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PubMed1999

Analysis of gonadotropin pulsatility in hirsute women with normal menstrual cycles and in women with polycystic ovary syndrome.

OBJECTIVE: To study the relation between plasma gonadotropin pulsatility, androgen levels, and estrogen levels in patients with polycystic ovary syndrome (PCOS), in hirsute women with normal menstrual cycles, and in healthy women. DESIGN: Prospective study. SETTING: University medical center-based cellular and molecular endocrinology laboratory. PATIENT(S): Eight healthy women (group 1), 9 hirsute women with normal menstrual cycles (group 2), and 19 women with PCOS (group 3). INTERVENTION(S): Plasma concentrations of LH and FSH were measured by RIA every 15 minutes for 12 hours. MAIN OUTCOME MEASURE(S): Rhythmic parameters of 12-hour LH and FSH secretion. RESULT(S): Rhythmic parameters of 12-hour LH secretion were significantly higher in patients with PCOS (group 3) than in controls (group 1) or in hirsute women with normal menstrual cycles (group 2). The frequency of LH pulses was statistically higher in patients with PCOS (group 3) than in controls (group 1). Statistically significant correlations were found when the frequency of LH pulses was plotted against basal LH concentrations and rhythmic parameters of 12-hour LH secretion. CONCLUSION(S): Luteinizing hormone pulse amplitude was higher in patients with PCOS than in hirsute women with normal menstrual cycles or in healthy women. The LH pulse frequency was increased only in patients with PCOS compared with healthy women and not in hirsute women with normal menstrual cycles.

Adolescent↗

PubMed1999

Bone mineral density and body composition in lean women with polycystic ovary syndrome.

OBJECTIVE: To examine bone mineral density (BMD) and fat distribution in lean women with polycystic ovary syndrome (PCOS) compared with matched control women. DESIGN: Controlled clinical study. SETTING: An academic clinical research center. PATIENT(S): Twelve non-Hispanic white women with PCOS and a body mass index of <26 and 10 healthy control women matched for age, ethnicity, and weight. INTERVENTION(S): Biometric measures, blood sample collection, and total body/regional bone density and fat analysis were performed. MAIN OUTCOME MEASURE(S): Serum levels of androgens, glucose, and insulin were measured. Bone density and fat distribution were measured by total body dual-energy x-ray absorptiometry. RESULT(S): Androgen levels were elevated significantly in the lean women with PCOS compared with the controls. There was no statistically significant difference in total body BMD between the two groups. A significant increase in BMD was noted in the left arm, right arm, and left ribs of the lean PCOS group. Evaluation of upper body BMD showed a significant correlation between testosterone levels and BMD. No statistically significant differences were noted in body fat distribution, although the lean PCOS group tended to have lower mean percentages of body fat. CONCLUSION(S): Lean women with PCOS have regional differences in BMD, with significantly increased BMD in the upper skeleton compared with control women.

Absorptiometry, Photon↗

PubMed2003

Relative impact of insulin resistance and obesity on cardiovascular risk factors in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) affects 5% to 7% of women of reproductive age. Insulin resistance and obesity are components of this important syndrome that may contribute to excess cardiovascular risk. We analyzed data from 69 patients with PCOS who had undergone quantitative assessment of insulin sensitivity, blood pressure, lipid profiles, and androgen levels to determine the impact of insulin resistance and obesity on parameters of cardiovascular risk. Homeostasis model assessment (HOMA) was used to stratify patients in terms of insulin resistance. To obtain a reference population, we used data from the National Health and Nutrition Examination Study (NHANES III, 1988 to 1994). The most insulin-resistant tertile of patients exhibited higher body mass index (BMI), androgen levels, systolic and diastolic blood pressure (DBP), triglyceride (TG) levels, and decreased high-density lipoprotein cholesterol (HDL-C) levels. Insulin resistance, not BMI, was the main determinant of HDL-C and TG levels and systolic blood pressure (SBP) in PCOS. Among normal women, both BMI and insulin resistance influenced cardiovascular risk factors. Insulin resistance was a more significant predictor of TGs in women with PCOS than in normal women (P =.008). In contrast to normal women, insulin resistance in PCOS appears to be the prime determinant of abnormal lipids, blood pressure, and androgens. Thus, early detection of insulin resistance, as well as weight reduction, should be emphasized for all patients with PCOS.

