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PubMed1995

Polycystic ovary syndrome patients as oocyte donors: the effect of ovarian stimulation protocol on the implantation rate of the recipient.

OBJECTIVE: To evaluate the outcome of oocytes donated by women with polycystic ovarian syndrome (PCOS) compared with oocytes donated by women with mechanical infertility. DESIGN: A retrospective study. PATIENTS: The outcome of 159 oocyte donation cycles with oocyte donated by PCOS patients were compared with 69 oocyte donation cycles with oocytes donated by patients with mechanical infertility. We compared the stimulation protocols in the donors to assess if the combination of GnRH analogue (GnRH-a), FSH, and hMG has an advantage over FSH and hMG alone with respect to their effect on fertilization and implantation rates in oocyte donation cycles. RESULTS: When treated with GnRH-a, pregnancy rates in PCOS and mechanical infertility donors were higher than those treated with FSH and hMG alone. The comparison between PCOS and mechanical factor oocyte recipients revealed no significant difference in the pregnancy and abortion rates, but the oocytes of patients with PCOS that were exposed to GnRH-a had a significantly higher implantation rate than those not exposed to GnRH-a. CONCLUSIONS: Oocytes obtained from PCOS patients had a fertilization potential equal to oocytes obtained from mechanical infertility donors. Furthermore, because the oocytes of patients with PCOS exposed to GnRH-a had a significantly higher implantation rate, a detrimental role of high LH on oocyte quality seems probable. However, because PCOS has a high familial prevalence, some reservations may arise due to a possible propagation of the problem in the next generation of oocyte donation programs.

Embryo Implantation↗

PubMed1996

Serum free testosterone in polycystic ovary syndrome measured with a new reference method.

OBJECTIVE: To quantify the actual serum free T with a specific new reference method in women with polycystic ovary syndrome (PCOS) and to analyze the effects of serum free T, total T, and the T:sex hormone-binding globulin (SHBG) ratio on the diagnosis of PCOS. SETTING: Outpatient clinic of reproductive endocrinology at Turku University Central Hospital, Turku, Finland. PATIENTS: Forty-four oligomenorrheic women with PCOS and 26 weight-matched control women with regular menstrual cycles. MAIN OUTCOME MEASURES: The concentrations of free T, total T, androstenedione (A), LH, FSH, SHBG, and insulin in serum. RESULTS: The mean concentrations of free T, total T, A, and LH as well as the LH:FSH and T:SHBG ratios were higher, whereas the mean concentrations of FSH was lower in the women with PCOS than in healthy women. No differences were found in the free T, total T, or T:SHBG levels or in the body mass indexes (BMIs) between the hirsute (n=26) and nonhirsute (n = 18) women with PCOS. Both elevated free T concentrations and high T:SHBG ratios were associated with obesity, but serum total T was independent of BMI. The serum free T measurement discriminated PCOS women from controls to a similar extent as total T and T:SHBG ratio as judged by a receiver operating characteristics analysis. CONCLUSIONS: The present data indicate that determination of free T provides little additional information in the diagnosis of hirsutism or PCOS and does not have to be included to the basic evaluation of these patients. Only half of women with PCOS exhibited elevated serum free T concentrations.

Adolescent↗

PubMed1999

Effect of chronic administration of cabergoline on uterine perfusion in women with polycystic ovary syndrome.

OBJECTIVE: To confirm whether patients with polycystic ovary syndrome (PCOS) have a reduction in uterine perfusion and to verify whether chronic administration of cabergoline can decrease this high vascular resistance. DESIGN: Prospective randomized trial. SETTING: Endocrinological Centre of the Department of Obstetrics and Gynecology, University of Cagliari, Cagliari, Italy. PATIENT(S): Thirty patients were enrolled in the study: 20 affected by PCOS and 10 healthy controls. Patients with PCOS were randomly assigned to one of two treatments for 3 months: oral administration of cabergoline (0.5 mg) every week or oral administration of placebo every week. INTERVENTION(S): All patients underwent transvaginal ultrasonography associated with Doppler flow measurement of the uterine artery, and serum hormone concentrations were determined during the early follicular phase. In women with PCOS, Doppler flow measurement and hormonal assessment were repeated in the early follicular phase of the third month of treatment. MAIN OUTCOME MEASURE(S): Pulsatility index of the uterine artery before and during treatment. RESULT(S): The mean pulsatility index of the uterine artery in patients with PCOS was significantly higher than that of the control group (3.29+/-0.5 and 2.01+/-0.2, respectively). Patients with PCOS treated with cabergoline showed a significant increase in uterine perfusion, with a pulsatility index of 3.14+/-0.6 before and 2.39+/-0.5 during the treatment. No difference was found in patients with PCOS treated with placebo. CONCLUSION(S): Patients with PCOS have high resistance in the uterine arteries, but chronic administration of cabergoline can increase uterine perfusion.

