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[Glucose and lipid metabolism in patients with polycystic ovary syndrome].

Glucose and lipid metabolism were studied in 30 patients with polycystic ovary syndrome (PCOS), divided into obese (n = 17) and non-obese (n = 13) groups according to BMI > 27 or < 24. Another 30 healthy controls were also divided into obese (n = 14) and nonobese (n = 16) normal groups on the same index. Cubital venous blood was drawn from each participant for oral glucose tolerance test (OGTT), insulin and lipid profile determination, for PCOS groups at the end of 3 months amenorrhea and control groups within the first 10 days of the menstrual cycle. The results showed: (1) the PCOS groups had much higher insulin level before and after OGTT than the normal groups. There was a significant positive correlation between fasting insulin level and testosterone concentration; (2) in lipid profile, the triglyceride levels in both obese groups were significantly higher than that in the non-obese groups, in whom a strong positive correlation between triglyceride and BMI was found. It is concluded that the obese and non-obese PCOS were correlated with insulin alteration, and the changed serum lipid in obese PCOS patients might be the effect of obesity but not PCOS.

Adult↗

Hemostatic and metabolic variables in women with polycystic ovary syndrome.

OBJECTIVE: To study whether a previously demonstrated increased morbidity in cardiovascular disease (CVD) and diabetes mellitus in women with polycystic ovary syndrome (PCOS) is associated with certain hemostatic variables that are known to be markers for CVD. DESIGN: The study was a trans-sectional follow-up study from a cohort of women with PCOS. SETTING: The women with PCOS were recruited from hospital clinics and referents were randomized from a population study of women from the same area. PARTICIPANTS: The investigation involved 28 women aged 43 to 62 years diagnosed to have PCOS on ovarian histopathology at wedge resection 25 to 34 years previously and 56 referents who were matched by age and body mass index. MAIN OUTCOME MEASURES: In connection with a clinical investigation, the hemostatic variables fibrinogen, von Willebrand factor antigen, factor VII procoagulant activity, factor VII antigen, and plasminogen activator inhibitor as well as the metabolic variables serum insulin and serum triglycerides were assayed. RESULTS: There was a strong positive correlation between serum concentrations of triglyceride, basal insulin, and abdominal obesity on the one hand, and plasminogen activator inhibitor, fibrinogen, and von Willebrand factor on the other, among women with PCOS as well as among referents. There were significantly higher mean concentrations of fibrinogen and factor VII:Ag among referents, but the mean values of most hemostatic variables studied showed no differences between the groups. CONCLUSION: Women with an altered metabolic profile were also found to have affected hemostatic factors, but PCOS in itself did not seem to influence them.

Adult↗

Benefits of continuous physiological pulsatile gonadotropin-releasing hormone therapy in women with polycystic ovarian syndrome.

OBJECTIVE: Can continuous pulsatile GnRH from one ovulatory cycle to another enhance the endocrine milieu of women with polycystic ovarian syndrome (PCOS)? DESIGN: Five women with well-characterized, clomiphene citrate (CC)- and hMG-resistant PCOS were treated with a 100 ng/kg per bolus of IV pulsatile GnRH (Lutrepulse; Ortho Pharmaceutical Corporation, Raritan, NJ) every 90 minutes for two consecutive ovulatory cycles. Weekly vaginal ultrasonography and daily blood sampling for LH (mIU/mL), FSH (mIU/mL), E2 (pg/mL), and P (ng/mL) were performed. These data were compared with a control group of normally cycling women. RESULTS: First ovulatory cycles on therapy were characterized by significantly increased mean follicular phase LH = 88 (arbitrary units area under the curve [AUC]) compared with second cycles (28 mean AUC units) and controls (13 mean AUC units). Luteal phase E2 (3,081 mean AUC units) was significantly increased in first cycles compared with second cycles (880 mean AUC units) and controls (1,562 mean AUC units in PCOS). Luteal phase E2 secretion was elevated in second cycles when compared with normal but not significantly. The changes occurring between the first and second ovulatory cycles in women with PCOS resulted in a more physiological overall pattern of gonadotropin and sex steroid secretion in the second cycles. Two singleton pregnancies were achieved in the second cycle. CONCLUSIONS: Low-dose pulsatile IV GnRH can successfully induce ovulation in women with PCOS who have failed to conceive on all previous conventional therapy (CC, hMG, and/or GnRH agonist, and hMG). Continuous cycle-to-cycle physiological GnRH replacement normalized the endocrine parameters of second cycles. Women with PCOS, even when ovulatory on pulsatile GnRH, do not display entirely normal gonadotropin and sex steroid dynamics.

