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PubMed2002

Neck circumference a good predictor of raised insulin and free androgen index in obese premenopausal women: changes with weight loss.

OBJECTIVE: Severe obesity can be associated with evidence of androgen excess and insulin resistance, which are features of the metabolic and polycystic ovary syndromes (PCOS). In this study, we examined the association between clinical and biochemical features of these syndromes and assess changes with weight loss. DESIGN: A consecutive series of 107 severely obese premenopausal women presenting for obesity surgery. MEASUREMENTS: Pre-operative assessment included details of clinical comorbidity, anthropometric measures and biochemical measures, including fasting insulin, glucose, lipid profile and sex hormone analysis. Changes in these measures for 42 of 52 (81%) patients at 1 year post surgery are reported. RESULTS: Neck circumference and younger age were independent predictors of higher free androgen index (FAI) (combined r2 = 0.36). If neck circumference is not included, then younger age, higher body mass index and raised fasting insulin levels were all independent predictors of FAI (r2 = 0.29). Waist to hip ratio showed no predictive value (r = 0.14). Neck circumference was also a good clinical predictor of menstrual irregularity, hirsutism, infertility, insulin resistance and the PCOS. Neck circumference of less than 39, 39-42 and greater than 42 cm reflect a low, intermediate and high risk of the metabolic and PCOS syndromes in obese premenopausal women. For 42 patients who were followed for 1 year after surgery, the weight loss was associated with reduction of FAI, less insulin resistance and improved menstrual regularity and resolution of the PCOS in 11 of 12 cases. CONCLUSIONS: Neck circumference is a good predictive measure of hyperinsulinaemia and raised androgens in obese premenopausal women. Weight loss following surgery improves ovarian function and vasculopathic risk.

Adult↗

PubMed1998

Ultrasonographic and color Doppler analysis in the treatment of polycystic ovary syndrome.

OBJECTIVE: To compare the effect of a gonadotropin releasing hormone (GnRH) analog plus 'add-back' oral contraceptive (OC) therapy with OC therapy alone on the clinical and hormonal parameters that are characteristic of polycystic ovary syndrome (PCOS). DESIGN: Prospective, randomized study. SUBJECTS: Thirty PCOS patients were randomly assigned to treatment with leuprolide acetate for depot suspension plus a combined monophasic OC (Group I) or to OC alone (Group II). METHODS: Hormonal (luteinizing hormone (LH), follicle stimulating hormone (FSH), LH : FSH concentration ratio, estradiol, androstenedione, testosterone), clinical (Ferriman-Gallwey score), ultrasonographic (ovarian volume, number of subcapsular follicles, stromal score) and Doppler (uterine artery and ovarian intraparenchymal vessels' pulsatility index, ovarian stromal vascularization) parameters were evaluated during 6 months' therapy and 6 months' follow-up. RESULTS: Significant changes in all the parameters analyzed occurred as a result of therapy and the changes were more marked in the group undergoing treatment with GnRH analog plus OC. CONCLUSIONS: GnRH analog plus OC use has a more rapid and marked effect on the hormonal milieu as well as the ovarian architecture and vascularization in patients with PCOS than OC used alone. The former treatment may be a more efficient therapy for PCOS.

Adolescent↗

PubMed2005

Polycystic ovary syndrome in adolescent girls.

Polycystic ovary syndrome (PCOS) has traditionally been thought of as a triad of oligomenorrhea, hirsutism, and obesity. PCOS is now recognized as a heterogeneous disorder that results in overproduction of androgens primarily from the ovary leading to anovulation and hirsutism and is associated with insulin resistance. Symptoms in the adolescent include oligomenorrhea, hirsutism, acne, and weight gain. These symptoms are often attributed to normal pubertal events, which can lead to a delay in diagnosis. Insulin resistance, impaired glucose tolerance and diabetes have been shown to occur in adolescents with PCOS. Treatment should be instituted early to decrease symptoms and long-term sequellae of PCOS. Weight loss, oral contraceptives and antiandrogens are very effective in treating the symptoms of this disorder. Insulin-sensitizing medications show promise, but should be used with caution until larger randomized trials have shown short- and long-term benefit and efficacy over traditional therapies in the adolescent population.

