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PubMed1988

Serum inhibin levels in polycystic ovary syndrome: basal levels and response to luteinizing hormone-releasing hormone agonist and exogenous gonadotropin administration.

Serum inhibin levels were measured by RIA twice weekly for 4 weeks in 5 women with the polycystic ovary syndrome (PCOS). These were compared to those in 10 women with normal menstrual cycles. Serum inhibin levels were similar in the 5 PCOS women (mean, 199; range, 126-266 U/L) and were not significantly different from those in the normal women during the early follicular phase (227; 100-485 U/L) or midfollicular phase (243; 143-412 U/L) of their cycles. Inhibin levels were higher (P less than 0.001) in the late follicular phase (408; 227-732 U/L), at midcycle (623; 367-1058 U/L), and during the midluteal phase (1245; 898-1727 U/L) in the normal women compared to those in the PCOS group. Serum inhibin levels were also measured in PCOS (n = 8) and infertile (n = 14) women after the rise and subsequent diminished gonadotropin secretion that occurred during LHRH agonist administration. In both groups, serum LH and FSH increased after initiation of LHRH agonist administration; this increase was accompanied by parallel rises in serum estradiol and inhibin before suppression (PCOS women: r = 0.71; P less than 0.001; n = 108; infertile women: r = 0.42; P less than 0.05; n = 163). All hormone levels, including inhibin, decreased during continued LHRH administration. Five PCOS women underwent ovulation induction using combined LHRH agonist and human menopausal gonadotropin administration. Serum estradiol and inhibin rose in parallel in response to exogenous gonadotropins (r = 0.92; P less than 0.001; n = 77). In conclusion, we found no evidence of a primary defect in ovarian inhibin physiology in women with PCOS in terms of either basal or gonadotropin-stimulated (exogenous or endogenous) secretion.

Adult↗

PubMed1992

Follicular fluid insulin-like growth factor binding protein profiles in polycystic ovary syndrome.

Insulin-like growth factor binding proteins (IGFBPs) are believed to modulate the actions of IGF-I and IGF-II at the cellular level. We have examined, by Western ligand blot analysis, the IGFBP profiles in follicular fluid (FF) from patients with polycystic ovarian syndrome (a disorder of ovarian folliculogenesis), compared to FF from atretic and developing (estrogenic) follicles from normally cycling women. IGFBPs with apparent mol wts (Mr) of 41.5, 38.5, 31, 28, and 24kDa were detected in PCOS FF. The profile of IGFBPs in PCOS FF was indistinguishable from that seen in atretic follicles in cycling women. However, higher levels of the 31, 28, and 24kDa IGFBPs were observed in PCOS FF, compared to healthy, estrogenic follicles. Using specific antisera, the 41.5 and 38.5kDa IGFBPs were identified as IGFBP-3, and the 31kDa IGFBP as IGFBP-2. IGFBP-1, however, was not appreciably detectable in PCOS FF, by Western ligand blotting. Endoglycosidase F treatment of FF decreased the Mr of the 28kDa IGFBP to 24kDa, and neither the 28kDa nor the 24kDa IGFBP was immunoprecipitated by antibodies to IGFBP-1, -2, or -3. Elevated levels of 28kDa and 24kDa IGFBPs in PCOS FF may represent glycosylated and core forms of IGFBP-4. The data presented herein show that in PCOS FF, as well as in FF from atretic follicles from normally cycling women, IGFBP-2 and 28 and 24kDa IGFBPs are present in greater amounts, compared to levels in FF from healthy, developing, estrogenic follicles. One or more of the IGFBP species elevated in atretic and PCOS follicles may bind IGFs in FF, thereby inhibiting IGF action on the granulosa during normal folliculogenesis.

Blotting, Western↗

PubMed1993

The role of adrenal hyperandrogenism, insulin resistance, and obesity in the pathogenesis of polycystic ovarian syndrome.

