), also referred to as Stein-Leventhal syndrome, is one of the most common endocrinopathies. It is characterized by hyperandrogenism, hyperinsulinemia, central obesity, polycystic ovaries, and anovulation. However, some of these manifestations, including the polycystic ovaries, are neither specific for the disorder, nor found in all affected individuals. PCOS appears to be due to one or more primary defects in the upstream gonadotropin/androgen and/or insulin pathway, with the polycystic ovaries being one of many downstream manifestations. Yet, the pathophysiology of PCOS is not completely elucidated. Since the primary defect underlying PCOS may be an upstream endocrine and/or metabolic disturbance, rather than a defect in the ovaries themselves, we hypothesize that this aberration can also arise in men and that the absence of polycystic ovaries in men with other stigmata of the disorder should not eliminate the diagnosis. Our hypothesis is supported by the observation that a genetic susceptibility to PCOS exists, and that PCOS-type manifestations are not limited to women. Indeed, male relatives may suffer from insulin resistance, obesity, diabetes mellitus, and cardiovascular disease. Therefore, recognition of this syndrome in men is important, since pharmacologic treatments identified for women with PCOS may alleviate metabolic problems related to insulin resistance and its sequelae in men with a similar underlying defect. We suggest that first-degree relatives of patients with PCOS should be examined not only for phenotypic features characteristic of PCOS but also for biochemical evidence of hyperinsulinemia and hyperandrogenism. In addition to examining these individuals for obesity, the women should be evaluated for hirsutism and the men should be screened for early-onset male-pattern alopecia and excess hairiness. Serologic evaluation should included the ratio of fasting levels of glucose to insulin, a glucose tolerance test, the free testosterone level and the sex hormone-binding globulin level. Finally, both male and female first-degree relatives of patients with PCOS should be tested for the underlying molecular defect(s) of this condition, once it is identified. As new treatments for PCOS emerge, e.g. insulin-sensitizing drugs, it will be important to determine if these treatments have beneficial effects on the metabolic symptoms and complications in all afflicted patients, regardless of gender.     

Clinical presentation of PCOS following development of an insulinoma: case report

A 24 year old woman presented with a prolonged clinical history of fasting and exertional hypoglycaemia, and was subsequently diagnosed with an insulinoma. Concurrent symptoms of oligomenorrhoea and hyperandrogenism of similar duration were noted. Biochemically, hyperinsulinaemia was observed in association with a raised serum luteinizing hormone (LH), raised testosterone and androstendione concentrations. Surgical removal of the insulinoma resulted in resolution of the clinical and biochemical features of the polycystic ovarian syndrome (PCOS) but minimal change was observed in the ovarian ultrasound appearances. This case demonstrates the role of insulin in mediating the hypersecretion of both LH and androgens in women with polycystic ovaries. We suggest that hyperinsulinaemia converted occult 'polycystic ovaries' to become clinically manifest as 'polycystic ovary syndrome'. This paradigm has clear implications for women with insulin dependent diabetes mellitus who presumably have systemic hyperinsulinaemia.     

Cardiovascular risk in postmenopausal women with the polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is one of the commonest endocrine disorders, affecting 5-10% of the female population of reproductive age. "Classic" PCOS is characterized by clinical or biochemical hyperandrogenism and oligo-ovulation. According to the 2003 Rotterdam criteria, two additional phenotypes are recognized: (1) the ovulatory patient with androgen excess and polycystic ovarian morphology and (2) the anovulatory patient with polycystic ovarian morphology without androgen excess. PCOS is associated with an adverse cardiometabolic profile, consisting of increased total or central adiposity, increased blood pressure, a pro-atherogenic lipid profile, increased inflammatory markers, insulin resistance and abnormal glucose metabolism. Furthermore, the incidence of overt or gestational diabetes mellitus, as well as of preeclampsia is significantly higher in PCOS patients. Among the various PCOS phenotypes, those with evidence of androgen excess have the highest burden of cardiovascular risk. Studies evaluating the incidence of cardiovascular disease in postmenopausal women with PCOS are extremely sparse. The available data so far indicate that coronary heart disease, as well as cerebrovascular disease is more common in postmenopausal PCOS patients. Persisting high androgen levels through the menopause, obesity and maturity onset diabetes mellitus are proposed as the main mechanisms accounting for the increased risk.     