Administration, Oral↗

PubMed1999

Obesity regulates bioavailable testosterone levels in women with or without polycystic ovary syndrome.

OBJECTIVE: To evaluate [1] the effects of levels of sex hormone-binding globulin (SHBG), albumin, and total testosterone on the distribution of testosterone between SHBG-bound and non-SHBG-bound fractions; [2] the independent effects of polycystic ovary syndrome (PCOS) and body mass index on serum levels of total testosterone, non-SHBG-bound testosterone, SHBG, and albumin; and [3] the usefulness of levels of total testosterone and non-SHBG-bound testosterone and of the free androgen index in the diagnosis of PCOS. DESIGN: Retrospective clinical study. SETTING: An academic research environment. PATIENT(S): Forty-three women with oligomenorrhea and PCOS. Twenty-five women with regular menstrual cycles and without hirsutism served as controls. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Levels of non-SHBG-bound testosterone, total testosterone, SHBG, and albumin in serum. RESULT(S): Levels of total testosterone and non-SHBG-bound testosterone, and the free androgen index were higher in patients with PCOS than in healthy controls. PCOS did not have an effect on the levels of SHBG or albumin, or on the percentage of non-SHBG-bound testosterone. Levels of SHBG and albumin were inversely related to body mass index. The percentage and concentration of non-SHBG-bound testosterone and the free androgen index were directly related to body mass index. Hirsutism did not have an effect on any outcome measure. CONCLUSION(S): The distribution of total testosterone into SHBG-bound and non-SHBG-bound fractions is associated with body mass index, not with PCOS. The high levels of non-SHBG-bound testosterone and the high free androgen index in patients with PCOS reflect mainly high levels of total testosterone. Thus, the measurement of levels of non-SHBG-bound testosterone and the calculation of the free androgen index provide no further information in the diagnosis of PCOS beyond that provided by the measurement of levels of total testosterone.

Adult↗

PubMed1999

Ovarian stromal echogenicity in women with clomiphene citrate-sensitive and clomiphene citrate-resistant polycystic ovary syndrome.

OBJECTIVE: To compare stromal echogenicity in women with clomiphene citrate (CC)-sensitive and CC-resistant polycystic ovary syndrome (PCOS), and to compare stromal echogenicity before and after laparoscopic ovarian drilling in women with CC-resistant PCOS. DESIGN: Prospective study. SETTING: University teaching hospital. PATIENT(S): Twenty-two infertile women. INTERVENTION(S): Transvaginal ultrasound examination and laparoscopic ovarian drilling. MAIN OUTCOME MEASURE(S): Ovarian stromal index (ratio of mean ovarian stromal echogenicity to mean echogenicity of the entire ovary). RESULT(S): The mean (+/- SD) ovarian stromal index was 1.26+/-0.27 in the women with CC-sensitive PCOS and 1.22+/-0.11 in the women with CC-resistant PCOS. The ovarian stromal index and ovarian volume of the women with CC-resistant PCOS before and after ovarian drilling were not significantly different. CONCLUSION(S): There was no difference in the stromal index and ovarian volume between women with CC-sensitive PCOS and women with CC-resistant PCOS. There was no overall difference in the stromal index and ovarian volume in women with CC-resistant PCOS before and after ovarian drilling.

Adult↗

PubMed1999

Treatment with flutamide improves hyperinsulinemia in women with idiopathic hirsutism.

