Pre-polycystic ovary syndrome and polymenorrhoea as new facets of polycystic ovary syndrome (PCOS): Evidences from a single centre data set.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is a complex disorder with diverse metabolic implications. Diagnosis typically relies on oligo-amenorrhoea (OA), hyperandrogenism (HA), and polycystic ovarian morphology (PCOM). However, the role of polymenorrhoea in PCOS remains understudied. Additionally, limited information exists regarding metabolic disturbances in women with partial PCOS phenotypes that do not meet diagnostic criteria. This extensive database aims to provide substantial evidence on the metabolic implications of polymenorrhoea and partial PCOS phenotypes. DESIGN: Prospective observational study. PATIENTS AND MEASUREMENTS: In this single-centre study, 6463 women with PCOS-like characteristics and 3142 age-matched healthy women were included. The study compared clinical (anthropometry, modified Ferriman Gallwey [mFG] score), hormonal (serum testosterone), and metabolic (plasma glucose, serum lipids, insulin) characteristics between women diagnosed with PCOS, those with partial PCOS phenotypes, and the healthy control group RESULTS: In all, 5174 women met Rotterdam criteria for PCOS diagnosis, while 737 were classified as Pre-PCOS, including HA (n = 538), OA (n = 121), or PCOM (n = 78). Common clinical features included oligomenorrhoea (75.5%), hirsutism (82.9%), obesity (27.2%), hypertension (1.6%), metabolic syndrome (19.6%), and diabetes mellitus (5.6%). Women diagnosed with PCOS, HA only, and OA only exhibited higher average body mass index, plasma glucose levels (both fasting and 2 h after the oral glucose tolerance test), and lipid fractions in comparison to those with PCOM and the healthy controls. However, indices of insulin resistance were similar among women with PCOS, HA, PCOM, and OA, albeit higher than in the healthy controls. The polymenorrhoea subgroup (5.9%) had lower BMI and serum testosterone, but similar mFG score, plasma glucose, insulin, and lipid levels as the oligomenorrhoea subgroup. CONCLUSION: The metabolic disturbances observed in Pre-PCOS women highlight the need to reassess diagnostic criteria. Including the polymenorrhoea subcategory in PCOS criteria is recommended due to similar metabolic dysfunctions as the oligomenorrhoea group.

Vitamin D status among Kashmiri tribal population: A cross-sectional community-based study.

Background & objectives: Vitamin D deficiency (VDD) is prevalent across all age groups in general population of India but studies among tribal populations are scanty. This study aimed to evaluate the prevalence of VDD in the indigenous tribal population of the Kashmir valley and examine associated risk factors. Methods: In this cross-sectional investigation, a total of 1732 apparently healthy tribal participants (n=786 males and n=946 females) were sampled from five districts of Kashmir valley by using probability proportional to size method. Serum 25-hydroxy vitamin D (25(OH)D) levels were classified as per the Endocrine Society (ES) recommendations: deficiency (<20 ng/ml), insufficiency (20-30 ng/ml) and sufficiency (>30 ng/ml). The serum 25(OH)D levels were assessed in relation to various demographic characteristics such as age, sex, education, smoking, sun exposure, body mass index and physical activity. Results: The mean age of the male participants was 43.79±18.47 yr with a mean body mass index (BMI) of 20.50±7.53 kg/m[2], while the mean age of female participants was 35.47±14.92 yr with mean BMI of 22.24±4.73 kg/m2. As per the ES guidelines 1143 of 1732 (66%) subjects had VDD, 254 (14.71%) had insufficient and 334 (19.3%) had sufficient serum 25(OH)D levels. VDD was equally prevalent in male and female participants. Serum 25(OH)D levels correlated positively with serum calcium, phosphorous and negatively with serum alkaline phosphatase. Gender, sun exposure, altitude, physical activity and BMI did not seem to contribute significantly to VDD risk. Interpretation & conclusions: VD deficiency is highly prevalent among Kashmiri tribals, although the magnitude seems to be lower as compared to the general population. These preliminary data are likely to pave way for further studies analyzing the impact of vitamin D supplementation with analysis of functional outcomes.

Prevalence, pattern & correlates of hypertension among tribal population of Kashmir, India: A cross-sectional study.

