Serum immunoreactive leptin concentrations in women with polycystic ovary syndrome

Recent data in the mouse demonstrate that leptin, a protein hormone produced by fat cells, is required for fertility. In the absence of leptin the mice become obese, diabetic and infertile. Polycystic ovary syndrome (PCOS), a common cause of infertility in women, is associated with obesity and insulin resistance. Because of the increased frequency of PCOS in obese women we tested the hypothesis that alterations in serum leptin concentrations might be associated with PCOS. Immunoreactive leptin concentrations were measured in 58 women with PCOS and 70 regularly menstruating (control) women. As has previously been shown there was a positive correlation between leptin levels and body mass index (BMI). Although the leptin levels in the majority of women with PCOS fell within the control range, 29% of PCOS women had leptin levels above the 99% prediction interval for their BMI and none had low leptin levels. There were also positive correlations of leptin levels with free testosterone and insulin sensitivity in control women. In women with PCOS, 13% and 9.5% exhibited higher than expected leptin concentrations with respect to free testosterone and insulin sensitivity, respectively. Insulin resistant PCOS women had higher leptin levels than controls. The data demonstrate that a substantial proportion of women with PCOS have leptin levels that are higher than expected for their BMI, free testosterone and insulin sensitivity. These results suggest that abnormalities in leptin signaling to the reproductive system may be involved in certain cases of PCOS.     

Endocrino-metabolic features in women with polycystic ovary syndrome during pregnancy

Three isolates of Plasmodium elongatum were obtained from 3 species of raptors (red-tailed hawk [Buteo jamaicensis], bald eagle [Haliaeetus leucocephalus], and eastern screech owl [Otus asio]) from Florida using isodiagnostic techniques in Pekin ducks (Anas platyrhynchos). Six to 10 species of mosquitoes were tested for susceptibility to these 3 isolates. Complete development of the sporogonic cycle of the 3 isolates of P. elongatum occurred in 3 species of mosquitoes, Culex nigripalpus, Culex restuans, and Culex salinarius. The pattern of susceptibility was similar among the 3 isolates of P. elongatum in Cx. nigripalpus. Culex restuans and Cx. salinarius were significantly more susceptible than Cx. nigripalpus to the 3 isolates of P. elongatum tested. Culex nigripalpus transmitted all 3 isolates of P. elongatum from duck to duck both by bite and after intraperitoneal injection of sporozoites. Infections of the 2 isolates tested occurred in ducks after intraperitoneal injection of sporozoites from Cx. restuans and Cx. salinarius. The results suggest that these 3 Culex species are potential vectors of P. elongatum from raptors in Florida.     

Acute insulin response to intravenous glucagon in polycystic ovary syndrome

In order to evaluate the acute insulin response after i.v. injection of glucagon in polycystic ovary syndrome (PCOS), 35 women affected by PCOS and 11 normo-ovulatory controls underwent a 75 g oral glucose tolerance test (OGTT) and, 2 days later, a glucagon test (1 mg i.v.). Patients were analysed according to their degree of obesity; the insulin release after glucagon injection for lean PCOS subjects and control women was not statistically significantly different. Conversely obese PCOS patients had higher insulin secretion after both i.v. glucagon and OGTT when compared to the other groups. Moreover the insulin secretory patterns were heterogeneously represented in lean and obese PCOS women. When the patients were analysed according to their insulinaemic response to OGTT, normoinsulinaemic PCOS women and control subjects had a similar insulin response to i.v. glucagon whereas the hyperinsulinaemic PCOS group had a higher insulin response (P < 0.0001). Moreover, a highly significant relationship was found between the insulin response to OGTT and to glucagon administration in the PCOS population (P < 0.0001; r = 0.73), which was maintained also after controlling for obesity. Our results are consistent with the hypothesis that PCOS patients could have an insulin hyper-response to glucagon administration, that is partially independent from obesity and related to their insulinaemic status. Moreover, the glucagon test could represent an effective alternative to OGTT in screening insulin disorders of PCOS patients (at least in the absence of other risk factors), due to its reliability, simplicity, and speed of performance.     

