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PubMed1996

Optimal use of hormone determinations in the biochemical diagnosis of the polycystic ovary syndrome.

OBJECTIVE: To investigate, using logistic regression analysis and receiver operator characteristic analysis, the biochemical diagnosis of polycystic ovary syndrome (PCOS) and if it could be improved by using an array of hormone measurements chosen to yield optimal and cost-effective discrimination between women with PCOS and healthy women. DESIGN: Retrospective clinical study. SETTING: Outpatient clinic of reproductive endocrinology at Turku University Central Hospital, Turku, Finland. PATIENTS: Fifty-four oligomenorrheic women with PCOS diagnosed by ovarian ultrasonography, and 29 healthy regularly menstruating women with normal ovarian morphology. MAIN OUTCOME MEASURES: Concentrations of LH, FSH, androstenedione (A), T, and sex hormone-binding globulin in serum. RESULTS: Luteinizing hormone, FSH and A, when used in combination, were the hormonal analytes of highest clinical utility. Diagnostic sensitivity, specificity, and overall concordance of 98%, 93%, and 96%, respectively, were attained. Each of the analytes used alone yielded lower degree of discrimination. CONCLUSIONS: Simultaneous use of the levels of LH, FSH, and A in serum can be used effectively for classification between women with PCOS and healthy women.

Adolescent↗

PubMed1987

Pulsatile intravenous gonadotropin-releasing hormone for ovulation-induction in infertile women. II. Analysis of follicular and luteal phase responses.

Pulsatile intravenous gonadotropin releasing hormone (IV-GnRH) was used in 36 infertile patients with primary amenorrhea (n = 5), secondary amenorrhea due to hypothalamic chronic anovulation (HCA) (n = 22), hyperprolactinemia (n = 1) or polycystic ovary syndrome (PCOS) (n = 5), and oligomenorrhea (n = 3), using several dosage and timing regimens. Early follicular phase responses showed four patterns: type 1 consisted of a delayed follicle-stimulating hormone (FSH) peak and was seen with severe hypothalamic suppression (n = 4); type 2 consisted of a brisk and dominant FSH peak on the first day of treatment, and occurred with mild to moderate hypothalamic suppression (n = 19); type 3, which consisted of an FSH peak accompanied by an immediate and exaggerated luteinizing hormone (LH) rise, occurred with mild PCOS and some cases of HCA (n = 5); and type 4, in which LH levels were high to begin with and neither FSH nor LH levels rose with GnRH, occurred with severe PCOS (n = 2). Exaggerated estradiol responses within 24 hours of therapy were seen in eight cycles: in four cases no ovarian abnormality was apparent; in three cases a dominant follicle was already present; and in one case ovarian hyperstimulation was diagnosed ultrasonographically. With standard human chorionic gonadotropin luteal phase support, luteal phase defects were rare with HCA but common with PCOS.

Estradiol↗

PubMed1997

Effects of oral glucose administration on plasma growth hormone levels in women with polycystic ovary syndrome.

OBJECTIVE: To evaluate the sensitivity of GH secretion to the suppressive effect of oral glucose administration in women with polycystic ovary syndrome (PCOS). DESIGN: Comparison of the GH response to an oral glucose load in women with PCOS and in weight-matched normally menstruating women (controls). SETTING: Reproductive endocrinology unit. PATIENT(S): Eighteen obese and 11 nonobese patients and 10 obese and 10 nonobese controls. INTERVENTION(S): After an overnight fast, each woman underwent a 75-g, 3-hour oral glucose tolerance test (OGTT). MEAN OUTCOME MEASURE(S): Growth hormone, glucose, and insulin responses to OGTT. RESULT(S): No significant differences in the glycemic and insulinemic responses were found between the patients and the weight-matched controls. No decrease in plasma GH was observed in both obese and nonobese patients and in obese controls during the OGTT, whereas a significant GH decrease occurred in nonobese controls 60 and 120 minutes after glucose intake. CONCLUSION(S): Oral glucose administration was unable to suppress GH levels in nonobese as well as in obese women with PCOS and in obese control women. These data suggest that both PCOS and obesity are associated with a reduced sensitivity of GH secretion to glucose suppression.

Administration, Oral↗

PubMed1998

The plasminogen activator system in women with polycystic ovary syndrome.

