Ovulatory Controls Research Articles

Serum brain natriuretic peptide and C-reactive protein levels in adolescent with polycystic ovary syndrome

Objective: Our primary aim was to investigate whether N-terminal pro-brain natriuretic peptide (NT-proBNP) increases in adolescent with polycystic ovary syndrome (PCOS) compared with healthy controls and secondary aim was to determine whether metabolic and hormonal differences exist between groups. Methods: In this cross-sectional study, 25 adolescent patients with PCOS and 25 normal ovulatory control not suffering from PCOS were involved in the study. Fasting serum NT-proBNP, C-reactive protein (CRP), homocystein, insulin levels and biochemical and hormonal parameters were measured. Results: Serum NT-proBNP was not significantly different in PCOS subjects (0.62 ± 0.80 vs 1.12 ± 1.51 ng/mL, p = 0.154). The mean serum fasting insulin levels (22.64 ± 10.51 vs 13.32 ± 3.97 mIU/mL, p = 0.001) and Homeostasis Model Assessment Insulin–Resistance Index (HOMA-IR) levels (5.16 ± 1.81 vs 2.97 ± 0.89, p = 0.001) were significantly high in the study group. The median serum CRP levels were not significantly different between groups (1 [1–12] vs 1 [1–19] g/dL, p = 0.286). Conclusions: The present study demonstrated that the levels of BNP, CRP and homocystein were not different in PCOS subjects. Serum insulin levels and HOMA-IR were significantly higher in PCOS subjects. Possible serum markers for PCOS-related metabolic abnormalities and cardiovascular events, may not present in the adolescent years.

Mulheres com síndrome dos ovários policísticos apresentam maior frequência de síndrome metabólica independentemente do índice de massa corpóreo Women with polycystric ovary syndrome have a higher frequency of metabolic syndrome regardless of body mass index

To assess the prevalence of metabolic syndrome and of its defining criteria in women with polycystic ovary syndrome from the Brazilian Southeast, who were stratified according to body mass index and compared to ovulatory controls. This was a cross-sectional study conducted on 332 women of reproductive age, who were divided into two groups: Control, consisting of 186 women with regular menstrual cycles and ovulatory symptoms and without a diagnosis of polycystic ovary syndrome or other type of chronic anovulation, and the Polycystic ovary syndrome,Group, consisting of 146 women with a diagnosis of polycystic ovary syndrome (Rotterdam Consensus ASRM/ESHRE). Each group was stratified according to the body mass index, as follows: body mass index ( < 25 ≥25 and <30, and ≥ 30 kg/m²). The frequencies of metabolic syndrome and of its defining criteria and the clinical and hormonal characteristics (follicle stimulating hormone, total testosterone, dehydroepiandrostenedione sulfate) were analyzed. The frequency of metabolic syndrome was six times higher in the obese Polycystic ovary syndrome Group than among control women with the same body mass index (Control with 10.5 versus Polycystic ovary syndrome with 67.9%, p<0.01); twice higher in the Polycystic ovary syndrome Group with body mass index ≥ 25 and <30 kg/m² (Control with 13.2 versus Polycystic ovary syndrome with 22.7%, p<0.01), and three times higher in the Polycystic ovary syndrome Group with body mass index <25 kg/m² (Control with 7.9 versus Polycystic ovary syndrome with 2.5%, p<0.01), compared to control women paired for the same body mass index. Regardless of the body mass index, women with polycystic ovary syndrome had a higher frequency of all the criteria defining metabolic syndrome. Women with polycystic ovary syndrome have higher frequency of metabolic syndrome and of its defining criteria regardless of the body mass index. Hyperinsulinemia and hyperandrogenism are important characteristics of the origin of these alterations, especially in obese women with polycystic ovary syndrome.

