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PubMed2005

Androgen receptor gene CAG length polymorphism in women with polycystic ovary syndrome.

OBJECTIVE: To determine whether the CAG repeat length of the androgen receptor (AR) gene contributes to individual differences in the susceptibility to the development of polycystic ovary syndrome (PCOS). DESIGN: Retrospective case-control study. SETTING: University-based clinic. PATIENT(S): One hundred six nondiabetic women with PCOS and 112 nonhirsute fertile controls. INTERVENTION(S): Androgen receptor gene CAG repeat length was analyzed in women with PCOS and their controls. MAIN OUTCOME MEASURE(S): Androgen receptor gene CAG repeat length in both groups. RESULT(S): The mean CAGn was 21.5 repeats in both groups (NS; t-test). Furthermore, when the CAGn lengths were divided into three categories (CAGn < or =18, 19-24, > or =25), the distribution was similar in both groups (NS; chi2 test). However, all five women carrying < or =15 CAG repeats belonged to the PCOS group. In the PCOS group, CAGn did not correlate with body mass index or serum testosterone concentration. CONCLUSION(S): Androgen receptor CAGn is not a major determinant of PCOS. However, it may be a significant modulator of androgen-related diseases in some individuals.

Adenine↗

PubMed2006

Pregnancy outcome in infertile patients with polycystic ovary syndrome who were treated with metformin.

OBJECTIVE: To analyze pregnancy complications and outcome in patients with polycystic ovary syndrome (PCOS) treated with metformin. DESIGN: Single center retrospective case analysis. SETTING: Private regional nonurban referral subspecialty practice. PATIENT(S): After 7 months of average metformin use, 188 patients with PCOS (average infertility: 27 months) achieved 237 pregnancies. INTERVENTION(S): Of pregnancies established, metformin alone was used before conception in 124/237 (52%), oral fertility agents (CC or letrozole) in 81 (34%), gonadotropin therapy in 7 (3.0%), assisted reproduction in 17 (7.2%), and other fertility-promoting regimens in 8 (3.4%). MAIN OUTCOME MEASURE(S): Analysis of prepregnancy health parameters (weight, blood pressure, glucose tolerance, fasting and stimulated insulin levels) and pregnancy outcomes (miscarriage, pregnancy length, hypertension, gestational diabetes, weight gain, birth weight, sex ratio, congenital malformations, and breastfeeding success). RESULT(S): Metformin appears to decrease the rate of spontaneous abortion. The co-morbidities of PCOS including obesity, insulin resistance, and glucose sensitivity served as indicators of increased risk for pregnancy complications, especially gestational diabetes. No increase in pregnancy-induced hypertension was evident. Prematurity was increased. Neither PCOS nor metformin use appears to increase the rate of congenital anomaly. PCOS did not affect lactation. CONCLUSION(S): PCOS or its co-morbidities are associated with poorer pregnancy outcome. Implications and interventions are discussed.

Adolescent↗

PubMed2006

Plasma metastin levels are negatively correlated with insulin resistance and free androgens in women with polycystic ovary syndrome.

OBJECTIVE: This study was designed to: [1] measure, for the first time, metastin (kisspeptin) levels in women with polycystic ovary syndrome (PCOS), a condition associated with hypersecretion of LH and hyperandrogenemia; and [2] investigate the possible correlations between metastin and PCOS-related reproductive and metabolic disturbances. DESIGN: Clinical study. SETTING: University hospital. PATIENT(S): Twenty-eight obese and overweight (body mass index [BMI] >25 kg/m2) women with PCOS, 28 normal weight (BMI <25 kg/m2) women with the syndrome, and 13 obese and overweight controls (ovulatory women without clinical or biochemical hyperandrogenemia) were selected. INTERVENTION(S): Blood samples were collected between day 3 and day 6 of a spontaneous bleeding episode in the PCOS groups and a menstrual cycle of the controls, at 9:00 AM, after an overnight fast. MAIN OUTCOME MEASURE(S): Circulating levels of LH, FSH, PRL, T, Delta4-androstenedione (A), DHEAS, 17alpha-OH-P, sex hormone-binding globulin (SHBG), insulin, glucose, and metastin were measured. RESULT(S): Both normal weight women with PCOS and obese controls were less insulin resistant and had significantly higher metastin levels, compared to obese and overweight women with the syndrome. Plasma kisspeptin levels were negatively correlated with BMI, free androgen index, and indices of insulin resistance. CONCLUSION(S): These results indicate that metastin is negatively associated with free androgen levels. The PCOS-associated insulin resistance and consequent hyperinsulinemia probably contribute to this effect by [1] stimulating androgen synthesis by the polycystic ovary (PCO) and [2] suppressing SHBG production in the liver.