OBJECTIVE: To evaluate the plasminogen activator system in women with polycystic ovary syndrome (PCOS). DESIGN: Case-control study. SETTING: A district general hospital in the United Kingdom. PATIENT(S): Eleven women with PCOS and 12 controls. INTERVENTION(S): Venipunctures for assays of the plasminogen activator system. MAIN OUTCOME MEASURE(S): Euglobulin clot lysis times, plasminogen activator inhibitor 1 (PAI-1) activity, fibrinogen, plasminogen, and alpha-2 antiplasmin concentrations in plasma. RESULT(S): Women with PCOS may had a significantly longer euglobulin clot lysis time (mean +/- SD, 389 +/- 164 minutes vs. 220 +/- 110 minutes), a higher PAI-1 activity (mean +/- SD, 19.7 +/- 12 arbitrary units (AU) per mL vs. 10.9 +/- 7.9 AU/mL), and a higher fibrinogen level (mean +/- SD, 4.02 +/- 0.64 g/L vs. 3.15 +/- 0.6 g/L) compared to controls. CONCLUSION(S): Women with the PCOS may have an imbalance in the plasminogen activator system that is tilted toward a reduced production of the proteolytic enzyme plasmin. Systemically, this may increase their risk of cardiovascular disease, but at cellular level in the ovaries, it may result in impaired follicular rupture and anovulation.

Adult↗

PubMed1997

The significance of polycystic-appearing ovaries versus normal-appearing ovaries in patients with polycystic ovary syndrome.

OBJECTIVE: To evaluate what hormonal or biochemical parameters are most highly associated with the finding of polycystic-appearing ovaries as compared with normal-appearing ovaries in women with polycystic ovary syndrome (PCOS). DESIGN: Prospective randomized study. SETTING: Academic medical center. PATIENTS: Ten women with PCOS-five with normal-appearing ovaries and five with polycystic-appearing ovaries-were matched for age and body mass index. All had serum T levels between 80 and 150 ng/dL (conversion factor to SI unit, 3.467). INTERVENTION(S): Insulin infusion for the purpose of performing insulin tolerance testing to evaluate insulin resistance or sensitivity. MAIN OUTCOME MEASURE(S): We measured serum T, DHEAS, androstenedione, sex-hormone binding globulin, 5 alpha-androstane-3 alpha-17 beta-androstenediol glucuronide, FSH, LH, insulin-like growth factor-I, insulin-like growth factor binding protein-1, and insulin-like growth factor binding protein-3. Insulin resistance, measured by insulin tolerance testing, also was done on the same day after the patient had fasted for at least 8 hours. RESULT(S): Serum androgens and binding proteins were not significantly different in both groups. Insulin tolerance testing demonstrated a slower glucose disappearance in the polycystic appearing ovary group (Kitt glucose was 4.58% +/- 1.4%/min in the normal-appearing ovaries group versus 2.07% +/- 1.07%/min in the polycystic-appearing ovaries group). CONCLUSION(S): Women with PCOS and polycystic-appearing ovaries do not demonstrate any definitive serum hormonal differences compared with women with PCOS and normal-appearing ovaries. The presence of polycystic-appearing ovaries correlates significantly with the presence of insulin resistance.

Adult↗

PubMed1999

Effect of troglitazone on endocrine and ovulatory performance in women with insulin resistance-related polycystic ovary syndrome.

OBJECTIVE: To investigate the effect of troglitazone, a new antidiabetic agent that improves insulin resistance, on endocrine, metabolic, and ovulatory performance in women with insulin resistance-related polycystic ovary syndrome (PCOS). DESIGN: Prospective clinical study. SETTING: Infertility outpatient clinic, Niigata University Hospital, Niigata, Japan. PATIENT(S): Thirteen women with PCOS and insulin resistance. INTERVENTION(S): Troglitazone (400 mg/d) was administered for 12 weeks. MAIN OUTCOME MEASURE(S): Insulin and other hormone (gonadotropins, androgens) levels; various parameters relating to glucose and lipid metabolism before, during, and after troglitazone administration; and ovulation rate. RESULT(S): The mean (+/-SD) fasting insulin concentration was significantly reduced, from 18.3+/-8.9 to 10.5+/-7.1 microU/mL. The LH level was reduced from 9.7+/-3.4 to 4.8+/-3.9 mIU/mL and the testosterone level was reduced from 0.9+/-0.5 to 0.5+/-0.3 ng/mL in accordance. Atherosclerotic lipid levels also were normalized. Before troglitazone administration, the ovulation rate during clomiphene citrate therapy was 34.9% per cycle (15/43). This increased significantly to 72.7% (8/11) during troglitazone coadministration. Further, an ovulation rate of 42.3% (11/26) was achieved with troglitazone alone. CONCLUSION(S): In women with PCOS and insulin resistance, the reduction of hyperinsulinemia that is produced by troglitazone improves the hyperandrogenism that characterizes PCOS, restoring ovulation.

