Anju Jain

ORIGINAL RESEARCH—ENDOCRINOLOGY: A Comparative Study of the Effects of Local Estrogen With or Without Local Testosterone on Vulvovaginal and Sexual Dysfunction in Postmenopausal Women

INTRODUCTION A significant number of postmenopausal women suffer from distressing problems because of urogenital atrophy secondary to the decline in circulating estrogen levels. Treatment with topical hormones may provide relief in such women when used judiciously. AIM To study the effects of local estrogen with or without local testosterone on urogenital and sexual health in postmenopausal women. METHODS Seventy-five postmenopausal women symptomatic for urogenital atrophy and sexual dysfunction were randomly divided into two study groups and one control group. The women in study group 1 received local estrogen cream; study group 2 received local estrogen and testosterone cream; the control group received nonhormonal lubricant KY gel for 12 weeks. The urogenital and sexuality score, along with the vaginal health index and the vaginal maturation index (VMI), was calculated at the beginning of therapy and 12 weeks later. MAIN OUTCOME MEASURES Changes in the urogenital and sexuality score along with vaginal health index and VMI. RESULTS After 12 weeks of therapy, there was a significant improvement in all the four study parameters, which correlated well with the improvement in symptoms of urogenital atrophy and sexual dysfunction in both the study groups as compared with the control group. Improvement in sexuality score was greatest with combined estrogen-androgen therapy. There were no adverse effects and the therapies were well accepted without any compliance issue. CONCLUSION Local estrogen either alone or with androgen is highly effective in relieving symptoms of urogenital atrophy and in improving sexual function in symptomatic postmenopausal women.

Vitamin D as a predictor of insulin resistance in polycystic ovarian syndrome.

INTRODUCTION Polycystic Ovary Syndrome (PCOS) is the most common endocrinological disorder in women in the reproductive age group. The salient features of this condition include hyperandrogenic features, infertility and insulin resistance among others. Mechanisms behind these features are a matter of debate. Vitamin D has been implicated lately in the etiology of many disorders. The aim of our study was to assess the role of vitamin D as an etiological and predictive factor in PCOS. MATERIALS AND METHODS The study comprised 60 proven cases of PCOS diagnosed on the basis of Rotterdam criteria. The parameters assessed include HOMA-IR, vitamin D besides the routine anthropometric and biochemical parameters. RESULTS The study population was divided into 3 groups according to vitamin D status. Insulin resistance was most severe in the sub group with vitamin D deficiency. Multiple regression analysis established the role of vitamin D as the best predictor of insulin resistance in our study. CONCLUSION Vitamin D has an important role in the pathogenesis of insulin resistance in PCOS.

Soluble and membranous vascular endothelial growth factor receptor-1 in pregnancies complicated by pre-eclampsia

Vascular endothelial growth factor receptor-1 (VEGFR-1) is essential for the normal development and function of the placenta. Defective placental vasculogenesis and trophoblast function may lead to pre-eclampsia, a pregnancy-specific syndrome of hypertension and proteinuria. In order to study the association of VEGFR-1 with the development of pre-eclampsia, a cross-sectional study was carried out to evaluate the concentration of soluble VEGFR-1 (sVEGFR-1) in 360 serum samples and to analyze the expression of membranous VEGFR-1 in 40 placental samples of normal and pre-eclamptic pregnant women. Serum and placental samples at different gestational ages were collected from the Department of Obstetrics and Gynaecology, VMMC and Safdarjang Hospital, New Delhi. The serum levels of sVEGFR-1 and the expression of membranous VEGFR-1 were estimated by enzyme-linked immunosorbent assay and immunohistochemistry, respectively. The serum levels of sVEGFR-1 were seen to be positively increased (p=0.0001) in patients with pre-eclampsia at different gestational intervals as compared to the healthy pregnant women they were matched with. However, receiver operating characteristic (ROC) curve analysis showed a higher sensitivity (89.17%) and specificity (90.0%) in early onset (< or =34 weeks) in contrast with the late-onset (>34 weeks) pre-eclamptic group. Also, significant up-regulation of membranous VEGFR-1 immunoreactivity was observed in all placental cells (syncytiotrophoblast, cytotrophoblast, endothelial cells and Hofbauer cells) of pre-eclamptic groups in both < or =34 weeks (p=0.0001) and >34 weeks (p=0.0001) as compared to the normal group. Elevated sVEGFR-1 serum levels and up-regulated membranous VEGFR-1 expression in placenta denote abnormality in VEGF-mediated function in all placental cells, and thus may contribute to etiopathogenesis of pre-eclampsia. Nevertheless, this study also shows the possible diagnostic utility of sVEGFR-1 as a sensitive and specific biomarker for the early onset (< or =34 weeks) of pre-eclampsia.