Serum vascular endothelial growth factor concentrations and ovarian stromal blood flow are increased in women with polycystic ovaries

The aim of this study was to determine basal serum vascular endothelial growth factor (VEGF) concentrations and Doppler blood flow changes within the ovarian stroma of women with polycystic ovaries (PCO) and women with normal ovaries. Pulsed and colour Doppler blood flows within the ovarian stroma were recorded, and serum VEGF concentrations measured, in the early follicular phase (days 2-3 of a menstrual cycle) in 60 women undergoing ovarian stimulation for in-vitro fertilization. 36 women had normal ovaries, 14 women had PCO as seen on pelvic ultrasound examination and 10 had polycystic ovarian syndrome (PCOS). Mean+/-SD serum VEGF concentrations were significantly higher (P < 0.001) in women with PCO and PCOS (3.4+/-0.7 and 3.2+/-0.66 ng/ml respectively) compared with women with normal ovaries (2.3+/-0.5 ng/ml). Mean peak systolic blood flow velocity (PSV) and time-averaged maximum flow velocity (TAMXV) were significantly higher (P < 0.001) in women with PCO and PCOS compared with women with normal ovaries. The mean PSV were 15+/-4 and 16+/-4 cm/s in women with PCO and PCOS respectively, compared with 9+/-2 cm/s in women with normal ovaries. The TAMXV were 9+/-3 and 11+/-3 cm/s in women with PCO and PCOS respectively compared with women with normal ovaries (5.8+/-1.5 cm/s). Serum VEGF concentrations were positively correlated with PSV (r=0.44, P=0.001) and TAMXV (r=0.45, P < 0.000) in all three groups of women. Higher serum concentrations of VEGF in women with PCO and PCOS may relate to the increased vascularity that underlies the increased blood flow demonstrated by Doppler blood flow velocity measurements in these women. The results may explain the higher risk of ovarian hyperstimulation syndrome in programmes of ovarian stimulation in patients with PCO compared with those with normal ovaries.      

Insulin stimulation of lactate accumulation in isolated human granulosa- luteal cells: a comparison between normal and polycystic ovaries

Polycystic ovary syndrome (PCOS) is often associated with hyperinsulinaemia and peripheral insulin resistance. Whether the ovary is resistant to insulin is a matter of controversy. The aim was therefore to study the effect of insulin on lactate accumulation, an indicator of glucose metabolism, in granulosa-luteal cells from women with PCOS and from women with normal ovarian function. The cells were obtained from women undergoing clinical in-vitro fertilization-embryo transfer, either from patients with normal ovarian function and tubal or male infertility, or from women with PCOS, with or without tubal factor. The patients were down-regulated with buserelin and stimulated with urofollitrophin and human chorionic gonadotrophin (HCG). Follicle aspiration was performed under ultrasound guidance. Following oocyte recovery the granulosa-luteal cells were isolated, washed and cultured (2-3 x 10(4) viable cells/well) in serum-free Eagle's minimal essential medium for 48 h. After washing, the cells were then cultured in medium containing HCG (0.1-10 IU/ml) or insulin (0.05-0.5 microg/ml) for 24-48 h. Lactate accumulation in the media and cellular protein were analysed. Basal lactate accumulation did not differ in granulosa-luteal cells obtained from normal or PCOS ovaries, and averaged 46 and 49 nmol/g protein/24 h, respectively. A significant stimulation (40-60%) was obtained by HCG in both groups. Insulin caused a dose-dependent increase in lactate in granulosa-luteal cells obtained from normal ovaries (control: 45.5 +/- 6.3; insulin 0.5 microg/ml: 77 +/- 10 nmol/microg protein). Lactate accumulation in granulosa-luteal cells from PCOS ovaries was not altered in the presence of insulin. These results suggest that granulosa-luteal cell glucose metabolism is resistant to insulin in PCOS.      

Visceral fat is associated with cardiovascular risk in women with polycystic ovary syndrome

BACKGROUND: Women with polycystic ovary syndrome (PCOS) have been reported to have subclinical cardiovascular disease (CVD) and increased abdominal fat. The aim of this study was to evaluate the relationship between visceral fat (VF) and early markers of CVD in PCOS women. METHODS: Two hundred overweight PCOS women [(mean +/- SD) age 24.6 +/- 3.2 years, body mass index (BMI) 28.5 +/- 2.8 kg/m2] and 100 healthy age- and BMI-matched volunteer controls entered this cross-sectional study. In all subjects, the amount of VF was measured by ultrasonography. Anthropometric measurements [BMI and waist circumference (WC)], complete hormonal and metabolic pattern, carotid intima-media thickness (IMT), brachial arterial flow-mediated dilation (FMD) and inflammatory biomarkers [C-reactive protein (CRP), fibrinogen, white blood cells count and plasminogen activated inhibitor-1] were also obtained from all subjects. A stepwise linear regression model was used in PCOS patients to verify if IMT or FMD as dependent variables are affected by other independent variables. RESULTS: VF amount was significantly (P < 0.001) higher in PCOS subjects than in healthy controls [31.4 +/- 7.3 versus 28.0 +/- 6.1 (mean+/-SD) mm, respectively] and directly related to insulin resistance: HOMA (r = 0.918, P < 0.001) and AUC(INS) (r = 0.879, P < 0.001), and to WC (r = 0.658; P < 0.001). In PCOS, the two linear regression analyses showed that IMT is positively affected by VF and CRP, whereas FMD is positively affected by IMT and negatively by VF and CRP. CONCLUSIONS: VF amount is associated with subclinical CVD in PCOS patients.     