Late endocrine effects of ovarian electrocautery in women with polycystic ovary syndrome

Intravenous (i.v.) bolus injection of calcitonin gene-related peptide (CGRP) caused a depressor response, which was significantly larger in 12-week-old spontaneously hypertensive rats (SHR) than in Wistar-Kyoto rats (WKY). CGRP also caused decreases in carotid and hindquarter vascular resistance, the magnitude of which was larger in the carotid than the hindquarter. In both regions, the vasodilator response to CGRP was significantly larger in SHR than WKY. Plasma CGRP level was significantly lower in SHR than WKY. These results suggest that depressor and vasodilator responses to CGRP are enhanced in SHR and that decreased plasma CGRP level in SHR may contribute to the enhanced responses.     

Premature response to luteinizing hormone of granulosa cells from anovulatory women with polycystic ovary syndrome: relevance to mechanism of anovulation

Polycystic ovary syndrome is the most common cause of anovulatory infertility. Anovulation in polycystic ovary syndrome is characterized by the failure of selection of a dominant follicle with arrest of follicle development at the 5-10 mm stage. In an attempt to elucidate the mechanism of anovulation associated with this disorder we have investigated at what follicle size human granulosa cells from normal and polycystic ovaries respond to LH. Granulosa cells were isolated from individual follicles from unstimulated human ovaries and cultured in vitro in serum-free medium 199 in the presence of LH or FSH. At the end of a 48-h incubation period, estradiol (E2) and progesterone (P) were determined in the granulosa cell-conditioned medium by RIA. In ovulatory subjects (with either normal ovaries or polycystic ovaries), granulosa cells responded to LH once follicles reached 9.5/10 mm. In contrast, granulosa cells from anovulatory women with polycystic ovaries responded to LH in smaller follicles of 4 mm. Granulosa cells from anovulatory women with polycystic ovaries were significantly more responsive to LH than granulosa cells from ovulatory women with normal ovaries or polycystic ovaries (E2, P < 0.0003; P, P < 0.03). The median (and range) fold increase in estradiol and progesterone production in response to LH in granulosa cell cultures from size-matched follicles 8 mm or smaller were E2, 1.0 (0.5-3.9) and P, 1.0 (0.3-2.5) in ovulatory women and E2, 1.4 (0.7-25.4) and P, 1.3 (0.3-7.0) in anovulatory women. Granulosa cells from anovulatory (but not ovulatory) women with polycystic ovaries prematurely respond to LH; this may be important in the mechanism of anovulation in this common endocrinopathy.     

In vitro fertilization with low-dose clomiphene citrate stimulation in women who respond poorly to superovulation

PURPOSE: Our experience with IVF using low-dose clomiphene citrate for stimulation in "non-" and "poor" responders was reviewed and the treatment outcomes with the previous controlled ovarian stimulation cycles in which hMG and GnRH agonist were used were compared. METHODS: The treatment outcome in 11 non- and 20 poor responders having 30 and 53 clomiphene citrate IVF treatment cycles, respectively, were compared with the treatment outcome in the previous long-protocol buserelin/hMG cycles. RESULTS: The clinical pregnancy rates per oocyte collection achieved in the first clomiphene citrate cycle in non (9.1%)- and poor (10%) responders were comparable to those achieved by poor responders (11.9%) who had buserelin/hMG using the long protocol. Although the numbers were small, a similar pregnancy rate could still be achieved in poor responders up to the third attempt using clomiphene citrate. CONCLUSIONS: IVF using long-protocol buserelin/hMG is more successful than using clomiphene citrate stimulation. However, this advantage may not be significant in those women with a previous poor response to buserelin/hMG. It is suggested that for such poor responders, three attempts of IVF in a clomiphene citrate cycle may offer a viable therapeutic alternative before reverting to more stressful, expensive, and time-consuming treatment.     

Hyperexpression of epidermal growth factor receptors in granulosa cells from women with polycystic ovary syndrome

We report the characterization of two distinct binding sites with receptor characteristics for leukotriene (LT)D4 and LTC4 in membranes from human lung parenchyma. The use of S-decyl-glutathione allowed us to characterize a previously unidentified high affinity binding site for LTC4. Computerized analysis of binding data revealed that each leukotriene interacts with two distinct classes of binding sites (Kd = 0.015 and 105 nM for LTC4 and 0.023 and 230 nM for LTD4) and that despite cross-reactivity, the two high affinity sites are different entities. LTD4 binding sites displayed features of G protein-coupled receptors, whereas LTC4 binding sites did not show any significant modulation by guanosine-5'-(beta, gamma-imido)triphosphate or stimulation of GTPase activity. The antagonists ICI 198,615 and SKF 104353 were unselective for the high and low affinity states of LTD4 receptor, whereas only SKF 104353 was able to recognize the two [3H]LTC4 binding sites although with different affinities. These data indicate that in human lung parenchyma, LTD4 and LTC4 recognize two different binding sites; these binding sites are different entities; and for LTD4, the two binding sites represent the interconvertible affinity states of a G protein-coupled receptor, whereas for LTC4, the high affinity site is likely to be a specific LTC4 receptor.     