Latent autoimmune diabetes in adults: A distinct but heterogeneous clinical entity

Latent autoimmune diabetes in adults (LADA) accounts for 2%-12% of all cases of diabetes. Patients are typically diagnosed after 35 years of age and are often misdiagnosed as type II Diabetes Mellitus (DM). Glycemic control is initially achieved with sulfonylureas but patients eventually become insulin dependent more rapidly than with type II DM patients. Although they have a type II DM phenotype, patients have circulating beta (β) cell autoantibodies, a hallmark of type I DM. Alternative terms that have been used to describe this condition include type 1.5 diabetes, latent type I diabetes, slowly progressive Insulin Dependent Diabetes Mellitus, or youth onset diabetes of maturity. With regards to its autoimmune basis and rapid requirement for insulin, it has been suggested that LADA is a slowly progressive form of type I DM. However, recent work has revealed genetic and immunological differences between LADA and type I DM. The heterogeneity of LADA has also led to the proposal of criteria for its diagnosis by the Immunology of Diabetes Society. Although many workers have advocated a clinically oriented approach for screening of LADA, there are no universally accepted criteria for autoantibody testing in adult onset diabetes. Following recent advances in immunomodulatory therapies in type I DM, the same strategy is being explored in LADA. This review deals with the contribution of the genetic, immunological and metabolic components involved in the pathophysiology of LADA and recent approaches in screening of this distinct but heterogeneous clinical entity.

A Comparison of the Hormonal Profile of Early Androgenetic Alopecia in Men With the Phenotypic Equivalent of Polycystic Ovarian Syndrome in Women.

IMPORTANCE Early androgenetic alopecia (AGA) is patterned hair loss occurring before age 30 years. Early AGA in men is frequently reported as the phenotypic equivalent of polycystic ovarian syndrome (PCOS) in women, which carries the risk of developing obesity, metabolic syndrome, and cardiovascular diseases. Very few studies have been conducted to evaluate this. OBJECTIVE To study the hormonal profile of men with early AGA and to evaluate if early AGA in men can be considered as the phenotypic equivalent of PCOS, the associated risks of which are well known. DESIGN, SETTING, AND PARTICIPANTS This case-control study was conducted from January 1, 2014, to March 31, 2015, in a tertiary care government hospital. Fifty-seven men aged 19 to 30 years presenting with patterned hair loss were recruited as study participants. Thirty-two age-matched men with no evidence of hair loss were recruited as controls. Men who had any established endocrine disorder, diabetes mellitus, or cardiovascular disease and those who took any oral medication or hormonal treatment for hair loss were excluded from the study. The serum concentrations of total testosterone, sex hormone-binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEAS), luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin, fasting plasma glucose, and insulin levels were measured. Insulin resistance (IR) and free androgen index (FAI) were calculated and compared with age- and sex-matched controls. MAIN OUTCOMES AND MEASURES The primary outcome was to measure the clinico-endocrinological profiles (LH, FSH, SHBG, DHEAS, and testosterone levels) of men with early AGA and to compare it with the PCOS profile; the secondary outcome was to establish a relationship between this endocrinological profile and IR. RESULTS Compared with the 32 controls, the 57 participants with AGA showed significantly increased mean (SD) levels of testosterone (24.61 [7.97] vs 20.57 [4.9] nmol/L; P = .04), DHEAS (3.63 [2.19] vs 2.64 [1.49] µg/mL; P = .02), LH (7.78 [3.19] vs 4.56 [2.01] mIU/mL; P < .001), and prolactin (14.14 [9.48] vs 9.97 [3.12] ng/mL; P = .01) and decreased mean levels of FSH (4.02 [2.69] vs 5.66 [1.93] mIU/mL; P < .001) and SHBG (35.07 [11.11] vs 46.41 [14.03] nmol/L; P < .001). The mean FAI and LH/FSH ratio were was also increased in the AGA group. These hormonal parameters resemble the well-known profile of women with PCOS. The mean (SD) insulin levels did not show any significant difference between the cases and controls (6.34 [3.92] vs 5.09 [3.38] μIU/mL; P = .07). There was no statistically significant association between hormone levels and AGA or IR grade severity. CONCLUSIONS AND RELEVANCE Men with early AGA could be considered as male phenotypic equivalents of women with PCOS. They can be at risk of developing the same complications associated with PCOS, including obesity, metabolic syndrome, IR, cardiovascular diseases, and infertility.

XANTHELASMA PALPEBRARUM-CLINICAL AND BIOCHEMICAL PROFILE IN A TERTIARY CARE HOSPITAL OF DELHI

Xanthelasma Palpebrarum is the most common of the xanthomas with asymptomatic, symmetrical, bilateral, soft, yellow, velvety, polygonal papules around the eyelids. Xanthelasmas may be associated with hyperlipidemia. This prospective study included 66 clinically diagnosed patients with Xanthelasma Palpebrarum and 50 controls with non-inflammatory skin disorders. Serum triglyceride, cholesterol, HDL, LDL and VLDL estimated in all cases indicated that patients with Xanthelasma Palpebrarum have underlying lipid abnormalities.