Background & objectives: The prevalence of hypertension is increasing among all ethnic groups across the globe with only a handful of studies from India addressing the prevalence of hypertension among tribal population. In view of paucity of data, this study was aimed at estimating the prevalence of hypertension and associated risk factors among tribal population of Kashmir, India. Methods: This cross-sectional survey included 6808 tribals aged >20 yr (5695 Gujjars and 1113 Bakarwals) from five randomly selected districts of Kashmir. Modified WHO-STEPS surveillance questionnaire was used to collect relevant data. Hypertension was defined by Joint National Committee on Prevention, Detection, Evaluation and Treatment of Hypertension (JNC 8) criteria. Results: The mean age of our study participants was 43.12 ± 15.69 years. Overall prevalence of hypertension [95% confidence interval (CI)] was 41.4% (39.9-42.9%) [men=46.7% (44.1-49.1%); women=37.9% (35.9-39.9%)]. The prevalence of prehypertension (95% CI) in our study was 35 per cent (33.7-36.6%). Higher age [adjusted odds ratio (OR) (95% CI): >70 yr-2.2 (1.9-2.4)], passive smoking [OR-1.3 (1.1-1.5)], family history of hypertension [OR-1.6 (1.4-1.7)] and obesity [OR-1.3 (1.1-1.6)] were significantly associated with hypertension. A weak positive correlation was observed between BP (systolic/diastolic) with haemoglobin, red blood cell count and haematocrit (P<0.05). Interpretation & conclusions: Gujjar and Bakarwal tribes of Jammu and Kashmir showed high prevalence of hypertension. Hence, urgent policies and reforms are needed to tackle this silent epidemic and further studies focusing on community-based interventions are required.

Prevalence of polycystic ovary syndrome (PCOS) among reproductive age women from Kashmir valley: A cross-sectional study.

OBJECTIVE: To estimate the prevalence of polycystic ovary syndrome (PCOS) among women of reproductive age across educational institutions in the Kashmir valley. METHODS: A cross-sectional study was conducted from May 2013 to May 2015. Eligible girls and women aged 15-40 years were included using a multistage random selection process from five out of 12 districts in turn housing 14 educational institutions. They were screened through a brief questionnaire in a staged manner. After obtaining consent, women underwent detailed clinical, biochemical, hormonal, and sonographic evaluation to satisfy Rotterdam 2003 criteria. The participants were also evaluated using NIH and AE-PCOS criteria. RESULTS: Out of a total of 3300 eligible women, 964 women were evaluated using a structured questionnaire. Among these, 446 (46.4%) were identified as "probable PCOS" cases. Out of 171 probable PCOS women who completed all biochemical, hormonal, and sonographic assessment, 35.3% qualified for a diagnosis of PCOS using Rotterdam criteria. The prevalence of PCOS was 28.9% by NIH criteria and 34.3% by AE-PCOS criteria. CONCLUSION: The prevalence of PCOS is high among Kashmiri women and is probably the highest in a published series globally. A countrywide systematic prevalence study is warranted to reconfirm the findings.

Coadministration of metformin or spironolactone enhances efficacy of rosiglitazone in management of PCOS.

The aim of this study was to compare the efficacy and safety of adding metformin or spironolactone to rosiglitazone in women with polycystic ovary syndrome (PCOS). This is a prospective non-randomized study in a tertiary care with at in a tertiary care endocrine clinic. Women (n = 138) diagnosed with PCOS on the basis of Rotterdam criteria 2003 were categorized into three groups on the basis of drug intake as - rosiglitazone (R), rosiglitazone with spironolactone (R + S), and rosiglitazone with metformin (R + M). Clinical, biochemical, hormonal, and insulin sensitivity parameters were assessed at baseline and after six months of follow up. There was a significant improvement in number of menstrual cycles per year and Ferriman Gallwey (FG) score in all three groups after 6 months. Plasma insulin (0, 2 h), HOMA-IR and serum total testosterone levels decreased after six months in all the three groups. The inter group comparison showed higher efficacy of R + S in improving hyperandrogenism whereas R + M was most effective in decreasing body weight and plasma insulin levels compared to R and R + S (p<.05). Treatment of women with PCOS using rosiglitazone alone and in combination with spironolactone or metformin is safe and efficacious with limited adverse events however randomized trials with longer duration of follow up are warranted.