Adult↗

PubMed2003

Serum and follicular fluid cytokines in polycystic ovary syndrome during stimulated cycles.

OBJECTIVE: To investigate the serum and intrafollicular tumor necrosis factor-alpha and interleukin-6 concentrations in infertile women with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization (IVF). METHODS: Thirty-one patients with PCOS undergoing IVF were studied. Thirty-nine normally ovulating women matched for age and body mass index and undergoing IVF for male infertility were the control group. Serum tumor necrosis factor-alpha, interleukin-6, and estradiol levels were assayed before recombinant follicle-stimulating hormone stimulation under gonadotropin-releasing hormone analogue suppression and 34-36 hours after human chorionic gonadotropin (hCG) administration at the time of the oocyte retrieval. Cytokine and estradiol concentrations were also evaluated in the follicular fluids obtained at the time of oocyte retrieval. RESULTS: The patients with PCOS had higher serum and follicular fluid tumor necrosis factor-alpha and interleukin-6 concentrations (P <.001) and lower follicular fluid estradiol levels (P <.05) than control women. In both groups, the serum tumor necrosis factor-alpha, interleukin-6, and estradiol values increased significantly after hCG stimulation. In both groups, the follicular fluid cytokine concentrations were higher than those found in the serum. In the PCOS women the follicular fluid tumor necrosis factor-alpha values were significantly and inversely correlated to the follicular fluid estradiol values (rho = -0.79; P <.001); this correlation was not found in the control subjects. CONCLUSION: In infertile women with PCOS, 1). serum and follicular fluid interleukin-6 and tumor necrosis factor-alpha values were higher than those found in control women, 2). the cytokine concentrations were higher in the follicular fluid than in the serum, and 3). the intrafollicular tumor necrosis factor-alpha concentrations were significantly and inversely correlated to the estradiol levels. These results suggest an involvement of the immune system in PCOS.

Case-Control Studies↗

PubMed1999

Menstrual disorders in adolescents. Excess androgens and the polycystic ovary syndrome.

The fundamental clinical features of PCOS include hirsutism and menstrual irregularities from the time of menarche. Obesity is present in approximately 50% of these patients, some of whom also carry a diagnosis of NIDDM. The biochemical abnormalities associated with the clinical picture include LH hypersecretion, hyperandrogenism, acyclic estrogen production, subnormal SHBG levels, and hyperinsulinemia. Hirsutism usually progresses slowly in patients with PCOS; however, the clinical presentation can resemble virilizing tumors, late-onset CAH, or Cushing syndrome. Virilization or rapidly progressive hirsutism requires immediate investigation to rule out a virilizing tumor. Goals of therapy for teenage patients include decreasing levels of bioavailable androgen, blockade of androgen action at target tissues, stabilization of the endometrium, and reduction of insulin resistance. Although the original description of PCOS by Stein and Leventhal was published in 1935, the cause of PCOS remains unknown. This reason, coupled with the fact that PCOS-related insulin resistance is an important cause of NIDDM in women, has caused this disorder to become one of interest and active investigation. Future research will likely be able to delineate mechanisms behind the defects of carbohydrate metabolism and ascertain large multigeneration kindreds for linkage analyses to identify affected genes. Future studies are also likely to confirm whether young women with PCOS are at increased risk for cardiovascular disease and other long-term health complications. As new pathophysiologic mechanisms are identified, the promise of new therapies arises, including treatments that could potentially reduce the long-term incidence of adverse health consequences.

Adolescent↗

PubMed2003

Polycystic ovary syndrome: a review for primary providers.

