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IJCRR - 9(23), December, 2017

Pages: 15-21

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Effect of Iron Overload on Gonadotrophins and Organ Sex Steroids in Pubertal Thalassemia
Patients

Author: Manali Sinharay, Surabhi Mitra, Anindya Dasgupta

Category: Healthcare

Abstract:Background: Iron overload being one of the major adverse effect related to blood transfusion in \? Thalassemia major,leads to various endocrinal disorders among which hypogonadism is noteworthy.Pituitary or gonadal iron deposition or both may lead to this.
Objectives: The main purpose of this study was to evaluate the effect of iron overload measured by serum ferritin on pituitary gonadotrophins (FSH, LH) and gonadal steroids (Estrogen in females,Testosterone in males) levels and the correlation between them in pubertal thalassemic subjects(cases).
Methods: Serum harvested from blood samples collected from 30 cases(15 males,15 females) and 30 controls were used to estimate Serum ferritin, LH, FSH, Estradiol in females and Testosterone in males.
Results: The serum LH (p< 0.001), FSH (p< 0.001), Estradiol in females (p 0.002) and Testosterone in males (p 0.002) were significantly low in cases than controls. There was significant negative correlation between Ferritin:FSH (ρ-0.706, P< 0.001- females, ρ-0.838, P< 0.001-males), Ferritin: LH (ρ-0.885, P< 0.001-females, ρ-0.806, P< 0.001-males) Ferritin: Estradiol (ρ- 0.584, P< 0.001-females), Ferritin: Testosterone ( ρ-0.664, P< 0.001-males) and significant positive correlation between FSH:LH (ρ0.623, P< 0.001-females, ρ-0.871, P< 0.001-males), FSH: Estradiol (ρ0.839, P-0.01- females), FSH: Testosterone (ρ-0.860, P-0.001-males), LH: Estradiol (ρ0.913, P< 0.001-females, LH: Testosterone (ρ-0.849, P< 0.001-males).
Conclusions: The current study reveals that iron overload has significantly reduced pituitary gonadotrophins as well as gonadal sex steroids,but the effect being more due to iron deposition in pituitary as indicated by the higher rho(ρ) value between ferritin and LH, FSH than between ferritin and estradiol, testosterone. The deficiencies of gonadotrophins have failed to stimulate the gonads leading to hypogonadotrophic hypogonadism and delayed puberty.

Keywords: ? Thalassemia major, Gonadotrophins, Hypogonadism, Delayed puberty

DOI: 10.7324/IJCRR.2017.9234

Full Text:

Introduction

β-thalassemia is the commonest single-gene disorder in the Indian population [1]. Ten percent of the total world thalassemics are born in India every year [2]. Certain communities in India, like Sindhis, Gujratis, Punjabis, and Bengalis, are more commonly affected with beta thalassemia, the incidence varying from 1 to 17% [3]

Iron overload which is a common complication of thalassaemic syndromes could lead per se to the development of organ damage and increased mortality [4]. In these patients, iron deposition in parenchymal tissues starts within 1 year of starting the regular transfusions [5].  Blood transfusions are important for survival of these patients, but chronic transfusions inevitably lead to iron overload as humans cannot remove excess iron actively. The cumulative effects of iron overload, if untreated, lead to significant morbidity and mortality [ 6]. The current management of thalassemia (TM) includes regular transfusion programs and chelation therapy. Current guidelines recommend a pretransfusion threshold not exceeding 9.5% g/dl, which seems to be associated with adequate marrow inhibition and a relatively low iron burden.[7] Research also indicates that iron overload can occur in patients with non-transfusion dependent thalassaemias(NTDT) [8]