Observation of phenotypic variation among Indian women with polycystic ovary syndrome (PCOS) from Delhi and Srinagar.

Polycystic ovary syndrome (PCOS) is a heterogeneous disorder that demonstrates ethnic and regional differences. To assess the phenotypic variability among Indian PCOS women, we evaluated clinical, biochemical and hormonal parameters of these women being followed in two tertiary care institutions located in Delhi and Srinagar. A total of 299 (210 PCOS diagnosed by Rotterdam 2003 criteria and 89 healthy) women underwent estimation of T4, TSH, LH, FSH, total testosterone, prolactin, cortisol, 17OHP, and lipid profile, in addition to post OGTT, C-peptide, insulin, and glucose measurements. Among women with PCOS, mean age, age of menarche, height, systolic, diastolic blood pressure, and serum LH were comparable. PCOS women from Delhi had significantly higher BMI (26.99 ± 5.38 versus 24.77 ± 4.32 kg/m(2); P = 0.01), glucose intolerance (36 versus 10%), insulin resistance as measured by HOMA-IR (4.20 ± 3.39 versus 3.01 ± 2.6; P = 0.006) and QUICKI (0.140 ± 0.013 versus 0.147 ± 0.015; P = 0.03) while PCOS from Srinagar had higher FG score (12.12 ± 3.91 versus 10.32 ± 2.22; P = 0.01) and serum total testosterone levels (0.65 ± 0.69 versus 0.86 ± 0.41 ng/ml; P = 0.01. Two clear phenotypes, i.e. obese hyperinsulinaemic dysglycemic women from Delhi and lean hyperandrogenic women from Srinagar are emerging. This is the first report on North Indian women with PCOS showing phenotypic differences in clinical, biochemical and hormonal parameters despite being in the same region.

Impact of hypovitaminosis D on clinical, hormonal and insulin sensitivity parameters in normal body mass index polycystic ovary syndrome women.

Earlier data on the relationship of 25 hydroxyvitamins (25OHD) levels with various components of polycystic ovary syndrome (PCOS) has been conflicting. We studied 122 normal body mass index (BMI) women with PCOS (cases) and 46 age and BMI-matched healthy women (controls) and assessed the impact of serum 25OHD levels on clinical, biochemical and insulin sensitivity parameters in these lean Indian women with PCOS. The mean age and BMI of the cases and controls were comparable. Mean serum 25OHD levels respectively were 10.1 ± 9.9 and 7.9 ± 6.8 ng/ml with 87.7% and 91.1% vitamin D (VD) deficient. No significant correlation was noted between 25OHD levels and clinical, biochemical and insulin sensitivity parameters except with the total testosterone levels (p = 0.007). Also, no significant difference in these parameters was observed once the PCOS women were stratified into various subgroups based on the serum 25OHD levels. We conclude that VD deficiency being common in normal BMI Indian women with or without PCOS does not seem to alter the metabolic phenotype in these women.

Oral glucose tolerance test significantly impacts the prevalence of abnormal glucose tolerance among Indian women with polycystic ovary syndrome: lessons from a large database of two tertiary care centers on the Indian subcontinent.

OBJECTIVE: To estimate the prevalence of abnormal glucose tolerance (AGT) among Indian women with polycystic ovary syndrome (PCOS) and analyze the role of oral glucose tolerance (OGTT) test on its estimation. DESIGN: Cross-sectional clinical study. SETTING: Tertiary care center. PATIENT(S): A total of 2,014 women with PCOS diagnosed on the basis of the Rotterdam 2003 criteria were enrolled, and the data of 1,746 subjects were analyzed. INTERVENTION(S): In addition to recording clinical, biochemical, and hormone parameters, a 75 g OGTT was administered. MAIN OUTCOME MEASURE(S): Prevalence of AGT and impact of age, body mass index (BMI), family history, and OGTT on its prevalence. RESULT(S): The mean age of subjects was 23.8 ± 5.3 years, with a mean BMI of 24.9 ± 4.4 kg/m(2). The overall prevalence of AGT was 36.3% (6.3% diabetes and 30% impaired fasting plasma glucose/impaired glucose tolerance) using American Diabetes Association criteria. The glucose intolerance showed a rising trend with advancing age (30.3%, 35.4%, 51%, and 58.8% in the second, third, fourth, and fifth decades, respectively) and increasing BMI. Family history of diabetes mellitus was present in 54.6% (953/1,746) subjects, and it did not correlate with any of the studied parameters except waist circumference and BMI. Sensitivity was better with 2-hour post-OGTT glucose values as compared with fasting plasma glucose, since using fasting plasma glucose alone would have missed the diagnosis in 107 (6.1%) subjects. CONCLUSION(S): We conclude that AGT is high among young Indian women with PCOS and that it is not predicted by family history of type 2 DM. OGTT significantly improves the detection rate of AGT among Indian women with PCOS.