Adult↗

PubMed1999

The pathogenesis of ovarian hyperstimulation syndrome: in vivo studies investigating the role of interleukin-1beta, interleukin-6, and vascular endothelial growth factor.

OBJECTIVE: To evaluate systemic and ovarian changes in levels of interleukin (IL)-1beta, IL-6, and vascular endothelial growth factor (VEGF) in response to hCG administration to determine which may be the potential initiator of vascular effects and to identify the main source of the substance; to evaluate serum and follicular fluid levels of these cytokines as markers of ovarian hyperstimulation syndrome (OHSS), and to compare levels of these cytokines under basal conditions in women with normal ovulation and those with polycystic ovary syndrome (PCOS). DESIGN: Prospective controlled study. SETTING: In vitro fertilization program at the Instituto Valenciano de Infertilidad, Valencia, Spain. PATIENT(S): Women undergoing IVF, in whom the first two study objectives were analyzed, and women with normal ovulation and patients with PCOS undergoing retrieval of immature oocytes in natural cycles or cycles stimulated for IUI but cancelled during induction of ovulation, in whom the third study objective was analyzed. INTERVENTION(S): Serum was collected before and after hCG administration, and follicular fluid was collected at ovum pick-up. MAIN OUTCOME MEASURE(S): Serum and follicular fluid levels of IL-1beta, IL-6, and VEGF. RESULT(S): There was a significant increase in serum VEGF levels after hCG administration in patients who were at risk for OHSS compared with those who were not at risk for OHSS. Significantly lower VEGF levels were found in the follicular fluid of patients who were at risk; this decrease was the only useful marker to discriminate between the two groups. Moreover, both groups had similar cytokine production under basal conditions. An increase in serum E2 occurred coincident with a decrease in IL-1beta, IL-6, and VEGF in patients with PCOS. CONCLUSION(S): Vascular endothelial growth factor seems to be the mediator of hCG on the vascular tree. There was an early systemic increase in VEGF that may have significance in the development of OHSS. A decrease in the follicular fluid VEGF concentration is a valid marker to identify women in whom OHSS will develop. The pattern of cytokine release in patients with PCOS under basal conditions was not different from that in women with normal ovulation.

Chorionic Gonadotropin↗

PubMed1999

Alternate pathway 17,20-lyase enzyme activity in the adrenals is enhanced in patients with polycystic ovary syndrome.

OBJECTIVE: To assess the activity of the enzyme cytochrome P450c17alpha in patients with polycystic ovary syndrome (PCOS). DESIGN: Prospective clinical study. SETTING: Outpatients at Erciyes University Medical School, Kayseri, Turkey. PATIENT(S): Twenty-eight women with PCOS aged 25.44 +/- 4.37 years (mean +/- SD) and 18 normal women aged 26.94 +/- 3.17 years. MAIN OUTCOME MEASURE(S): Serum levels of 11-deoxycortisol, androstenedione (A), and 17alpha-hydroxy progesterone were measured before and 30 and 60 minutes after ACTH (0.25 mg i.v.) injection. RESULT(S): There was a statistically significant correlation between basal levels of 11-deoxycortisol (4.05 +/-1.16 ng/mL) and A (3.36 +/- 0.97 ng/mL) (r = 0.539). The peak level of 11-deoxycortisol (7.82 +/- 2.36 ng/mL) was also significantly correlated with the peak level of A (6.66 +/- 1.32 ng/mL) (r = 0.570) in women with PCOS. There was no statistically significant correlation between basal A (2.33 +/- 0.50 ng/mL) and basal 11-deoxycortisol (2.71 +/- 0.59 ng/mL) or between peak A (3.38 +/- 0.50 ng/mL) and peak 11 -deoxycortisol (3.68 +/- 0.48 ng/mL) levels in control subjects. CONCLUSION(S): We believe that PCOS is characterized by enhanced activity of 17,20-lyase enzyme in an alternate pathway between 11-deoxycortisol and A in the adrenal glands.