Delayed puberty and hypogonadism are among the most common clinical consequences of iron overload. Iron deposition in the pituitary gonadotrophic cells leads to disruption of gonadotropin (LH and FSH) production. In the majority of well-chelated patients, the gonadal function is normal; however, gonadal iron deposition occasionally occurs. TM patients with a favorable genotype manifest less severe gonadal dysfunction, due to less iron loading. [9] The precise mechanism of iron overload-induced organ dysfunction leading to delayed puberty is not clear. It is still not known whether iron deposition in the pituitary gonadotrophic cells or gondal iron deposition or both causes the hypogonadism. Some studies[10] found significant difference in mean serum ferritin level between thalassemic patients with primary amenorrhea, irregular mense, hypogonadism and those without endocrinopathies. These findings yield the importance of iron overload in development of endocrine disorders among which hypogonadism is most frequent. In contrast, there are some othereports which have suggested no relation between the level of ferritin and some other endocrinopathies [11,12]. Based on the above mentioned information, we set out to study the effect of iron overload on pituitary gonadotrophins and the gonadal sex steroids in pubertal thalassemics and to conclude whether the former or later is most affected.

Aims and Objectives

1. To measure serum ferritin to detect iron overload pubertal thalassemic patients(cases) as well as in controls

2. To measure pituitary gonadotrophins-Luteinizing hormone (LH), Follicle Stimulating

Hormone (FSH) in the study subjects (cases and controls).

3. To measure gonadal steroids-Estrogen in female subjects, Testosterone in male subjects

5. To assess any correlation between serum ferritin, pituitary gonadotrophins and gonadal steroids in the case group.

Materials and Method

Study type: It was a hospital based observational study.

Study design: The study design was cross-sectional and non interventional.

Study population: The study population included pubertal thalassemic patients. The control

group were selected from the healthy relatives of the patients who will accompany them being age matched.

Selection criteria:

Cases were taken from the thalassemia unit of the institution as per the following criteria:

*INCLUSION CRITERIA

a) The age of the β-thalassemia major subjects were between the ages of 13to 17yrs to detect pubertal delay

b) They had already received multiple blood transfusions or iron therapy.

*EXCLUSION CRITERIA

a) The newly diagnosed patients were excluded.

b) The subject who were diabetic and had other inborn metabolic diseases.

c) Subject who had active infection and inflammation.

d) Subjects who were alcoholics and cigarette smokers.

Controls were selected from healthy individuals (without any metabolic diseases,

haematological diseases, chronic or active infection and inflammation).

Place of study: Selection of cases was done from the thalassemia unit of the institution.

Biochemical investigations and result analysis were performed in the dept. of Biochemistry,

Calcutta National Medical College, Kolkata.

Study duration: Two months after getting approval for the project as well as the instituitional ethical clearance certificate.

Sample size: Following inclusion and exclusion criteria thirty patients- fifteen male and fifteen female were selected by the method of convenience in each group of the cases and controls.

Ethical considerations: The study was conducted by strictly adhering to the guidelines from the Helsinki declaration, 1975 revised in 2000. Written and informed consents were obtained from participants as per protocol.

Data collection procedure: The valid written consents of the subjects were taken and proper ethical guidelines were followed. The patients were asked to come at a specific date. We collected demographic and anthropometric data and the history of menstruation, family history of diabetes, initiation and duration of blood transfusion, as well as chelation therapy. After the collection of the samples and carrying them to the Department of Biochemistry, the clotted blood was centrifuged at 1500 rpm for 5 min and the serum was harvested from which estimation of serum ferritin, Luteinizing hormone(LH), Follicle Stimulating hormone(FSH), Estradiol in female subjects, Testosterone in male subjects were done by ELISA.

Instruments required were:

1. ELISA Kit, ELISA Reader and Washer.

2. Micropipettes and microtips.

3. Syringes and cottons.

Principle of measurement:

  • Serum ferritin- Solid phase sandwitch assay method (CalBiotech Inc.)
  • Luteinizing hormone (LH), Follicle stimulating hormone(FSH)-Solid phase sandwitch ELISA (AccuDiag )
  • Estrogen, Testosterone-Solid phase competitive ELISA (DiaMetra-Italy)

In each analysis, standard and controls were tested along with the samples.

Confidentiality: Data would be kept strictly confidential and will be stored at least for three years.

Statistical analysis:

The data obtained from the above tests were analyzed for differences between the medians of the analytes studied between cases (pubertal thalassemics) and controls (neonates delivered by ND).

Kolmogorov and Smirnov method

The  Kolmogorov and Smirnov method was used to check whether the data were normally distributed.