Hyperandrogenism, insulin resistance, and obesity are common features of polycystic ovarian syndrome (PCOS). This study was designed to investigate the relationship among these factors and how they might contribute to ovulatory dysfunction in PCOS. Adrenal androgen secretion and insulin resistance were quantified in oligomenorrheic women with PCOS and in three groups of eumenorrheic women: weight-matched hirsute women, obese nonhirsute women, and thin nonhirsute women. Adrenal androgen secretion was defined as the androstenedione response to synthetic corticotropin. Insulin resistance was estimated by calculating the area under the curve for serum insulin levels in response to a 75 g oral glucose load. The mean serum androstenedione response (nmol/L) to corticotropin in PCOS (5.6 +/- 1.3) was greater than that in eumenorrheic hirsute women (3.4 +/- 0.5; P < 0.10), obese nonhirsute women (1.8 +/- 0.8; P < 0.05), and lean nonhirsute women (1.9 +/- 0.5; P < 0.05). The serum androstenedione response was not correlated with body mass index (BMI). The area under the curve for serum insulin (mU/L.min/1000) in PCOS (29.1 +/- 5.3) was greater (P < 0.001) than in eumenorrheic hirsute women (9.1 +/- 1.7), obese nonhirsute women (5.8 +/- 1.0), and lean nonhirsute women (4.5 +/- 0.4). The serum insulin response was highly correlated with BMI (P < 0.001) in the three groups of obese women, but women with PCOS became significantly more insulin resistant with increasing BMI (P < 0.02). There was no correlation between adrenal androgen secretion and insulin resistance in any of the groups. We conclude that adrenal hyperandrogenism and insulin resistance are independent predictors of anovulation in hirsute women. These conditions are present in both oligomenorrheic and eumenorrheic hirsute women, but are present to a greater extent in anovulatory women. Obese women with PCOS also differ from eumenorrheic controls by developing a greater degree of insulin resistance as body mass increases.

Adrenal Gland Diseases↗

PubMed1995

Metabolic effects of oral contraceptives in women with polycystic ovary syndrome.

Insulin resistance and dyslipidemia have been described in women with polycystic ovary syndrome (PCOS), a disorder characterized by hyperandrogenism and oligomenorrhea. Although oral contraceptives (OC) are often instituted to regulate menses and suppress HA in women with PCOS, their use has been postulated to cause a deterioration in insulin sensitivity and to adversely affect circulating lipids. To investigate these effects, 9 women with PCOS and 10 age- and weight-matched control women were studied before and during the third month of therapy with a low-dose norethindrone-containing triphasic combination OC using the hyperglycemic clamp technique. At baseline, the PCOS group had higher androgen, triglyceride, and glycosylated hemoglobin concentrations, with a greater insulin response to oral glucose and a lower insulin sensitivity index (ISI) than controls. During OC therapy, a reduction in ISI was observed in both groups, whereas an increase in triglycerides was observed only in controls, removing any observed difference between the two groups in ISI or lipids. In women with PCOS, an increase in insulin concentrations during hyperglycemia accounted for the decline in ISI (P = 0.026), whereas in control women the decrease in ISI was attributable to a decrease in glucose disposal (P = 0.004). In conclusion, PCOS is characterized by insulin resistance in the untreated state. Short-term therapy with a triphasic OC results in a further decline in ISI in women with PCOS, without inducing additional adverse effects on lipids. A more pronounced decline in ISI together with an elevation in triglyceride levels occurs in normal women with OCs. The mechanisms leading to this decrease in ISI are different for each group.

Adult↗

PubMed1997

Cellular insulin resistance in adipocytes from obese polycystic ovary syndrome subjects involves adenosine modulation of insulin sensitivity.