OBJECTIVE: To investigate insulin metabolism and its modifications induced by the administration of flutamide, a specific antiandrogen compound, in women with idiopathic hirsutism (IH) and in nonobese women with polycystic ovary syndrome (PCOS). DESIGN: Prospective, randomized trial. SETTING: Endocrinological Centre of the Department of Obstetrics and Gynecology, University of Caligari, Caligari, Italy. PATIENT(S): Thirty-two women with normal body mass index participated in the study: 11 with clinical and hormonal features of PCOS and 21 age- and weight-matched normally cycling women with IH (n = 11) and without IH (n = 10, controls). INTERVENTION(S): Each subject with PCOS or IH was assigned randomly to receive either flutamide tablets (250 mg twice a day) or placebo for > or =5 months. Twelve subjects (6 with PCOS, 6 with IH) received flutamide and 10 (5 with PCOS, 5 with IH) received placebo. All subjects ingested 75 g of glucose and then underwent an oral glucose tolerance test (OGTT), 3-7 days after spontaneous or medroxyprogesterone acetate (5 mg daily for 5 days)-induced menses. In women with PCOS or IH, the OGTT was repeated at the fourth month of treatment. MAIN OUTCOME MEASURE(S): Fasting and OGTT-stimulated levels of glucose, insulin, and C peptide. RESULT(S): Both fasting and OGTT-stimulated levels of insulin and C peptide were significantly higher in women with PCOS and in those with IH than in controls. Placebo did not modify parameters of glucose metabolism. Flutamide was capable of significantly blunting fasting and OGTT-stimulated secretion of insulin only in women with IH. CONCLUSION(S): Hyperinsulinemia exists in women with IH as well as in nonobese women with PCOS. Treatment with flutamide can completely reverse hyperinsulinemia only in women with IH, which suggests that the efficacy of the drug is dependent on peripheral androgen hyperactivity.

Adult↗

PubMed2000

Hyperinsulinemia in polycystic ovary syndrome correlates with increased cardiovascular risk independent of obesity.

OBJECTIVE: To assess the role of insulin resistance, independent of obesity, in determining cardiovascular risk among women with the polycystic ovarian syndrome (PCOS). DESIGN: Cross-sectional study examining the relationships between hyperinsulinemia, composite cardiovascular risk scores, and prevalence of individual risk factors among lean and obese women with PCOS and healthy controls. SETTING: University-based tertiary care outpatient endocrinology clinic. PATIENT(S): 57 women with clinically defined PCOS and 45 unselected healthy age-matched controls. INTERVENTION(S): Clinical and anthropomorphic measurements and laboratory determinations of insulin and lipid levels. MAIN OUTCOME MEASURE(S): Fasting serum insulin and a cardiovascular risk score. RESULTS: Hyperinsulinemic women with PCOS carried more cardiovascular risk than their normoinsulinemic counterparts, who in turn had more risk than the control women (P=.004 by analysis of covariance). In addition to the lipid changes expected with insulin resistance (high triglyceride and low HDL cholesterol levels), there was an excess of LDL cholesterol among the women with PCOS (P=.006 by analysis of covariance). Across the range of body mass index, women with PCOS had greater insulin resistance than controls, suggesting that PCOS itself and body mass index both contribute to the observed insulin resistance. CONCLUSIONS: Our data support the hypothesis that insulin resistance in PCOS is a determinant of overall cardiovascular risk independent of obesity. The mechanism of this relationship remains uncertain and is the subject of ongoing research.

Adult↗

PubMed2000

Influence of insulin resistance on total renin level in normotensive women with polycystic ovary syndrome.

OBJECTIVE: To evaluate the influence of insulin resistance on the plasma total renin level in normotensive women with polycystic ovary syndrome (PCOS). DESIGN: Prospective, controlled study. SETTING: University hospital. PATIENT(S): Twenty-five normotensive women with PCOS were compared with 11 normotensive control women with regular cycles and no features of PCOS. INTERVENTION(S): Clinical, ultrasonographic, and hormonal findings were used to define PCOS. Insulin resistance was estimated by continuous infusion of glucose with model assessment in the early follicular phase. MAIN OUTCOME MEASURE(S): Plasma levels of total renin and angiotensin II and serum levels of gonadotropins, DHEAS, total T, free T, 17 alpha-hydroxyprogesterone, and PRL were determined. RESULT(S): Plasma concentrations of angiotensin II were similar in the PCOS group and the control group. The concentration of total renin in plasma was higher in women with PCOS than in healthy women independent of insulin resistance. The sensitivity and specificity of the plasma total renin level to diagnose women with PCOS were calculated as 80% and 71.4%, respectively. CONCLUSION(S): The plasma total renin level is higher in normotensive women with PCOS than in healthy women independent of insulin resistance.