Mann–Whitney U-test

In order to study the significance in the differences between the two groups, the Mann–Whitney U-test was performed for all analytes, since the data did not pass the normality test.

Spearman’s correlation

Spearman’s correlations were done between all analytes. All of the tests were completed with a P <0.05 as the significance level, and all statistical analyses were carried out using the SPSS 17 soft ware (SPSS Inc. Chicago, USA).

RESULTS

Table no.1 shows that in thalassemic males(cases),there is significant iron overload as the ferritin level is significantly high( p value <0.001)  compared to the control group.Pituitary gonadotrophins FSH(Follicle stimulating hormone)  and LH(Lutenizing hormone) are significantly low in the case group(FSH- p value <0.001, LH- p value <0.001).There is significant difference in Testosterone level between the case and the control group(p-0.002)-the median being significantly low in the thalassemic males(cases). These results indicate gonadotrophin deficiency as well as gonadal steroid deficiency in the male Thalassemics who are sufferring from iron overload.

In thalassemic females(cases),there is significant iron overload as the ferritin level is significantly high( p value <0.001)  compared to the control group as shown in Table no.2.Pituitary gonadotrophins FSH  and LH levels are significantly low in the case group(FSH- p value <0.001,LH- p value <0.001).There is significant difference in 17ßEstradiol  level between the case and the control group(p-0.003)-the median being significantly low in the thalassemic females(cases) These results indicate gonadotrophin deficiency as well as gonadal steroid deficiency  in the female Thalassemics who are sufferring from iron overload.

Table no.3 shows the Spearman’s correlation between analytes in male cases where there is significant negative correlation between Ferritin: FSH(ρ-0.838,P<0.001), Ferritin:LH (ρ-0.806,P<0.001) and Feritin: Testosterone(ρ-0.664,P<0.001). Thus iron overload (high ferritin) has decreased the secretion of pituitary gonadotrophins-LH,FSH as well as gonadal sex steroid-Testosterone in male thalassemic cases, but iron overload has affected the pituitary more than the gonads as the rho value is less Feritin:Testosterone(ρ-0.664) than between ferritin and the gonadotrophins. There is significant positive correlation between FSH:LH (ρ0.871,P<0.001), FSH:Testosterone (ρ0.860,P-0.01), LH:Testosterone (ρ0.849,P<0.001). This indicates the deficiency of gonadotrophins has been unable to stimulate the gonads to produce Testosterone in male thalassemic cases.

The Spearman’s correlation between analytes in female cases as in Table no. 4 shows significant negative correlation between Ferritin:FSH(ρ-0.706,P<0.001), Ferritin:LH (ρ-0.885,P<0.001) and Feritin:Estradiol(ρ-0.584,P<0.001). Thus iron overload (high ferritin) has decreased the secretion of pituitary gonadotrophins-LH, FSH as well as gonadal sex steroid- Estradiol in female thalassemic cases, but iron overload has affected the pituitary more than the gonads as the rho value is less between ferritin:testosterone(ρ-0.584) than between ferritin and the gonadotrophins.. There is significant positive correlation between FSH:LH (ρ0.623,P<0.001), FSH:Estradiol (ρ0.839,P-0.01), LH:Estradiol (ρ0.913,P<0.001). This indicates the deficiency of gonadotrophins has been unable to stimulate the gonads to produce Estradiol in female thalassemic cases. The average age of puberty onset in the thalassemic cases in current study was 15.5±2 yrs which indicates delayed puberty in the male as well as female thalassemic cases

Discussion

In normal individuals, iron absorption controls iron homeostasis mainly rather than iron excretion excretion [13]. Thalassemic patients receiving a blood transfusion (usually 1mg of iron per 1mL of blood) inevitably experience significant iron overload as they lack adequate excretory mechanisms. Normally, iron bound to transferrin is transported to bone marrow and tissue, where iron is taken up by transferrin receptor and stored as ferritin. As a consequence of iron overload in thalassemic patients, either from blood transfusion or excessive iron absorption, transferrin is fully saturated or non-transferrin-bound iron (NTBI) is found excessively in the blood. The current study shows iron overload in both thalassemic males and females as evidenced statistically significant by the high ferritin level in them compared to controls.