Cellular insulin resistance in polycystic ovary syndrome (PCOS) has been shown to involve a novel postbinding defect in insulin signal transduction. To find possible mechanisms for this defect, adipocytes were isolated from age- and weight-matched obese normal cycling (NC) and PCOS subjects. Insulin sensitivity for glucose transport stimulation was impaired in PCOS adipocytes (EC50 = 290 +/- 42 pmol/L) compared to that in NC cells (93 +/- 14; P < 0.005). The lipolytic responses to isoproterenol as well as maximal suppression by insulin were similar in NC and PCOS adipocytes. However, PCOS cells were less sensitive to the antilipolytic effect of insulin (EC50 = 115 +/- 33 pmol/L) compared to NC cells (42 +/- 8; P < 0.01). Treatment of adipocytes from NC subjects with the adenosine receptor agonist N6-phenylisopropyl adenosine had no effect on either insulin responsiveness or sensitivity for glucose transport stimulation. However, N6-phenylisopropyl adenosine treatment was able to normalize insulin sensitivity in PCOS cells (EC50 = 285 +/- 47 vs. 70 +/- 15 pmol/L, before and after treatment; P < 0.05). In conclusion, our results suggest that insulin resistance in PCOS, as accessed in the adipocyte, occurs at an early step in insulin signaling that is common for glucose transport and lipolysis. In addition, this insulin resistance involves an impairment of the system by which adenosine acts to modulate insulin signal transduction.

Adenosine↗

PubMed1998

Use of a gonadotropin-releasing hormone antagonist as a physiologic probe in polycystic ovary syndrome: assessment of neuroendocrine and androgen dynamics.

The majority of patients with polycystic ovary syndrome (PCOS) exhibit an increase in both the frequency and amplitude of LH secretion, which is thought to contribute to the hyperandrogenism associated with this disorder. The increase in LH pulse amplitude may reflect either enhanced pituitary sensitivity to GnRH and/or an increase in hypothalamic GnRH secretion. To determine whether endogenous GnRH secretion is increased in PCOS and to document the degree and time course of androgen suppression after acute LH inhibition, the Nal-Glu GnRH antagonist was administered s.c. at 4 doses (5, 15, 50, and 150 micrograms/kg) to 11 women with PCOS. The response to GnRH receptor blockade was compared with data from regularly cycling women (n = 50) studied in the early and late follicular, and early luteal phases. The response to more prolonged GnRH receptor blockade was determined in a subset of patients, in whom 150 micrograms/kg of the GnRH antagonist was administered s.c. every 24 h for 3 days (n = 7) and continued for 7 days in 3 subjects. LH levels decreased in a dose-dependent fashion after administration of the GnRH antagonist (P < 0.0001), with a maximum percent inhibition of 83 +/- 2%. At all except the 5 micrograms/kg dose, mean LH levels remained significantly lower than baseline for up to 20 h post antagonist (P < 0.002). At all antagonist doses, both the degree and duration of LH suppression were similar in PCOS and normal women. The maximum percent inhibition of FSH was 39 +/- 2%, which was significantly less than that of LH (P < 0.001). Testosterone (T) levels fell significantly within 4 h of antagonist administration, with maximum percent inhibition of 39 +/- 3% occurring at 8 h. In the patients in whom 150 micrograms/kg of the antagonist was given for 3-7 days, no further suppression of either gonadotropins or T was noted. Our conclusions were: 1) The equivalent susceptibility of LH to submaximal GnRH receptor blockade in normal and PCOS women suggests that the elevated LH levels in PCOS are not the result of an increase in the quantity of GnRH secreted. These data imply that it is the frequency of GnRH stimulation per se and/or enhanced pituitary sensitivity to endogenous GnRH that underlie the gonadotropin abnormalities in PCOS; and 2) The rapid suppression of T with increasing GnRH antagonist dose is consistent with acute regulation of T secretion by LH.

Adolescent↗

PubMed1999

5alpha-reductase activity in women with polycystic ovary syndrome.