Adolescent↗

PubMed2006

Genetic variants in peroxisome proliferator-activated receptor gamma influence insulin resistance and testosterone levels in normal women, but not those with polycystic ovary syndrome.

OBJECTIVE: To investigate the relationship of the peroxisome proliferator-activated receptor gamma (PPARG) Pro12Ala and silent exon 6 (His447His) polymorphisms with the clinical features of polycystic ovary syndrome (PCOS). DESIGN: Patients with PCOS and control subjects were genotyped for Pro12Ala and His447His. Associations between genotype, diagnosis, and hormonal/metabolic parameters were assessed. SETTING: Subjects were recruited from the reproductive endocrinology clinic at the University of Alabama at Birmingham, Birmingham, Alabama. Control subjects were recruited from the surrounding community. Genotyping was performed at the Cedars-Sinai Medical Center in Los Angeles, California. PATIENT(S): Participants included 285 white women with PCOS and 187 controls. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The Pro12Ala and His447His genotypes, and hormonal and metabolic phenotypes. RESULT(S): The Pro12Ala and His447His genotypes did not influence risk of PCOS or its component phenotypes in patients with PCOS. In controls, Pro12Ala did not influence measures of insulin resistance or androgen production. However, carriers of the His447His T-allele had significantly decreased free and total T levels, and a significantly decreased homeostasis model assessment index of insulin resistance. Furthermore, haplotypes in controls bearing the His447His T-allele were also associated with decreased T. CONCLUSION(S): Peroxisome proliferator-activated receptor gamma does not appear to be an important modifier gene in PCOS. In controls, however, the His447His T-allele may be in linkage disequilibrium with a functional variant that influences insulin resistance and T production.

Adolescent↗

PubMed2004

Pathogenesis of polycystic ovary syndrome: what is the role of obesity?

Both obesity and the polycystic ovary syndrome (PCOS) are commonly seen in women of reproductive age. Fifty percent of all patients with PCOS are obese, and the presence of obesity affects the clinical manifestations of PCOS. The underlying pathogenetic mechanisms appear to involve insulin resistance and hyperinsulinemia, the magnitude of which is greater in obese than in non-obese women with PCOS. Specific effects of obesity on the manifestations of PCOS, underlying mechanisms of the interactions between obesity and PCOS, and therapeutic implications of these interactions are discussed in this article.

Endocrine System Diseases↗

PubMed2006

Short-term effect of orlistat on dietary glycotoxins in healthy women and women with polycystic ovary syndrome.

Exogenous advanced glycation endproducts (AGEs, known atherogenic molecules) abundant in everyday precooked, rich in fat, overheated meals can possibly contribute to the increased risk for diabetes and cardiovascular disease in women with polycystic ovary syndrome (PCOS). The aim of the present study was to investigate the effect of a lipase inhibitor on absorbed food glycotoxins in healthy women and those with PCOS. A 2-day protocol was followed. In the first day, a meal rich in AGE was provided, which on the second day was followed by two 120-mg capsules of lipase inhibitor, orlistat. Serum AGE levels were evaluated at baseline (0 hours), and at 3 and 5 hours postmeal during the study. Thirty-six women were studied, 15 controls (mean age, 28.80 +/- 5.47 years; body mass index, 25.85 +/- 6.73 kg/m(2)) and 21 with PCOS (mean age, 25.29 +/- 5.06 years; body mass index, 30.40 +/- 7.51 kg/m(2)) (University Hospital, Athens, Greece, institutional practice). Serum AGE levels, on day 1, were significantly increased both in the control group and in the PCOS group as compared with basal values (control group, 14.1%; PCOS group, 6.0%; P < .001). The corresponding rise was significantly lower on day 2 when the same meal was combined with orlistat (control group, 4.1%; PCOS group, 2.0%; P < .01). A limitation of the study is that it is a nonplacebo, nonrandomized therapeutic trial where each subject is considered as its own control. In conclusion, this study demonstrated the beneficial effect of orlistat on the absorption of food glycotoxins.

Absorption↗

PubMed2004

Secondary forms of polycystic ovary syndrome.