Adult↗

Hypothalamic-pituitary-ovarian response to clomiphene citrate in women with polycystic ovary syndrome.

OBJECTIVE: To examine the hypothalamic-pituitary sites of clomiphene citrate (CC) action in women with polycystic ovarian syndrome (PCOS). DESIGN: Prospective controlled trial. PATIENTS, PARTICIPANTS: Seventeen women with PCOS and 9 normal-cycling women. INTERVENTIONS: Subjects with PCOS received CC, 150 mg/d for 5 days. MAIN OUTCOME MEASURES: Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels and LH pulse characteristics and their response to gonadotropin-releasing hormone (GnRH, 10 micrograms) were examined before and after 3 days of CC in PCOS subjects during a 12-hour frequent sampling study (n = 8). Daily urinary estrone glucuronide and pregnanediol glucuronide levels after CC were compared with concentrations in normal-cycling women through one menstrual cycle. In another nine PCOS subjects, pituitary and ovarian hormonal cyclicity was monitored by daily blood sampling. RESULTS: Thirteen of 17 treated cycles were ovulatory with normal luteal phases. In the ovulatory cycles, serum LH, FSH, estradiol (E2), and estrone levels increased after CC. Luteinizing hormone pulse frequency was unchanged, but LH pulse amplitude increased significantly after CC. Both LH and FSH response to exogenous GnRH was significantly attenuated after CC treatment. In anovulatory cycles, serum LH, FSH, and E2 increased initially and then returned to baseline and remained unchanged for the ensuring 40 days. CONCLUSIONS: Clomiphene citrate-induced ovulation in women with PCOS is accompanied by increased secretion of LH and FSH with enhanced estrogen secretion. The increased LH pulse amplitude after CC, together with decreased pituitary sensitivity to GnRH, suggests a hypothalamic effect.

Adolescent↗

Evidence for heterogeneous etiologies of adrenal dysfunction in polycystic ovary syndrome.

OBJECTIVE: To examine the hypothesis that, in polycystic ovary syndrome (PCOS), ovarian steroids induce adrenal enzyme dysfunction or adrenal androgen hyperresponsiveness to ACTH. DESIGN: Prospective controlled clinical study. SETTING: Reproductive endocrinology unit of an academic medical center. PATIENTS: Twelve women with PCOS who had adrenal androgen excess were compared with five weight-matched ovulatory women. In half of the women with PCOS, prestudy screening was suggestive of mild 3 beta-hydroxysteroid dehydrogenase (HSD) deficiency. INTERVENTIONS: Basal and adrenal dynamic blood sampling before and after GnRH agonist (GnRH-a) administration for 6 months. MAIN OUTCOME MEASURES: Basal E2 and androgen levels as well as dexamethasone-suppressed, ACTH-stimulated 17 alpha-hydroxyprogesterone, 17 alpha-hydroxypregnenolone, and androgen levels before and after ovarian suppression. RESULTS: Although none of the subjects with PCOS proved to have mild 3 beta-HSD deficiency, the majority of them (58%) met the criteria for 17,20 lyase hyperactivity before and after GnRH-a therapy. As a group, the remaining subjects with PCOS exhibited an elevated DHEAS response to ACTH before GnRH-a treatment, which may have normalized after GnRH-a treatment. CONCLUSION: Adrenal androgen excess in PCOS may be heterogeneous in etiology, whereas 17,20 lyase hyperactivity appears to be an intrinsic adrenal disorder, adrenal androgen hyperresponsiveness to ACTH may be ovarian induced. Reliance on historical controls may lead to overdiagnosis of mild 3 beta-HSD deficiency.

17-alpha-Hydroxypregnenolone↗

[Polycystic ovary syndrome--Doppler parameters].