The recent demonstration of high concentrations of 5alpha-androstane-3,17-dione in the follicular fluid of polycystic ovaries suggests a potential role for 5alpha-reduced androgens in the etiology of polycystic ovary syndrome (PCOS). The purpose of the present study was to determine whether there is increased 5alpha-reductase activity or messenger ribonucleic acid (mRNA) expression in polycystic ovaries. 5alpha-Reductase 1 and 5alpha-reductase 2 mRNAs were measured in thecal (TC) and granulosa (GC) cells from individual follicles of 18 women with PCOS and 26 regularly cycling control women. Both 5alpha-reductase 1 and 2 mRNA expression was higher in GC than in TC, and 5alpha-reductase 2 mRNA levels were approximately 3-fold higher than 5alpha-reductase 1 mRNA. 5alpha-Reductase 1 and 2 mRNA expression were similar in GC from PCOS and control women, but 5alpha-reductase mRNA was decreased in TC from PCOS follicles. In control women, 5alpha-reductase 2 mRNA was highest in GC from 3- to 5-mm follicles and decreased to undetectable levels in GC from 7-mm follicles. A similar pattern of expression was present in GC from PCOS follicles, but detectable levels of 5alpha-reductase 2 mRNA were present in GC from 7-mm follicles. 5alpha-Reductase activity was measured in whole follicles by measuring the conversion of radiolabeled testosterone to dihydrotestosterone. Kinetic analysis of total 5alpha-reductase activity at physiological pH revealed a Km of 1.46 micromol/L and a maximal velocity of 0.31 nmol/min x mg protein, indicating predominantly type 1 activity. The total 5alpha-reductase activity was approximately 4-fold higher in PCOS follicles than in control follicles. These data demonstrate elevated 5alpha-reductase activity in polycystic ovaries and support the hypothesis that 5alpha-reduced androgens may play a role in the pathogenesis of PCOS.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

PubMed2000

Normal endothelial function despite insulin resistance in healthy women with the polycystic ovary syndrome.

Women with the polycystic ovarian syndrome (PCOS) carry a number of cardiovascular risk factors, including insulin resistance, lipid abnormalities, and an altered pattern of sex steroid exposure. Noninvasive measurements of endothelial function, which can demonstrate abnormalities well in advance of clinically apparent disease, have not been previously reported in this patient group. We undertook a cross-sectional evaluation of endothelium-dependent and -independent vascular function using brachial artery ultrasound. We studied healthy women with clinical and laboratory evidence of PCOS (n = 18) and age-matched controls (n = 19), not taking any antihypertensive, cholesterol-lowering, or hormonal therapies. Laboratory parameters of insulin resistance, glycemia, cholesterol status, and hormone levels were also measured. Despite marked differences in glucose/insulin ratio [6.1 +/- 1.1 mmol/pmol (PCOS) vs. 9.9 +/- 0.6 (controls)] and free androgen index [11.9 +/- 2.3 (PCOS) vs. 3.7 +/- 0.6 (controls); normal, <5], we did not find evidence of impaired endothelial function in our patients with PCOS. Both endothelium-dependent (8.7 +/- 3.1%) and endothelium-independent (23.2 +/- 3.4%) vascular responses were normal, and practically identical to the responses seen in the control group (endothelium-dependent, 9.0 +/- 0.7; endothelium-independent, 23.0 +/- 1.2%). The PCOS women were more obese, but baseline brachial arterial diameters were not different between groups. There was no correlation between degree of insulin resistance or hyperandrogenism and the brachial response. This group of healthy obese young women with insulin resistance and hyperandrogenism due to PCOS had normal endothelium-dependent and -independent vascular responses compared to age-matched controls. The factors resulting in preservation of these response are unclear and warrant further investigation.

Adult↗

PubMed2001

Specific factors predict the response to pulsatile gonadotropin-releasing hormone therapy in polycystic ovarian syndrome.