Adolescent↗

PubMed1998

Low-dose FSH stimulation in polycystic ovary syndrome: comparison of 3 FSH-preparations.

In patients with PCOS low dose administration of follicle stimulating hormone is accepted as a safe treatment modality with low risk for an ovarian hyperstimulation syndrome or a multiple pregnancy. In this study we have retrospectively compared the efficacy of 3 different FSH preparations in low dose protocols-urinary FSH (FSH), highly purified urinary FSH (FSHHP) and recombinant FSH (rec. FSH). A total of 68 PCOS-patients, 36 lean and 32 moderately obese patients, were treated in 116 stimulation cycles. The mean age did not differ between the groups. A mean number of 1.7 cycles per patient was performed. PCOS was diagnosed in all patients by hormonal and sonographic means. Treatment was performed with daily injections of one ampoule FSH from day 3 onwards. Ovulation was induced with 10,000 IU HCG, when the leading follicle exceeded 16 mm in diameter and no more than 3 follicles were seen. The rate of monofollicular cycles was lowest in obese patients after FSHHP stimulation (30%) and after rec. FSH (66.6% in lean and 58.3% in obese patients, respectively). The number of FSH ampoules did not differ significantly between the groups. No severe hyperstimulation syndrome was registered. 21 pregnancies were achieved without significant differences between the different FSH preparations. Besides two abortions and one ectopic implantation, 12 pregnancies were ongoing singleton pregnancies, 3 twin pregnancies and 3 sets of triplets were noted. In conclusion, low-dose stimulation with FSH offers a safe and successful treatment option in patients with PCOS with an acceptable risk for multiple gestations.

Adult↗

PubMed2002

Homocysteine and steroids levels in metformin treated women with polycystic ovary syndrome.

UNLABELLED: Risk for atherosclerosis is increased in women with polycystic ovary syndrome (PCOS). Homocysteine (Hcy) is one of the independent risk factors for ischemic heart disease. We examined the effect of metformin (M) treatment on Hcy levels, steroids and glycide tolerance in PCOS. MATERIAL AND METHODS: 9 women with PCOS (defined as hyperandrogenemia and chronic anovulation); age 20 +/- 3.8 yrs, BMI 28.1 +/- 6.5 kg/m(2); examined in the follicular phase of spontaneous menstrual cycle before and after 27 +/- 4 weeks of treatment with M 1000 mg/day. The plasma concentrations of Hcy, DHEA, DHEA-S, cortisol (F), allopregnanolone (HPO), 17OHpregnenolone (17OHPl), insulin (I) and blood glucose (G) before and after the course of M were measured. RESULTS: After the course of M, Hcy significantly increased (10.1 +/- 2.6 to 13.4 +/- 5.1 micromol/l, p < 0.05.). There was no significant change in levels of I, HPO, F, DHEA-S and 17OHPl. DHEA levels increased significantly (from 26.9 +/- 15.7 to 44.4 +/- 24.6 nmol/l, p < 0.05). A borderline significant trend towards reduction in waist-hip ratio was seen (from 0.986 +/- 0.042 to 0.951 +/- 0.085; p < 0.06). CONCLUSIONS: Treatment with metformin in women with PCOS can lead to the increase in homocysteine levels--a risk factor for atherosclerosis.

17-alpha-Hydroxypregnenolone↗

PubMed2003

Diagnostic criteria in polycystic ovary syndrome.

Part of the difficulty in understanding polycystic ovary syndrome (PCOS) and interpreting the dense literature surrounding it is that there is no universally accepted clinical definition. The varying definitions influence the incidence, prevalence of sequelae, and response to treatment. PCOS is clearly heterogeneous and its etiology is still speculative. Over the years it has evolved from a "disease" to a "syndrome," the latter which includes a variety of potential signs and symptoms, including oligo-ovulation, biochemical or clinical hyperandrogenism, polycystic ovaries, and insulin resistance. There is no single diagnostic criterion that can be recommended for diagnosis of PCOS. While hyperandrogenemia, specifically elevated bioavailable testosterone, is intellectually appealing, the evidence in terms of long-term sequelae identified by such a test is still weak. The recognition of oligo-ovulation primarily relies on patient history. Currently both consensus and the preliminary evidence-based trials support a combination of hyperandrogenemia and oligo-ovulation, in the absence of known causes, as diagnostic criteria, but there are also strong proponents of using ovarian morphology to identify and diagnose the syndrome. There are no simple clinically validated biochemical tests of insulin resistance. Further identification of specific causes, and elimination of the multiple phenocopies that make up PCOS, will ease its diagnosis.