OBJECTIVE: To evaluate the value of transvaginal color and pulsed Doppler measurements of the uterine and ovarian arteries in infertile patients with polycystic ovarian syndrome (PCOS). STUDY DESIGN: Prospective controlled trial included forty (40) patients with PCOS and 40 healthy women. All the patients were examined by transvaginal color and pulsed Doppler on the 5th, 10th, 12th, 15th, 21st and 24th day of the menstrual cycle. The hormonal profile (estradiol (E2), luteinizing hormone (LH), follicular stimulating hormone (FSH), progesterone, testosterone and prolactin) was correlated to the Doppler results. RESULTS: The flow velocity patterns of uterine and ovarian vessels showed changes during the normal ovulatory menstrual cycle, while in the patients with PCOS these changes did not occur. The high resistance index (RI = 1.0) with reverse flow was detected in both ovarian arteries in PCOS group, and showed no cyclic changes. Ovarian stromal and hilar arterial impedance (0.54 +/- 0.05) as well as uterine artery resistance index (0.91 +/- 0.09) did not show significant changes during the menstrual cycle. CONCLUSIONS: Our study suggests that a large fraction of patients suffering from PCOS has elevated uterine artery resistance index despite normal plasma E2 levels. It can be postulated that excessive production of ovarian factor (other than E2) may increase the uterine resistance and alter the endometrial receptivity. This finding may explain why endometrial receptivity is shown to be poor in patients with PCOS. Estimation of uterine and ovarian arterial impedance values seems to have clinical impact in the management of these patients attending an in vitro fertilization program.

Adolescent↗

Evidence of a disturbance of the hypothalamic-pituitary-adrenal axis in polycystic ovary syndrome: effect of naloxone.

DESIGN: There are conflicting data on hypothalamic-pituitary-adrenal (HPA) axis function in women with polycystic ovary syndrome (PCOS). We have evaluated the HPA axis responses to naloxone in patients with PCOS compared to control subjects. PATIENTS: Twenty PCOS patients and 10 control women participated in the study. MEASUREMENTS: On days 5-6 of a spontaneous or progestin induced cycle each patient received an intravenous bolus (5 mg) of naloxone (time 0 min), followed by a 2-mg naloxone infusion in 100 ml of 0.9% saline over one hour. Samples were collected at -30, 0, 15, 30, 60, 90 and 120 minutes. ACTH and cortisol levels were measured in all plasma samples. RESULTS: PCOS patients showed significantly greater response than controls to naloxone of ACTH (peak value 261 vs 172% of basal value) and cortisol (peak value 237 vs 165% of basal value); also, ACTH and cortisol incremental areas were higher in PCOS patients (P < 0.05 and P < 0.04 respectively). The cortisol/ACTH ratio of AUCs percentage increase was found to be near unity for all patients without significant difference between PCOS and control groups, suggesting a direct correspondence between ACTH circulating levels and adrenal cortisol production. CONCLUSIONS: Polycystic ovary syndrome patients showed a hypothalamic-pituitary-adrenal axis hyper-responsiveness to naloxone infusion compared with control subjects. These data support the hypothesis that this disturbance could be central in origin.

Adolescent↗

Altered regulation of insulin-like growth factor binding protein-1 in patients with polycystic ovary syndrome.

OBJECTIVE: Insulin-like growth factor (IGF-I) action is influenced by circulating as well as tissue levels of its binding proteins. Because serum IGF binding protein-1 (IGFBP-1) levels have been found to be decreased in patients with polycystic ovary syndrome (PCOS), we tested the hypothesis that regulation of IGFBP-1 secretion may be different in patients with PCOS compared with normal women. METHODS: We studied 15 normal ovulatory women and 15 women with PCOS of similar age (21 +/- 1 and 22 +/- 1 years, respectively). All subjects were studied after an overnight fast between days 5-8 after spontaneous or progestin-induced menses. Perturbations included the administration of insulin intravenously, maintenance of a euglycemic clamp, and, in a subsequent cycle, the administration of a long-acting somatostatin analogue (octreotide, 100 micrograms) given subcutaneously. Blood samples were collected before treatment, every 15 minutes for 6 hours after insulin, and every 30 minutes for 3 hours after octreotide administration. Serum levels of IGF-I, IGFBP-1, IGFBP-3, and insulin were measured by specific immunoassays. RESULTS: Compared with the controls, patients with PCOS had significantly higher insulin levels, similar IGF-I and IGFBP-3 levels, and significantly lower IGFBP-1. Insulin did not change serum IGF-I levels in either group, although a significant decrease in IGFBP-1 levels occurred in normal women but not in patients with PCOS. Octreotide treatment also did not change serum IGF-I levels in either group, but serum insulin levels decreased significantly and IGFBP-1 levels increased significantly in both groups; this response was significantly greater in controls. CONCLUSIONS: Our data are compatible with the notion that regulation of IGFBP-1 is altered in women with PCOS and that several factors may be involved.