Non-transferrin-bound iron (NTBI) enters non-hematopoietic cells by other cellular channels in forms that can possibly damage cells via iron-mediated cellular oxidative damage[14].

Endocrine dysfunction has been reported as the most common and earliest organ toxicity seen in iron-overloaded subjects with thalassaemia[15]. A study  observed disease-specific differences in endocrinopathy may be related to observations of greater cellular oxidative injury in iron overloaded thalassemia versus sickle cell  disease (SCD) subjects[16]. Thalassemics are more prone to iron mediated endocrinal gland dysfunction than other hemoglobinopathies like SCD. Hypogonadism is the most frequently reported endocrine complication, affecting 70–80% of thalassemia major patients. The prevalence and severity of hypogonadism in thalassemia major varies among studies, depending on the age group studied, genotype of thalassemia[17,18], extent of transfusion, age at the beginning and type of iron chelation therapy [18,19].The anterior pituitary gland is sensitive, in a dose-dependent fashion, to the effects of iron overload from transfusions [20]. Studies of human anterior pituitary adenomas showed that gonadotropes require more iron as compared with other pituitary cell types [21]. Thus, these cells are most affected, resulting in declining synthesis of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). A study found significant difference in mean serum ferritin level between thalassemic patients with primary amenorrhea, irregular mense, hypogonadism and those without endocrinopathies [10].The current study shows statistically significant low FSH and LH levels as well as significant negative correlation between ferritin and the gonadotrophins in both male and female thalassemic group.

Hypogonadism is likely to be caused by iron deposits in the gonads, pituitary gland or both. However, hypogonadotropic hypogonadism resulting from iron deposition in the pituitary gonadotrope is more commonly found. Gonadal iron deposition in ovaries or testes occurs less frequently, as the majority of amenorrheic women can still ovulate after hormonal treatment [13]. The direct effect of iron, in particular that of NTBI, on the ovaries and testes is currently unknown. The ovarian reserve is preserved in the majority of female thalassemia patients, even in women with amenorrhea. In males, histological examination of testicular tissues from autopsies demonstrated testicular interstitial fibrosis with small, heavily pigmented, undifferentiated seminiferous tubules and an absence of Leydig cells [22]. In a case report a 26-year-old female patient was referred to clinic with a 3 year history of amenorrhea. Her medical history showed a diagnosis of ????-thalassemia major since the age of one and treatment with regular blood transfusions to maintain adequate levels of haemoglobin. Even after stimulation with LH Releasing hormone, pituitary response was subnormal, consistent with hypogonadotropic hypogonadism[23]. All these studies have findings similar to the current study which has revealed that iron overload has affected the pituitary more than the gonads as as the negative correlation- rho value is less negative between Feritin and Testosterone(ρ-0.664) as well as Estradiol( ρ-0.584) than between ferritin and the gonadotrophins.(Table 3,4). The deficiency of gonadotrophins has been unable to stimulate the gonads to produce Estradiol in female thalassemic cases and Testosterone in male thalassemic cases as the current study indicated significant positive correlation between FSH: Testosterone(ρ0.839,P0.01), LH: Testosterone(ρ0.913,P<0.001), FSH: Estradiol(ρ0.839,P-0.01), LH: Estradiol (ρ0.913,P<0.001). 

HPG axis dysfunction can manifest as low estradiol or testosterone with low to normal serum LH and FSH as commonly seen in hypogonadotropic hypogonadism. There are three main clinical presentations of the HPG axis derangement in thalassemia major, including delayed puberty, arrested puberty and hypogonadism. Delayed puberty is defined as the absence of any pubertal signs by 14 years in boys and 13 years in girls [24]. Arrested puberty is defined as the absence of further pubertal progression for more than 1 year after puberty has started.