Role of the CAG Repeat Polymorphism of the Androgen Receptor Gene in Polycystic Ovary Syndrome (PCOS)

Polycystic ovary syndrome (PCOS) is a frequent heterogenic disorder with a familial background. Androgenic effects, determining the clinical features of the syndrome, are mediated by the androgen receptor (AR), whose activity is modulated by a genetic polymorphism. We investigated the role of the CAG repeat polymorphism of the androgen receptor in PCOS. In the infertility unit of a university clinic, 72 PCOS patients were compared with 179 ovulatory controls undergoing a standardized diagnostic work-up. The number of CAG repeats was determined by PCR, labelling with IR-800 and PAGE. X-chromosome inactivation was assessed by a methylation-sensitive assay. Compared to controls, PCOS patients displayed a shorter mean CAG repeat length, encoding for higher AR activity (P=0.001). CAG repeat length correlated inversely with oligomenorrhea, a central androgen dependent feature of the syndrome (P=0.005). In a binomial regression analysis including BMI, LH and free testosterone, CAG repeat length was identified as an independent risk factor for PCOS (P=0.002). The CAG repeat polymorphism could constitute one of the genetic factors modulating the syndrome's phenotype, contributing to its clinical heterogeneity and associated metabolic consequences.

The influence of obesity on Androstenedione to Testosterone ratio in women with polycystic ovary syndrome (PCOS) and hyperandrogenemia

The aim of the present study was to evaluate the impact of obesity and insulin resistance on testosterone formation from androstenedione and its contribution to biochemical hyperandrogenemia in all different phenotypic subgroups of PCOS patients. The case-control study included 1087 PCOS women and 206 regularly menstruating, ovulatory controls. The main clinical measurements included anthropometric and basal hormonal characteristics and evaluation of hyperandrogenic and insulin resistance-related features. The results were the following: In PCOS women with biochemical hyperandrogenemia, obesity significantly lowers serum A levels and increases T to A ratio. These findings were not present in PCOS women with clinical hypeandrogenemia and in normal ovulatory controls.

Evaluation of serum antimullerian hormone and inhibin B concentrations in the differential diagnosis of secondary oligoamenorrhea

To evaluate the performance of antimullerian hormone (AMH) and inhibin B as ovarian function markers for differentiating common causes of secondary oligoamenorrhea, namely hypogonadotrophic hypogonadism (HH), polycystic ovary syndrome (PCOS), premature ovarian failure (POF), and hyperprolactinemia (HPRL). Retrospective analysis. Two university hospitals. A total of 124 women with secondary oligoamenorrhea and 26 women with normal ovulation. Serum samples from the subjects were analyzed for AMH and inhibin B. Serum AMH and inhibin B concentrations. Serum AMH concentration was significantly raised in women having World Health Organization group 2 anovulation, either with or without PCOS, and was significantly decreased to very low levels in POF; the diagnostic accuracy in both conditions was excellent, with areas under the receiver operating characteristic curve (AUC) of 0.913 and 0.977, respectively. The discriminatory performance between HH and PCOS was also good, with AUC 0.861. AMH remained unchanged in HH and HPRL compared with ovulatory control subjects. There were large overlap of serum inhibin B levels in the different conditions, and a significant difference from control subjects existed only in the POF group. Serum AMH, but not inhibin B concentration, serves as a useful diagnostic tool in the differential diagnosis of secondary oligoamenorrhea.

Higher Metabolic Risk with National Institutes of Health Versus Rotterdam Diagnostic Criteria for Polycystic Ovarian Syndrome in Turkish Women

Polycystic ovary syndrome (PCOS) is a heterogeneous disease with well-established metabolic abnormalities in women of reproductive age. There are various diagnostic criteria to define and establish PCOS. However, data conflict regarding the optimal diagnostic criteria for PCOS and its metabolic consequences. We have evaluated the clinical, endocrine, and metabolic features between main PCOS phenotypes according to different diagnostic criteria. In this prospective, case-control study, 175 consecutive women with PCOS, 41 ovulatory women with idiopathic hirsutism, and 109 healthy, nonhirsute, ovulatory controls were enrolled. The following diagnostic criteria were assessed: Hirsutism; ovulatory function; ovarian sonography; gonadotropin, testosterone, dehydroepiandrosterone (DHEA), 17-hydroxyprogesterone, fasting insulin, and lipid levels; oral glucose tolerance test; homeostasis model assessment for insulin resistance (HOMA-IR); body mass index (BMI); waist circumference; and the presence of metabolic syndrome. Of the 175 women meeting the Rotterdam criteria for PCOS, 121 (69%) had both androgen excess and ovulatory dysfunction, thus also meeting the National Institutes of Health (NIH) criteria. The other 54 (31%) had either androgen excess or ovulatory dysfunction. Women meeting the NIH criteria had the largest mean BMI, waist circumference, and HOMA-IR score; the highest mean testosterone, DHEA, triglyceride, and fasting insulin levels; the lowest mean progesterone level; and the greatest prevalence of insulin resistance (HOMA-IR score >3) among the groups. The NIH criteria identify women at high risk for insulin resistance and metabolic syndrome. The Rotterdam criteria include women who have less severe metabolic implications.