Adult↗

[The secretion and receptor gene of insulin-like growth factor-I quantitative expression in ovarian stroma in polycystic ovarian syndrome patients].

OBJECTIVE: To explore varying different degrees of the action of insulin-like growth factor-I (IGF-I) and its receptor gene quantitative expression in the ovarian stroma of women with obese and nonobese polycystic ovarian syndrome (PCOS). METHOD: The expression of IGF-I receptor gene in the ovarian stroma from 35 cases of PCOS (obese: 15 cases; nonobese: 20 cases) and 20 cases of control were quantitatively determined by reverse transcript polymerase chain reaction (RT-PCR) combined with beta(2) micro globlin (beta(2) MG) gene as inner-control to amplificate sychronously. The grey value ratio of them were determined. The PCR-amplified cDNA fragments were put in restriction analysis (DdeI). RESULTS: The expression of IGF-I receptor in PCOS ovary stroma was significantly greater than in the control group (P < 0.001). The nonobese group presents more enhancement than obese group in IGF-I receptor gene expression. The restrictive fragments were same between the PCOS and the control group. CONCLUSIONS: The expression of IGF-I receptor in PCOS ovarian stroma is abnormally excessive and the nonobese PCOS have more potential action of IGF-I system in ovary stroma.

Adult↗

Polycystic ovary syndrome and hyperandrogenism as a risk factor for cardiovascular disease.

About 30% of infertility is caused by anovulation, associated most commonly with the polycystic ovary syndrome (PCOS). PCOS is a common endocrinopathy in women, especially at the age of 30 to 35 years, characterized by irregular menses, infertility and signs of hyperandrogenism. The pathogenetic mechanisms leading to PCOS are not fully understood, although several theories have been proposed. PCOS patients commonly have hyperinsulinemia and insulin resistance which are also known risk factors for the development of diabetes mellitus, hypertension and cardiovascular disease. However, it is not known, how well the presence of PCOS symptoms would predict the appearance of the long-term sequelae of insulin resistance. Also more data is needed e.g. of the role of intrauterine factors and birth weight in the development of PCOS and hyperandrogenism.

Adult↗

Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome.

Since the 1990 National Institutes of Health-sponsored conference on polycystic ovary syndrome (PCOS), it has become appreciated that the syndrome encompasses a broader spectrum of signs and symptoms of ovarian dysfunction than those defined by the original diagnostic criteria. The 2003 Rotterdam consensus workshop concluded that PCOS is a syndrome of ovarian dysfunction along with the cardinal features hyperandrogenism and polycystic ovary (PCO) morphology. PCOS remains a syndrome, and as such no single diagnostic criterion (such as hyperandrogenism or PCO) is sufficient for clinical diagnosis. Its clinical manifestations may include menstrual irregularities, signs of androgen excess, and obesity. Insulin resistance and elevated serum LH levels are also common features in PCOS. PCOS is associated with an increased risk of type 2 diabetes and cardiovascular events.

Clinical Trials as Topic↗

Pulsatile luteinising hormone releasing hormone for ovulation induction in subfertility associated with polycystic ovary syndrome.

