Are circulating leptin and luteinizing hormone synchronized in patients with polycystic ovary syndrome?

Animal and human studies suggest that leptin modulates hypothalamic-pituitary-gonadal axis functions. Leptin may stimulate gonadotrophin-releasing hormone (GnRH) release from the hypothalamus and luteinizing hormone (LH) and follicle stimulating hormone (FSH) secretion from the pituitary. A synchronicity of LH and leptin pulses has been described in healthy women, suggesting that leptin probably also regulates the episodic secretion of LH. In some pathological conditions, such as polycystic ovarian syndrome (PCOS), LH-leptin interactions are not known. The aim of the present investigation was to assess the episodic fluctuations of circulating LH and leptin in PCOS patients compared to regularly menstruating women. Six PCOS patients and six normal cycling (NC) women of similar age and body mass index (BMI) were studied. To assess episodic hormone secretion, blood samples were collected at 10-min intervals for 6 h. LH and leptin concentrations were measured in all samples. For pulse analysis the cluster algorithm was used. To detect an interaction between LH and leptin pulses, an analysis of copulsatility was employed. LH concentrations were significantly higher in the PCOS group in comparison to NC women, however serum leptin concentrations and leptin pulse characteristics for PCOS patients did not differ from NC women. A strong synchronicity between LH and leptin pulses was observed in NC women; 11 coincident leptin pulses were counted with a phase shift of 0 min (P = 0.027), 18 pulses with a phase shift of -1 (P = 0.025) and 24 pulses with a phase shift of -2 (P = 0.028). PCOS patients also exhibited a synchronicity between LH and leptin pulses but weaker (only 20 of 39 pulses) and with a phase shift greater than in normal women, leptin pulses preceding LH pulses by 20 min (P = 0.0163). These results demonstrate that circulating leptin and LH are synchronized in normal women and patients with PCOS. The real significance of the apparent copulsatility between LH and leptin must be elucidated, as well as the mechanisms that account for the ultradian leptin release.     

What is polycystic ovarian syndrome? A proposal for a consensus on the definition and diagnosis of polycystic ovarian syndrome

The criteria for diagnosis and definition of polycystic ovarian syndrome used by clinicians and investigators are almost as heterogeneous as the syndrome itself. This has confused and seriously hindered the clarification of the genetics, aetiology, clinical associations and assessment of treatment and later sequelae of the syndrome. This article proposes a consensus for a unifying balanced and practical working definition for use as a standard. The proposal incorporates confirmation of the diagnosis suggested by clinical symptoms by ultrasound, and the use of hormonal estimations if typical ultrasound features are not seen and for the purpose of defining subsets of the syndrome. This consensus proposal attempts to bridge the gap between predominately American biochemical marker-based diagnosis and predominately European reliance on ultrasound as a sine qua non for diagnosis. It has been deliberately designed to be simple, practical and cheap, and if universally adopted as a standard could contribute much to all future work involving this most prevalent of syndromes.     

Should patients with polycystic ovary syndrome be treated with metformin? Benefits of insulin sensitizing drugs in polycystic ovary syndrome--beyond ovulation induction

The debate on metformin use in polycystic ovary syndrome (PCOS) has mainly focused on its treatment for infertility in ovulation induction and menstrual cyclicity. Here we will summarize the data supporting the effect of metformin on improving hyperandrogenaemia and hyperinsulinaemia in PCOS patients. We propose that metformin benefits PCOS patients undergoing gonadotrophin therapy and IVF as well as ovulation induction. We also advocate the use of insulin sensitizing drugs to reduce miscarriage rates, and risks associated with coronary artery disease, gestational diabetes and obesity.     

Proinsulin serum concentrations in women with polycystic ovary syndrome: a marker of beta-cell dysfunction?