PCOS is a metabolic syndrome that exists throughout the world with much clinical heterogeneity. PCOS is now appreciated as encompassing two interrelated metabolic phenomena--insulin resistance and hyperandrogenism. Patients present with oligo-amenorrhea and clinical hyperandrogenism, and the diagnosis is based on clinical grounds with few laboratory tests necessary. Because patients are at higher than normal risk for diabetes, glucose intolerance, and hyperlipidemia, and perhaps at higher risk for coronary heart disease, newly diagnosed patients with PCOS should be evaluated for glucose intolerance and hyperlipidemia. The cornerstone of therapy today includes weight management, and further therapeutic intervention is focused on reproductive and cardiovascular health and treatment of insulin resistance. Clinical case continued The 17-year-old mentioned in the beginning of this article probably does have PCOS. She fits the clinical criteria: oligo-ovulation and hyper-androgenism (the acne and hirsutism). In addition, she is obese, which is also associated with PCOS. Her TSH and prolactin were normal, and as her presentation was not suggestive of an adrenal tumor or congenital adrenal hyperplasia (she had mild hirsutism, and those diagnoses are associated with more severe hyperandrogenism), no further laboratory evaluation was deemed necessary. Once the diagnosis was made, she was screened for lipid abnormalities and for glucose intolerance. Her LDL was 150, HDL 35; oral glucose tolerance test (OGTT) was normal. A pregnancy test was negative, and she was started on OCPs. Devoting herself to exercise and dietary change, she lost 10 pounds in her first 3 months after diagnosis. Her hirsutism and acne have improved with the OCPs and weight loss, and her menses are regular. She has elected to defer oral insulin sensitizers until her weight loss has stabilized. Findings PCOS is common in reproductive-aged women. Diagnosis is clinical and is supported by lab findings; there is significant clinical heterogeneity. Insulin resistance is likely central to the pathophysiology along with androgen excess. Health implications include infertility, diabetes, endometrial cancer, hyperlipidemia, and possibly coronary heart disease. Treatment is evolving and includes weight loss, OCPs, and insulin sensitizers.

Adolescent↗

PubMed2001

Neuromodulation in polycystic ovary syndrome.

Although central and peripheral factors have been implicated in the neuromodulation of GnRH in PCOS, there are no definitive or conclusive data to establish a primary causal role for any one factor. Because increased GnRH pulse frequency is at least a contributor to the secretion of excess LH and insufficient FSH that are the proximate cause of chronic anovulation in PCOS, strategies to slow the GnRH pulse generator are likely to promote ovulation in women with PCOS. Several pharmacologic agents, such as dopamine agonists and antagonists, have been tried, but the lack of consistent effects in women with PCOS limits their clinical utility. Current treatment strategies include the use of the combined oral contraceptive pills, antiandrogens or androgen receptor blockers, and insulin sensitizers. Oral contraceptive preparations are effective in suppressing ovarian hyperandrogenemia, regulating menstrual cycles, and reducing the risk of endometrial hyperplasia. Androgen blockade and antiandrogens provide symptomatic relief from androgen-induced acne and hirsutism and have been reported to restore ovulation in women with PCOS. Whether this effect is mediated peripherally or centrally remains to be clarified. The most recent class of pharmacologic agents to gain popularity are the "insulin modifiers." With increasing evidence that insulin resistance constitutes a key metabolic element, it seems logical that improving insulin sensitivity and glucose disposal might wholly, or partially, reverse certain features of PCOS, including anovulation. To date, insulin modifiers have proved most promising in improving the clinical features and promoting fertility, but whether this effect is centrally mediated is yet to be elucidated.

Female↗

PubMed1998

Adverse lipid and coronary heart disease risk profiles in young women with polycystic ovary syndrome: results of a case-control study.