Adult↗

PubMed2000

Hypothalamic-pituitary-adrenal axis sensitivity to opioids in women with polycystic ovary syndrome.

OBJECTIVE: To evaluate the influence of the opioid system on the hypothalamic-pituitary-adrenal axis in women with polycystic ovary syndrome (PCOS). DESIGN: Controlled clinical study. SETTING: Academic research environment. PATIENT(S): Eight lean and 12 obese women with PCOS, and seven lean and 5 obese control subjects. INTERVENTION(S): Each patient received an i.v. bolus of naloxone at a dose of 125 microgram per kilogram of body weight; 48 hours later, each patient received 16 mg of loperamide p.o. MAIN OUTCOME MEASURE(S): Samples were collected for 2 hours for the naloxone test and for 3 hours for the loperamide test. Levels of adrenocorticotropic hormone (ACTH) and cortisol were measured in all plasma samples. RESULT(S): The obese women with PCOS had a greater ACTH and cortisol response to opiate blockade than either the lean women with PCOS or the control subjects, but there was no difference between the lean or obese control subjects and the lean women with PCOS. There was no difference in the responsiveness of the hypothalamic-pituitary-adrenal axis to loperamide between the PCOS and control groups. CONCLUSION(S): The data indicate that the sensitivity of the hypothalamic-pituitary-adrenal axis to opioids cannot be altered in women with PCOS. However, abnormalities of the hypothalamic-pituitary-adrenal axis in women with PCOS could be central in origin, as suggested by the effects of naloxone administration, and probably are related to the anthropometric characteristics of these hyperandrogenic patients.

Adrenal Glands↗

PubMed2003

Incidence and treatment of metabolic syndrome in newly referred women with confirmed polycystic ovarian syndrome.

In 138 oligo-amenorrheic white women with polycystic ovary syndrome (PCOS) (31+/-9-years-old), our first specific aim was to assess the incidence of the metabolic syndrome and to compare metabolic syndrome abnormalities in women with PCOS to those in the National Health and Nutrition Examination Survey (NHANES) III cohort of 1,887 white women. Our second aim was to determine whether metformin (2.55 g/d) and a diet of 1,500 calories, 26% protein, 44% carbohydrate (42% of carbohydrate complex), 30% fat (polyunsaturate/saturate ratio [P/S]=2/1), would ameliorate metabolic syndrome abnormalities in women with both PCOS and metabolic syndrome. The metabolic syndrome was present in 64 (46%) of the women with PCOS. In these 64 women, there were abnormalities in waist circumference (98%), high-density lipoprotein cholesterol (HDL-C) (95%), blood pressure (70%), triglycerides (56%), and glucose (11%). In these 64 women, mean +/- SD waist circumference was 116+/-15 cm, triglyceride 192+/-152 mg/dL, HDL-C 39+/-7 mg/dL, systolic blood pressure 131+/-13 mm Hg, diastolic blood pressure 83+/-7 mm Hg, and serum glucose 94+/-22 mg/dL. Serum insulin was high (>17 microU/mL) in 42 of the 64 women (66%). After age adjustment, 46.4%+/-4.2% of women with PCOS had the metabolic syndrome (> or =3 abnormalities) versus 22.8%+/-1.1% of NHANES III women, P<.0001 versus 6% of 20 to 29-year-old and 15% of 30 to 39-year-old NHANES III women. Of the 64 women with both PCOS and the metabolic syndrome, 50 had follow-up studies after an average of 6 months on metformin and diet. At 6 months follow-up, mean percent reductions were as follows: body weight 4.7% (111 to 106 kg, P<.0001), triglycerides 14% (197 to 136 mg/dL, P=.0001), systolic blood pressure 5.2% (131 to 124 mm Hg, P=.0002), diastolic blood pressure 6% (83 to 77 mm Hg, P=.0007), and insulin 31% (25 to 17 microU/mL, P<.0001); mean percent HDL-C increased 6% (39 to 41 mg/dL, P=.013). Of these 50 women, 29 had pretreatment baseline abnormal triglycerides (> or =150 mg/dL), 47 had low HDL-C (<50 mg/dL), 26 had high systolic blood pressure (> or =130 mm Hg), 16 had high diastolic blood pressure (> or =85 mm Hg), and 5 had glucose > or = 110 mg/dL. On metformin plus diet at 6 months, triglycerides moved within guidelines in 10 of 29 (34%) women, HDL-C in 6 of 47 (13%), systolic blood pressure in 16 of 26 (62%), diastolic blood pressure in 10 of 16 (63%), and glucose in 3 of 5 (60%). Metformin and diet ameliorate many of the features of the metabolic syndrome, present in 46% of women with PCOS in the current study, and should reduce risk for atherothrombosis and type 2 diabetes mellitus (DM) in PCOS.