BACKGROUND: The aim of this study was to establish the effect of polycystic ovary syndrome (PCOS) adjusted for adiposity on proinsulin concentrations. METHODS: Ninety-one women with PCOS and 72 normal cycling (NC) women were recruited. A 2 h, 75 g oral glucose tolerance test was performed. Glucose and insulin were measured in each sample. Proinsulin and C-peptide were determined at 0 and 30 min and the fasting proinsulin/insulin ratio (PI/I) was calculated. Insulin sensitivity was estimated by insulin sensitivity index (ISI) composite, and beta-cell function was estimated by insulinogenic index. RESULTS: Insulin, proinsulin and C-peptide concentrations were higher in women with PCOS than in NC women (P < 0.05). PI/I and insulinogenic index were similar in both groups. Proinsulin concentrations increased with body mass index (P < 0.05) only in women with PCOS; therefore, proinsulin concentrations were higher in obese PCOS patients compared with obese control women (P < 0.05). Moreover, a positive association between proinsulin concentrations and waist diameter adjusted for C-peptide (P < 0.05) and a negative association between proinsulin concentrations and ISI composite values were observed in PCOS patients (P < 0.05). CONCLUSIONS: Data suggest that in PCOS patients an elevated proinsulin concentration could reflect insulin resistance more than beta-cell dysfunction. However, the elevated concentration of proinsulin in these patients could also result from impaired beta-cell function resulting from intra-abdominal obesity independently of insulin resistance.     

Do young women with polycystic ovary syndrome show early evidence of preclinical coronary artery disease?

BACKGROUND: It is thought that women with polycystic ovary syndrome (PCOS) are at increased risk of developing cardiovascular diseases. METHODS: In this study, we used transthoracic echocardiography to measure coronary flow reserve (CFR) in 28 women with PCOS and in 26 healthy women. RESULTS: The PCOS and the control groups were similar in terms of age (27.1 +/- 4.5 versus 28.8 +/- 4.4 years) and BMI (26.6 +/- 5.7 versus 24.7 +/- 4.4 kg/m2). Fasting insulin levels and homeostasis model assessment insulin resistance index were higher in the PCOS group. LH, the LH/FSH ratio, total testosterone, free testosterone and androstenedione were higher in the PCOS group. FSH, estradiol, prolactin, progesterone, cholesterol, triglyceride and high-sensitive C-reactive protein were similar between the two groups, but homocysteine levels were higher in the PCOS group. Baseline diastolic peak f low velocity (DPFV) (25.0 +/- 4.6 versus 23.3 +/- 2.7 cm/s, P > 0.05), hyperaemic DPFV (71.2 +/- 12.8 versus 73.0 +/- 12.9 cm/s, P > 0.05) and CFR (2.8 +/- 0.8 versus 3.2 +/- 0.8 cm/s, P > 0.05) of the left anterior descending coronary artery were similar between the two groups. CONCLUSION: We conclude that in young women with PCOS and without cardiovascular risk factors, CFR is preserved.     

Reply to: Are laparoscopic ovarian diathermy and gonadotropin administration the only therapeutic second-steps in clomiphene-citrate resistant women with polycystic ovary syndrome?

Sir, We would like to thank Dr Palomba and colleagues for their interestin our paper (van Wely et al., 2004). In Western Europe, recombinantFSH is most commonly used for ovulation induction in women withpolycystic ovary syndrome (PCOS) that     

Polycystic ovary syndrome: a component of metabolic syndrome?

In 1935, Stein and Leventhal first described the polycystic ovary (PCO) as a frequent cause of irregular ovulation in women seeking treatment for subfertility. Although the initial management was surgical with wedge resection of ovary, the availability of radioimmunoassay and increased clinical use of ultrasound made it clear that many women had the ultrasound characteristics of PCO with or without the biochemical or clinical features of PCOS and therefore that PCO were not associated with a single syndrome. The association between increased insulin resistance and PCOS is a consistent finding in all ethnic groups. Obesity is a common factor in the majority of women with PCOS. It is postulated that a woman may be genetically predisposed to developing PCOS but it is only the interaction of environmental factors (obesity) with the genetic factors that results in the characteristic metabolic and menstrual disturbances. Weight loss, altered diet and exercise have been shown to be effective in the management of PCOS. Importance of early recognition, proper intervention, long-term monitoring and health implications needs more concern.     