17-alpha-Hydroxyprogesterone↗

PubMed1999

Molecular analysis of the gonadotropin-releasing hormone receptor in patients with polycystic ovary syndrome.

OBJECTIVE: To determine whether a mutation in the GnRH receptor gene is responsible for polycystic ovary syndrome (PCOS). DESIGN: Molecular analysis of human genomic DNA. SETTING: Academic research environment. PATIENT(S): Eighty patients with PCOS. INTERVENTION(S): Extraction and polymerase chain reaction (PCR) analysis of genomic DNA, confirmation of PCR products by ethidium bromide staining of agarose gels after electrophoresis, denaturing gradient gel electrophoresis of PCR products, and photography. MAIN OUTCOME MEASURE(S): Mutations in the GnRH receptor of women with PCOS. RESULT(S): Denaturing gradient gel electrophoresis revealed no mutations in the exonic sequence encoding the open reading frame of the GnRH receptor. CONCLUSION(S): A mutation in the GnRH receptor gene is unlikely to be the underlying cause of PCOS in most patients. The molecular basis of this disorder remains unknown.

Adolescent↗

PubMed1999

Effects of metformin on adrenal steroidogenesis in women with polycystic ovary syndrome.

OBJECTIVE: To determine whether the administration of metformin, an insulin-sensitizing agent, is followed by changes in adrenal steroidogenesis in women with polycystic ovary syndrome (PCOS). DESIGN: Prospective trial. SETTING: Department of Obstetrics and Gynecology, University of Siena, Siena, Italy. PATIENT(S): Fourteen women with PCOS. INTERVENTION(S): Blood samples were obtained before (-15 and 0 minutes) and after (15, 30, 45, and 60 minutes) the administration of ACTH (250 microg). Metformin then was given at a dosage of 500 mg three times a day for 30-32 days, at which time the pretreatment study was repeated. MAIN OUTCOME MEASURE(S): The adrenal androgen responses to ACTH before and after treatment with metformin. RESULT(S): Ovulation occurred in two women (14%) in response to metformin treatment. A significant reduction in basal concentrations of free testosterone and a significant increase in concentrations of sex hormone-binding globulin were observed. The administration of metformin was associated with a significant reduction in the response of 17alpha-hydroxyprogesterone, testosterone, free testosterone, and androstenedione to ACTH. The ratio of 17alpha-hydroxyprogesterone to progesterone, which indicates 17alpha-hydroxylase activity, and the ratio of androstenedione to 17alpha-hydroxyprogesterone, which indicates 17,20-lyase activity, were significantly lower after a month of metformin treatment, indicating a reduction in the activities of these enzymes. CONCLUSION(S): The administration of metformin to unselected women with PCOS led to a reduction in the adrenal steroidogenesis response to ACTH. This finding supports the hypothesis that high insulin levels associated with PCOS may cause an increase in plasma levels of adrenal androgens.

Adrenal Cortex Hormones↗

PubMed2003

Idiopathic intracranial hypertension: associations with coagulation disorders and polycystic-ovary syndrome.

To better understand potentially reversible causes of idiopathic intracranial hypertension (IIH), also known as pseudotumor cerebri, and an apparent association of IIH with polycystic-ovary syndrome (PCOS), we assessed associations of IIH with coagulation disorders and with PCOS in 38 women with well-documented IIH. Fifteen women were found to have PCOS; 14 of them were obese, with a body-mass index (BMI) greater than 30 kg/m(2), and 10 were extremely obese (BMI > or = 40). Factor VIII concentration was high (>150%) in 9 of 38 (24%) IIH cases, compared with 0 of 40 healthy adults controls (P(f) =.0009). Familial aggregation of high concentrations of factor VIII, associated with thrombophilia, was documented in all 5 of the 9 high-level factor VIII probands' families who were sampled. Activated partial thromboplastin time (APTT) was prolonged (> or =31.5 seconds) in 10 of 38 (26%) IIH cases, compared with 1 of 32 (3%) controls (P(f) =.009) and, in 4 of these cases, was accompanied by the lupus anticoagulant. Plasminogen activator inhibitor activity (PAI-Fx) was high (>21.1 U/mL) in 9 of 38 cases (24%), compared with 1 of 40 controls (3%) (P(f) =.006). Lipoprotein A was high (> or =35 mg/dL) in 13 of 37 cases (35%), compared with 5 of 40 controls (13%) (P(f) =.03). IIH cases did not differ (P >.05) from controls for homocysteine, proteins C and S, free S, antithrombin III, ACLAs IgG and IgM, dilute Russell's viper venom time, Factor XI, factor V Leiden G1691A, G20210A prothrombin, C677T MTHFR, plasminogen activator inhibitor 4G/5G, or platelet glycoprotein PL A1A2 mutations. Exogenous estrogens (n = 23), clomiphene (n = 1), or pregnancy (n = 4) accompanied the first appearance of IIH in 28 women. PCOS and coagulation disorders, often augmented by exogenous estrogens or pregnancy, are associated with IIH.