Exercising women with menstrual disturbances consume low energy dense foods and beverages

Women with exercise-associated menstrual cycle disturbances (EAMD) restrict energy intake. Reducing energy density (ED; kcals·g(-1) of food or beverage) may be a strategy employed by EAMD women to maintain lower energy intake. The purpose of this study was 3-fold: to determine whether EAMD women consume low ED diets; to identify food groups associated with low ED; and to determine concentrations of total peptide YY (PYY), a satiety factor. Twenty-five active females were divided into 2 groups, according to menstrual status: EAMD (n = 12) and ovulatory controls (OV) (n = 13). Two 3-day diet records were analyzed for ED and other parameters. Body composition, fitness, resting metabolic rate, and PYY were measured. Groups did not differ in age, age of menarche, body mass index, maximal aerobic capacity(), body fat (%), or amount of exercise per week. For fat mass (12.4± 1.7 vs. 14.9± 3.5kg; p = 0.046), energy availability (28.8± 11.5 vs. 42.1± 9.2kcal·kg(-1) FFM; p = 0.006), and energy intake (29.8± 9.2 vs. 36.3± 10.6 kcals·kg(-1) BW; p = 0.023), EAMD was lower than OV. ED was lower in EAMD than in OV (0.77± 0.06 vs. 1.06± 0.09kcal·g(-1); p = 0.018) when all beverages were included, but not when noncaloric beverages were excluded. Vegetable (p = 0.047) and condiment (p = 0.014) consumption and fasting PYY (pg·mL(-1)) (p = 0.006) were higher in EAMD. EAMD ate a lower ED diet through increased vegetable, condiment, and noncaloric beverage consumption, and exhibited higher PYY concentrations. These behaviors may represent a successful strategy to restrict calories and maximize satiety.

Imbalanced circulating matrix metalloproteinases in polycystic ovary syndrome

Altered levels of matrix metalloproteinases (MMPs) may reflect relevant pathogenetic mechanisms of disease conditions. The objective of this study was to compare the plasma levels of MMPs and tissue inhibitors of MMPs (TIMPs) in polycystic ovary syndrome (PCOS) patients with those found in healthy ovulatory controls and to examine whether the levels of these biomarkers are associated with clinical and biochemical features of this syndrome. Sixty-five healthy ovulatory subjects (controls) and 80 patients with PCOS were include in this study. MMP-2, MMP-8, MMP-9, TIMP-1, TIMP-2 concentrations were measured in plasma samples by gelatin zymography or enzyme-linked immunoassays. MMP-2, MMP-8, MMP-9, and TIMP-1 levels were similar in PCOS patients and in healthy controls (P > 0.05). PCOS patients had lower plasma TIMP-2 levels than healthy controls (P < 0.05). We found higher MMP-2/TIMP-2 and MMP-9/TIMP-1 ratios in PCOS patients than in healthy controls (all P < 0.05). Testosterone levels correlated positively with the MMP-9/TIMP-1 ratio and negatively with TIMP-2 levels (r = 0.26, P < 0.01 and r = -0.21, P = 0.02, respectively). In addition, only testosterone was an independent predictor of TIMP-2 levels (estimate = -0.35, P = 0.04) and the MMP-9/TIMP-1 ratio (estimate = 0.01, P = 0.04). We found evidence indicating that the balance between MMPs and TIMPs in women with PCOS is altered, probably due to androgen excess found in these women.