Polycystic ovary syndrome (PCOS), a disorder of hyperandrogenism and chronic anovulation affects 5%-10% of all women. Women with PCOS often have elevated cardiovascular risk factors. A total of 244 PCOS cases were identified through the Division of Reproductive Endocrinology at Magee-Womens Hospital and were age-matched to 244 neighborhood controls. The average age of cases and controls was 35.3 +/- 7.4 and 36.7 +/- 7.7. Women with PCOS compared to controls had substantially higher LDL-C and total cholesterol levels at each age group under 45 years after adjustment for body mass index, hormone use, and insulin levels. In the over 40-year age group, little difference was noted between cases and controls. Among cases and controls (<40), PCOS predicted LDL-C, total cholesterol and triglycerides, but did not have a significant effect on lipid levels in older cases and controls after controlling for the other variables. The primarily pre- to perimenopausal PCOS cases > or =40 years of age have similar LDL-C and total cholesterol levels as their age-matched controls, probably reflecting the LDL-C increase with age among controls.

Adult↗

PubMed2000

Toward a new approach: primary and preventive care of the woman with polycystic ovarian syndrome.

Polycystic ovarian syndrome (PCOS), characterized by chronic anovulation and hyperandrogenism, affects approximately 5%-10% of reproductive-age women. The reproductive consequences of this syndrome, such as menstrual irregularities and infertility, are well understood and managed by obstetrician/gynecologists. However, less is known about the metabolic consequences of PCOS. As primary physicians for women, we are obligated to promote disease prevention. This can be done by recognizing the significant impact that the metabolic consequences of PCOS have on long-term health while continuing to recognize and treat the reproductive abnormalities. This article reviews the metabolic consequences of PCOS, discusses the use of insulin-sensitizing agents in PCOS, and discusses the role of the obstetrician/gynecologist in the primary and preventive care of women with PCOS.

Journal Article↗

PubMed2003

Correction of insulin resistance and hyperandrogenism in polycystic ovary syndrome by combined rosiglitazone and clomiphene citrate therapy.

OBJECTIVE: To investigate the effects of combined rosiglitazone and clomiphene citrate versus clomiphene citrate monotherapy on serum insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGFBP-3) levels in polycystic ovary syndrome (PCOS) and to evaluate these therapeutic interventions in the link between hyperinsulinemia and hormonal perturbations in PCOS. METHODS: We performed a randomized clinical study at the King Abul-Aziz and Cairo University Hospitals. We studied 50 women with PCOS. Clinical diagnosis was based on hyperandrogenism; hyperinsulinism; oligomenorrhea; or amenorrhea, anovulatory cycles, and ultrasonographic findings. They were randomly assigned to two groups of 25 women each. One group was treated with rosiglitazone and clomiphene citrate; the other was treated only with clomiphene citrate. Serum concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, dehydroepiandrosterone sulfate (DHEAS), free testosterone, IGF-1, and IFGBP-3 were measured by specific radioimmunoassays before and after treatment. RESULTS: Combined rosiglitazone and clomiphene treatment led to a significant reduction in area under the insulin curve (AUC insulin), whereas clomiphene monotherapy did not lead to this reduction. Both types of treatment induced a significant decrease in LH, LH:FSH ratio, free testosterone, and IGF1:IGBP-3 ratio and were associated with a significant increase in IGFBP-3 levels. These changes were more pronounced in PCOS patients treated with combined rosiglitazone and clomiphene than in those treated with clomiphene monotherapy. Regular menstrual cycles occurred in 72% of the former group and 48% of the latter. CONCLUSION: Combined rosiglitazone and clomiphene was an effective therapeutic regimen for correcting insulin resistance in patients with PCOS, possibly by reducing IGF1 bioavailability to the ovaries, thus modifying the hyperandrogenic intrafollicular milieu that occurs in PCOS. In addition, the clinical and hormonal responses were better than with clomiphene alone.

Adult↗

PubMed2004

Assisted reproduction in the treatment of polycystic ovarian syndrome.