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.     

The polycystic ovary syndrome associated with ovarian tumor

Case report of a girl with PCOD (polycystic ovarian disease) and Sertoli-Leydig ovarian tumour. A sixteen-year old girl was clinically, endocrinologically, echosonographically and laparoscopically examined, and polycystic ovarian disease was diagnosed. After a two-year period she was reexamined: normal adrenal function was confirmed and left ovarian tumour was discovered echosonographically. Therefore, she was operated on and adnexectomy of the left ovarian tumour and biopsy of the right ovary were done. The histopathologic analysis revealed the Sertoli-Leydig tumour of the left ovary and polycystic degeneration of the right ovary. In conclusion, because of the greater frequency of ovarian tumours in women with PCOD, the permanent follow-up of women with PCOD is necessary.     

Impaired adipocyte lipolysis in nonobese women with the polycystic ovary syndrome: a possible link to insulin resistance?

The polycystic ovary syndrome (PCOS) is the most common hyperandrogenic disorder among women and is characterized by metabolic and cardiovascular aberrations similar to those seen in the so-called insulin resistance syndrome. The regulation of lipolysis was investigated in isolated abdominal sc adipocytes from 10 nonobese women with PCOS and in 11 age- and body mass index-matched healthy women. Eight PCOS women were reinvestigated after 3 months of treatment with combined oral contraceptives containing ethinyl estradiol and norethisterone, which normalized hyperandrogenicity. The PCOS women showed a marked resistance to the lipolytic effect of noradrenaline due to defects at two different levels in the lipolytic cascade: first, a 7-fold reduction in sensitivity to the beta 2-selective agonist terbutaline (P < 0.005), which could be ascribed to a 50% lower beta 2-adrenoceptor density (P < 0.02) as determined with radioligand binding; there was no difference with regard to dobutamine (beta 1) or clonidine (alpha 2-sensitivity) or beta 1-adrenoceptor density; second, the maximum lipolytic response was also 35% lower (P < 0.02) in the PCOS women compared to that in the healthy women. This was seen with all beta-adrenergic agonists and the postreceptor-acting agents forskolin (activating adenylyl cyclase) and dibutyryl cAMP (activating protein kinase). Neither beta 2-adrenoceptor sensitivity or density nor the reduced lipolytic responsiveness was restored by 3 months of oral contraceptives treatment. The results indicate the existence of a marked impairment of catecholamine-induced lipolysis in nonobese PCOS women displaying early features of the insulin resistance syndrome due to multiple lipolysis defects as a lower beta 2-adrenoceptor density and reduced function of the protein kinase, hormone-sensitive lipase complex. These lipolysis defects are identical to those observed in the insulin resistance (metabolic) syndrome and could be a primary pathogenic mechanism for the development of these disorders.     

The frequency of late-onset 21-hydroxylase and 11 beta-hydroxylase deficiency in women with polycystic ovary syndrome