With modern medications, iron-induced hypogonadism may be reversible with intensive iron chelation regimens [25] .Sex steroid or pulsatile GnRH can be utilized to induce puberty if the HPG axis is functionally intact, especially at an early stage of hypogonadotropic hypogonadism. Later on, if the HPG axis is irreversibly damaged, sex steroid replacement therapy is the only option to induce puberty. Generally, it is advisable to initiate puberty with sex steroid replacement therapy by age 13 in women and age 14 in men [26]. Factors such as severity of iron overload, liver disease and growth hormone deficiency should be considered before pubertal induction[27]. Sex steroids are important for the maintenance of normal body composition, skeletal health and induction and maturation of secondary sexual characteristics. It is the most important form of replacement therapy in patients not desirous of fertility. When fertility is desired, gonadotropin therapy is necessary to induce spermatogenesis [27]. Different treatment protocols can be used. The typical gonadotropin regimen combines human chorionic gonadotropin (hCG) and FSH [28, 29]. Adverse events are reduced high-density lipoprotein cholesterol, thromboembolism,osteoporosis, increased prostatic symptoms in males and increased cardiovascular risk [30]. Therefore, testosterone therapy should be accompanied by a standardized monitoring plan and general health evaluation. Timely recognition and prevention of the endocrine complications, by early and regular chelation therapy is mandatory for the improvement of the quality of life and favourable psychological outcome of thalassemic patients.

Our study had various limitations like multiple serum ferritin measurements over time would be more valuable in predicting complications of iron overload than a single one as done by us in short span of time. Moreover, hypogonadotropic hypogonadism in thalassemia is related not only to iron toxicity on gonadotrope cells but also to adipose tissue leptin [31], liver disorders, chronic hypoxia and zinc deficiency which remains unexplored by us. Larger sample size was also required to improve the statistical importance of this study which was also one of our limitations.

 

Conclusion:

The current study explores the effect of iron overload on the pituitary gonadotrophin secretion whose deficiency fails to stimulate the gonadal sex steroid secretion leading to hypogonadotrophic hypogonadism and delay of puberty affecting the lives of these thalassemic subjects. Thus intensive and timely iron chelation therapy can reverse iron induced organ damage leading to hypogonadism among various endocrinopathies. Gonadotrophins and sex steroids are the main treatment modalities for induction of puberty and fertility thus ensuring normal reproductive lives for these thalassemic patients.

Acknowledgement

Authors acknowledge the immense help received from the scholars whose articles are cited and included in references of this manuscript. The authors are also grateful to authors / editors / publishers of all those articles, journals and books from where the literature for this article has been reviewed and discussed.

 

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8. Taher AT, Porter J, Viprakasit V, Kattamis A, Chuncharunee S, Sutcharitchan P. et al – Deferasirox reduces iron overload significantly in nontransfusion-dependent thalassemia: 1-year results from a prospective, randomized, double-blind, placebo-controlled study. Blood 2012; 120:970-7