Adult↗

PubMed1997

Metformin therapy is associated with a decrease in plasma plasminogen activator inhibitor-1, lipoprotein(a), and immunoreactive insulin levels in patients with the polycystic ovary syndrome.

Sixteen nondiabetic women with polycystic ovary syndrome (PCOS) aged 18 to 33 years were studied before and after 8 weeks on metformin (1.5 g/d) therapy to assess whether reducing hyperinsulinemia would reduce the levels of the major inhibitor of fibrinolysis, antigenic plasminogen activator inhibitor type 1 (PAI-1). Compared with six normal control women, PCOS women had a higher body mass index (BMI), waist to hip ratio, fasting insulin (Izero), insulin area under the curve during oral glucose tolerance testing (IA), glucose area under the curve during oral glucose tolerance testing (GA), IA/GA ratio, PAI-1, luteinizing hormone (LH) and ratio of LH to follicle-stimulating hormone (FSH), and free testosterone, and lower high-density lipoprotein (HDL) cholesterol (all P < .025). On metformin, BMI decreased 1.3% (P = .04), Izero 43% (P = .002), IA 31% (P = .03), GA 11% (P = .02), PAI-1 16% (P = .01), lipoprotein(a) [Lp(a)] 42% (P = .004), free testosterone 46% (P = .0006), LH 44% (P = .004), and the LH/FSH ratio 41% (P = .0001). On metformin, absolute and percent reductions in Izero correlated with absolute and percent reductions in PAI-1 (r = .60, P = .015 and r = .64, P = .008). On metformin, by stepwise multiple regression, the absolute reduction in Izero was a significant determinant of the absolute reduction in PAI-1 (partial R2 = 35%, P = .02), and the percent reduction in Izero was a significant determinant of the percent reduction in PAI-1 (partial R2 = 52%, P = .003). Metformin decreases Izero in hyperinsulinemic PCOS patients, reverses the hyperinsulinemia-driven endocrinopathy, decreases PAI-1, and decreases Lp(a), and should thus reduce the increased risk of atherothrombosis in PCOS.

Adolescent↗

PubMed2001

Ultrasound and menstrual history in predicting endometrial hyperplasia in polycystic ovary syndrome.

OBJECTIVE: To assess the role of endometrial thickness on vaginal ultrasound assessment and menstrual history in predicting endometrial hyperplasia in women with polycystic ovary syndrome (PCOS) who presented with infertility due to anovulation. METHODS: This was a prospective study in a university referral-based fertility and endocrine clinic. Fifty-six women with PCOS presenting with infertility due to anovulation underwent both vaginal ultrasound assessments and endometrial biopsies. The main outcome measures were the predictive value of sonographic endometrial thickness (primary objective) and the menstrual history with other clinical characteristics (secondary objective) for proliferative endometrium and endometrial hyperplasia in logistic regression analysis. Their predictive value was further examined by receiver operating characteristic curve analysis. RESULTS: Thirty-six PCOS patients (64.3%) had proliferative endometrium and 20 (35.7%) had endometrial hyperplasia. Five of the latter (25%) had cytologic atypia. Endometrial thickness less than 7 mm or intermenstrual interval less than 3 months (corresponding to more than four menstrual periods yearly) was associated with proliferative endometrium only. The endometrial thickness correlated positively with endometrial hyperplasia (P =.018) and, together with the average intermenstrual interval, were significant predictors of endometrial hyperplasia (P <.001). CONCLUSION: These findings point to the usefulness of obtaining a detailed menstrual history in women with PCOS by identifying those at increased risk of endometrial hyperplasia and who require an endometrial biopsy. The endometrial thickness corroborates this clinical impression and is particularly useful when the menstrual history is uncertain. Endometrial hyperplasia in this population is effectively excluded when the endometrial thickness is less than 7 mm.