OBJECTIVE: To determine the frequency of late-onset adrenal hyperplasia (LOCAH) due to 21-hydroxylase (21-OH) and 11 beta-hydroxylase (11 beta-OH) deficiency in women with clinical and biochemical features of polycystic ovary syndrome (PCOS). DESIGN: Eighty-three consecutively selected women with PCOS and eighteen normal women were included in the study. METHODS: Ultrasound, clinical and hormonal parameters were used to define PCOS. Basal FSH, LH, testosterone, free testosterone, androstenedione, dehydroepiandrosterone sulfate (DHEA-S), sex hormone-binding globulin (SHBG) and cortisol levels were measured. Serum 17-hydroxyprogesterone (17-OHP) and 11-deoxycortisol (11-DOC) levels were also measured before, 30 and 60 min after a single bolus injection of 0.25 mg ACTH (1-24) at 0900 h during the mid-follicular phase of the cycle. ACTH-stimulated 17-OHP levels > 30 nmol/l were considered as the criteria of 21-OH deficiency. The diagnosis 11 beta-OH deficiency was made if the adrenal 11-DOC response to ACTH stimulation exceeded threefold the 95th percentile of controls. RESULTS: Basal serum testosterone, free testosterone, androstenedione, DHEA-S, cortisol and 11-DOC levels were significantly higher in PCOS than in control subjects. ACTH-stimulated 17-OHP (P < 0.05) and 11-DOC (P < 0.0005) levels were found to be significantly higher in patients with PCOS than in controls. Seven (8.4%) patients had an 11-DOC response to ACTH higher than threefold the 95th percentile of controls, while no patients showed evidence of 21-OH deficiency. CONCLUSIONS: We have found that 8.4% of the women with clinical and biochemical features of PCOS could be presumed to have 11 beta-OH deficiency. No patients among the women with PCOS showed evidence of 21-OH deficiency. 11 beta-OH deficiency is unexpectedly more common than 21-OH deficiency in women with PCOS.     

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

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

A fasting glucose to insulin ratio is a useful measure of insulin sensitivity in women with polycystic ovary syndrome

Women with polycystic ovary syndrome (PCOS) are profoundly insulin resistant, and the resultant hyperinsulinemia exacerbates the reproductive abnormalities of the syndrome. Agents that ameliorate insulin resistance and reduce circulating insulin levels could provide a new therapeutic modality for PCOS. Identifying the subset of PCOS women who are most insulin resistant may therefore be useful for selecting women who will respond to this therapy. We examined the correlation of basal and oral glucose-stimulated glucose and insulin levels and fasting and stimulated glucose/insulin (G:I) ratios with parameters of insulin sensitivity obtained by frequently sampled i.v. glucose tolerance test (FSIGT) to assess whether there is a simple screening test for insulin resistance in PCOS. Forty PCOS women (aged 18-40 yr; body mass index, >26 kg/m2) and 15 control women matched for age, weight, and ethnicity underwent both a 75-g oral glucose tolerance test (OGTT) and a FSIGT. The insulin sensitivity index (S(I)) was calculated by application of the minimal model of glucose kinetics to the dynamics of plasma glucose and insulin levels during the FSIGT. The best correlation in PCOS between S(I) and a fasting level was found with fasting G:I ratios (r = 0.73; P < 0.0001). A less substantial, but significant, correlation was found with fasting insulin levels (r = 0.50; P < 0.001), and no significant correlation was found with fasting glucose levels (r = 0.24; P = NS). The fasting G:I was more strongly correlated with S(I) than with integrated glucose and insulin responses during the OGTT. The only stronger correlation was with the OGTT 2 h G:I ratio (r = 0.74; P < 0.001). Stepwise regression analysis with S(I) as the dependent variable and fasting glucose and insulin levels, area under the curve for glucose and insulin, and a fasting G:I ratio showed that only the fasting G:I ratio was significantly predictive of S(I) in the model (F to remove value = 38.1; P < 0.001). When viewed as a screening test for insulin resistance in PCOS, setting a value of the fasting G:I ratio of less than 4.5 as abnormal (using an S(I) value below the 10th percentile of our control population as evidence for insulin resistance), the sensitivity of a fasting G:I ratio was 95%, the specificity was 84%, the positive predictive value was 87%, and the negative predictive value was 94%. Receiver operator curve analysis showed that this fasting G:I ratio was the single best screening measure for detecting insulin resistance. We conclude that a fasting G:I ratio may be useful as a screening test for insulin resistance in obese non-Hispanic white PCOS women. This may be a clinically useful parameter for selecting PCOS women most likely to respond to therapeutic interventions that improve insulin sensitivity.     