Supplementation of equine early spring transitional follicles with luteinizing hormone stimulates follicle growth but does not restore steroidogenic activity

This study was conducted to test the hypothesis that supplementation of growing follicles with LH during the early spring transitional period would promote the development of steroidogenically active, dominant follicles with the ability to respond to an ovulatory dose of hCG. Mares during early transition were randomly assigned to receive a subovulatory dose of equine LH (in the form of a purified equine pituitary fraction) or saline (transitional control; n = 7 mares per group) following ablation of all follicles >15 mm. Treatments were administered intravenously every 12 h from the day the largest follicle of the post-ablation wave reached 20 mm until a follicle reached >32 mm, when an ovulatory dose of hCG (3000 IU) was given. Saline-treated mares during June and July were used as ovulatory controls. In a preliminary study, injection of this pituitary fraction (eLH) to anestrus mares was followed by an increase in circulating levels of LH (P < 0.01) but not FSH (P > 0.6). Administration of eLH during early transition stimulated the growth of the dominant follicle (Group x Day, P < 0.00001), which attained diameters similar to the dominant follicle in ovulatory controls (P > 0.1). In contrast, eLH had no effect on the diameter of the largest subordinate follicle or the number of follicles >10 mm during treatment (P > 0.3). The numbers of mares that ovulated in response to hCG in transitional control, transitional eLH and ovulatory control groups (2 of 2, 3 of 5 and 7 of 7, respectively) were not significantly different (P > 0.1). However, after hCG-induced ovulation, all transitional mares returned to an anovulatory state. Circulating estradiol levels increased during the experimental period in ovulatory controls but not in transitional eLH or transitional control groups (Group x Day, P = 0.013). In addition, although progesterone levels increased after ovulation in transitional control and transitional eLH groups, levels in these two groups were lower than in the ovulatory control group after ovulation (Group, P = 0.045). In conclusion, although LH supplementation of early transitional waves beginning after the largest follicle reached 20 mm promoted growth of ovulatory-size follicles, these follicles were developmentally deficient as indicated by their reduced steroidogenic activity.

Circadian Control of Kisspeptin and a Gated GnRH Response Mediate the Preovulatory Luteinizing Hormone Surge

In spontaneously ovulating rodents, the preovulatory LH surge is initiated on the day of proestrus by a timed, stimulatory signal originating from the circadian clock in the suprachiasmatic nucleus (SCN). The present studies explored whether kisspeptin is part of the essential neural circuit linking the SCN to the GnRH system to stimulate ovulation in Syrian hamsters (Mesocricetus auratus). Kisspeptin neurons exhibit an estrogen-dependent, daily pattern of cellular activity consistent with a role in the circadian control of the LH surge. The SCN targets kisspeptin neurons via vasopressinergic (AVP), but not vasoactive intestinal polypeptide-ergic, projections. Because AVP administration can only stimulate the LH surge during a restricted time of day, we examined the possibility that the response to AVP is gated at the level of kisspeptin and/or GnRH neurons. Kisspeptin and GnRH activation were assessed after the administration of AVP during the morning (when AVP is incapable of initiating the LH surge) and the afternoon (when AVP injections stimulate the LH surge). Kisspeptin, but not GnRH, cellular activity was up-regulated after morning injections of AVP, suggesting that time-dependent sensitivity to SCN signaling is gated within GnRH but not kisspeptin neurons. In support of this possibility, we found that the GnRH system exhibits pronounced daily changes in sensitivity to kisspeptin stimulation, with maximal sensitivity in the afternoon. Together these studies reveal a novel mechanism of ovulatory control with interactions among the circadian system, kisspeptin signaling, and a GnRH gating mechanism of control.

The Subcutaneous Abdominal Fat and Not the Intra-Abdominal Fat Compartment Is Associated With Anovulation in Women With Obesity and Infertility