Adult↗

PubMed2003

Metformin for the treatment of polycystic ovary syndrome.

OBJECTIVE: To familiarize obstetrician-gynecologists with the use of metformin for the treatment of polycystic ovary syndrome (PCOS). DATA SOURCES: Using OVID, 94 English-language articles published after 1966 indexed with the key words "metformin" and "polycystic ovary syndrome" were identified. METHODS OF STUDY SELECTION: Studies were excluded if they did not have a control group, did not use the National Institutes of Health definition of PCOS, did not have a clinical outcome as an end point, and were not in the English language. Reviews were also excluded, leaving 21 articles for inclusion. TABULATION, INTEGRATION, AND RESULTS: Three clinical trials reported that for the treatment of anovulatory infertility caused by PCOS, metformin plus clomiphene is more effective than clomiphene alone in inducing ovulation. For the treatment of irregular menses caused by PCOS in women not attempting conception, metformin therapy may restore ovulatory menses in the majority of women. However, most women will require 4-6 months of metformin therapy before they achieve ovulatory menses. In obese women, metformin plus a low-calorie diet may be associated with more weight loss than a low-calorie diet alone. CONCLUSION: Polycystic ovary syndrome is a common gynecologic endocrine disorder. Obstetrician-gynecologists should be familiar with the indications and contraindications for the use of metformin in their practice.

Clinical Trials as Topic↗

PubMed1997

Menstrual cyclicity after metformin therapy in polycystic ovary syndrome.

OBJECTIVE: To assess the effect of insulin-lowering treatment on menstrual cyclicity in polycystic ovary syndrome (PCOS). METHODS: Forty oligoamenorrheic women with PCOS were recruited in a prospective clinical study to receive metformin for a minimum period of 6 months. Twenty-two women completed the study. Serum LH, FSH, free testosterone, and glucose and insulin response to oral glucose load were measured both before and after 8 weeks of metformin treatment. Menstrual cyclicity and serum progesterone levels at the midluteal phase were assessed at the 30th week of metformin treatment. RESULTS: Twenty-one of 22 women had restoration of menstrual cyclicity (95.7%). Four of these women (19%) became pregnant within the 6th and 7th months of treatment. All four of the pregnant women delivered, and the infants were healthy. Thirteen of 15 women who had regular menses demonstrated a serum progesterone level within the ovulatory range (3.1-28 ng/mL). Fasting (P < .001) and the integrated insulin response to the glucose load decreased (P < .001) after 8 weeks of metformin treatment. This was accompanied by significant decreases in serum LH (P < .001) and free testosterone (P < .001) levels and LH/FSH ratio (P < .001). There was a small but significant reduction in body mass index after 8 weeks of metformin treatment (P < .001). CONCLUSION: A 6-month course of metformin may improve menstrual cyclicity and fertility in women with the PCOS. Insulin-sensitizing agents provide a rational approach to the treatment of the metabolic and endocrine abnormalities in PCOS women.

Adult↗

PubMed2003

Gene expression of type 2 17 beta hydroxysteroid dehydrogenase in scalp hairs of hirsute women.

Androgens are the main hormonal regulators of human hair growth and they are related to clinical conditions such as hirsutism. The aim of this study was to analyze the gene expression of androgen receptor (AR) and type 2 17 beta hydroxysteroid dehydrogenase (17 beta-HSD) in keratinocytes of plucked scalp hairs from hirsute patients and normal subjects. We studied 58 women with hirsutism (31 with polycystic ovary syndrome (PCOS), 27 with idiopathic hirsutism (IH)); 15 control women; and 10 control men. Hirsutism was assessed by a modified Ferriman-Gallwey method. Hormonal status was assessed between days 2 and 10 of the menstrual cycle or on any day when the patients were amenorrheic. AR and type 2 17 beta-HSD mRNA levels were estimated by reverse transcription-polymerase chain reaction (RT-PCR). AR expression was similar in all groups. Type 2 17 beta-HSD gene expression in untreated hirsute patients was lower (2.1+/-0.10) than in normal women (3.1+/-0.17), and similar to men (1.8+/-0.22). Comparing hirsute patients, type 2 17 beta-HSD expression was higher in treated PCOS (3.0+/-0.34 versus 2.2+/-0.13) and IH patients (2.5+/-0.19 versus 2.0+/-0.15); hirsutism score was lower (P=0.003, PCOS; P=0.003, IH); and SHBG levels were higher (P=0.001, PCOS; P=0.024, IH) in treated patients. The free androgen index was lower in treated women (P=0.024 for the IH group). In conclusion, the lower expression of type 2 17 beta-HSD mRNA in scalp hairs of untreated hirsute patients suggests androgen metabolism disturbances with predominance of more potent androgens, as occurs in men. The enzyme's higher gene expression in treated hirsute patients could be an indirect evidence of restored enzyme activity and intracellular androgen metabolism.