Treatment of patients with polycystic ovary syndrome (PCOS) with assisted reproductive techniques is a great challenge for the infertility specialist. Patients with PCOS demonstrate many problems, such as excessive body weight and hyperinsulinaemia, that render management more complex. Prior to treatment with IVF, the PCOS patient should be thoroughly evaluated for disclosure of endometrial neoplasia, hyperinsulinaemia, and other general health related problems. Ovarian stimulation for IVF carries the risks of overstimulation and severe hyperstimulation, which should be avoidable in most cases with preventive measures. The outcome in terms of pregnancy and implantation rates is similar for patients with PCOS when compared with patients undergoing IVF for other indications. There are some questions regarding oocyte and embryo quality in women with PCOS. This manifests itself in lower fertilization rate and decreased embryo quality in some studies. However, increased numbers of oocytes available for insemination or ICSI compensate for decreased fertilization rates and embryo quality. More recent studies suggest higher cumulative conception rates in women with PCOS when compared with controls. In-vitro maturation (IVM) of oocytes retrieved from non-stimulated or minimally stimulated cycles represents a viable option that should be considered seriously when assisted conception is attempted. Results of IVM, however, should be improved further and generalized before the technique can be advocated as the initial treatment approach in these patients.

Cellular Senescence↗

PubMedDate not supplied

A pharmacokinetic and endocrine comparison of recombinant follicle-stimulating hormone and human menopausal gonadotrophin in polycystic ovary syndrome.

Elevated LH concentrations are frequently encountered in patients with polycystic ovary syndrome (PCOS) and increased LH (either endogenous or superimposed through the use of HMG) may have detrimental effects on reproductive function. In spite of this, FSH-only products and HMG have been used indiscriminately for ovulation induction - on the basis that the administration of HMG to patients with PCOS, who are not receiving GnRH agonists, does not result in significant increases in serum LH concentrations as judged by daily single blood samples. However, both endogenous and exogenous LH have a relatively short terminal half-life and studies have reported normal serum LH, but abnormal urinary LH and emphasized that early morning urinary measurements are more informative than those in serum because they reflect nocturnal LH secretion. Therefore, the present study was undertaken to perform a pharmacokinetic and endocrine comparison of recombinant human FSH and HMG in PCOS patients including LH measurements in the urine. Five PCOS patients receiving s.c. recombinant human FSH (rhFSH) and five PCOS patients receiving i.m. HMG for ovulation induction according to a chronic low-dose step-up regimen underwent blood and urine sampling at the following study points: Point 0 was the day of HCG injection; Points 1 to 5 corresponded to days HCG -1 to -2; -3 to -4; -5 to -6; -7 to -8; and -9 to -10; respectively. Serum hormone measurements included oestradiol, FSH, LH, progesterone, inhibin A, androstenedione, testosterone, and free testosterone index. FSH and LH were also measured daily in 8-h urine samples reflecting overnight renal urine secretion. Hormone concentrations calculated as the area under the curve showed that both FSH and LH concentrations in urine were significantly higher in HMG group than in group rhFSH. It is concluded that both LH and FSH concentrations significantly accumulate in the urine of PCOS patients receiving HMG for ovulation induction in a chronic low-dose protocol as compared with rhFSH treatment.

Adult↗

PubMedDate not supplied

The polycystic ovary syndrome: what does insulin resistance have to do with it?

About half of infertility cases are attributable to female factors, of which anovulation is the leading cause. Most cases of anovulation are due to the polycystic ovarian syndrome (PCOS). Clinically PCOS, present in 5% of all women, consists of anovulation, acne, hirsutism, reversed LH-to-FSH ratio and often resistance to insulin. In some cases PCOS appears in familial clusters but its genetic cause is unknown. Several genes were suggested as possible culprits for PCOS but their involvement has not been proven. The central paradox regarding the role of insulin in PCOS is the high responsiveness to insulin by the ovary, as opposed to the resistance of the whole body. On the backdrop of knowledge of several paralogous genes for each of the participating proteins in the insulin signal transduction pathways, it is possible that different paralogues propagate the intracellular signal in the ovary as opposed to peripheral tissues. Studies by microarray techniques of the different gene expression profiles in the two ovarian cells and peripheral cells such as adipocytes could clarify whether the ovarian defect in PCOS is identical to the peripheral defect in insulin signal transduction, or whether serum insulin concentrations simply serve to reveal the ovarian defect.

Female↗

PubMed2005

Insulin responses to the oral glucose tolerance test in women of different ethnicity with polycystic ovary syndrome.