Current concepts of polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) may be loosely defined as unexplained hyperandrogenism, with variable degrees of cutaneous symptoms, anovulatory symptoms, and obesity. The vast majority of patients with the full-blown Stein-Leventhal syndrome have functional ovarian hyperandrogenism (FOH). However, FOH often occurs without the LH excess or polycystic ovaries of classic PCOS. Functional adrenal hyperandrogenism (FAH) is often found in the syndrome, but it is less closely associated with anovulatory symptoms than is FOH. The vast majority of FOH seems to arise from abnormal regulation (dysregulation) of ovarian androgen secretion. This typically is due to escape from desensitization to luteinizing hormone (LH); this appears to occur because of a breakdown in the processes that normally coordinate ovarian androgen and oestrogen secretion so as to prevent hyperoestrogenism. Similar dysregulation of adrenal androgen secretion in response to ACTH seems to account for most FAH. Dysregulation of androgen secretion may affect the ovary alone (isolated FOH), the adrenal alone (isolated FAH), or both together. Modest insulin resistance is common in PCOS/FOH, and the resultant hyperinsulinaemia is a major candidate as the cause of the dysregulation. The hyperinsulinaemia may arise from either 'nature' (genetic defects) or 'nurture' (exogenous obesity). Although hyperinsulinaemia alone does not have an obvious effect on steroidogenesis, it may act in genetically predisposed women as a 'second hit' to unmask latent abnormalities in steroidogenesis. The ovary, the adrenal cortex, and several other organs paradoxically function as if responding to the hyperinsulinaemic state in spite of resistance to the effects of insulin on glucose metabolism. PCOS should be viewed as an early manifestation of a hyperinsulinaemic condition that will predispose to cardiovascular and metabolic complications later in life. A subset of PCOS patients appear to have not only insulin resistance but also beta-cell secretory dysfunction, which may indicate a relationship of the disorder to NIDDM. The fundamental genetic defects remain to be elucidated.     

Successful induction of ovulation in normogonadotrophic clomiphene resistant anovulatory women by combined naltrexone and clomiphene citrate treatment

Patients suffering from normogonadotrophic anovulation and infertility are initially treated with clomiphene citrate. Those who do not respond to clomiphene citrate usually receive gonadotrophin treatment which is labour-intensive, expensive, and associated with an increased risk of multiple pregnancies and ovarian hyperstimulation syndrome. We treated 22 patients with clomiphene resistant normogonadotrophic anovulation with naltrexone (an opioid receptor blocker) alone or naltrexone in combination with an antioestrogen. In 19 patients ovulation and resumption of a regular menstrual cycle was achieved and in 12 out of 19 a singleton pregnancy was observed. In conclusion, ovulation can be induced successfully using naltrexone alone or naltrexone in combination with an anti-oestrogen in clomiphene citrate resistant anovulatory patients. Compared to gonadotrophin induction of ovulation, this method is safe, simple and inexpensive.     

Dual effect of clomiphene citrate on pituitary gonadotropin secretion in postmenopausal women

This is a report on a series of 100 consecutive patients who had undergone microvascular arterial bypass surgery as an aid in the treatment of occlusive ischemic cerebrovascular disease. The results to date are encouraging in cases of transient ischemic attacks (TIA) with significant hemodynamic vascular lesions previously considered inaccessible or inoperable by conventional vascular surgical techniques. The permanent morbidity rate is low. The operative mortality rate is acceptable. Postoperative patency rates of the surgical bypass remain high. In analyzing the cases presenting with TIA, the total incidence postoperatively to stroke is 6% in the series to date. The average postoperative follow-up is 20 months.     

Serum lipoprotein lipid profile in women with the polycystic ovary syndrome: relation to anthropometric, endocrine and metabolic variables