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A Study by Mokhtar M Sh et al. entitled "Prevalence of Hospital Mortality of Critically Ill Elderly Patients" is awarded Best Article for Vol 14 issue 12
A Study by Vidya S. Bhat et al. entitled "Effect of an Indigenous Cleanser on the Microbial Biofilm on Acrylic Denture Base - A Pilot Study" is awarded Best Article for Vol 14 issue 11
A Study by Pandya S. et al. entitled "Acute and 28-Day Repeated Dose Subacute Toxicological Evaluation of Coroprotect Tablet in Rodents" is awarded Best Article for Vol 14 issue 10
A Study by Muhammad Zaki et al. entitled "Effect of Hemoglobin Level on the Severity of Acute Bronchiolitis in Children: A Case-Control Study" is awarded Best Article for Vol 14 issue 09
A Study by Vinita S & Ayushi S entitled "Role of Colour Doppler and Transvaginal Sonography for diagnosis of endometrial pathology in women presenting with Abnormal Uterine Bleeding" is awarded Best Article for Vol 14 issue 08
A Study by Prabhu A et al. entitled "Awareness of Common Eye Conditions among the ASHA (Accredited Social Health Activist) Workers in the Rural Communities of Udupi District- A Pilot Study" is awarded Best Article for Vol 14 issue 07
A Study by Divya MP et al. entitled "Non-Echoplanar Diffusion-Weighted Imaging and 3D Fiesta Magnetic Resonance Imaging Sequences with High Resolution Computed Tomography Temporal Bone in Assessment and Predicting the Outcome of Chronic Suppurative Otitis Media with Cholesteatoma" is awarded Best Article for Vol 14 issue 06
A Study by Zahoor Illahi Soomro et al. entitled "Functional Outcomes of Fracture Distal Radius after Fixation with Two Different Plates: A Retrospective Comparative Study" is awarded Best Article for Vol 14 issue 05
A Study by Ajai KG & Athira KN entitled "Patients’ Gratification Towards Service Delivery Among Government Hospitals with Particular Orientation Towards Primary Health Centres" is awarded Best Article for Vol 14 issue 04
A Study by Mbungu Mulaila AP et al. entitled "Ovarian Pregnancy in Kindu City, D.R. Congo - A Case Report" is awarded Best Article for Vol 14 issue 03
A Study by Maryam MJ et al. entitled "Evaluation Serum Chemerin and Visfatin Levels with Rheumatoid Arthritis: Possible Diagnostic Biomarkers" is awarded Best Article for Vol 14 issue 02
A Study by Shanthan KR et al. entitled "Comparison of Ultrasound Guided Versus Nerve Stimulator Guided Technique of Supraclavicular Brachial Plexus Block in Patients Undergoing Upper Limb Surgeries" is awarded Best Article for Vol 14 issue 01
A Study by Amol Sanap et al. entitled "The Outcome of Coxofemoral Bypass Using Cemented Bipolar Hemiarthroplasty in the Treatment of Unstable Intertrochanteric Fracture of Femur in a Rural Setup" is awarded Best Article Award of Vol 13 issue 24
A Study by Manoj KP et al. entitled "A Randomized Comparative Clinical Trial to Know the Efficacy of Ultrasound-Guided Transversus Abdominis Plane Block Against Multimodal Analgesia for Postoperative Analgesia Following Caesarean Section" is awarded Best Article Award of Vol 13 issue 23
A Study by Karimova II et al. entitled "Changes in the Activity of Intestinal Carbohydrases in Alloxan-Induced Diabetic Rats and Their Correction with Prenalon" is awarded Best Article of Vol 13 issue 22
A Study by Ashish B Roge et al. entitled "Development, Validation of RP-HPLC Method and GC MS Analysis of Desloratadine HCL and It’s Degradation Products" is awarded Best Article of Vol 13 issue 21
A Study by Isha Gaurav et al. entitled "Association of ABO Blood Group with Oral Cancer and Precancer – A Case-control Study" is awarded Best Article for Vol 13 issue 20
A Study by Amr Y. Zakaria et al. entitled "Single Nucleotide Polymorphisms of ATP-Binding Cassette Gene(ABCC3 rs4793665) affect High Dose Methotrexate-Induced Nephrotoxicity in Children with Osteosarcoma" is awarded Best Article for Vol 13 issue 19
A Study by Kholis Ernawati et al. entitled "The Utilization of Mobile-Based Information Technology in the Management of Dengue Fever in the Community Year 2019-2020: Systematic Review" is awarded Best Article for Vol 13 issue 18