High-sensitivity C-reactive protein (hs-CRP) levels and its relationship with components of polycystic ovary syndrome in Indian adolescent women with polycystic ovary syndrome (PCOS).

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.

An unexpected cause of orbital apex syndrome in an immune-competent elderly male.

Invasive aspergillosis causing orbital apex syndrome (OAS) in an immune-competent individual is a very rare phenomenon, scarcely reported in medical literature. A 68-year-old male presented with progressive loss of vision in the right eye, starting after a cataract surgery. Neurological examination suggested OAS. Imaging was suggestive of mass lesion causing destruction of ethmoid bone. Biopsy of the lesion could not be done initially in view of its proximity to the major neuro-vascular bundle in the orbital apex and cavernous sinus and the major risk involved in the procedure relative to its yield. There was no response to empirical therapy with antibacterials, steroids or Amphotericin-B. Gradually the mass increased in size and was amenable to biopsy. Endoscopy guided biopsy revealed invasive aspergillosis. Switching over to voriconazole lead to successful management. This case highlights the importance of early diagnosis and selection of an appropriate antifungal therapy in the management of invasive aspergillosis.

Improved efficacy of low-dose spironolactone and metformin combination than either drug alone in the management of women with polycystic ovary syndrome (PCOS): a six-month, open-label randomized study.

CONTEXT: To improve the treatment outcomes in women with polycystic ovary syndrome (PCOS), various drugs like glitazones, oral contraceptive pills, or antiandrogens have been combined with metformin. OBJECTIVE: The aim of the study was to compare the efficacy of the combination of low-dose spironolactone and metformin with either drug alone in the management of women with PCOS. DESIGN AND SETTING: The present study was an open-label, randomized study conducted at a tertiary care referral center. PATIENTS AND INTERVENTION: Of 204 women who met the 2006 Androgen Excess-PCOS criteria for PCOS, 198 were randomized into 3 equal groups to receive metformin (1000 mg/d), low-dose spironolactone (50 mg/d), or a combination of both drugs for a period of 6 months. A total of 169 subjects (n = 56 metformin, 51 spironolactone, 62 combination) completed the study. MAIN OUTCOME MEASURES: Menstrual cycle pattern, Ferriman-Gallwey score, body mass index (BMI), waist-hip ratio, blood pressure, LH, FSH, total T, glucose and insulin sensitivity indices were measured at baseline (0 mo) and 3 and 6 months after the intervention. Recording of adverse events and drug compliance was assessed at each of the visits. RESULTS: The 3 groups had comparable mean age and BMI at baseline. By 6 months, menstrual cycles/y increased, whereas Ferriman-Gallwey score, serum total T, and area under the curve-glucose and -insulin decreased significantly (P < .05) in the combination group as compared to either drug alone. There was no significant change in body weight, BMI, waist-hip ratio, and blood pressure in any of the 3 groups. The combination group had better compliance than either drug alone, and the adverse event rate was not higher. CONCLUSION: The combination of low-dose spironolactone with metformin seems superior to either drug alone in terms of clinical benefits and compliance in women with PCOS.

Universal salt iodization is successful in Kashmiri population as iodine deficiency no longer exists in pregnant mothers and their neonates: Data from a tertiary care hospital in North India.