Anovulation↗

PubMed2003

Cardiovascular health in women with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is arguably the most common endocrinopathy among women of reproductive age. Women with PCOS have clinical characteristics that are associated with insulin resistance, vascular dysfunction, hypertension, and dyslipidemia. Although definitive data for increased cardiovascular events in women with PCOS are lacking, case-control studies have documented an increased risk of preclinical cardiovascular disease. Thus, PCOS should be viewed as a chronic condition that may ultimately have long-term health impacts and patients should be counseled to reduce cardiovascular risk factors through weight control, exercise, and/or pharmacologic treatments.

Blood Coagulation Factors↗

PubMed2004

Urinary 6-sulfatoxymelatonin excretion in hyperandrogenic women: the effect of cyproterone acetate-ethinyl estradiol treatment.

Evidence for a relationship between melatonin and the reproductive hormones in humans is based on observations of abnormal melatonin secretion in clinical disorders of the pituitary-gonadal axis. The aim of this study was to investigate melatonin production in hyperandrogenic women before and during treatment with cyproterone acetate and ethinyl estradiol (Diane 35). Twelve women with polycystic ovary syndrome (PCOS), 10 women with idiopathic hirsutism (IH), and 10 women with late onset adrenal hyperplasia due to 21-hydroxylase deficiency (LOCAH) were studied. Patients were treated with Diane 35 for four months. Fasting blood samples for the determination of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone and dihydroepiandrosterone sulfate (DHEAS) and 24-hour urine collections for the determination of 6-sulfatoxymelatonin (aMT6s) excretion were obtained from all patients at baseline and after 4 months of treatment. Results were compared with those obtained in 15 control women. At baseline, women with PCOS and LOCAH had significantly higher testosterone and aMT6s values than women with IH and controls. Diane 35 treatment significantly decreased testosterone, LH, FSH and aMT6s values in PCOS and LOCAH patients compared with pretreatment values. These results indicate that hyperandrogenic women with PCOS and LOCAH have increased melatonin production. The decrease in aMT6s excretion together with reduced serum LH, FSH, DHEAS and testosterone values during treatment with cyproterone acetate-ethinyl estradiol, suggest that sex steroids either directly or through the suppression of gonadotropins, modulate melatonin secretion in these patients.

Adrenal Hyperplasia, Congenital↗

PubMed1997

Role of hyperinsulinemia in the pathogenesis of the polycystic ovary syndrome, and its clinical implications.

The polycystic ovary syndrome (PCOS) is a prevalent disorder affecting approximately 6% of women of reproductive age, and is characterized by anovulation and hyperandrogenism. It has also become apparent that a frequent feature of women with PCOS is insulin resistance accompanied by compensatory hyperinsulinemia, and increasing evidence suggests that hyperinsulinemia plays an important role in the pathogenesis of PCOS. This article will review (1) evidence indicating that insulin contributes to the hyperandrogenism of PCOS by stimulating ovarian androgen production and decreasing serum sex hormone-binding globulin (SHBG) concentrations; (2) possible direct effects of hyperinsulinemia on folliculogenesis; (3) the relationship between insulin and adrenal androgens in women; and (4) therapeutic and clinical implications of these findings.

Adrenal Glands↗

PubMed2001

Polycystic ovary syndrome and insulin-resistant hyperinsulinemia.