A Study by Bhat Asifa et al. entitled "Efficacy of Modified Carbapenem Inactivation Method for Carbapenemase Detection and Comparative Evaluation with Polymerase Chain Reaction for the Identification of Carbapenemase Producing Klebsiella pneumonia Isolates" is awarded Best Article for Vol 13 issue 17
A Study by Gupta R. et al. entitled "A Clinical Study of Paediatric Tracheostomy: Our Experience in a Tertiary Care Hospital in North India" is awarded Best Article for Vol 13 issue 16
A Study by Chandran Anand et al. entitled "A Prospective Study on Assessment of Quality of Life of Patients Receiving Sorafenib for Hepatocellular Carcinoma" is awarded Best article for Vol 13 issue 15
A Study by Rosa PS et al. entitled "Emotional State Due to the Covid – 19 Pandemic in People Residing in a Vulnerable Area in North Lima" is awarded Best Article for Vol 13 issue 14
A Study by Suvarna Sunder J et al. entitled "Endodontic Revascularization of Necrotic Permanent Anterior Tooth with Platelet Rich Fibrin, Platelet Rich Plasma, and Blood Clot - A Comparative Study" is awarded Best Article for Vol 13 issue 13
A Study by Mona Isam Eldin Osman et al. entitled "Psychological Impact and Risk Factors of Sexual Abuse on Sudanese Children in Khartoum State" is awarded Best Article for Vol 13 issue 12
A Study by Khaw Ming Sheng & Sathiapriya Ramiah entitled "Web Based Suicide Prevention Application for Patients Suffering from Depression" is awarded Best Article for Vol 13 issue 11
A Study by Purushottam S. G. et al. entitled "Development of Fenofibrate Solid Dispersions for the Plausible Aqueous Solubility Augmentation of this BCS Class-II Drug" is awarded Best article for Vol 13 issue 10
A Study by Kumar S. et al. entitled "A Study on Clinical Spectrum, Laboratory Profile, Complications and Outcome of Pediatric Scrub Typhus Patients Admitted to an Intensive Care Unit from a Tertiary Care Hospital from Eastern India" is awarded Best Article for Vol 13 issue 09
A Study by Mardhiah Kamaruddin et al. entitled "The Pattern of Creatinine Clearance in Gestational and Chronic Hypertension Women from the Third Trimester to 12 Weeks Postpartum" is awarded Best Article for Vol 13 issue 08
A Study by Sarmila G. B. et al. entitled "Study to Compare the Efficacy of Orally Administered Melatonin and Clonidine for Attenuation of Hemodynamic Response During Laryngoscopy and Endotracheal Intubation in Gastrointestinal Surgeries" is awarded Best Article for Vol 13 issue 07
A Study by M. Muthu Uma Maheswari et al. entitled "A Study on C-reactive Protein and Liver Function Tests in Laboratory RT-PCR Positive Covid-19 Patients in a Tertiary Care Centre – A Retrospective Study" is awarded Best Article of Vol 13 issue 06 Special issue Modern approaches for diagnosis of COVID-19 and current status of awareness
A Study by Gainneos PD et al. entitled "A Comparative Evaluation of the Levels of Salivary IgA in HIV Affected Children and the Children of the General Population within the Age Group of 9 – 12 Years – A Cross-Sectional Study" is awarded Best Article of Vol 13 issue 05 Special issue on Recent Advances in Dentistry for better Oral Health
A Study by Alkhansa Mahmoud et al. entitled "mRNA Expression of Somatostatin Receptors (1-5) in MCF7 and MDA-MB231 Breast Cancer Cells" is awarded Best Article of Vol 13 issue 06
A Study by Chen YY and Ghazali SRB entitled "Lifetime Trauma, posttraumatic stress disorder Symptoms and Early Adolescence Risk Factors for Poor Physical Health Outcome Among Malaysian Adolescents" is awarded Best Article of Vol 13 issue 04 Special issue on Current Updates in Plant Biology to Medicine to Healthcare Awareness in Malaysia
A Study by Kumari PM et al. entitled "Study to Evaluate the Adverse Drug Reactions in a Tertiary Care Teaching Hospital in Tamilnadu - A Cross-Sectional Study" is awarded Best Article for Vol 13 issue 05
A Study by Anu et al. entitled "Effectiveness of Cytological Scoring Systems for Evaluation of Breast Lesion Cytology with its Histopathological Correlation" is awarded Best Article of Vol 13 issue 04
A Study by Sharipov R. Kh. et al. entitled "Interaction of Correction of Lipid Peroxidation Disorders with Oxibral" is awarded Best Article of Vol 13 issue 03