INTRODUCTION: Normal pregnancy results in a number of important physiological and hormonal changes that alter thyroid function. In pregnancy, the thyroid gland being subjected to physiological stress undergoes several adaptations to maintain sufficient output of thyroid hormones for both mother and fetus. Consequently, pregnant women have been found to be particularly vulnerable to iodine deficiency disorders (IDD), and compromised iodine status during pregnancy has been found to affect the thyroid function and cognition in the neonates. OBJECTIVES: Two decades after successful universal salt iodization (USI) in the country, there is scarce data on the iodine status of the pregnant women and their neonates. This is more relevant in areas like Kashmir valley part of sub-Himalayan belt, an endemic region for IDD in the past. The objective was to estimate Urinary Iodine status in pregnant women, the most vulnerable population. MATERIALS AND METHODS: We studied thyroid function [free T3 (FT3), T3, free T4 (FT4), T4, thyroid stimulating hormone (TSH)] and urinary iodine excretion (UIE) in the 1(st), 2(nd), and 3(rd) trimesters and at early neonatal period in neonates in 81 mother-infant pairs (hypothyroid women on replacement) and compared them with 51 control mother-infant pairs (euthyroid). RESULTS: Mean age of cases (29.42 + 3.56 years) was comparable to that of controls (29.87 + 3.37 years). The thyroid function evaluation done at baseline revealed the following: FT3 2.92 ± 0.76 versus 3.71 ± 0.54 pg/ml, T3 1.38 ± 0.37 versus 1.70 ± 0.35 ng/dl, FT4 1.22 ± 0.33 versus 1.52 ± 0.21 ng/dl, T4 9.54 ± 2.34 versus 13.55 ± 2.16 µg/dl, and TSH 7.92 ± 2.88 versus 4.14 ± 1.06 µIU/ml in cases versus controls (P > 0.01), respectively. The 2(nd) to 6(th) day thyroid function of neonates born to case and control mothers revealed T3 of 1.46 ± 0.44 versus 1.48 ± 0.36 ng/dl, T4 of 12.92 ± 2.57 versus 11.76 ± 1.78 µg/dl, and TSH of 3.64 ± 1.92 versus 3.82 ± 1.45 µIU/ml, respectively. DISCUSSION: UIE was similar (139.12 ± 20.75 vs. 143.78 ± 17.65 µg/l; P = 0.8), but TSH values were higher in cases (7.92 ± 2.88) as compared to controls (4.14 ± 1.06). Although UIE gradually declined from 1(st) trimester to term, it remained in the sufficient range in both cases and controls. Thyroid function and UIE was similar in both case and control neonates. CONCLUSION: We conclude that pregnant Kashmiri women and their neonates are iodine sufficient, indicating successful salt iodization in the community. Large community-based studies on thyroid function, autoimmunity, malignancies, etc., are needed to see the long-term impact of iodization.

Association of subclinical hypothyroidism and phenotype, insulin resistance, and lipid parameters in young women with polycystic ovary syndrome.

OBJECTIVE: To determine whether subclinical hypothyroidism (SCH) alters the phenotype, insulin resistance, or lipid parameters in young women with polycystic ovary syndrome (PCOS). DESIGN: Prospective case-control study. SETTING: Tertiary care setting. PATIENT(S): Sixty-two young women with PCOS and SCH (group I) and 291 euthyroid women with PCOS (group II). INTERVENTION(S): Recording of clinical, biochemical, hormonal profile, and parameters of insulin resistance. MAIN OUTCOME MEASURE(S): Whether SCH has any association with clinical parameters like hirsutism, menstrual disturbances, lipid profile, and parameters of insulin sensitivity. RESULT(S): Mean (±SD) TSH was 7.13±1.28 IU/L in group I and 2.51±1.21 IU/L in group II, with comparable free triiodothyronine and free thyroxine. The two groups were comparable in age, weight, and body mass index. Parameters like blood pressure, menstrual pattern, and degree and duration of hirsutism did not differ between the two groups. Serum concentrations of triglycerides were significantly higher in the SCH group compared with controls. Plasma glucose concentrations both in fasting and after oral glucose tolerance test were similar between the two groups. Fasting insulin and other parameters of insulin resistance were not altered by SCH. CONCLUSION(S): Mild TSH elevation in the face of normal serum free triiodothyronine and free thyroxine results in a mild increase in serum lipids. Subclinical hypothyroidism is not associated with alteration in phenotypic expression and insulin resistance in young women with PCOS.