In a broad sense, polycystic ovary syndrome (PCOS) may be considered to be synonymous with chronic unexplained hyperandrogenemia, which accounts for approximately 95% of hyperandrogenism in women. PCOS comprises a mosaic of classic and nonclassic forms, which may ultimately prove to have distinct genetic determinants. The hyperandrogenism appears to arise from generalized abnormal regulation (dysregulation) of steroidogenesis. This dysregulation seems to result from imbalance among the various extrinsic and intrinsic factors involved in the modulation of trophic hormone action. Hyperinsulinemia seems to be an important extrinsic factor in many cases of PCOS; it results from resistance to the effects of insulin on glucose metabolism. The elevation in insulin levels may precipitate hyperandrogenemia in genetically vulnerable individuals by unmasking latent abnormalities in the regulation of steroidogenesis. One of these may be a polycystic ovary gene that is expressed in the male as pattern baldness. Insulin also seems to be one of many factors that interact with androgen to regulate pilosebaceous unit development. Treatment of PCOS with antidiabetic insulin-lowering agents may improve ovarian function and androgen levels; it remains to be determined whether it will benefit the pilosebaceous unit manifestations of the disorder.

Female↗

PubMed2005

The optimal diet for women with polycystic ovary syndrome?

An optimal diet is one that not only prevents nutrient deficiencies by providing sufficient nutrients and energy for human growth and reproduction, but that also promotes health and longevity and reduces the risk of diet-related chronic diseases. The composition of the optimal diet for women with polycystic ovary syndrome (PCOS) is not yet known, but such a diet must not only assist short term with weight management, symptoms and fertility, but also specifically target the long-term risks of type 2 diabetes, CVD and certain cancers. With insulin resistance and compensatory hyperinsulinaemia now recognised as a key factor in the pathogenesis of PCOS, it has become clear that reducing insulin levels and improving insulin sensitivity are an essential part of management. Diet plays a significant role in the regulation of blood glucose and insulin levels, yet research into the dietary management of PCOS is lacking and most studies have focused on energy restriction rather than dietary composition per se. On the balance of evidence to date, a diet low in saturated fat and high in fibre from predominantly low-glycaemic-index-carbohydrate foods is recommended. Because PCOS carries significant metabolic risks, more research is clearly needed.

Cardiovascular Diseases↗

PubMed2003

Is ovarian surgery effective for androgenic symptoms of polycystic ovarian syndrome?

The effectiveness of laparoscopic ovarian drilling for treatment of anovulation in polycystic ovarian syndrome (PCOS) has been proved. The role of ovarian surgery in the treatment of symptoms related to hyperandrogenaemia, such as hirsutism and acne, has been less clear. This review sought to evaluate the effectiveness of ovarian surgery in the treatment of non-infertility symptoms related to PCOS. A systematic literature review was undertaken, by searching the Medline database for the years 1966-2002 inclusive. The search yielded 19 studies recording the outcomes of hirsutism, acne or androgen levels from surgical treatment for women with PCOS: three assessed unilateral oophorectomy; two ovarian wedge resection; and 14 ovarian drilling. There was no consensus of a clear improvement in hirsutism or acne in women undergoing surgery. There was a trend towards a decrease in serum androgen levels in most studies. We conclude that, while there is evidence that ovarian surgery may decrease androgen levels in some women with PCOS, the evidence that this translates into a clear improvement in hirsutism and acne is less clear. Further high quality clinical research, including data from randomisation, would be required to answer this question.

Acne Vulgaris↗

PubMed2004

Low-dose ovulation induction with urinary gonadotropins or recombinant follicle stimulating hormone in patients with polycystic ovary syndrome.

Patients with polycystic ovary syndrome (PCOS) are highly sensitive to gonadotropins. In recent years a number of publications have shown that chronic low-dose protocols are effective in reducing complications, in particular ovarian hyperstimulation syndrome (OHSS), especially if recombinant human follicle stimulating hormone (rhFSH) is used. The aim of the present study was to compare the efficacy and safety of rhFSH (Gonal-F, Serono) versus urinary human FSH (uhFSH) (Metrodin, Serono) in a low-dose step-up protocol for ovulation induction in clomiphene-resistent infertile PCOS patients. Twenty PCOS patients were recruited in two centers for an open randomized comparative study. A starting dose of a 75-IU ampule of rhFSH or uhFSH was used for 14 days with an increment of 37.5 IU every 7 days. Human chorionic gonadotropin (hCG) (10,000 IU, Profasi, Serono) was administered if one to three follicles achieved a diameter of > or = 16 mm. Sonographic and hormonal (serum estradiol and progesterone) monitoring of the cycles was performed. All the six pregnancies induced were in the rhFSH group, but two of them ended with miscarriage. There were no differences between the two groups concerning the number of ampules used, the stimulation days, the estradiol levels on the day of hCG administration, and the progesterone levels 7 days after hCG administration. Three patients had grade II, and one patient grade III OHSS. In conclusion, our results support the literature data that rhFSH is superior to uhFSH regarding pregnancy rates, not only in in vitro fertilization cycles, but also with a low-dose protocol in patients with PCOS.