BACKGROUND: In normal menstrual cycles, gonadotrophin releasing hormone (GnRH) secretion is pulsatile, with intervals of 60-120 minutes in the follicular phase. Treatment with pulsatile GnRH infusion by the intra-venous or subcutaneous route using a portable pump has been used successfully in patients with hypogonadotrophic hypogonadism. Assuming that the results would be similar in polycystic ovary syndrome (PCOS), pulsatile GnRH has been used to induce ovulation in patients with PCOS. But, although ovulation and pregnancy has been achieved, the use of pulsatile GnRH in PCOS patients is controversial. OBJECTIVES: To assess the effectiveness of pulsatile GnRH administration in women with clomiphene-resistant polycystic ovary syndrome (PCOS), in terms of ovulation induction, pregnancy, miscarriage, multiple pregnancy and ovarian hyperstimulation syndrome (OHSS). SEARCH STRATEGY: The search strategy of the Menstrual Disorders and Subfertility review group was used to identify all relevant trials. Please see Review Group details. SELECTION CRITERIA: All relevant published RCTs were selected. Non-randomised controlled trials were eligible for inclusion if treatment consisted of GnRH administration versus another treatment to induce ovulation in subfertile women with PCOS. DATA COLLECTION AND ANALYSIS: A computerised MEDLINE and EMBASE search was used to identify randomised and non randomised controlled trials. The reference lists of all studies found were checked for relevant articles. One RCT (Bringer 1985a) and one abstract (Coelingh 1983) were identified this way. Relevant data were extracted independently by two reviewers (NB, MW). Validity was assessed in terms of method of randomization, completeness of follow-up, presence or absence of cross-over and co-intervention. All trials were screened and analysed for predetermined quality criteria. DATA SYNTHESIS: 2X2 tables were generated for all the relevant outcomes. Odds ratios were generated using the Peto modified Mantel-Haenszel technique. MAIN RESULTS: Three RCTs and one non-randomised comparative trial were identified comparing four different treatments: GnRH versus HMG, GnRH following GnRHa pre-treatment versus no pre-treatment, GnRH and FSH versus FSH, and GnRH following GnRHa pre-treatment versus GnRH following oral contraceptive pre-treatment. This means that there was only one trial in any one comparison. In the first two studies, data of pre- and post-cross-over were not described separately. Therefore, these results could not be included in the MetaView analysis. The odds ratio for ovulation rate was 16 (95 % CI: 1.1-239) in the study comparing GnRH and FSH with FSH. When GnRH after GnRHa pre-treatment was compared with GnRH after oral contraceptive pre-treatment, an odds ratio of 7.5 (95 % CI: 1.2-46) was obtained. All trials were small and of too short duration to show any significance in pregnancy results. Per study only one to four pregnancies occurred. Multiple pregnancies were not seen. OHSS was seen only in the patients stimulated with HMG. REVIEWER'S CONCLUSIONS: The four trials describing four different comparisons with a short follow up (1 to 3 cycles) were too small to either prove or discard the value of pulsatile GnRH treatment in patients with polycystic ovary syndrome.

Female↗

Insulin-sensitising drugs (metformin, troglitazone, rosiglitazone, pioglitazone, D-chiro-inositol) for polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is characterised by anovulation, hyperandrogenaemia and insulin resistance. Hyperinsulinaemia is known to be associated with an increase in cardiovascular risk and the development of diabetes mellitus. If insulin sensitising agents such as metformin are effective in treating features of PCOS, then they could have wider health benefits than just treating the symptoms of the syndrome. OBJECTIVES: To assess the effectiveness of insulin sensitising drugs in improving clinical and biochemical features of PCOS. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders & Subfertility Group trials register (December 2002), the Cochrane Central Register of Controlled Trials (Cochrane Library, Issue 4, 2002), MEDLINE (January 1966 to December 2002), and EMBASE (January 1985 to December 2002). SELECTION CRITERIA: Randomised controlled trials which investigated the effect of insulin sensitising drugs compared with either placebo or no treatment, or compared with an ovulation induction agent. DATA COLLECTION AND ANALYSIS: Performed by two reviewers, one blinded to information that could have identified the authors, publisher or results of each study. Fifteen trials were included for analysis, 13 of them using metformin and involving 543 participants. MAIN RESULTS: Meta-analysis showed that metformin is effective in achieving ovulation in women with PCOS with odds ratios of 3.88 (CI 2.25 to 6.69) for metformin versus placebo and 4.41 (CI 2.37 to 8.22) for metformin and clomifene versus clomifene alone. An analysis of pregnancy rates suggests a significant treatment effect for metformin and clomifene (OR 4.40, CI 1.96 to 9.85). Metformin has a significant effect in reducing fasting insulin levels (WMD -5.37, CI -8.11 to -2.63), blood pressure and low-density lipoprotein cholesterol (LDL). There was no evidence of effect on body mass index or waist:hip ratio. Metformin was associated with a significantly higher incidence of nausea, vomiting and other gastrointestinal disturbance, but no serious adverse effects were reported. REVIEWER'S CONCLUSIONS: Metformin is an effective treatment for anovulation in women with PCOS. Its choice as a first line agent seems justified, and there is some evidence of benefit on parameters of the metabolic syndrome. Ovulation rates are higher when combined with clomifene (76% versus 46% when used alone), but there is no evidence to indicate whether there is an increased multiple pregnancy rate with this combination. There is no data regarding its safety in long-term use in young women. It should be used as an adjuvant to general lifestyle improvements, and not as a replacement for increased exercise and improved diet.

