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Background: Polycystic ovary syndrome (PCOS) is a multifactorial endocrine disorder characterized by anovulation, hyperandrogenism, and polycystic ovarian morphology. The pathophysiology of PCOS is not clear; however, disturbance in hypothalamic-pituitary-ovarian axis and abnormal steroidogenesis along with genetic and environmental factors act as main contributors to this disorder. Main text: Hyperandrogenism, the hallmark feature of PCOS, is clinically manifested as hirsutism, acne, and alopecia. Excessive androgen production by ovaries as well as from adrenals contributes to hyperandrogenism. Abnormalities in the neuroendocrine system like increased pulse frequency of gonadotropin-releasing hormone, stimulating the pituitary for excessive production of luteinizing hormone than that of follicle-stimulating hormone is seen in PCOS women. Excess LH stimulates ovarian androgen production, whereas a relative deficit in FSH impairs follicular development. The imbalance in LH: FSH causes proliferation of ovarian theca cells leading to increased steroidogenesis, and ultimately leading to hyperandrogenism in PCOS women. Various genetic factors have been shown to be associated with abnormal steroidogenesis. CYP genes involved in steroidogenesis play an important role in androgen production and are considered as key players in hyperandrogenism in PCOS. Conclusion: Polymorphisms in CYP genes can aggravate the hyperandrogenic phenotype in women with PCOS by either upregulating or downregulating their expression, thus increasing androgens further. However, this hypothesis needs to be validated by further studies.

The activity and conformational change of human placental cystatin (HPC), a low molecular weight thiol proteinase inhibitor (12,500) has been investigated in presence of guanidine hydrochloride (GdnHCl) and urea. The denaturation of HPC was followed by activity measurements, fluorescence spectroscopy and Circular Dichroism (CD) studies. Increasing the denaturant concentration significantly enhanced the inactivation and unfolding of HPC. The enzyme was 50% inactivated at 1.5 M GdnHCl or 3 M urea. Up to 1.5 M GdnHCl concentration there was quenching of fluorescence intensity compared to native form however at 2 M concentration intensity increased and emission maxima had 5 nm red shift with complete unfolding in 4-6 M range. The mid point of transition was in the region of 1.5-2 M. In case of urea denaturation, the fluorescence intensity increased gradually with increase in the concentration of denaturant. The protein unfolded completely in 6-8 M concentration of urea with a mid-point of transition at 3 M. CD spectroscopy shows that the ellipticity of HPC has increased compared to that of native up to 1.5 M GdnHCl and then there is gradual decrease in ellipticity from 2 to 5 M concentration. At 6 M GdnHCl the protein had random coil conformation. For urea the ellipticity decreases with increase in concentration showing a sigmoidal shaped transition curve with little change up to 1 M urea. The protein greatly loses its structure at 6 M urea and at 8 M it is a random coil. The urea induced denaturation follows two-state rule in which Native-->Denatured state transition occurs in a single step whereas in case of GdnHCl, intermediates or non-native states are observed at lower concentrations of denaturant. These intermediate states are possibly due to stabilizing properties of guanidine cation (Gdn+) at lower concentrations, whereas at higher concentrations it acts as a classical denaturant.

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C-reactive protein (CRP) is a risk marker for type 2 diabetes mellitus and cardiovascular diseases. In polycystic ovary syndrome (PCOS), limited data are available on high-sensitivity C-reactive protein (hs-CRP) levels and its relationship with components of PCOS especially in Indian women. The objective was to determine serum hs-CRP concentration in adolescent women with and without PCOS and to assess possible correlations of serum hs-CRP levels with components of PCOS in Indian women. One hundred and sixty women with PCOS and sixty non-PCOS women having normal menstrual cycles were included. Clinical assessment included anthropometry, Ferriman-Gallwey (FG) score and blood pressure (BP) measurement. Laboratory evaluation included estimation of T4, TSH, LH, FSH, total testosterone, prolactin, cortisol, 17OHP, hs-CRP, lipid profile, and insulin, and glucose after 2-h oral glucose tolerance test. Homeostasis Model Assessment Insulin resistance index (HOMA-IR) and Quantitative Insulin Sensitivity Check Index (QUICKI) and glucose intolerance was calculated. FG score, LH, FSH, total Testosterone, HOMA-IR and QUICKI were significantly different among women with or without PCOS (p < 0.01). Although hs-CRP levels showed a higher trend in women having PCOS, there was no significant difference between the groups (p > 0.05). A significant and positive correlation was found between hs-CRP and body mass index (BMI) (r = 0.308, p < 0.01) among PCOS group. The results in Indian adolescent women suggest that hs-CRP levels may not per se be associated with PCOS, rather can be related to fat mass in this subset of subjects.

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Metformin has been proven to be one of the most safe and effective antihyperglycemic agents. Through more than six decades of metformin use, it became the most studied hypoglycemic agent; through these studies, it showed a marvelous non-glycemic related effect. These effects include modulation of different points of cancer timeline, weight reduction, cardiovascular health, thyroid diseases, polycystic ovaries disease and many other medical conditions. The aim of this review was to assess the effect of metformin on non-diabetes related medical diseases. We have examined the studies published in PubMed and summarized different randomized controlled trials, observational trials and review articles. This review has summarized most of the non-glycemic effects of metformin. Metformin has been solidly shown to be effective in weight control with certain medications, effective in neuroprotection, in endothelial health, in control of anti-HIV agent side effects and many other crucial health jeopardies. The effects in cancer timeline modulation have taken the biggest part, since it was the most studied area outside the diabetes field. Having mentioned all the above privileges, and in addition to the robust evidence in glycemic control, this consolidates the position of metformin as a first line agent in treatment of diabetes and pre-diabetes. Perhaps in the near future, we may see other indications to use metformin in non-diabetes patients.