A new perspective in diagnosing polycystic ovary syndrome

Recently, the term of "possible" polycystic ovary syndrome (PCOS) has been used for defining cases in which biochemical evaluations are incomplete but clinical phenotypes are suggestive of PCOS. The aim of this study was, by using Rotterdam 2003 criteria, to detect possible PCOS cases and compare their characteristics and insulin sensitivity status with confirmed PCOS subjects. One-hundred-eighteen women who admitted with complaints and symptoms suggesting PCOS were included. Insulin sensitivity status of the cases was calculated with Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). Cases fulfilling Rotterdam 2003 criteria were defined as confirmed PCOS, whereas indeterminate subjects as possible PCOS. Confirmed PCOS was detected in 70 (59.3%) and possible PCOS in 48 (40.7%) cases. Confirmed PCOS was most prevalent among subjects with hirsutism and menstrual dysfunction; 32 (80.0%) vs. 8 (20%), (p=0.000). Body mass index and HOMA-IR values did not differ between groups: confirmed PCOS versus possible PCOS; 25.46+/-5.55 kg/m(2) vs. 26.75+/-7.55 kg/m(2), 3.37+/-4.12 vs. 3.21+/-2.50, (p>0.05). Family history of type-2 diabetes mellifus was similar within both groups (p>0.05). Many PCOS patients seem to be undiagnosed due to inadherence to diagnostic work-up and/or to not fulfill Rotterdam 2003 criteria. These criteria may not be sufficient to cover the entire spectrum of PCOS.     

Selective alterations in insulin receptor substrates-1, -2 and -4 in theca but not granulosa cells from polycystic ovaries

The elevated insulin concentrations that occur in many women with polycystic ovary syndrome (PCOS) can contribute significantly to ovarian hyperandrogenism. The objective of the present study was to compare the content of proximal insulin signalling molecules in theca and granulosa cells between polycystic ovaries and regular cycling controls. Individual follicles (3-7 mm) were obtained from 11 women with PCOS and 10 regularly cycling control women. The theca and granulosa cells were microdissected from each follicle. Total protein was extracted and signalling proteins were measured by western blot analysis. There was no difference in insulin receptor content between PCOS and controls in either theca or granulosa cells. Insulin receptor substrate (IRS)-1 and -2 were increased (P<0.05), but IRS-4 was decreased (P<0.03) in PCOS theca cells. There were no changes in IRS-1, -2 or -4 in granulosa cells. IRS-3 was undetectable in all samples. There were no changes in phosphatidyl inositol-3 kinase catalytic subunits p110alpha or p110beta in either theca or granulosa cells. These data demonstrate cell-specific alterations in IRS protein concentrations in theca cells from polycystic ovaries that are consistent with an exaggerated amplification of the insulin signal and which may play an important role in ovarian hyperandrogenism and thecal hyperplasia.     

Microvascular dysfunction in women with polycystic ovary syndrome

BACKGROUND: Polycystic ovary syndrome (PCOS) is associated with multiple cardiovascular risk factors and an increased prevalence of arterial dysfunction. However, microvascular dysfunction in PCOS has not been assessed. METHODS: Subjects comprised 12 women with PCOS and 12 age-matched controls with normal ovaries. Microvascular function was assessed by observing forearm skin microvascular erythrocyte flux responses, to cumulative iontophoretic doses of 1% (w/v) acetylcholine (ACh) and 1% (w/v) sodium nitroprusside (SNP), using laser Doppler imaging. RESULTS: Basal microvascular perfusion was comparable in PCOS and controls. The increase in skin microvascular perfusion in response to ACh was however generally blunted in PCOS women (P = 0.018). Peak ACh-induced erythrocyte flux was also less (p < 0.04) in PCOS women (125.1 +/- 21.7, i.e. 5.3-fold basal flux) than in controls (200.8 +/- 28.5, i.e. 8.3-fold basal flux). Analysis of covariance indicated this effect was unrelated to differences in body mass index or serum testosterone but serum insulin may be a weak confounder. No differences were noted between the PCOS and control groups in their response to SNP. CONCLUSION: Despite its limited sample size studied, this is the first demonstration that women with PCOS exhibit microvascular endothelial dysfunction, indicated by an inhibited vasodilatory response to ACh.     