Anovulation↗

Role of the pentanucleotide (tttta)n polymorphisms of Cyp11alpha gene in the pathogenesis of hyperandrogenism in Chinese women with polycystic ovary syndrome.

To determine the (tttta)n repeat polymorphisms at the promoter region of CYP11alpha gene, and study its linkage to hyperandrogenism of polycystic ovary syndrome (PCOS) in Chinese women, a case-control study was conducted in the Reproductive Medical Center of the Second Affiliated Hospital of Zhengzhou University (Zhengzhou, China). 96 PCOS patients and 78 healthy control women were included. CYP11alpha (tttta)n repeat-polymorphism genotyping analysis was performed by using polymerase chain reaction (PCR). Serum pituitary hormone and total testosterone levels were measured by ELISA. 4 different CYP11alpha (tttta)n allelles were identified, corresponding to 4-, 6-, 8-, and 9-repeat-unit alleles. The frequency and distribution of these alleles are 0.16, 0.33, 0.38, and 0.13 respectively in PCOS patients, as compared with 0.20, 0.34, 0.35, and 0.11 respectively in healthy controls. There were no significant differences between these two groups. Moreover, no correlation between the polymorphism of CYP11alpha gene and serum testosterone level of patients with PCOS and controls was observed. It is concluded that microsatellite polymorphism (tttta)n of gene CYP11alpha exists in Chinese women and the polymorphism of CYP11alpha gene does not play an important role in the pathogenesis of Chinese patients with PCOS, especially in patients with hyperandrogenism.

Adult↗

Expression of resistin mRNA in adipose tissue of rat model with polycystic ovarian syndrome and its implication.

To investigate the relationship between the insulin resistance (IR) of polycystic ovarian syndrome (PCOS) rat model induced by dehydroeplandrosterone (DHEA) and hormonal changes in the ovarium and the resistin mRNA levels in adipose tissue, 21-day-old female SD rats were divided into two groups in pairs. The rats in group 1 were injected daily (s.c.) with DHEA for up to 20 days and the rats in group 2 injected with oil at the same time. Ovarian weight, serum insulin levels and sex hormone levels in rat blood of both groups were determined. Oral glucose tolerance tests, light microscopic and electronic microscopic examination were performed. The levels of resistin mRNA in adipose tissue were measured by reverse transcription-polymerase chain reaction (RT-PCR). Our results showed that the ovarian weight in group 1 was greater than that in group 2 (P<0.05). The ovaria in group 1 showed multiple follicular cysts, The serum testeosterone and etrasdiol concentration were significantly higher in group 1 than those in group 2 (P<0.001 and P<0.05 respectively), so as the fasting serum glucose (P<0.001) and fasting serum insulin (P<0.05). The value of 1/FINS x FGC was significantly higher in group 1 than that in group 2 (P<0.001). Moreover, the resistin mRNA level of white adipose tissue in the DHEA-induced group was significantly higher than that in the control rats (P<0.05). It is concluded that the DHEA-induced PCOS rat models were similar to those of the patients with PCOS, and the IR was observed. Resistin secreted by adipose tissue may mediate IR in PCOS, and it is likely involved in the pathogenesis and development of PCOS.