Drug Administration Schedule↗

PubMed2003

Urinary 6-sulfatoxymelatonin excretion in hyperandrogenic women with polycystic ovary syndrome: the effect of ethinyl estradiol-cyproterone acetate treatment.

The role of melatonin in human reproduction is still unknown. Data obtained in patients with hypogonadism and precocious puberty suggest that melatonin and the reproductive hormones are interrelated. The aim of this study was to determine melatonin production in hyperandrogenic women. We studied 12 women with polycystic ovary syndrome (PCOS) and 10 women with idiopathic hirsutism (IH). Patients were treated with cyproterone acetate-ethinyl estradiol (Diane 35) for 4 months. Fasting blood samples for the determination of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone and dehydroepiandrosterone sulfate (DHEAS) and 24-h urine collections for the determination of 6-sulfatoxymelatonin (alpha MT6s) excretion were obtained from all patients at baseline and after 4 months of treatment. The results were compared with those obtained in 15 control women. At baseline, women with PCOS had significantly higher LH and testosterone levels than those with IH and controls. Their alpha MT6s values (52.6 +/- 20.3 micrograms/24 h) were significantly higher than the values in women with IH (34.3 +/- 7.1) and controls (30.5 +/- 6.5) (p < 0.001). Diane 35 treatment significantly decreased LH, FSH, testosterone and alpha MT6a values in PCOS (28.0 +/- 13.9 micrograms/24 h) (p < 0.0001). These results indicate that women with PCOS have increased melatonin production. The normalization of alpha MT6s and testosterone values during Diane 35 treatment suggests that sex steroids modulate melatonin secretion in these patients either directly or through the suppression of gonadotropin.

Adolescent↗

PubMed2004

Management of anovulatory infertility associated with polycystic ovary syndrome: tamoxifen citrate an effective alternative compound to clomiphene citrate.

Clomiphene citrate (CC) is widely used as first-line treatment for ovulation induction in anovulatory women with polycystic ovary syndrome (PCOS). Tamoxifen citrate (TMX), another non-steroidal selective estrogen receptor modulator, may also be effective on the resumption of ovulation in these women. The aim of this controlled observational study was to compare the efficacy and safety of ovulation induction with TMX versus CC in anovulatory infertile women with PCOS. A total of 102 consecutive women (mean age+/-SD: 31+/-3.6 years; range: 26-38) with PCOS were studied. Following a spontaneous or progesterone-induced withdrawal bleed, women received either 50 mg daily of CC (days 2-6) or 20 mg daily of TMX (days 2-5). In case ovulation failed to occur, the dose was sequentially increased to 100 mg daily of CC and 40 mg daily of TMX, respectively. Serum progesterone levels were measured on cycle day 21 to monitor the ovulation pattern. The overall ovulation rate was significantly higher in women who received TMX compared with those who received CC (61/98, 62.2% vs. 60/127, 47.2%, p=0.03). Although not statistically significant, the pregnancy rate per ovulatory cycle was higher in the TMX group compared to the CC group (14/61, 22.9% vs. 11/60, 18.3%, respectively). All pregnancies were single and there were no side-effects in either group of treatment. Collectively, these data demonstrate that TMX is a safe and effective agent, and a suitable alternative to CC for anovulatory infertility in women with PCOS.

Adult↗

PubMed2005

Gonadotropin pulsatility in Cushing's syndrome compared with polycystic ovary syndrome.