Epigenetic abnormality: a possible mechanism underlying the fetal origin of polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is one of the most common, yet heterogeneous and complex, endocrine disorders in women of reproductive age. Although the aetiology of PCOS remains uncertain, emerging evidence has indicated that exposure of the female fetus to the hyperandrogenism milieu in utero may result in PCOS phenotype after birth. Such a phenomenon has been formulated as the fetal origin of PCOS, which intends to give a possible explanation for PCOS aetiology. Given that the epigenetic modifications are usually involved in the development and inheritance of many adult diseases with fetal origin, we propose a hypothesis here referred to as "epigenetic abnormality underlying the fetal origin of PCOS". It states that in utero hyperandrogenism exposure may disturb the epigenetic reprogramming in fetal reproductive tissue, thereby resulting in postnatal POCS phenotype in women of reproductive age. Meanwhile, the incomplete erasure of such epigenetic abnormality in germ cells after fertilization may promote the transgenerational inherence of POCS. Thus, this epigenetic abnormality hypothesis has established a novel mechanism for PCOS development and inheritance. If verified, our hypothesis would open new avenues for the possible intervention at the critical period of prenatal life to prevent PCOS development and inheritance in adult women. Moreover, analysis of the epigenetic phenotypes and identification of specific epigenetic changes may help develop new tools for monitoring fetal development under an in utero hyperandrogenism environment.     

High neutrophil count in girls and women with hyperinsulinaemic hyperandrogenism: normalization with metformin and flutamide overcomes the aggravation by oral contraception

BACKGROUND: The endocrine hallmark of polycystic ovary syndrome (PCOS) is hyperinsulinaemic hyperandrogenism; another facet of PCOS is low-grade inflammation. METHODS: In adolescents and young women with hyperinsulinaemic hyperandrogenism (n = 118; mean age 16 years, body mass index 22 kg/m(2)), we analysed whether the PCOS-associated rise in leukocyte count is already detectable at young age and, if so, whether such elevation is lowered by metformin, flutamide-metformin, oral contraception (OC), or their combination. RESULTS: Leukocyte count (x 1000/mm(3)) in patients was high versus controls (7.5 +/- 0.1 versus 6.4 +/- 0.1; P < 0.001) due to a rise in neutrophils (4.2 +/- 0.1 versus 3.0 +/- 0.1; P < 0.001). Randomized studies at mean ages of 12.5 years (n = 24) and 15.2 years (n = 33) demonstrated normalizing effects of metformin (850 mg/day; P < 0.001) and, respectively, metformin plus flutamide (62.5 mg/day) on neutrophil counts; in young women (18.3 years; n = 41), the neutrophil count rose further on OC monotherapy (P = 0.003), but normalized on the same OC plus flutamide-metformin (P < 0.001 versus OC alone). CONCLUSIONS: (i) A high leukocyte count is already present in girls with hyperinsulinaemic hyperandrogenism, and this is due to a raised neutrophil count; (ii) this hyperneutrophilia is attenuated by metformin or flutamide-metformin, and is amplified by OC monotherapy; (iii) if these treatments are combined, the normalizing effect of flutamide-metformin overcomes the OC effect on neutrophil count.     

Metabolic syndrome in young Czech women with polycystic ovary syndrome

METHODS: Sixty-nine young women with polycystic ovary syndrome (PCOS) [age 25.2+/- 4.7 years, with body mass index (BMI) 24.3 +/- 4.8 kg/m2; mean 6 SD] and 73 age-matched healthy females (BMI 22.3 +/- 3.3 kg/m2; mean +/- SD) were evaluated for the occurrence of features of metabolic syndrome according to the Adult Treatment Panel III. RESULTS: Overt metabolic syndrome (the presence of three and more risk factors) was not more common in PCOS women (1/64, 1.6%) than in healthy controls (0/73, 0%). On the other hand, in nearly 50% of PCOS women isolated features of metabolic syndrome, most often a decrease in high-density lipoprotein (HDL) cholesterol, were found. Women with at least one feature of metabolic syndrome were, in comparison with women without any of these features, significantly more obese (P = 0.0001), with lower insulin sensitivity (P = 0.05). When comparing PCOS women according to the degree of insulin sensitivity, as determined by euglycaemic clamp, isolated features of metabolic syndrome were found in 8/17 women above the upper quartile, compared with 11/16 women below the lower quartile of insulin sensitivity (P = 0.20). CONCLUSIONS: Overt metabolic syndrome is only rarely encountered in young Czech females affected by PCOS but its isolated features are relatively frequent, both in young PCOS patients and in age-matched control women.     