Adult↗

PubMed1999

Impaired glucose tolerance in pregnant women with polycystic ovary syndrome.

OBJECTIVE: To determine whether women with polycystic ovary syndrome (PCOS) are more likely to develop gestational diabetes mellitus compared with age- and weight-matched controls. METHODS: This retrospective cohort study compared reproductive-age women with and without PCOS who received prenatal care at the University of North Carolina Hospitals between April 1989 and June 1998. We reviewed the medical charts of 22 women with PCOS diagnosis before pregnancy based on menstrual histories, elevated androgen levels, and LH-FSH ratios greater than 2. These women were compared with 66 women without PCOS matched for age and weight. Gestational diabetes mellitus (GDM) was diagnosed in women if they had abnormal results on a 50-g glucose screening test and at least two abnormal plasma glucose values during a 100-g glucose tolerance test. Medical complications of pregnancy, pregnancy complications, and birth outcomes were compared between women with and without PCOS. RESULTS: Nine of 22 women with PCOS also had GDM diagnosis, compared with two of 66 controls (odds ratio [OR] 22.2; 95% confidence interval [CI] 3.8, 170.0), and these women exhibited increased plasma glucose values for all measurements except fasting. Five of 22 women with PCOS developed preeclampsia compared with one of 66 controls (OR 15.0; 95% CI 1.9, 121.5). CONCLUSION: Women with PCOS are at increased risk of glucose intolerance and preeclampsia during pregnancy.

Adult↗

PubMed2003

Polycystic ovary syndrome and endometrial carcinoma.

CONTEXT: An association between polycystic ovary syndrome (PCOS)and endometrial carcinoma was first suggested in 1949, 14 years after the original description of the syndrome. Since then several studies have been published that seem to support this association. The prescription of hormonal treatment to reduce the risk of this complication is supported by the Guidelines for Good Clinical Practice of the Royal College of Obstetricians and Gynaecologists, UK, the Health Information website of the National Library of Medicine, USA, and in textbooks of gynaecological oncology. STARTING POINT: A recent practice bulletin from the American College of Obstetricians and Gynecologists on the clinical management of PCOS (Obstet Gynecol 2002; 100: 1389-402) says that there is still no consensus on the "optimal progestin, duration and frequency of treatment to prevent endometrial cancer in women with PCOS". Chronic anovulation, obesity, and hyperinsulinaemia are all associated with PCOS as well as with endometrial carcinoma. It has been assumed that PCOS predisposes to endometrial cancer. However, the evidence for such an association is inconclusive. Although PCOS is associated with risk factors for endometrial cancer, it does not necessarily follow that the incidence or mortality from endometrial cancer is increased. WHERE NEXT: Large-scale studies of morbidity and mortality in unselected populations of women with PCOS are needed. Women with PCOS are increasingly aware of the possible risks, and it will be necessary to identify which of them, if any, are at increased risk and how this risk can be effectively reduced.

Adult↗

PubMed1985

The adrenal cortex and virilization.