Many of the presenting features in women with Cushing's syndrome (CS) are similar to those observed for patients with polycystic ovary syndrome (PCOS). The aim of this study was to compare gonadotropin pulsatility characteristics in CS and PCOS. We evaluated 32 females divided into three groups. The first group comprised 12 females with clinically and biochemically proven CS, subsequently confirmed by histology (seven with Cushing's syndrome, five with adrenal adenoma). The second group comprised ten females with clinical, endocrine and ultrasonographic parameters for PCOS, while the third group comprised ten healthy females with regular menstrual cycles to serve as controls. Blood samples were taken at 15-min intervals for 6 h in the follicular phase, for determination of luteinizing hormone (LH) and follicle-stimulation hormone (FSH). Pulse analysis was carried out using the PulsDetekt program, and statistical analysis was done using the Kruskal-Wallis test. The following data, presented as median (minimum-maximum), were found for the three groups respectively. Number of LH pulses: 0 (0-5), 7 (3-8) and 3 (2-7); LH pulse amplitude: 2.29 (1.98-3.49), 2.27 (1.15-5.90) and 2.03 (1.02-4.46) mU/l; LH pulse mass: 17.81 (14.82-26.20), 29.85 (8.59-185.82) and 27.57 (7.63-66.69) mU/l x min. Number of FSH pulses: 3 (0-3), 2 (0-5) and 3 (1-5); FSH pulse amplitude: 1.62 (1.29-1.94), 1.49 (1.19-4.40) and 2.02 (1.37-2.52) mU/l; FSH pulse mass: 12.17 (9.64-41.69), 11.18 (8.92-33.02) and 15.16 (10.31-18.93) mU/l x min. Only the number of pulses was compared because other parameters of pulsatile secretion cannot be estimated when no pulses are detected. The difference in number of LH pulses between groups was statistically significant (p < 0.05); however, there was no difference in the number of detected FSH pulses between groups (p > 0.05). Attenuation of pulsatile LH secretion indicating gonadotropin deficiency in the majority of women with CS is mostly due to alterations in serum cortisol levels. Our data also suggest that different mechanisms alter LH pulsatile secretion in CS and PCOS.

Adult↗

PubMed2005

Acanthosis nigricans: clinical predictor of abnormal glucose tolerance in Asian women with polycystic ovary syndrome.

The aim of this retrospective study was to assess whether acanthosis nigricans is a predictive factor for abnormal glucose tolerance (AGT) in Asian women with polycystic ovary syndrome (PCOS). Data from the record forms and electronic form of 121 PCOS women who consecutively attended the Reproductive Endocrinology and Infertility Unit were reviewed. In accordance with the unit's guidelines, all women received a physical examination, had anthropometric measurements taken and underwent as a 75-g oral glucose tolerance test after diagnosis. Their age, body mass index (BMI) and waist/hip ratio (WHR) was 29.1+/-6.1 years, 27.4+/-6.8 kg/m2 and 0.84+/-0.6 (mean+/-standard deviation), respectively. The prevalence of AGT was 42.9%, with 1.6% having impaired fasting glucose, 32.3% having impaired glucose tolerance and 9.1% having type 2 diabetes mellitus. The PCOS women with acanthosis nigricans had significantly higher BMI, WHR, fasting glucose, 2-h post-load glucose, fasting insulin, 2-h post-load insulin and prevalence of AGT compared with those without acanthosis nigricans. By logistic regression analysis, acanthosis nigricans and WHR were independent predictors for AGT, with an odds ratio (95% confidence interval) of 2.7 (1.1-7.1) and 10.1 (1.8-20.7), respectively. In conclusion, acanthosis nigricans was demonstrated as a predictive factor for AGT in Asian women with PCOS.

Acanthosis Nigricans↗

PubMed2005

Cerebral artery hemodynamics in polycystic ovary syndrome.

OBJECTIVE: The aim of the present study was to investigate hemodynamic changes in the medial cerebral artery and also the internal carotid artery in young women with polycystic ovary syndrome (PCOS) and polycystic ovaries (PCO). METHODS: Twenty-eight patients with PCOS, 16 patients with PCO and 24 healthy control subjects were included in the study. Blood flow rate, pulsatility index and back pressure of both the medial cerebral artery and the internal carotid artery were determined by transcranial Doppler ultrasonography and the results compared between groups. RESULTS: There were no significant differences between the groups in bilateral medial cerebral artery and internal carotid artery blood flow rate, pulsatility index and back pressure. CONCLUSION: Our results do not indicate whether the risk of cerebrovascular events will increase for PCOS patients in middle and advanced age, but do show that changes in cerebral hemodynamics are not likely in PCOS at an early stage.

Adolescent↗