Imbalance between protective (adiponectin) and prothrombotic (Plasminogen Activator Inhibitor-1) adipokines in metabolic syndrome

AIMS The metabolic syndrome (MS) consists of a constellation of metabolic abnormalities that confer increased risk of cardiovascular disease (CVD) and diabetes mellitus (DM). Visceral adipose tissue actively produces a variety of adipokines that interact in various obesity related disorders such as metabolic syndrome, diabetes mellitus and heart diseases. Adiponectin has protective role in the vascular physiology while Plasminogen Activator Inhibitor-1 (PAI-1) has a prothrombotic and consequent deleterious effect on the endothelium. We attempted to assess the putative imbalance if any between these two mediators in subjects with metabolic syndrome in the Indian context. MATERIALS AND METHODS We enrolled 50 diagnosed case of metabolic syndrome as per International Diabetes Federation (IDF) criteria and 50 healthy volunteers as control. Clinical evaluation included anthropometric, routine biochemical analysis as well as adiponectin and PAI-1 measurement. RESULT Subject with MS had significantly lower adiponectin (9.8±1.0 vs 16±1.1 μg/ml) and higher PAI-1 (232±87 vs 185±96 ng/ml). A statistically significant correlation was observed between adiponectin and HDL levels (r=0.388, p=0.005). CONCLUSION Subjects with MS have lower adiponectin and higher PAI-1 levels as compared to controls. The subsequent tilt toward a more prothrombotic and pro inflammatory milieu in the vascular endothelium may be pathognomonic of metabolic syndrome. This understanding of the still undiscovered subtle vascular alterations may help in the better management of obesity and MS.

The study of markers of endothelial dysfunction in metabolic syndrome

Abstract Background: Metabolic syndrome (MetS) consists of a constellation of metabolic abnormalities that confer increased risk of cardiovascular disease (CVD) and diabetes mellitus (DM). Endothelial dysfunction is one of the key components of MetS which is caused by imbalance between vasodilatory substances like nitric oxide (NO) and vaso-constrictive substances like endothelin and prothrombotic factors like plasminogen activator inhibitor-1 (PAI-1). Objective: To study the markers of endothelial dysfunction (NO and endothelin) and prothrombotic markers (PAI-1) among the study subjects. Materials and methods: We enrolled 50 diagnosed cases of MetS as per International Diabetes Federation (IDF) criteria and 50 healthy volunteers as controls. Clinical evaluation included anthropometric, routine biochemical, hematological, serum insulin, NO, endothelin and PAI-1 measurements. Results: Subjects with MetS had higher insulin, endothelin and PAI-1 levels and low NO levels as compared to controls and the difference was found to be significant. The serum insulin levels were positively correlated with PAI-1 and endothelin, and negatively correlated with NO. Conclusion: Endothelial functional status as reflected by decreased NO and increased serum endothelin levels along with insulin resistance is seen in MetS. Moreover, higher serum level of PAI-1 also tilts towards a more prothrombotic milieu in the vascular endothelium. Hence endothelial dysfunction and prothrombotic markers may be used to guide for early diagnosis of cardiovascular disease and type 2 diabetes in patients with MetS.

Unusual changes in colostrum composition in lactating Indian women having medical complications during pregnancy—A pilot study

Colostrum, the mammary secretion during first 2–4 days of lactation, provides all the essential components of nutrition and passive immunity required by the newborn. Pregnancy induced hypertension (PIH), glucose intolerance and anaemia are common medical complications observed during pregnancy in Indian women and their effects were studied on the composition of colostrum collected within 24 hours of delivery from lactating women included in the study. PIH during pregnancy significantly decreased colostrum IgA and total proteins, but showed a significant increase in K+ levels, where as women with glucose intolerance showed a significant decrease in total lipids and lactose and an increase in Na+ levels in colostrum compared to normal controls. The group with anaemia also showed a significant decrease in colostrum IgA and total protein levels when compared with the control group. Awareness about the changes that occur in the composition of colostrum during complicated pregnancies can be an important and useful tool for preventive and protective paediatrics.

Effect of soy proteins Vs soy isoflavones on lipid profile in postmenopausal women

Soy isoflavones and soy proteins are being considered as possible alternatives to postmenopausal hormone replacement therapy. This study was undertaken to evaluate effects of these two preparations on symptoms and lipid profile in postmenopausal women. The study was done in 75 postmenopausal women with FSH levels = 30 mIU/ml. These women were randomly divided into 3 groups (n=25). Study group I was given soy proteins 30gm/day containing 60 mg soy isoflavones. Study group II was given soy isoflavones (60 mg/day). The control group was given casein protein 30 gm/day. The menopausal symptoms were assessed by Kupperman Index. Fasting blood samples were analyzed for serum lipid profile, apolipoprotein A1 and B, Leutenizing Hormone (LH) and Follicle-Stimulating Hormone (FSH) at the beginning of therapy, 4 and 12 weeks after initiation of therapy. A highly significant improvement in postmenopausal symptoms was observed in both the study groups. A highly significant improvement was seen in serum lipid profile and Apolipoprotein A1 and B in women taking soy proteins whereas women taking soy isoflavones demonstrated significant improvement in serum triglycerides only. Both soy proteins and soy isoflavones are helpful in alleviating postmenopausal symptoms but soy proteins offer a greater health advantage due to their beneficial effect on serum lipid profile.