Hyperandrogenism and chronic anovulation are the most common endocrine disorders of premenopausal women. Most patients have polycystic ovary syndrome (PCOS), which is essentially benign, but might be associated with increased cardiovascular morbidity; PCOS is associated with specific endocrine and ultrasonographic features. Some patients exhibiting similar features to PCOS might have other underlying diagnoses, such as adrenal and ovarian steroidogenic deficiencies, adrenal and ovarian androgen-secreting tumours, other medical or endocrine disorders, and/or be on medications thought to cause PCOS, such as anti-epileptics. Unlike PCOS, some of these conditions can occasionally be life threatening and require prompt diagnosis and treatment. Here, we focus on these disorders, including their pathogenesis, and attempt to define the clinical and biochemical features that distinguish them from PCOS.

Endocrine System Diseases↗

PubMed2000

Postprandial triglyceride response in patients with polycystic ovary syndrome: relationship with waist-to-hip ratio and insulin.

OBJECTIVE: To examine the postprandial triglyceride response to a high-fat meal in women with polycystic ovary syndrome (PCOS) compared with a matched control group. DESIGN: Controlled clinical study. SETTING: Department of Endocrinology and Pathophysiology, School of Medicine, Universidad de Los Andes. PATIENT(S): 18 Hispanic women with PCOS (nine overweight and nine nonobese) and 9 healthy control women. INTERVENTION(S): Biometric measures and blood sample collection. MAIN OUTCOME MEASURE(S): Insulin and glucose levels during a standard oral glucose tolerance test. Plasma triglyceride, cholesterol, and high-density lipoprotein cholesterol levels were measured at baseline and at 4, 5, and 6 h after a high-fat meal. RESULT(S): Both obese and nonobese PCOS women had higher waist-to-hip ratios than controls. PCOS women had higher levels of fasting and postglucose insulin and fasting triglyceride and postprandial triglyceride response and had lower levels of postprandial high-density lipoprotein cholesterol response, but no significant differences within PCOS groups were observed. CONCLUSION(S): An expanded postprandial hypertriglyceridemia in PCOS women is related to a higher waist-to-hip ratio and insulin resistance, regardless of obesity, and contributes to increase the risk for coronary artery disease.

Adult↗

PubMed2000

Are women with polycystic ovary syndrome resistant to activated protein C?

OBJECTIVE: This study was performed to test the hypothesis that an increased prevalence of activated protein C (APC) resistance in women with polycystic ovary syndrome (PCOS) puts them at increased risk of miscarriage and thrombosis. DESIGN: Case control study. SETTING: A district general hospital in the United Kingdom. PATIENT(S): Forty-one women with PCOS and 25 controls. INTERVENTION(S): Clinical histories, ultrasound scans, and venepunctures. MAIN OUTCOME MEASURE(S): Diagnosis of PCOS or control, clinical histories, APC resistance according to an activated partial thromboplastin time-based assay. RESULT(S): There was no significant difference in the proportion of women with APC resistance in both groups (three women in the PCOS group [7%] vs. one woman in the control group [4%]). The prevalence of APC resistance in the entire study population was 6.5%. In the PCOS group, 29% (12/41) gave a positive family history of thrombosis compared with 8% (2/25) in the control group. None of the women with a positive family history of thrombosis had abnormal antithrombin 111, protein C, or protein S levels. CONCLUSION(S): This study suggests that women with PCOS may have the same prevalence of APC resistance as the background population and that APC resistance may not put them at a higher risk of thrombosis or miscarriage compared with the case of the general population.

Abortion, Spontaneous↗

PubMed2001

Diastolic dysfunction and increased serum homocysteine concentrations may contribute to increased cardiovascular risk in patients with polycystic ovary syndrome.