A marked increase in anovulation occurs in overweight and obese women. Rates of conception decline both in spontaneous conception and in assisted reproduction with the accumulation of fat around the waist and trunk in women, with a waist-to-hip ratio >0.8, independent of body weight. Although several studies have investigated the contribution of intra-abdominal fat (IAF) and subcutaneous abdominal fat (SAF) compartments to anovulation and reduced conception, their differential effect on anovulation is unclear. This study investigated the individual contribution of IAF and SAF to anovulation in women with obesity and infertility. The participants were 57 volunteers at a mean age of 30 and a mean body mass index (BMI) of 37.7, who were stratified on the basis of ovulatory status into anovulatory (n = 40) and ovulatory (n = 17) groups. The distribution of body fat was measured using anthropometric assessment (body weight, BMI, waist circumference, and waist-to-hip ratio), dual-energy x-ray absorptiometry, and single-sliced abdominal computed tomography scan. Multiple logistic regression analysis was used to determine the independent contribution of IAF, SAF, and other variables to anovulation after adjustment for BMI, testosterone, and fasting insulin. The data showed that anovulatory obese women had a significantly higher waist circumference (113 ± 11 cm vs. 104 ± 9 cm; P < 0.01), abdominal fat (4.4 ± 1.3 kg vs. 3.5 ± 0.9 kg; P < 0.05), and trunk fat (23.0 ± 5.3 kg vs. 19.1 ± 4.2 kg; P < 0.01) on dual-energy x-ray absorptiometry scan compared with the ovulatory obese women, despite nonsignificant differences in BMI, age, and total fat mass. Anovulatory obese women had significantly more SAF than ovulatory women (992 ± 198 vs. 864 ± 146 cm 3 ; P < 0.05). In contrast, IAF made no contribution to anovulatory status. There was no significant difference between anovulatory and ovulatory obese women in the volume of IAF on single-sliced abdominal computed tomography (203 ± 56 vs.195 ± 71 cm 3 ; P < 0.65). Only trunk fat, abdominal fat, and SAF had an independent association with anovulation after adjustment for variables. These findings indicate a differential contribution of SAF and IAF to abdominal fat in anovulatory obese infertile women. SAF, and not the IAF, is significantly increased in anovulatory women compared with the ovulatory controls. SAF accumulation around the abdomen and trunk is associated with anovulation.

Oxidative stress markers in follicular fluid (FF) and assisted reproduction outcomes in patients with infertility due to polycystic ovary syndrome (PCOS) or to tubal and/or male factor

OBJECTIVE: Oxidative stress (OS) is related with worse oocyte quality in PCOS patients, but little is known about follicular environment and assisted reproduction outcomes. The objective was to compare OS markers in the follicular fluid (FF) of non-obese infertile PCOS women and non-obese ovulatory patients with infertility due to tubal and/or male factor (control) submitted to ovarian stimulation (COS) for intracytoplasmic sperm injection (ICSI). We also compared ovarian stimulation response and ICSI results. DESIGN: Prospective study. MATERIALS AND METHODS: The study was conducted on 16 cycles of 15 PCOS patients and 66 cycles of 57 infertile patients due to tubal and/or male factor submitted to COS for ICSI. FF was aspirated from 13 PCOS patients and 40 controls. Malondialdehyde, hydroperoxides, advanced oxidation protein products, glutathione and vitamin E were determined by absorbance and high performance liquid chromatography. The ovarian stimulation response and ICSI results were evaluated in both groups. RESULTS: No significant differences in OS markers levels in FF and ICSI outcomes were observed between the groups (Table 1).Table 1FF levels of OS markers and ICSI outcomes from infertile PCOS and controls.ResultsPCOSControlPMDA (μmol/g pt)23,0 ± 6,321,0 ± 4,40,09AOPP (μmol/L)112,1 ± 59,7107,3 ± 38,90,84FOX (μmol/g pt)5,4 ± 0,45,8 ± 0,70,15GSH (nmol/L)279,1 ± 59,7265,5 ± 71,00,27Vitamin E (μmol/L)8,5 ± 4,68,6 ± 2,80,71Number of produced embryos2,6 ± 1,43,1 ± 1,10,23Clinical Pregnancy rate (%)31,2 (5/16)24,2 (16/66)0,54MDA:Malondialdehyde, FOX:hydroperoxides, AOPP:advanced oxidation protein products, GSH:glutathione. Open table in a new tab MDA:Malondialdehyde, FOX:hydroperoxides, AOPP:advanced oxidation protein products, GSH:glutathione. CONCLUSION: The present study didn't demonstrate OS in FF or worse ICSI outcomes in non-obese, oligomenorrheic, and infertile PCOS women compared to infertile ovulatory controls submitted to controlled ovarian stimulation for ICSI.

Variation in metabolic and cardiovascular risk in women with different polycystic ovary syndrome phenotypes

The aim of this study was to compare clinical, hormonal, and metabolic variables in women with classic polycystic ovary syndrome (PCOS), in ovulatory women presenting hirsutism, normal androgen levels, and polycystic ovaries (H+PCO), and in a group with isolated hirsutism (IH) presenting with normal ovaries and androgen levels. Waist circumference, triglycerides, and homeostasis model assessment values were significantly higher in classic PCOS even after adjustment for body mass index, and metabolic syndrome was three times more frequent in classic PCOS than in H+PCO or IH (31.3% vs. 11.9% vs. 9%), but no differences were observed regarding metabolic profile and cardiovascular risk factors between the H+PCO and IH groups, which presented with significantly more metabolic syndrome than normal controls when only overweight and obese women were considered.