Adipose Tissue↗

Ovarian steroids modulate neuroendocrine dysfunction in polycystic ovary syndrome.

OBJECTIVE: Neuroendocrine dysfunction in polycystic ovary syndrome (PCOS) was addressed by studying the steroid hormone changes in women with PCOS with either high or normal LH levels leading to inferences regarding the primacy of elevated LH in the pathophysiology of PCOS. METHODS: A cross-sectional study was designed in an academic clinical facility involving 234 women with PCOS. Patients were divided into two groups based on an LH/FSH ratio < or >1 and hormonal and metabolic studies were performed in both groups. Factors were determined by binomial logistic regression that predicted group membership of these women. RESULTS: Higher follicular phase estradiol (E2) and androstenedione (A4) levels as well as greater insulin sensitivity were the only factors that predicted the presence of neuroendocrine dysfunction with elevated A4 being necessary for neuroendocrine dysfunction. CONCLUSIONS: It was concluded that uncoupling of hypothalamic E2 inhibition by elevated ovarian A4 associated with E2 related sensitization of pituitary LH leads to neuroendocrine dysfunction in PCOS.

17-alpha-Hydroxyprogesterone↗

Spironolactone in the treatment of polycystic ovary syndrome: effects on clinical features, insulin sensitivity and lipid profile.

This prospective clinical trial was designed to assess the effects of a long-term therapy with spironolactone, with and without dietary-induced weight-loss, on clinical features, lipid profile and insulin levels in women with polycystic ovary syndrome (PCOS). Twenty-five patients (range of age 16-32 yr; 13 lean and 12 overweight) fulfilling formal diagnostic criteria for PCOS (oligomenorrhea and/or amenorrhea, biochemical and/or clinical evidence of hyperadrogenism) were studied at baseline and then received oral spironolactone (100 mg/die) for 12 months; association with lifestyle modifications was recommended to all over-weight patients. Clinical, endocrine and metabolic parameters [oral glucose tolerance test (OGTT), lipid profile] were measured at baseline and at the end of the antiandrogen treatment. The therapy was associated with a significant average decline of triglycerides in overweight subjects and with increased HDL-cholesterol levels in lean patients. The insulin levels at 60 min during OGTT, homeostasis model assessment-insulin resistance and area under curve of insulin were significantly lowered in overweight women after 12 months of spironolactone and weight loss and no negative changes in insulin secretion and sensitivity were observed in PCOS women after pharmacological treatment alone. The efficacy of spironolactone on the androgenic clinical aspects of PCOS has been confirmed in this study. Furthermore, our data show that long-term treatment with spironolactone exerts no negative effects on lipoprotein profile and glucose metabolism; more relevant beneficial effects on glucose and lipid metabolism were observed when the antiandrogen was associated with weight loss in overweight PCOS women.

Adolescent↗

Diagnostic value of prostatic specific antigen in hirsute women.

Determination of prostatic specific antigen (PSA) in female tissues has become available recently. The expression of PSA gene is under androgenic regulation. Therefore, hyperandrogenemic states, such as polycystic ovary syndrome (PCOS), are expected to be presented with the higher levels of PSA. The current study aimed at evaluating PSA levels in hirsute women presumed to have PCOS or idiopatic hirsutism (IH). Thirty-three patients with PCOS, 40 patients with IH, and 20 healthy control subjects were enrolled in the study. Beside basal hormonal evaluation, total PSA (tPSA), and free PSA (fPSA) were determined in all subjects. Average level of tPSA was the highest in PCOS patients (0.099+/-0.267 ng/ml) when compared with IH and control subjects (p<0.05 and p<0.001, respectively). Besides, mean fPSA levels were found to be significantly higher in patients with PCOS than healthy controls (0.033+/-0.070 vs 0.010+/-0.001 ng/ml; p<0.05). Both total and free PSA levels were found to be higher in 73 hirsute women than in control subjects (p<0.01 and p<0.05, respectively). Women with hyperandrogenemia tended to have higher tPSA than women without hyperandrogenemia (p<0.01). PSA is likely to be used to discriminate hyperandrogenemic hirsutism. If more sensitive assays become available, PSA might be used as a diagnostic criteria for hirsutism and even for some diseases which have hirsutism as a component.

Adult↗