OBJECTIVE: To assess cardiac flow parameters in patients with polycystic ovary syndrome (PCOS). DESIGN: A prospective case-control study. SETTING: University-based hospital. PATIENT(S): Thirty consecutive patients with PCOS were enrolled. Thirty women with regular menstrual cycles served as the controls. INTERVENTION(S): Systolic and diastolic function parameters were assessed by standard two-dimensional and M-mode echocardiography. Insulin sensitivity was evaluated by a standard 75-g oral glucose tolerance test and area-under-curve insulin analysis. Serum hormones, lipid profile, homocysteine, vitamin B(12), folate, fibrinogen, uric acid, and plasminogen activator inhibitor-I concentrations were measured. MAIN OUTCOME MEASURE(S): Systolic and diastolic function parameters, insulin sensitivity and serum homocysteine levels. RESULT(S): The mean serum homocysteine and uric acid concentrations were significantly higher in the PCOS group. Patients with PCOS had significant hyperinsulinemia. All systolic function parameters were comparable between the two groups. However, patients with PCOS had significantly lower peak mitral flow velocity in early diastole and significantly lower ratio between the early and late peak mitral flow velocities and also had significantly longer isovolumic relaxation time, reflecting a trend for nonrestrictive-type diastolic dysfunction. The area-under-curve insulin correlated positively with peak mitral flow velocity in late diastole (r = 0.375). The mean cholesterol/high-density lipoprotein ratio correlated negatively with mean mitral flow velocity in early diastole (E) peak (r = -0.474). The mean fasting insulin level correlated negatively with mean E/A ratio (r = -0.387). CONCLUSION(S): Diastolic dysfunction and increased serum homocysteine concentrations may contribute to increased cardiovascular disease risk in patients with PCOS.

Adult↗

PubMed2002

Metformin therapy throughout pregnancy reduces the development of gestational diabetes in women with polycystic ovary syndrome.

OBJECTIVE: To assess whether metformin safely reduced development of gestational diabetes in women with the polycystic ovary syndrome (PCOS). DESIGN: Prospective and retrospective study. SETTING: Outpatient clinical research center. PATIENT(S): The prospective study included 33 nondiabetic women with PCOS who conceived while taking metformin and had live births; of these, 28 were taking metformin through delivery. The retrospective study included 39 nondiabetic women with PCOS who had live birth pregnancies without metformin therapy. INTERVENTION(S): Metformin, 2.55 g/d, throughout pregnancy in women with PCOS. MAIN OUTCOME MEASURE(S): Development of gestational diabetes in women with PCOS. RESULT(S): Before metformin therapy, after covariance adjustment for age, the two cohorts did not differ in height, weight, basal metabolic index, insulin, insulin resistance, or insulin secretion. Both cohorts had high fasting insulin, were insulin resistant, and had high insulin secretion. Among the 33 women who received metformin, gestational diabetes developed in 1 of 33 (3%) pregnancies versus 8 of 12 (67%) of their previous pregnancies without metformin. Among the 39 women who did not take metformin, gestational diabetes developed in 14 of 60 (23%) pregnancies. When all live births were combined, gestational diabetes occurred in 22 of 72 pregnancies (31%) in women who did not take metformin versus 1 of 33 pregnancies (3%) in those who took metformin. With gestational diabetes as the response variable and age at delivery and treatment group (metformin or no metformin) as explanatory variables, the odds ratio for gestational diabetes in women with metformin versus without metformin was 0.093 (95% CI: 0.011 to 0.795). With gestational diabetes in 93 pregnancies as the response variable and age at delivery and treatment group (metformin no metformin) as explanatory variables, the odds ratio of gestational diabetes in pregnancies in women taking metformin versus without metformin was 0.115 (95% CI: 0.014 to 0.938). CONCLUSION(S): In PCOS, use of metformin is associated with a 10-fold reduction in gestational diabetes (31% to 3%). It also reduces insulin resistance and insulin secretion, thus decreasing the secretory demands imposed on pancreatic beta-cells by insulin resistance and pregnancy.

Adult↗

PubMed2002

A C/T single nucleotide polymorphism at the tyrosine kinase domain of the insulin receptor gene is associated with polycystic ovary syndrome.

OBJECTIVE: To examine whether the insulin receptor (INSR) gene contributes to genetic susceptibility to the polycystic ovary syndrome (PCOS). DESIGN: Case-control study. SETTING: Academic endocrinology clinic. PATIENT(S): Ninety-nine women with PCOS as defined by the National Institutes of Health consensus and polycystic ovaries on ultrasonography, and 136 healthy controls. MAIN OUTCOME MEASURE: Frequency of genotypes of a single nucleotide polymorphism of the INSR gene in patients and controls. RESULT(S): After stratification of participants by body mass index, the frequency of the uncommon T allele of the INSR single nucleotide polymorphism was significantly increased in lean patients with PCOS (body mass index < or =27 kg/m2) compared with lean controls (relative risk, 2.1). CONCLUSION(S): The INSR gene is a susceptibility gene for PCOS among lean patients with PCOS. It remains to be determined whether the exon 17 C/T single nucleotide polymorphism is the susceptibility single nucleotide polymorphism for PCOS or whether it is in linkage disequilibrium with another INSR gene polymorphism.