Clinical and endocrine characteristics of the main polycystic ovary syndrome phenotypes

To evaluate the clinical and endocrine differences between main polycystic ovary syndrome (PCOS) phenotypes. To evaluate clinical and hormone parameters in a large group of consecutive women with PCOS diagnosed according Rotterdam criteria and divided according their phenotype. University department of medicine. Three hundred eighty-two consecutive women with PCOS and 85 ovulatory controls. Evaluation of clinical and hormone parameters. Blood levels of gonadotropins, testosterone, sex-hormone-binding globulin, dehydroepiandrosterone sulfate, 17α-hydroxyprogesterone, progesterone, glucose, and insulin, and calculation of the free androgen index and insulin sensitivity. The severe PCOS phenotype (hyperandrogenism, chronic anovulation, and polycystic ovaries: type I classic PCOS) was the most common phenotype in 53.9% of the patients. The phenotype of 8.9% of patients was characterized by hyperandrogenism and chronic anovulation but normal ovaries (type II classic PCOS). The two phenotypes of classic PCOS had similar clinical and endocrine characteristics, but the patients with polycystic ovaries had a higher luteinizing hormone/follicle-stimulating hormone (LH/FSH) ratio. Ovulatory PCOS was relatively common (28.8% of PCOS patients) and presented milder clinical and endocrine alterations than the classic PCOS phenotypes. The normoandrogenic phenotype was relatively uncommon. These patients had a normal body mass index, insulin sensitivity, and free androgen index but showed increased levels of LH and LH/FSH ratio. Ovulatory PCOS represents the mild form of classic PCOS, but the normoandrogenic phenotype, although part of the spectrum, may represent a different disorder or have a different pathogenetic pathway.

Decreased active, total and altered active to total ghrelin ratio in normal weight women with the more severe form of polycystic ovary syndrome

Objective To assess total, active and active to total serum ghrelin ratio in normal weight women with polycystic ovary syndrome (PCOS) and in healthy ovulatory control women.Study design: The study included 50 normal weight women with PCOS with a mean age of 23.70 ± 4.99 years and 10 control women with a mean age of 30 ± 5.80 years. The diagnosis of PCOS was based on the presence of biochemical hyperandrogenemia, chronic anovulation and polycystic ovarian morphology according to the Rotterdam ESHRE/ASRM-sponsored PCOS Consensus Workshop Group. Serum total and active ghrelin were measured by RIA, using commercially available kits. Results A significantly lower serum active/total ghrelin ratio was noted in the more severe form of PCOS with hyperandrogenemia, chronic anovulation and polycystic ovarian morphology. Both total and active serum ghrelin levels were negatively correlated to hirsutism score, to plasma glucose levels and to QUICKI and HOMA-IR indices of Insulin Resistance. A statistically significant difference was detected between the more severe and the milder forms of PCOS, concerning serum levels of total ghrelin ( p = 0.017), active ghrelin ( p = 0.007) and the active/total ghrelin ratio ( p = 0.026). Conclusions The results of the present study demonstrate an altered active to total ghrelin ratio, as well as a tendency towards lower both total and active fasting serum ghrelin levels in normal weight PCOS, more pronounced in the more severe forms of the syndrome.

Comparison of inhibin B and estradiol responses to intravenous FSH in women with polycystic ovary syndrome and normal women