The physiological control of adrenal androgen secretion has not been definitively established. However, there is evidence to suggest that a dexamethasone-suppressible factor other than ACTH may have a specific role to play. The majority of patients with idiopathic hirsutism (hirsutism associated with regular menstruation) have findings suggestive of adrenal androgen excess, including enhanced androgen responsiveness following administration of metyrapone, and respond to treatment with dexamethasone, 0.5 mg given each night. Patients with idiopathic hirsutism have elevated androgens but normal oestrogen and gonadotrophin levels. In contrast, while patients with polycystic ovary syndrome (PCOS) also demonstrate evidence of adrenal androgen excess, these patients have elevated oestrone levels and gonadotrophin secretion is abnormal. Approximately 50% of patients with PCOS treated with dexamethasone resume regular menstruation. Oestrone excess appears to be primary to the abnormal gonadotrophin secretion and to the development of PCOS. In non-obese patients with PCOS elevated oestrone appears to occur as a consequence of the availability of the excessive amounts of its immediate precursor, androstenedione, an androgen mainly of adrenal origin. Androstenedione is converted to oestrone in fat. Obese amenorrhoeic subjects have normal androstenedione values but elevated oestrone levels with abnormal gonadotrophin secretion as seen in PCOS. These findings indicate that abnormal gonadotrophin secretion is associated with elevated oestrone levels whether these occur as a consequence of excessive adrenal androgen secretion, or the excessive conversion of normal amounts of available androstenedione. Patients with idiopathic hirsutism and elevated androstenedione levels but normal oestrone values appeared to be protected against the development of PCOS by relatively poor conversion of androstenedione to oestrone. It is likely, therefore, that if patients with idiopathic hirsutism gain additional adipose tissue, elevated oestrone levels will result and PCOS will develop. These observations explain the frequent association of PCOS and obesity. There is a close clinical association between elevated androgen levels and hirsutism and between elevated oestrone levels and menstrual disturbances. However, some patients with amenorrhoea but without hirsutism may demonstrate marked elevations of androgens and oestrone, the correction of which leads to the resumption of regular ovulation. This presentation, 'amenorrhoea with cryptic hyperandrogenaemia', is probably explained by diminished sensitivity of androgen receptors.(ABSTRACT TRUNCATED AT 400 WORDS)

17-alpha-Hydroxyprogesterone↗

PubMed2000

Correction of hyperinsulinemia in oligoovulatory women with clomiphene-resistant polycystic ovary syndrome: a review of therapeutic rationale and reproductive outcomes.

Polycystic ovary syndrome (PCOS) describes a convergence of chronic multisystem endocrine derangements, including irregular menses, hirsutism, obesity, hyperlipidemia, androgenization, large and cystic-appearing ovaries, insulin resistance and subfertility. Few PCOS patients exhibit all of these features, and often only one sign or symptom is evident. The sequelae of PCOS reach beyond reproductive health, as women affected with PCOS have increased relative risks for myocardial infarction, hypertension, ischemic heart disease, thromboembolic disease and diabetes. Although the adverse health consequences associated with PCOS are substantial, unfortunately most women are not aware of these risks. Indeed, in infertility practice such concerns are secondary as most patients are referred for treatment specifically to achieve a pregnancy. Impairments in insulin metabolism appear central to the physiologic cascade of PCOS, yet clomiphene therapy fails to remedy this defect. Several investigators have described satisfactory reproductive outcomes for PCOS patients treated with oral insulin-lowering agents. In this report, we outline a diagnostic and therapeutic approach for women with PCOS refractory to clomiphene with attention to the underlying insulin imbalance associated with impaired fertility.

Clomiphene↗

PubMed1996

Polymorphism of glycogen synthetase gene in polycystic ovary syndrome.