17-Hydroxysteroid Dehydrogenases↗

PubMed2001

Peripheral cholinesterase inhibition by occupational chlorpyrifos exposure in Australian termiticide applicators.

Occupational exposure to organophosphorus insecticides (OPs), such as chlorpyrifos, may be monitored by the measurement of the activity of peripheral cholinesterase (ChE) enzymes, including erythrocyte acetylcholinesterase (EAChE) and serum cholinesterase (SChE). Lymphocyte neuropathy target esterase (NTE) is thought to have potential as a predictor of organophosphate-induced delayed neuropathy (OPIDN). This paper describes work performed in 39 Australian pest control operators (PCOs) exposed to a termiticide containing chlorpyrifos, and 34 unexposed control subjects. EAChE activities in PCOs did not differ from those of unexposed control workers. Mean NTE activity was slightly higher in PCOs than in controls and mean SChE was 52% of control activity. These results indicate that exposure of Australian PCOs to termiticides containing chlorpyrifos may be monitored using SChE but not EAChE or NTE, and that workers in this industry have sufficiently high OP exposure to significantly depress SChE activity. SChE inhibition of 70-80% may be associated with symptoms. Although no current symptoms were reported to be associated with occupational OP exposure, these workers may be at increased risk of acute effects following inadvertent spills or self-contamination due to their background level of exposure to OPs. While it is preferable to compare ChE enzyme activities between pre- and post-exposure periods to evaluate OP-related effects in individuals, in some cases there is an absence of pre-exposure data. The results of this study suggest that a screening value for SChE of 550 nmol/min/ml in a single blood sample may be useful to identify potentially OP-exposed individuals in the Australian population. Australian control subjects were similar with respect to EAChE, but displayed activities of NTE and SChE approximately 50 and 23% lower than an unexposed UK reference group. While these comparisons are presently speculative, they suggest that there may be differences in SChE and NTE activities in control populations of the two countries. The routine treatment of Australian homes with termiticides containing OPs, or differences in the availability and use of domestic OP-containing insecticides may explain these population differences. Further work is required to examine whether these differences are real, and if so their likely cause.

Australia↗

PubMed2001

Insulin resistance in polycystic ovary syndrome: hyperandrogenemia versus normoandrogenemia.

OBJECTIVE: The goal of this study was to evaluate the insulin resistance and glucose tolerance in hyperandrogenemic and normoandrogenemic groups of patients with polycystic ovary syndrome (PCOS). STUDY DESIGN: In this cross-sectional study, 17 hyperandrogenemic and 14 normoandrogenemic, age and weight-matched non-obese women with PCOS were studied. All patients had clinical hyperandrogenism and chronic anovulation with polycystic ovaries on ultrasound. Insulin resistance and glucose tolerance were determined by measuring insulin and glucose concentrations following a 75 g oral glucose tolerance test (OGTT). Fasting glucose to insulin ratio (FG:I ratio), insulin area under the curve (AUC(insulin)) during OGTT, and homeostasis model assessment for insulin resistance (HOMA-IR) were calculated. RESULTS: Hyperandrogenemic group of patients had fasting hyperinsulinemia, lower FG:I ratio, higher AUC(insulin), and HOMA-IR compared with normoandrogenemic group. The differences between two groups were statistically significant. CONCLUSION: PCOS has variable biochemical features. Hyperandrogenemia associated with insulin resistance differs from normoandrogenemia in this syndrome. Fasting insulin concentrations, FG:I ratio, AUC(insulin), and HOMA-IR are convenient markers for determining insulin resistance in PCOS.

Adult↗