Adolescent↗

PubMed2003

Two exonic single nucleotide polymorphisms in the microsomal epoxide hydrolase gene are associated with polycystic ovary syndrome.

OBJECTIVE: To determine whether genetic variability in the gene encoding microsomal epoxide hydrolase (EPHX) contributes to individual differences in susceptibility to the development of polycystic ovary syndrome (PCOS). DESIGN: Retrospective case-control study. SETTING: University-based clinic. PATIENT(S): One hundred twelve white women with PCOS and 115 healthy controls. INTERVENTION(S): None. MAIN OUTCOME MEASURES: The presence of two single nucleotide polymorphisms (SNPs), T-->C (Tyr113His) in exon 3 and A-->G (His139Arg) in exon 4, in the EPHX gene. Single point analysis was expanded to pair of loci haplotype analysis to examine the estimated haplotype frequencies of the two SNPs, of unknown phase, in the PCOS and control groups. Estimated haplotype frequencies were assessed using the maximum-likelihood method, using an expectation-maximization algorithm. RESULT(S): Single point allele and genotype distributions in exon 3 and exon 4 of the EPHX gene were not statistically different between the groups. However, according to the haplotype estimation analysis, we observed a significantly elevated frequency of haplotype C-G (His113-Arg139) in the PCOS group versus the control group. The odds ratio for PCOS associated with the low activity haplotype C-G (His113-Arg139) was 2.28 (95% confidence interval 1.1-4.8). CONCLUSION(S): The use of two intragenic single nucleotide polymorphisms jointly in haplotype analysis of association demonstrated that the genetically determined low activity haplotype C-G (His113-Arg139) was significantly associated with PCOS.

Case-Control Studies↗

PubMed1991

Three types of polycystic ovarian syndrome in relation to androgenic function.

OBJECTIVE: To re-evaluate the concept of polycystic ovarian syndrome (PCOS) in view of androgenic function. DESIGN: Patients were studied endocrinologically and ultrasonographically. SETTING: This study was performed as a clinical investigation. PATIENTS, PARTICIPANTS: Sixty-nine euprolactinemic anovulatory patients with luteinizing hormone (LH) hypersecretion and 18 normal volunteers were selected. INTERVENTIONS: One hundred micrograms of LH-releasing hormone were administered. MAIN OUTCOME MEASURE(S): It was possible to divide PCOS patients into three types. RESULTS: Patients with neither hirsutism nor elevation of serum androstenedione (delta 4) and/or testosterone (T) were designated as type I PCOS (n = 20). Patients without hirsutism but with elevated delta 4 and/or T were referred to as type II PCOS (n = 33). Patients with both hirsutism and elevation of delta 4 and/or T were defined as type III PCOS (n = 16). Concentrations of delta 4 appeared gradedly increasing in types I, II, and III in that order, whereas T concentrations were significantly higher in types II and III than in control. Ultrasonographically, cystic ovaries were found in 88%, 84%, and 100% of types I, II, and III patients, respectively. CONCLUSIONS: It is postulated that each type may represent a subset of whole spectrum of PCOS from Stein-Leventhal syndrome to simple anovulation with LH hypersecretion.

Adult↗

PubMed1992

Polycystic ovaries as a relative protective factor for bone mineral loss in young women with amenorrhea.

OBJECTIVE: To examine the impact of polycystic ovaries (PCO) on bone mineral density in amenorrheic women of reproductive age. DESIGN: A retrospective analysis and comparison of polycystic ovarian syndrome (PCOS) with non-PCOS amenorrheic women. A subgroup of patients with ultrasound (US)-diagnosed PCO was also investigated. SETTING: Specialist clinic in reproductive endocrinology. PATIENTS, PARTICIPANTS: Six hundred ten consecutive cases, mean age of 29.8 +/- 7.5 years, with current history of amenorrhea of various causes. MAIN OUTCOME MEASURE: Bone mineral density in the lumbar spine (L1 to L4) as measured by dual energy x ray absorptiometry, in relation to PCOS, US-diagnosed PCO, and US findings of normal ovaries. RESULTS: Amenorrheic patients with PCOS were found to be younger (P less than 0.001), with higher body mass index (P less than 0.001), were more estrogenized, as measured by endometrial thickness and uterine cross-sectional area (P less than 0.001), and had higher bone mineral density (P less than 0.001) compared with non-PCOS amenorrheic patients. CONCLUSIONS: Patients with amenorrhea because of PCOS and those with US-diagnosed PCO have a higher bone density compared with amenorrheic patients with normal ovaries as detected by US scan.