OBJECTIVE: Although often associated with insulin resistance and glucose intolerance, various lipoprotein abnormalities have been found in polycystic ovary syndrome (PCOS) but not invariably so when the degree of obesity is taken into account. We have therefore investigated the serum lipid profile in a group of women with polycystic ovary syndrome with and without obesity. DESIGN: Cross-sectional study of serum lipoprotein lipids and plasma free fatty acids in relation to anthropometric, metabolic and hormonal variables in women with PCOS and weight-matched controls. PATIENTS: Twenty-four obese (Pob, mean BMI +/- SD 30.6 +/- 3.3 kg/m2) and 25 non-obese (Pnob, 22.2 +/- 2.3 kg/m2) women with PCOS. Twenty obese (Cob, 30.2 +/- 3.5 kg/m2) and 20 non-obese (Cnob, 21.4 +/- 1.5 kg/m2) controls. MEASUREMENTS: Fasting concentrations of plasma free fatty acids, serum cholesterol and triglycerides in high density lipoproteins (HDL), low density lipoproteins (LDL) and very low density lipoproteins (VLDL) in relation to insulin sensitivity index (M/I; assessed with the euglycaemic insulin clamp), glucose tolerance (k-value; intravenous glucose tolerance test), basal serum hormone concentrations, and body fat distribution (skinfolds and waist hip ratio). RESULTS: Plasma concentrations of free fatty acids were markedly higher in Pob than in the other groups (all P < 0.001). The lipoprotein lipids did not differ between Pob and Cob, or between the non-obese groups, whereas both obese groups had higher serum concentrations of triglycerides, totally and in VLDL, and lower HDL-cholesterol than their non-obese counterparts. Pob also had higher serum levels of total and LDL-cholesterol than Pnob. Pob had a more pronounced subcutaneous truncal-abdominal adiposity, higher fasting insulin levels and lower M/I than the other groups, and a lower k-value than Cob. Cob had higher levels of fasting insulin than Cnob. Free fatty acid levels correlated with the k-value (inversely) in both women with PCOS and controls, and with M/I (inversely), age and testosterone levels in PCOS. Stepwise regression analysis for the total population, comparing endocrine, anthropometric and metabolic explanatory variables, showed that the serum levels of HDL-cholesterol and triglycerides were mainly correlated with body fat distribution (both) and fasting insulin levels (triglycerides), and levels of total and LDL-cholesterol with BMI and age. CONCLUSIONS: Plasma free fatty acid correlations were markedly increased in obese women with PCOS, closely associated with the lower insulin sensitivity and lower glucose tolerance in these women. In spite of these profound metabolic aberrations, the lipoprotein lipid profile was not significantly more abnormal in obese women with PCOS than in their weight-matched controls.     

Treatment of hyperandrogenic manifestations in polycystic ovary syndrome

Etiopathogenesis of the polycystic ovarian disease is not clarified. Therefore, optimum therapy of hyperandrogenic syndromes, menstrual and fertility disorders pose a difficult problem. Sequential therapy with estrogens and progestagens is of value in young women, who are not planning to conceive in order to reduce hirsutism and regulate menses. A reduction of hirsutism, acne and seborrhea is produced within 3 months. However, cessation of the treatment produces the symptoms of excessive androgen production. Another method is therapy with antiandrogens, especially cyproterone acetate. This drug inhibits androgens biosynthesis and has also peripheral activity. Spironolactone is another antiandrogen frequently used, but it is known as a primarily diuretic agent. It acts primarily at the androgen receptor sites. Other antiandrogens such as ketoconazole and flutamide are used less frequently. It has been shown, that cimetidine--known H2 receptor inhibitor--also decreases the symptoms of hyperandrogenism. However, cimetidine has not been used for the treatment of polycystic ovarian disease. In cases of enzymatic defects in adrenocortical steroido-synthesis glucocorticoids are used, mainly low doses of triamcinolone and dexamethasone. Other therapies are preferred in case of polycystic ovarian disease in women, who want to conceive. Clomiphene citrate and gonadotropins, mainly FSH, are used to induce ovulation. If pharmacotherapy does not produce ovulation, wedge resection of the ovaries must be performed.     

Idiopathic hirsutism or polycystic ovary syndrome?

Polycystic ovaries (PCO) were detected using ultrasound imaging in a series of 173 women who presented with significant hirsutism and in some cases with irregular menstruation. Patients were divided into 3 groups. Those with hirsutism and regular menstruation (cycles > 8 per year, Group 1, n = 96); those with hirsutism and oligomenorrhoea (cycles < 8 per year, Group 2, n = 44) and those with hirsutism and amenorrhoea (cycles < 2 per year, group 3, n = 33). These 3 groups were compared with subjects with normal ovaries and regular cycles of 26-34 days and without hirsutism (n = 29) and also with a group of women with PCO and regular cycles who had no sign of hirsutism (n = 90). PCO were found in 86% of Group 1, 97% of Group 2 and 94% of women within Group 3. The results suggest that the term 'idiopathic hirsutism' may not be appropriate. An abnormal biochemical test consisting of a luteinizing hormone level > 9 U/L, testosterone level > 2.2 nmol/L, sex hormone binding globulin < 32 nmol/L or free androgen index > 4.5 was 100%, 91% and 76% sensitive for detecting PCO amongst women with amenorrhoea, oligomenorrhoea and idiopathic hirsutism respectively.