Ovulation induction is particularly challenging in patients with polycystic ovarian syndrome (PCOS) and may be complicated by multifollicular development. Pulsatile GnRH stimulates monofollicular development in women with anovulatory infertility; however, ovulation rates are considerably lower in the subgroup of patients with PCOS. The aim of this retrospective study was to determine specific hormonal, metabolic, and ovarian morphological characteristics that predict an ovulatory response to pulsatile GnRH therapy in patients with PCOS. Subjects with PCOS were defined by chronic amenorrhea or oligomenorrhea and clinical and/or biochemical hyperandrogenism in the absence of an adrenal or pituitary disorder. At baseline, gonadotropin dynamics were assessed by 10-min blood sampling, insulin resistance by fasting insulin levels, ovarian morphology by transvaginal ultrasound, and androgen production by total testosterone levels. Intravenous pulsatile GnRH was then administered. During GnRH stimulation, daily blood samples were analyzed for gonadotropins, estradiol (E(2)), progesterone, inhibin B, and androgen levels, and serial ultrasounds were performed. Forty-one women with PCOS underwent a total of 144 ovulation induction cycles with pulsatile GnRH. Fifty-six percent of patients ovulated with 40% of ovulatory patients achieving pregnancy. Among the baseline characteristics, ovulatory cycles were associated with lower body mass index (P < 0.05), lower fasting insulin (P = 0.02), lower 17-hydroxyprogesterone and testosterone responses to hCG (P < 0.03) and higher FSH (P < 0.05). In the first week of pulsatile GnRH treatment, E(2) and the size of the largest follicle were higher (P < 0.03), whereas androstenedione was lower (P < 0.01) in ovulatory compared with anovulatory patients. Estradiol levels of 230 pg/mL (844 pmol/L) or more and androstenedione levels of 2.5 ng/mL (8.7 nmol/L) or less on day 4 and follicle diameter of 11 mm or more by day 7 of pulsatile GnRH treatment had positive predictive values for ovulation of 86.4%, 88.4%, and 99.6%, respectively. Ovulatory patients who conceived had lower free testosterone levels at baseline (P < 0.04). In conclusion, pulsatile GnRH is an effective and safe method of ovulation induction in a subset of patients with PCOS. Patient characteristics associated with successful ovulation in response to pulsatile GnRH include lower body mass index and fasting insulin levels, lower androgen response to hCG, and higher baseline FSH. In ovulatory patients, high free testosterone is negatively associated with pregnancy. A trial of pulsatile GnRH therapy may be useful in all PCOS patients, as E(2) and androstenedione levels on day 4 or follicle diameter on day 7 of therapy are highly predictive of the ovulatory response in this group of patients.

Adult↗

PubMed2001

Low grade chronic inflammation in women with polycystic ovarian syndrome.

Low grade chronic inflammation as reflected by increased C-reactive protein (CRP) concentrations independently predicts those at risk for coronary heart disease (CHD) and type 2 diabetes. Women with polycystic ovarian syndrome (PCOS) are insulin resistant and have increased risk for CHD and type 2 diabetes, but currently there are no data on markers of inflammation in women with PCOS. Seventeen women with PCOS (defined on the basis of elevated testosterone and oligomenorrhea) and 15 healthy women matched as a group for body mass index were recruited. Measurement of CRP concentrations was made using a highly sensitive assay. Insulin resistance was assessed using the hyperinsulinemic euglycemic clamp technique. The women with PCOS had significantly elevated CRP concentrations relative to controls (geometric means, 2.12 and 0.67 mg/L, respectively; P = 0.016). Log CRP correlated with body mass index in both PCOS and controls (r = 0.58; P < 0.05 and r = 0.78; P < 0.01, respectively) and inversely with insulin sensitivity (r = -0.57; P < 0.05 and r = -0.69; P < 0.01). Total testosterone did not correlate with log CRP in either group. On adjustment for body mass index and age, there remained a significant difference in log CRP between PCOS and controls (t = 2.13; P < 0.05). On further adjustment for insulin sensitivity, log CRP was no longer significantly different between groups (t = 1.51; P = 0.14). We conclude that women with PCOS have significantly increased CRP concentrations relative to women with normal menstrual rhythm and normal androgen levels. We propose low grade chronic inflammation as a novel mechanism contributing to increased risk of CHD and type 2 diabetes in these women.