Inhibin B (Inh B) is produced by pre-antral and early antral follicles whereas estradiol (E(2)) is a product of follicles undergoing antrum formation. This temporal distinction is evident in the patterns of Inh B and E(2) release earlier and later during the follicular phase of the menstrual cycle, respectively. However, in previous studies of women with polycystic ovary syndrome (PCOS) and normal controls, release of these granulosa cell (GC) products appears to be simultaneous in response to FSH stimulation. In order to reconcile these disparate findings, we conducted dose-response studies in both PCOS women and normal controls to determine whether GC product responses were due to the amount of FSH administered. In addition, we compared FSH-stimulated responses in PCOS women at various stages of recovery following ovarian suppression with a long-acting GnRH agonist to examine whether Inh B and E(2) responses reflected the level of ovarian follicle activity (i.e. circulating E(2) levels). Women with PCOS, 18-35 years (n = 23), and normal ovulatory controls, 18-35 years (n = 10) were recruited for study. Dose-responses were assessed over 24 h following intravenous administration of 0 (saline), 37.5, 75 and 150 IU of recombinant human FSH (r-hFSH) in PCOS and normal women. In addition, E(2) and Inh B responses to 150 IU of r-hFSH were assessed at baseline and 4, 6 and 8 weeks following suppression of ovarian steroidogenesis by a long-acting GnRH agonist in PCOS women. In PCOS women and normal controls, serum Inh B and E(2) exhibit similar and simultaneous dose-responsiveness to FSH stimulation. During recovery from ovarian suppression, basal and stimulated Inh B release appear to be restored earlier than that of E(2) in PCOS women. These findings are consistent with the notion that, in PCOS women, the level of ovarian follicle activity largely determines the earlier release of Inh B compared with E(2).

Hyperandrogenism is related to the circulating matrix metalloproteinase-9 response to hyperglycemia in women with polycystic ovary syndrome

OBJECTIVE: Hyperglycemia stimulates proatherogenic inflammation in Polycystic Ovary Syndrome (PCOS). Matrix Metalloproteinase-9 (MMP-9) secreted by leukocytes is a promoter of atherosclerotic plaque rupture. We examined the effect of in vivo glucose challenge on circulating MMP-9 levels in women with PCOS compared to ovulatory controls, and the relationship of this effect with LH and androgens. DESIGN: Prospective, controlled study MATERIALS AND METHODS: Twelve women with PCOS (6 lean, 6 obese) between ages 18-40, diagnosed on the basis of oligo- or amenorrhea and hyperandrogenemia, and 12 ovulatory controls (6 lean, 6 obese) of similar age were selected for study. Subjects with diabetes, inflammatory illnesses or other endocrinopathies were excluded. A 2-hour glucose tolerance test was performed within 5-8 days of menses. MMP-9 levels were measured by ELISA in plasma from blood samples drawn fasting (pre) and 2 hours after (post) glucose ingestion. Levels of LH, testosterone and androstenedione were measured in serum by RIA. RESULTS: There were no significant differences in age and body mass index in women with PCOS compared to weight-matched controls. The percent change in the mean concentration of MMP-9 between the pre - and post-glucose challenge samples of lean and obese women with PCOS (55.6±22.3%; 81.2±17.0%) was significantly higher (p<0.02) compared to that of lean and obese controls which decreased (-4.9±5.4%; -35.1±13.1%). The MMP-9 response was positively correlated with serum levels of LH (r=0.49; p<0.02), testosterone (r=0.73; p<0.0001) and androstenedione (r=0.76; p<0.0001). CONCLUSIONS: These preliminary data indicate that in response to hyperglycemia, circulating MMP-9 levels are increased in women with PCOS, independent of obesity. Hyperandrogenism may perpetuate this proinflammatory, proatherogenic phenomenon in PCOS.

Is antral follicle count (AFC) more than a marker of oocyte number? Women with infertility have lower AFC than normal women

OBJECTIVE: AFC has been used as a marker of ovarian aging, and may be associated with decreased odds of pregnancy in women undergoing ART. We sought to determine whether ovulatory infertile women have different AFC than a population-based cohort of ovulatory controls. DESIGN: Cross-sectional. MATERIALS AND METHODS: Subjects included women aged 25-45. The infertile group included women undergoing their first IVF cycle in our clinic. The control group was comprised of normal, ovulatory women aged 25-45 enrolled in the OVA (Ovarian Aging) study. Antral follicle count was performed by transvaginal ultrasound in a cycle prior to IVF in infertile women, and between day 2 and 5 of the menstrual cycle for controls. Women with oligo- or anovulation, surgically diagnosed endometriosis, ovarian failure, use of an oocyte donor or gestational surrogate, or ovarian surgery were excluded. Age was stratified into 5-year intervals. Median AFCs were compared between the 2 groups by age stratum using the median test. RESULTS: 1491 infertile women and 423 controls were included. Median AFCs were lower in infertile women than in controls across ages 25-40. AFCs did not differ significantly between infertile and control women aged 41-45.Tabled 1AFCs among infertile and control women, by age groupInfertile (AFC)Control (AFC)AgeNMedianRangeNMedianRangeP-value25-30941610-5371214-400.000231-35469115-48131151-35<0.000136-4064291-52130131-63<0.000141-4528681-339171-460.74 Open table in a new tab CONCLUSIONS: AFC has been shown to correlate with markers of ovarian aging including FSH, AMH and number of oocytes collected following stimulation. This is the first study to compare AFC in an infertile population to that seen in the general population. The lowered AFC in the infertile group suggests factors affecting the size of the remaining follicle pool may also affect oocyte quality and likelihood of conception.