OBJECTIVE: To evaluate insulin responses to the oral glucose tolerance test (OGTT) in women of different ethnic origins diagnosed with polycystic ovary syndrome (PCOS). METHODS: We evaluated 92 women diagnosed with PCOS. Their ethnic origins were Western European (n = 41), Middle Eastern (n = 18), African American (n = 15), East Indian (n = 9), and South American (n = 9). The clinical diagnosis of PCOS included at least 3 of the following symptoms: menstrual disturbances (amenorrhea or oligomenorrhea); ovulatory infertility, hirsutism, and elevated serum testosterone (> or = 2.0 nmol/L); or a luteinizing hormone/ follicle-stimulating hormone ratio of > or = 3. The diagnosis was also supported by ultrasonographic changes revealing the presence of multiple small antral follicles distributed peripherally. All investigations were performed after an overnight fast on days 2 through 5 of a spontaneous menstrual cycle or progesteroneinduced withdrawal bleeding. The women underwent an OGTT with a glucose loading of 75 g. The responses of glucose and insulin to the OGTT were analyzed as the area under the curve (AUC) and were calculated with the trapezoidal method. RESULTS: There were no significant differences in age or body mass index (BMI) among the different ethnic groups. All groups showed endocrine changes consistent with PCOS, but there were no differences in the hormonal levels among them. Middle Eastern women had higher AUC, glucose (P < 0.02; 95% confidence interval [CI], 0.5-3.5), and insulin (P < 0.04; 95% CI, 13.3-593.4) levels than did women with Western European origin. CONCLUSIONS: Middle Eastern women with PCOS expressed different insulin responses to OGTT than did Western European women, suggesting that Middle Eastern women with PCOS had poor carbohydrate metabolism.

Adult↗

PubMed2002

Metformin and polycystic ovary syndrome: a literature review.

Polycystic ovary syndrome (PCOS) is a common endocrine condition that affects women of reproductive age. Anovulation, menstrual irregularities, hirsutism, and infertility are common clinical presentations. Long-term health concerns such as type II diabetes mellitus and, possibly, cardiovascular disease, have been linked to PCOS. Metformin, an oral hypoglycemic agent, has been recently advocated as treatment for some women with PCOS due to the association of PCOS with hyperinsulinemia. Metformin is utilized as sole therapy for ovulation induction as well as in combination with traditional ovulation-induction therapies. This review identified 23 prospective studies addressing the effects of metformin on PCOS. Because of the heterogeneity of the published reports, only a qualitative assessment of the data was possible. Review of this literature confirms a beneficial role of metformin in reducing insulin resistance in some women with PCOS. Other favourable biochemical effects include reduced free testosterone levels and increased sex hormone-binding globulin (SHBG). Metformin may improve menstrual regularity, leading to spontaneous ovulation, and improve ovarian response to conventional ovulation-induction therapies. There is, however, little evidence supporting the use of metformin to facilitate weight reduction, or improve serum lipids or hirsutism. Further evaluation is required to define the long-term effectiveness of metformin, who will benefit from metformin treatment, and the optimal duration of metformin therapy.

Androgens↗

PubMed1998

Effect of hyperandrogenism and menstrual cycle abnormalities on bone mass and bone turnover in young women.