Adult↗

PubMed2002

Relationship of calpain-10 genotype to phenotypic features of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is associated with an increased risk of impaired glucose tolerance and type 2 diabetes. Recent evidence suggests that variation in the gene encoding the cysteine protease calpain-10 influences susceptibility to type 2 diabetes. The present study was undertaken to determine whether variation in this gene is associated with quantitative traits pertinent to the pathogenesis of PCOS and diabetes. We studied 212 women with PCOS (124 white of European ancestry, 57 African-American, 13 Hispanic, 13 Asian-American, and 5 Middle-Eastern). Each subject was genotyped for 3 DNA polymorphisms in the calpain-10 gene associated with type 2 diabetes (SNP-43, -19, and -63). The white and African-American subjects were examined for association of these polymorphisms with phenotypic features of PCOS and type 2 diabetes. There were not enough individuals in the other groups for similar genotype/phenotype analyses. Nineteen (9%) of the 212 women with PCOS were diabetic and were not included in the genotype/phenotype analyses. Twelve (63%) of these subjects were African-American. Phenotypic traits in nondiabetic white probands did not differ whether analyzed for each individual SNP (SNP-43, -19, -63) or haplotype combination. Nor was there association of SNP-43, -19, or -63 with any of the phenotypic features of type 2 diabetes or PCOS in nondiabetic African-Americans. However, nondiabetic African-Americans with the 112/121-haplotype combination had significantly higher insulin levels, in response to an oral glucose challenge, as reflected in the area under the insulin curve (257,021 +/- 95,384 vs. 136,240 +/- 11,468 pmol/min; P = 0.03), compared with those with other haplotypes. This finding was particularly notable because the 112/121 subjects were less obese. The difference between groups in area under the insulin response curve remained significant (P = 0.002 by analysis of covariance) after adjustment for body mass index. In addition to its association with insulin levels in African-Americans, the 112/121-haplotype combination was associated with an approximate 2-fold increase in risk of PCOS in both African-Americans and whites.

Administration, Oral↗

PubMed2005

Serum parathyroid hormone concentrations are increased in women with polycystic ovary syndrome.

BACKGROUND: The present study was designed to investigate the effects of polycystic ovary syndrome (PCOS) and of obesity on serum parathyroid hormone (RhoTauEta), 25-hydroxyvitamin D (25-OH-vitamin D), and 1,25-dihydroxyvitamin D [1,25-(OH)2-vitamin D] concentrations and the possible associations of the above calciotropic hormones with the hormonal and metabolic characteristics of the syndrome. METHODS: We studied 58 obese [body mass index (BMI)>30 kg/m2] women with PCOS, 64 overweight (BMI, 25-30 kg/m2) women with the syndrome, 169 normal-weight (BMI<25 kg/m2) women with PCOS, 29 obese controls (ovulatory women without clinical or biochemical hyperandrogenemia), 14 overweight controls, and 70 normal-weight controls. Blood samples were collected (at 0900 after an overnight fast) between the 3rd and 6th days of a menstrual cycle in the control groups and during a spontaneous bleeding episode in the PCOS groups. Circulating concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin (PRL), testosterone, Delta4-androstenedione, 17alpha-hydroxyprogesterone, sex-hormone-binding globulin (SHBG), insulin, glucose, PTH, 25-OH-vitamin D, and 1,25-(OH)2-vitamin D were measured. RESULTS: Both PCOS and increased body weight had a significant positive effect on serum PTH values. PTH concentrations were significantly correlated with age, BMI, glucose, PRL, SHBG, and testosterone. Only the correlations with testosterone and PRL were BMI-independent. The effect of PCOS on PTH concentrations remained significant after adjustment for BMI, but not after adjustment for testosterone concentration. Increased body weight also had a significant negative effect on 25-OH- and 1,25-(OH)2-vitamin D concentrations, but no association with the syndrome was observed. CONCLUSIONS: The results of the present study are in agreement with previous data supporting an association of increased PTH and decreased vitamin D metabolite concentrations with obesity. Moreover, the present findings indicate, for the first time, that PTH probably is also linked to PCOS-associated hyperandrogenism.

Adolescent↗

PubMed2006

Elevated serum levels of interleukin-18 are associated with insulin resistance in women with polycystic ovary syndrome.