Correlates of increased lean muscle mass in women with polycystic ovary syndrome

Muscle mass plays an important role in determining cardiovascular and metabolic risks in polycystic ovary syndrome (PCOS). In addition, whether lean mass influences carotid intima-media thickness (IMT) in PCOS has not been assessed. Prospective investigation. Ninety-five women with PCOS were age- and weight-matched to 90 ovulatory controls. All women had dual X-ray absorptiometry for lean, fat and bone mass, and bone mass density (BMD). Serum testosterone, sex hormone-binding globulin, insulin, and glucose and carotid IMT were determined. Free androgen index (FAI) and insulin resistance (by QUICKI) were calculated. In PCOS, waist circumference and insulin were higher and QUICKI lower than in controls (P<0.01). Trunk fat mass, % trunk fat, and lean mass were higher in PCOS compared to controls (P<0.01), while total bone mass and BMD were similar. IMT was increased in PCOS (P<0.01) but only 15% of PCOS patients had abnormal (> or = 0.9 mm) values. Lean mass correlated with fat parameters, insulin, QUICKI, and FAI, but not with total testosterone; and after adjustments for insulin and QUICKI, lean mass still correlated with fat mass (P<0.01) but not FAI. Lean mass correlated with IMT (P<0.01), but this was dependent on insulin. However, excluding those patients with abnormal IMT values, IMT correlated with lean mass independently of insulin. Bone mass correlated with lean and fat mass, but not with insulin or androgen. PCOS patients with 'pathological' IMT values had higher % trunk fat, lean mass, and insulin, lower QUICKI, and higher testosterone and FAI compared with those with normal IMT. Lean mass is increased in PCOS, while bone mass is similar to that of matched controls. The major correlates of lean mass are fat mass and insulin but not androgen. Lean mass also correlated with IMT, and although influenced by insulin, small changes in IMT may partially reflect changes in muscle mass, while clearly abnormal values relate to more severe abnormalities of PCOS.

Thrombin activatable fibrinolysis inhibitor and other hemostatic parameters in patients with polycystic ovary syndrome

Objectives. To investigate the plasma levels of thrombin-activatable fibrinolysis inhibitor (TAFI) in women with polycystic ovary syndrome (PCOS) and its correlation with various metabolic, hormonal and hemostatic parameters.Methods. Forty-eight women with PCOS and 43 age- and BMI-matched ovulatory controls were recruited during a 20-month study period. Blood samples were drawn for all tests, which included plasma lipids and lipoproteins, reproductive hormones, glucose, insulin, TAFI antigen concentration, plasminogen activator inhibitor-1 (PAI-1) activity, fibrinogen concentration, thrombomodulin, thrombin–antithrombin (TAT) complexes, D-dimer, Protein C Antigen, Protein S Antigen, Antithrombin III (AT III) and activated protein C (APC) resistance.Results. Plasma TAFI levels of PCOS patients were found to be significantly higher than in healthy controls (93.8%±30.6%vs. 79.8% ± 22.4%, p < 0.05). Plasma levels of D-dimer, AT III, PAI-1 and thrombomodulin were also significantly higher in women with PCOS compared with healthy controls. All the other hemostatic parameters (including TAT complexes; Protein C; APC; and Protein S) were comparable between the two study groups.Conclusion. This study showed that plasma levels of TAFI, PAI-1, D-dimer, AT III and thrombomodulin were significantly increased in women with PCOS compared with age- and BMI-matched controls.