Herbal medicine for the management of polycystic ovary syndrome (PCOS) and associated oligo/amenorrhoea and hyperandrogenism; a review of the laboratory evidence for effects with corroborative clinical findings

Background

Polycystic ovary syndrome (PCOS) is a prevalent, complex endocrine disorder characterised by polycystic ovaries, chronic anovulation and hyperandrogenism leading to symptoms of irregular menstrual cycles, hirsutism, acne and infertility. Evidence based medical management emphasises a multidisciplinary approach for PCOS, as conventional pharmaceutical treatment addresses single symptoms, may be contra-indicated, is often associated with side effects and not effective in some cases. In addition women with PCOS have expressed a strong desire for alternative treatments. This review examines the reproductive endocrine effects in PCOS for an alternative treatment, herbal medicine. The aim of this review was to identify consistent evidence from both pre-clinical and clinical research, to add to the evidence base for herbal medicine in PCOS (and associated oligo/amenorrhoea and hyperandrogenism) and to inform herbal selection in the provision clinical care for these common conditions.

Methods

We undertook two searches of the scientific literature. The first search sought pre-clinical studies which explained the reproductive endocrine effects of whole herbal extracts in oligo/amenorrhoea, hyperandrogenism and PCOS. Herbal medicines from the first search informed key words for the second search. The second search sought clinical studies, which corroborated laboratory findings. Subjects included women with PCOS, menstrual irregularities and hyperandrogenism.

Results

A total of 33 studies were included in this review. Eighteen pre-clinical studies reported mechanisms of effect and fifteen clinical studies corroborated pre-clinical findings, including eight randomised controlled trials, and 762 women with menstrual irregularities, hyperandrogenism and/or PCOS. Interventions included herbal extracts of Vitex agnus-castus, Cimicifuga racemosa, Tribulus terrestris, Glycyrrhiza spp., Paeonia lactiflora and Cinnamomum cassia. Endocrine outcomes included reduced luteinising hormone (LH), prolactin, fasting insulin and testosterone. There was evidence for the regulation of ovulation, improved metabolic hormone profile and improved fertility outcomes in PCOS. There was evidence for an equivalent effect of two herbal medicines and the pharmaceutical agents bromocriptine (and Vitex agnus-castus) and clomiphene citrate (and Cimicifuga racemosa). There was less robust evidence for the complementary combination of spirinolactone and Glycyrrhiza spp. for hyperandrogenism.

Conclusions

Preclinical and clinical studies provide evidence that six herbal medicines may have beneficial effects for women with oligo/amenorrhea, hyperandrogenism and PCOS. However the quantity of pre-clinical data was limited, and the quality of clinical evidence was variable. Further pre-clinical studies are needed to explain the effects of herbal medicines not included in this review with current clinical evidence but an absence of pre-clinical data.

     

A meta-analysis of pregnancy outcomes in women with polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a common reproductive disorder associated with many characteristic features, including hyperandrogenaemia, insulin resistance and obesity which may have significant implications for pregnancy outcomes and long-term health of the woman. This meta-analysis was conducted to evaluate the risk of pregnancy and neonatal complications in women with PCOS. Electronic databases were searched for the following MeSH headings: PCOS, hyperandrogenism, pregnancy outcome, pregnancy complications, diabetes mellitus, type II. A handsearch of human reproduction and fertility and sterility was also conducted. Studies in which pregnancy outcomes in women with PCOS were compared with controls were considered for inclusion in this meta-analysis. Fifteen of 525 identified studies were included, involving 720 women presenting with PCOS and 4505 controls. Women with PCOS demonstrated a significantly higher risk of developing gestational diabetes [odds ratio (OR) 2.94; 95% confidence interval (CI): 1.70-5.08], pregnancy-induced hypertension (OR 3.67; 95% CI: 1.98-6.81), pre-eclampsia (OR 3.47; 95% CI: 1.95-6.17) and preterm birth (OR 1.75; 95% CI: 1.16-2.62). Their babies had a significantly higher risk of admission to a neonatal intensive care unit (OR 2.31; 95% CI: 1.25-4.26) and a higher perinatal mortality (OR 3.07; 95% CI: 1.03-9.21), unrelated to multiple births. In conclusion, women with PCOS are at increased risk of pregnancy and neonatal complications. Pre-pregnancy, antenatal and intrapartum care should be aimed at reducing these risks.