Overproduction of proinflammatory factors is associated with obesity and diabetes. Interleukin (IL)-18 as a member of IL-1 cytokine family is increased in obese, in diabetic, and even in polycystic ovary syndrome (PCOS) patients. In the present study we evaluated the association of serum IL-18 levels with insulin resistance in PCOS women. Forty-two PCOS women and 38 control subjects were enrolled in this study and matched with respect to age and body mass index (BMI). Serum IL-18 levels and hormones were measured for all subjects. Furthermore, euglycemic hyperinsulinemic clamp test was performed in selected 30 PCOS women and 11 control subjects. Serum IL-18 levels were elevated in PCOS women compared with the control (p = 0.033). IL-18 levels were positively correlated with homeostasis model assessment index (HOMA) beta index, which assesses beta cell function (p = 0.035), but were inversely correlated with clamp indices, which best represent insulin resistance status: M, Clamp ISI*100, and MCRg values (p = 0.006, 0.010, and 0.009 respectively). No correlation was found between IL-18 and age, BMI, waist-to-hip ratio (WHR), lipid profile, dehydroepiandrosterone-sulfate (DHEAS), sex hormone- binding globulin (SHBG), or fasting insulin levels. In conclusion, in the present study, serum IL-18 levels were significantly increased in PCOS women and firmly associated with insulin resistance displayed by euglycemic hyperinsulinemic clamp test. It indicates that IL-18 may be a contributing factor linking inflammation and insulin resistance in PCOS women.

Blood Glucose↗

PubMed2005

Global fibrinolytic capacity is decreased in girls with premature adrenarche: a new pathological finding?

OBJECTIVE: Global fibrinolytic capacity (GFC) is a sensitive method reflecting all of the molecular components involved in the process of fibrinolysis. Recently, a decrease in GFC has been shown in women with polycystic ovary syndrome (PCOS). Girls with premature adrenarche (PA) have been shown to have hyperinsulinemia and dyslipidemia in addition to hyperandrogenemia, similar to women with PCOS. The aim of this study was to evaluate GFC levels in girls with PA. PATIENTS AND METHODS: Twenty-five girls with PA, who had developed pubic/axillary hair at age of 7.09 +/- 0.74 (5.1-7.9) years, were studied at the age of 10.04 +/- 1.53 years and compared with 20 age-matched healthy controls and 10 girls with PCOS (mean age 16.58 +/- 1.46 years). RESULTS: Median DHEAS and free testosterone levels were significantly higher in girls with PA than in the control group. The median serum sex hormone binding globulin (SHBG) level was higher in controls than in both PA and PCOS groups (49.85, 38.60 and 21.30 nmol/l, respectively). The median fasting glucose:insulin ratio (FGIR) levels were similarly low in PA and PCOS groups, while it was significantly higher in controls. The FGIR levels were less than 7 in 52% of girls with PA and 50% of girls with PCOS; however, in controls, only 5% of girls had FGIR <7. Median GFC in girls with PA (1.67 microg/ml) and PCOS (1.06 microg/ml) were significantly lower than that of the controls (3.48 microg/ml, p <0.001). The GFC level correlated positively with SHBG and FGIR. CONCLUSION: A reduction in GFC was demonstrated in girls with PA compared to healthy controls. This important finding, newly added to previous ones, may strengthen the view that PA is not a benign condition, and also points to the presence of potential risk factors for vascular diseases in these girls starting from childhood.

Adrenarche↗

PubMed2005

Insulin-sensitisers in the treatment of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a common endocrine condition with reproductive and metabolic implications. In the current setting there is an evolving, yet inadequate, understanding of the pathophysiology, long-term health implications and ideal therapies for women with PCOS. Insulin resistance, secondary to both genetic and lifestyle factors, is integrally involved in the pathogenesis, the metabolic and clinical features and the long-term sequelae of PCOS in a majority of patients. Therapeutic strategies targeting insulin resistance ameliorate clinical features and may reduce long-term sequelae of PCOS, including diabetes. The main benefit of improved insulin resistance is to improve fertility and potentially to improve clinical features of hyperandrogenism and lower androgen levels. Insulin sensitisers also have the potential to delay the development of diabetes and cardiovascular disease in PCOS. Lifestyle therapy is indicated as the first intervention; however, metformin as an insulin sensitising agent has a role in first-line medical therapy in women with PCOS. Further research is needed to define the role of insulin sensitisers in PCOS and to determine the long-term risks and benefits of these therapies.

Body Weight↗

PubMed1995

Adrenal androgen production in polycystic ovary syndrome.