OBJECTIVE: Prolonged period of amenorrhoea are regarded as a risk factor for the appearance of osteoporosis. Amenorrhoea is a feature of different pathological conditions with heterogeneous endocrine profiles. We evaluated bone mineral metabolism in patients with polycystic ovary syndrome (PCOS), hypothalamic amenorrhoea and idiopathic hirsutism in order to establish the relative importance for the maintenance of normal bone mass of ovulatory cycles and androgen and oestrogen production. PATIENTS AND MEASUREMENTS: Bone mineral density (BMD), bone turnover markers and endocrine profile were evaluated in 51 patients with PCOS, 24 patients with idiopathic hirsutism, 26 patients with hypothalamic amenorrhoea and 35 healthy women. Body mass index (BMI) ranged between 20.1 and 31.0 kg/m2, and age from 17 to 33 years. Thirty-eight of the PCOS patients were amenorrhoeic (< 4 menstrual cycles/year). RESULTS: Spine and femoral BMD were significantly decreased and bone markers (serum osteocalcin, and urinary excretion of free deoxypyridinoline, cross-linked N-telopeptide and hydroxyproline) significantly increased in the patients with hypothalamic amenorrhoea, when compared to control subjects and the other two patient groups. In the sub-group of PCOS patients with amenorrhoea, spine and femoral neck BMD was significantly lower than in patients with idiopathic hirsutism and the non-amenorrhoeic PCOS patients. In all PCOS patients, spine and neck BMD were positively correlated (P < 0.05) with serum androstenedione and free testosterone levels. CONCLUSIONS: The results of this study suggest that in patients with polycystic ovary syndrome the deleterious effect on bone of amenorrhoea is balanced by androgen overproduction.

Adolescent↗

PubMed1999

Mutation screening and isoform prevalence of the follicle stimulating hormone receptor gene in women with premature ovarian failure, resistant ovary syndrome and polycystic ovary syndrome.

OBJECTIVE: To determine whether mutations in the FSH receptor gene are associated with premature ovarian failure (POF) or resistant ovary syndrome (ROS) in women in the UK. To determine whether an allelic variant of the FSH receptor gene affects fertility parameters in women with polycystic ovary syndrome (PCOS). DESIGN: A mutation screen using DNA from women with POF and ROS. Restriction digest of amplified DNA from women with POF, ROS, PCOS and controls to determine allelic variant status. Fertility parameters were compared between allelic variant subgroups of women with PCOS. PATIENTS: The study population comprised 49 women with POF, 5 with ROS, 93 with PCOS and 51 controls. MEASUREMENTS: In women with PCOS, fertility and menstrual status was recorded and serum FSH and ovarian volume were measured. RESULTS: No mutation of the FSH receptor gene was found in women with POF or ROS. The allelic variant Thr307/Ser680 was found to be similarly prevalent in all study groups. The Thr307/Ser680 variant was found to have no phenotype in terms of fertility parameters in women with PCOS. CONCLUSIONS: Mutations of the FSH receptor gene are rare in women with premature ovarian failure or resistant ovary syndrome in the UK. Polymorphisms of the FSH receptor gene do not appear to have pathophysiological significance with regard to ovarian function.

Adult↗

PubMed2002

Hyperinsulinemia and uterine perfusion in patients with polycystic ovary syndrome.

OBJECTIVE: To determine whether hyperinsulinemia has a negative effect on uterine blood supply in patients with polycystic ovary syndrome (PCOS). METHODS: Sixty-three patients with normal body mass index were included prospectively in the study: 48 had clinical and hormonal features of PCOS and 15 were normo-ovulatory. All patients underwent Doppler flow measurement of the uterine artery, and determination of serum concentrations of luteinizing hormone, follicle stimulating hormone, prolactin, estradiol, androgens, insulin and C-peptide during the early follicular phase of the menstrual cycle. The 48 PCOS-patients were divided into two groups according to the pulsatility index (PI) value of the uterine artery: Group 1, PI < 3; Group 2, PI >or= 3 and the groups were compared. RESULTS: The mean PI of the uterine artery (3.01 +/- 1.0 vs. 1.93 +/- 0.3, respectively) and fasting levels of insulin (50.9 +/- 9.3 vs. 40.3 +/- 10.9) and C-peptide (366.9 +/- 118.4 vs. 243.6 +/- 120.3) of PCOS-patients were significantly higher than those of the control group. No correlation was found between insulinemia and C-peptide and PI of the uterine artery and no significant difference was found in insulin and C-peptide levels among the two groups of PCOS-affected patients. Only the serum level of dehydroepiandrosterone sulfate was significantly higher in Group 2, and a direct correlation was found between PI values of the uterine artery and DHEAS plasma levels. CONCLUSION: Insulin and C-peptide do not seem to interfere with uterine perfusion in PCOS-affected patients.

C-Peptide↗