OBJECTIVE: Polycystic ovary syndrome is a heterogeneous disorder associated with a moderate degree of insulin resistance and a higher risk of developing NIDDM. The exact mechanism of insulin resistance is unclear. This study examines the frequency of an Xbal polymorphism of the glycogen synthetase gene (A2 allele) as a marker of insulin resistance and seeks to relate the presence of the A2 allele to indices of insulin sensitivity in women with polycystic ovary syndrome (PCOS). METHODS: Insulin sensitivity was assessed by fasting insulin measurements, as well as following oral glucose tolerance test. An i.v. insulin tolerance test was performed to measure the rate of endogenous blood glucose disposal following an i.v. bolus of insulin. Restriction fragment length polymorphism was performed with Xbal digestion of PCR amplified product to detect the presence of A1 and A2 allele. PATIENTS: Seventy-one obese (BMI > 25.1) and 19 non-obese (BMI < 25) women with PCOS, and 62 controls (33 obese and 29 non-obese) participated in the study. RESULTS: Obese PCOS had significantly higher fasting insulin (P = 0.002) compared to obese controls. There was no difference between non-obese PCOS and controls. Twenty per cent of obese PCOS had impaired glucose tolerance. The A1A2 genotype was detected in 16 of the 150 (10.7%) subjects examined. Of these, 11/88 (12.5%) were PCOS and 5/62 (8%) were controls. The A2A2 genotype was not present in any of the subjects. The A1A2 genotype was not detected in any of the subjects with impaired glucose tolerance. There was no significant difference in the incidence of the A1A2 genotype between PCOS and controls or between the individual groups. There was no association between the presence of the A1A2 genotype and indices of insulin sensitivity. CONCLUSION: The Xbal polymorphism (A2 allele) of the glycogen synthetase gene was not over represented in the PCOS subject and did not relate to the indices of insulin sensitivity or glucose intolerance.

Adolescent↗

PubMed1996

Dyslipidaemia is associated with insulin resistance in women with polycystic ovaries.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is characterized by hyperinsulinaemia and insulin resistance. Previous reports of lipid abnormalities in the syndrome have produced conflicting results which may, in part, be related to the lack of appropriate controls for the obese women with PCOS. Only one study has related lipid levels to insulin sensitivity. The objective of this study was to assess lipids and lipoproteins in women with PCOS, to compare the results with weight matched controls, and to relate the findings to indices of insulin secretion and action, and to menstrual history. DESIGN: A cross-sectional study of insulin sensitivity and lipids in a cohort of PCO subjects compared to weight and ethnic group matched controls. PATIENTS AND METHODS: We have therefore investigated glucose tolerance, plasma lipids and lipoproteins in 19 lean (LP) and 55 obese (OP) patients with PCO and compared the results with those in 22 lean (LC) and 15 obese (OC) control women. Insulin sensitivity was measured in the same subjects with a short insulin (0.05 U/kg i.v. insulin) tolerance test (LP, n = 18; OP, n = 20; LC, n = 19; OC, n = 11). RESULTS: Results are expressed as mean +/- SEM or median (interquartile range). Fasting plasma glucose levels were similar in the four groups but the plasma glucose area was higher after oral glucose (75 g) in both the lean and obese PCOS groups than in their controls (LC 32.4 +/- 0.7 vs LP 35.2 +/- 1.2, P < 0.01; OC 34.7 +/- 1.8 vs OP 37.8 +/- 1.5 mmol/l/3 h, P < 0.01). Insulin sensitivity was significantly reduced in obese PCOS women (LC 196 +/- 9 vs LP 179 +/- 9, NS; OC 168 +/- 12 vs OP 133 +/- 9 mmol/l/min, P < 0.01). Total serum cholesterol levels were similar in the four groups but HDL2-cholesterol was reduced in both obese and lean PCOS (LC 0.42 (0.38-0.62), LP 0.31 (0.26-0.44), P < 0.05; OC 0.34 (0.21-0.47), OP 0.21 (0.12-0.32) mmol/l, P < 0.01). Total HDL-cholesterol was decreased significantly only in the obese PCOS group. Body mass index correlated significantly and negatively with total HDL-cholesterol and with HDL2-cholesterol levels both within the PCOS group and the control women. Using multiple regression insulin insensitivity contributes significantly beyond BMI to the low HDL-cholesterol in women with polycystic ovaries. CONCLUSION: Polycystic ovary syndrome is associated with biochemical risk factors for premature vascular disease, which cannot be explained by obesity alone.

Adult↗

PubMed1997

Circulating leptin concentrations in polycystic ovary syndrome: relation to anthropometric and metabolic parameters.