Secondary PCOS may occur in association with disorders characterized by adrenal androgen excess, e.g. congenital adrenal hyperplasia. Primary PCOS is associated frequently with more subtle abnormalities in adrenal androgen status. However, it has not been established that the mild adrenal androgen occurring in PCOS is causally involved in the development of PCOS, although adrenal hyperresponsiveness to stimulation appears to be characteristic of PCOS. It remains to be clarified whether this is due to excess stimulation of the adrenal by the putative CASH, which with ACTH probably coordinates adrenal androgen steroidogenesis, or whether adrenal hyperresponsiveness occurs as a consequence of increased cortisol clearance with compensatory hypersecretion of ACTH, which is associated with excessive adrenal androgen production. The possibility also exists that the enzyme system responsible for 17-hydroxyprogesterone production and its conversion to androgens is excessively active and may occur as a common defect in the adrenal and ovaries as a consequence of a congenital disorder. For at least some patients, treatment with a nocturnal low-dose glucocorticoid is an effective form of treatment. Indeed, this is the only hormonal form of treatment for hirsutism that also facilitates fertility and pregnancy. It is possible that PCOS may occur as a consequence of any disorder in which anovulation is associated with normal or elevated oestrogen levels. For some patients with PCOS, mild adrenal androgen excess is probably primary to development of the disorder. Thus, a trial of treatment with low-dose glucocorticoid at night appears to be a reasonable option in susceptible patients who can probably be recognized by demonstration of an excessive androgen response to ACTH or metyrapone.

Adrenal Glands↗

PubMed1997

Lack of relationship between 17-hydroxyprogesterone response to buserelin testing and hyperinsulinemia in polycystic ovary syndrome.

OBJECTIVE: To determine whether hyperinsulinism affects cytochrome P450c17 alpha activity by investigating the correlation between 17-hydroxyprogesterone (17-OHP) hyper-responsiveness to the gonadotropin-releasing hormone (GnRH) agonist, buserelin, and the insulin response to oral glucose in polycystic ovary syndrome (PCOS). DESIGN: Ultrasound, clinical and hormonal parameters were used to define PCOS in this prospective clinical study. We investigated the correlation between the 17-OHP response to buserelin testing and the insulin response to oral glucose in PCOS. METHODS: Twenty-eight women with PCOS and eighteen normal women were included in the study. 17-OHP response to buserelin, and insulin and C-peptide responses to oral glucose were measured. RESULTS: Twenty-five women with PCOS had an increased 17-OHP response. The PCOS patients showed significantly higher mean post-glucose load insulin and C-peptide levels than controls (P < 0.05). No significant correlations were found between basal 17-OHP and fasting insulin or fasting C-peptide, between peak 17-OHP and fasting insulin, peak insulin or peak C-peptide, between 17-OHP area under the curve (AUC) and insulin AUC or C-peptide AUC, and between percent increment in 17-OHP and insulin AUC or C-peptide AUC (P > 0.05). CONCLUSIONS: Lack of a relationship between the 17-OHP response to the GnRH agonist buserelin and hyperinsulinism suggests that hyperinsulinism may not play a role in the dysregulation of the cytochrome P450c17 alpha enzyme seen in PCOS.

17-alpha-Hydroxyprogesterone↗

PubMed1998

Serum levels of 3alpha-androstanediol glucuronide in hirsute and non hirsute women.

This study has evaluated the behaviour of 3alpha-androstanediol glucuronide (3alpha-diol G) in 170 women of whom 85 had polycystic ovary syndrome (PCOS), 35 had idiopathic hirsutism (IH) and 50 had regular cycles (control group). Of the women with PCOS, 45 were hirsute (PCOS-H) and 40 were non hirsute (PCOS-NH). Women in the control group were not hirsute. Hirsutism was assessed by the same physician using the Ferriman-Gallway score. The body mass index (BMI) was estimated in all of the women. Plasma concentrations of 3alpha-diol G were elevated only in hirsute patients, both with PCOS and with IH. Even in PCOS-NH, concentrations of 3alpha-diol G were higher compared with controls (P < 0.001), but significantly lower (P < 0.001) than those of the PCOS-H and of the IH groups. The behaviour of 3alpha-diol G was not affected by BMI.

Adolescent↗