To what extent does polycystic ovary syndrome influence the cut-off value of prolactin? Findings of a community-based study

PurposePolycystic ovary syndrome (PCOS) and hyperprolactinemia are the most frequent endocrine disorders in women which share several common features. There are inconsistent results regarding the existence of a possible pathophysiological interplay between these endocrinopathies and the elevation of prolactin (PRL) in PCOS. The purpose of this study was to explore the upper reference limit of PRL in PCOS women.Patients and methodsThis study is a cross-sectional analysis using data collected from two population-based PCOS prevalence studies. After considering the exclusion criteria, 216 women with PCOS diagnosed based on the Rotterdam criteria and 702 eumenorrheic non-hirsute controls, were enrolled. The age distribution of PRL and the effect of PCOS on the percentiles of serum PRL were compared between the PCOS group and controls. The possible contributing factors for the elevation of PRL were evaluated.ResultsIn the subgroup of women with PCOS, aged ≤35 years, the age-adjusted model of quantile regression revealed a significant elevation of PRL from the 60th percentile onwards, leading to an increase of nearly 10 ?ng/ml (p ?= ?0.023, 95% CI 1.3–17.62) of the 95th percentile of PRL. Hyperprolactinemic PCOS women had higher levels of luteinizing hormone (LH).ConclusionsIn PCOS women, aged ≤35 years, the upper reference limit of serum PRL was approximately 1.5-fold higher than in controls. The pathway underlying PRL elevation in PCOS might be attributed to a decline in central dopaminergic tone associated with PCOS which leads to an increase in levels of both - PRL and LH.     

What is the connection between red hair and Tourette syndrome?

Tourette syndrome is a chronic, idiopathic, childhood onset neuropsychiatric disorder with both motor and vocal tics. Tourette syndrome occurs worldwide and the clinical features are similar irrespective of the country of origin, with genetic causes suspected, but to date not proven. A link between red hair colour and Tourette syndrome has been hypothesised as a result of an observation that red hair is over represented in this condition. A causal association between red hair and melanocortin-1 receptor has been shown, and is the only gene that is known to explain physiological variation in human pigmentation. Melanocortins are believed to be involved in many disease states including pigmentary disorders, adrenal disorders, obesity, anorexia, prolonged and neuropathic pain, and inflammatory response. The mode of inheritance for Tourette syndrome is thought to be autosomal recessive, same as for red hair with both aggregating in families.To explore the hypothesis, 168 postal questionnaires sent to Tourette syndrome patients on the registry of the ‘Tourette Syndrome Association of Australia’, were analysed. In this study 22, 13% (95% CI 8.9-19.4) of the Tourette syndrome population had red hair. Data from Australian studies suggests, the normal population with red hair is 2–6%. The proportions of red haired individuals in this study were significantly higher than five of the eight population control groups. Fifty five percent of the Tourette syndrome patients had relatives with red hair. Of these 30% were first degree and 46% were second degree relatives, with a further 24% of more distant relatives. Many Tourette syndrome patients had multiple red haired relatives, since 90 patients yielded a total of 181 relatives with red hair.If this hypothesis is correct the MCIR gene, through a neurological effect, or a gene for Tourette syndrome, located on chromosome 16 in the vicinity of MC1R, could be on the causal pathway. As these figures demonstrate, the hypothesis that there is an association between red hair and Tourette syndrome needs further evaluation.     

What is anaphylaxis?

PURPOSE OF REVIEW: In the century since the discovery of anaphylaxis, research has yet to identify the mechanisms that cause a localized allergic response to become rapidly generalized, and particularly why only some sensitized individuals develop the clinical reaction on exposure. The possible components and steps in the process (proven and hypothetical) are reviewed with respect to their variation and regulation and their potential for therapeutic intervention. RECENT FINDINGS: Studies of insect sting allergy have revealed some of the gaps in our understanding, the relatively poor predictive value of our diagnostic tests, and more recently the early evidence for 'priming' of basophils and mast cells as a precursor or predictor of clinical reactivity. Recent literature has elucidated some of the products and regulatory pathways of the cells involved in the initiation of the anaphylactic response, the role of neurologic pathways, and the possible 'on-off switches' at the level of the immunoglobulin E receptors and their related signaling pathways. SUMMARY: This review incorporates old and new observations that may be related to the puzzling characteristics of anaphylaxis. Recognizing the gaps in our understanding helps to identify many areas that require further study and presents promising targets for future treatment and prevention of anaphylaxis.