Adult↗

PubMed1994

Prolonged opioid blockade with naltrexone and luteinizing hormone modifications in women with polycystic ovarian syndrome.

OBJECTIVE: To investigate whether enhanced LH levels of women with polycystic ovarian syndrome (PCOS) are the consequence of an absent hypothalamic opioid inhibitory control and/or an increased sensitivity of gonadotroph to GnRH, induced by sensitizing effects of circulating opioid peptides. DESIGN: Pulsatile LH secretion (10-minute sampling for 6 hours) and GnRH-stimulated (10 micrograms) LH release were investigated in 14 women with PCOS before and after the 5-day administration of placebo (n = 7) or the opioid antagonist naltrexone (50 mg/d; n = 7). Seven age- and weight-matched normal cycling women in follicular phase were used as controls. RESULTS: In comparison with normal cycling women, PCOS showed normal frequency and increased amplitude LH pulses, elevated mean LH levels, and increased LH response to GnRH. In PCOS, placebo administration was not associated with any LH modification, whereas naltrexone enhanced the frequency and decreased the amplitude of LH pulses, without modifying mean LH levels and the LH response to GnRH. CONCLUSIONS: The naltrexone-induced increment of LH frequency revealed a conserved central opioid tone in PCOS. Reduced LH pulse amplitude, induced by naltrexone, was not associated with a reduced LH response to GnRH or with a reduction in mean LH levels. Present data do not support a role for endogenous opioid peptides in the pathogenesis of increased LH levels in PCOS.

Adult↗

PubMed1994

The response of the growth hormone and insulin-like growth factor I axis to medical castration in women with polycystic ovarian syndrome.

OBJECTIVE: To assess the impact of ovarian hormone deprivation on serum concentrations of GH and insulin-like growth factor I (IGF-I) in women with polycystic ovarian syndrome (PCOS). DESIGN: Growth hormone and IGF-I levels were measured before, during, and at the end of a 6-month period of treatment with leuprolide acetate (LA) depot. Normal cycling and ovariectomized women served as controls. SETTING: The Clinical Research Center of Northwestern University Medical School. PATIENTS: Six women with PCOS, seven normal cycling women, and six ovariectomized women. INTERVENTIONS: The PCOS and normal cycling subjects were treated with six consecutive monthly injections of LA depot 3.75 mg IM. MAIN OUTCOME MEASURES: Circulating concentrations of GH and IGF-I. RESULTS: After 3 months of treatment, GH levels decreased modestly in the PCOS group; however, these changes were not significant. No further decline was observed at 6 months. Growth hormone levels were unaffected in the normal cycling group. Levels of IGF-I remained unchanged in both groups. Mean baseline levels of both GH and IGF-I in the ovariectomized group were lower than those of the normal cycling and PCOS groups at all time points, but not significantly so. CONCLUSIONS: Medical castration fails to significantly alter serum GH and IGF-I levels in either normal cycling or women with PCOS. These data indicate that GH secretion is not modulated by hormones of ovarian origin in either group, at least over the period of time studied.

Adult↗

PubMed1999

Influence of body mass on the hypothalamic-pituitary-adrenal-axis response to naloxone in patients with polycystic ovary syndrome.

OBJECTIVE: To evaluate the influence of body mass on the hypothalamic-pituitary-adrenal (HPA)-axis response to naloxone in polycystic ovary syndrome (PCOS). DESIGN: Controlled clinical study. SETTING: Academic research environment. PATIENT(S): Ten lean and 10 obese women with PCOS compared with 7 lean and 8 obese control subjects matched for body mass index. INTERVENTION(S): Each patient received an IV bolus of naloxone at a dosage of 125 microg/kg. MAIN OUTCOME MEASURE(S): Samples were collected 30 minutes before and 0, 15, 30, 60, 90, and 120 minutes after injection: ACTH and cortisol levels were measured in all plasma samples. RESULT(S): No significant differences were found in the ACTH and cortisol responses to opioid blockade between lean women with PCOS and lean as well as obese control subjects; conversely, obese patients with PCOS showed a higher ACTH and cortisol responses to naloxone compared with all other groups. CONCLUSION(S): Hypothalamic-pituitary-adrenal-axis abnormalities of PCOS may be central in origin and abdominal obesity seems to play a key role in the HPA-axis hyperactivity of women with PCOS when naloxone is administered.

Adrenocorticotropic Hormone↗