OBJECTIVE: To determine the relation between metabolic and anthropometric parameters and circulating leptin concentrations in women with polycystic ovary syndrome (PCOS). DESIGN AND PATIENTS: Correlation of fasting serum leptin concentrations with anthropometric measures and multiple metabolic parameters including insulin and glucose responses to a 2-hour 75-g oral glucose tolerance test (OGTT) in 85 women with PCOS (17-36 years, body mass index (BMI) 29.9 +/- 0.9 kg/m2, mean +/- SD) and 18 control women (25-47 years, BMI 25 +/- 1.7 kg/m2). Diagnostic criteria for PCOS: characteristic ovarian morphology on ultrasound plus at least two of (1) elevated serum testosterone; (2) elevated serum androstenedione; and (3) reduced serum SHBG concentrations. MEASUREMENTS: Concentrations of androgens, lipids, PRL, gonadotrophins, and leptin were measured in the baseline fasting blood sample from an OGTT. Insulin and glucose were measured throughout OGTT. Serum leptin concentrations were measured by radioimmunoassay. RESULTS: Log leptin levels in the PCOS group correlated significantly with BMI (r = 0.85, P < 0.0001) and with 8 other parameters including waist/hip ratio (r = 0.51, P = 0.0005). By stepwise regression analysis, only BMI (P < 0.0001) and plasma high density lipoprotein concentration (P = 0.02) were independently correlated with log leptin levels, both positively. There was no effect of fat distribution, as measured by waist/ hip ratio, on leptin concentrations. Comparison of control subjects to a BMI-matched subgroup of 55 PCOS subjects revealed significantly higher circulating concentrations of LH, testosterone, DHEAS, progesterone and androstenedione, and higher glucose and insulin responses to OGTT in the PCOS group. Leptin levels were not different between the PCOS subgroup and control group (14.8 +/- 1.3 vs 12.1 +/- 2.3 micrograms/l, mean +/- SE, P = 0.26) and the relation of BMI to leptin levels determined by linear regression analysis also did not differ between the two groups. CONCLUSIONS: Our results indicate that circulating leptin concentrations in women with PCOS, a condition characterized by hyperandrogenaemia, increased LH concentrations and insulin resistance, are strongly related to BMI and not independently affected by circulating levels of insulin, gonadotrophins or sex hormones.

Adolescent↗

PubMed2000

Spironolactone as a single agent for long-term therapy of hirsute patients.

OBJECTIVE: To assess the androgen-suppressing effect of spironolactone, and the use of this drug as a single agent in the long-term therapy of hirsute patients with either polycystic ovary syndrome (PCOS) or idiopathic hirsutism (IH). Standard cyproterone acetate (CPA) treatment was used to evaluate the results obtained with spironolactone. DESIGN: Prospective randomized study. PATIENTS: Forty-six hirsute women were separated randomly into two groups, stratified for polycystic ovary syndrome. For 12 months, Group 1 (21 patients, 10 PCOS) received spironolactone only (200 mg/day). Group 2 (23 patients, nine PCOS) received CPA (50 mg/day) with ethinyl oestradiol (35 microgram/day). MEASUREMENTS: Ferriman-Gallwey clinical score for hirsutism and serum testosterone, androstenedione, and LH levels. RESULTS: In IH patients, hirsutism regressed equally with spironolactone (21 +/- 2-14.5 +/- 2) and CPA (23 +/- 2-13 +/- 2). In PCOS patients, the mean score for hirsutism after 12 months was significantly lower with CPA (12 +/- 1) than with spironolactone (16 +/- 1). Testosterone levels did not change with spironolactone; with CPA there was a decrease from baseline in PCOS (47% and 51%, 6 and 12 months) and IH patients (31% and 30%). Androstenedione levels also declined from baseline in CPA-treated PCOS patients (38% and 39%, 6 and 12 months). Androgen levels were significantly different between the groups after 6 and 12 months. LH levels decreased with CPA (72%) but not with spironolactone. CONCLUSION: Our results suggest that spironolactone used as a single agent is as effective as cyproterone acetate combined with oestradiol for long-term treatment of patients with idiopathic hirsutism. In PCOS patients, spironolactone is still effective for reducing hirsutism; however, for treatment of the hormonal or metabolic manifestations associated with PCOS, it may be necessary to combine spironolactone with either an antigonadotrophic agent or a drug that improves peripheral insulin sensitivity.

Adolescent↗