A Study by Tarek Elwakil et al. entitled "Led Light Photobiomodulation Effect on Wound Healing Combined with Phenytoin in Mice Model" is awarded Best Article of Vol 13 issue 02
A Study by Mohita Ray et al. entitled "Accuracy of Intra-Operative Frozen Section Consultation of Gastrointestinal Biopsy Samples in Correlation with the Final Histopathological Diagnosis" is awarded Best Article for Vol 13 issue 01
A Study by Badritdinova MN et al. entitled "Peculiarities of a Pain in Patients with Ischemic Heart Disease in the Presence of Individual Combines of the Metabolic Syndrome" is awarded Best Article for Vol 12 issue 24
A Study by Sindhu Priya E S et al. entitled "Neuroprotective activity of Pyrazolone Derivatives Against Paraquat-induced Oxidative Stress and Locomotor Impairment in Drosophila melanogaster" is awarded Best Article for Vol 12 issue 23
A Study by Habiba Suhail et al. entitled "Effect of Majoon Murmakki in Dysmenorrhoea (Usre Tams): A Standard Controlled Clinical Study" is awarded Best Article for Vol 12 issue 22
A Study by Ghaffar UB et al. entitled "Correlation between Height and Foot Length in Saudi Population in Majmaah, Saudi Arabia" is awarded Best Article for Vol 12 issue 21
A Study by Siti Sarah Binti Maidin entitled "Sleep Well: Mobile Application to Address Sleeping Problems" is awarded Best Article for Vol 12 issue 20
A Study by Avijit Singh"Comparison of Post Operative Clinical Outcomes Between “Made in India” TTK Chitra Mechanical Heart Valve Versus St Jude Mechanical Heart Valve in Valve Replacement Surgery" is awarded Best Article for Vol 12 issue 19
A Study by Sonali Banerjee and Mary Mathews N. entitled "Exploring Quality of Life and Perceived Experiences Among Couples Undergoing Fertility Treatment in Western India: A Mixed Methodology" is awarded Best Article for Vol 12 issue 18
A Study by Jabbar Desai et al. entitled "Prevalence of Obstructive Airway Disease in Patients with Ischemic Heart Disease and Hypertension" is awarded Best Article for Vol 12 issue 17
A Study by Juna Byun et al. entitled "Study on Difference in Coronavirus-19 Related Anxiety between Face-to-face and Non-face-to-face Classes among University Students in South Korea" is awarded Best Article for Vol 12 issue 16
A Study by Sudha Ramachandra & Vinay Chavan entitled "Enhanced-Hybrid-Age Layered Population Structure (E-Hybrid-ALPS): A Genetic Algorithm with Adaptive Crossover for Molecular Docking Studies of Drug Discovery Process" is awarded Best article for Vol 12 issue 15
A Study by Varsha M. Shindhe et al. entitled "A Study on Effect of Smokeless Tobacco on Pulmonary Function Tests in Class IV Workers of USM-KLE (Universiti Sains Malaysia-Karnataka Lingayat Education Society) International Medical Programme, Belagavi" is awarded Best article of Vol 12 issue 14, July 2020
A study by Amruta Choudhary et al. entitled "Family Planning Knowledge, Attitude and Practice Among Women of Reproductive Age from Rural Area of Central India" is awarded Best Article for special issue "Modern Therapeutics Applications"
A study by Raunak Das entitled "Study of Cardiovascular Dysfunctions in Interstitial Lung Diseas epatients by Correlating the Levels of Serum NT PRO BNP and Microalbuminuria (Biomarkers of Cardiovascular Dysfunction) with Echocardiographic, Bronchoscopic and HighResolution Computed Tomography Findings of These ILD Patients" is awarded Best Article of Vol 12 issue 13 
A Study by Kannamani Ramasamy et al. entitled "COVID-19 Situation at Chennai City – Forecasting for the Better Pandemic Management" is awarded best article for  Vol 12 issue 12
A Study by Muhammet Lutfi SELCUK and Fatma entitled "Distinction of Gray and White Matter for Some Histological Staining Methods in New Zealand Rabbit's Brain" is awarded best article for  Vol 12 issue 11
A Study by Anamul Haq et al. entitled "Etiology of Abnormal Uterine Bleeding in Adolescents – Emphasis Upon Polycystic Ovarian Syndrome" is awarded best article for  Vol 12 issue 10
A Study by entitled "Estimation of Reference Interval of Serum Progesterone During Three Trimesters of Normal Pregnancy in a Tertiary Care Hospital of Kolkata" is awarded best article for  Vol 12 issue 09
A Study by Ilona Gracie De Souza & Pavan Kumar G. entitled "Effect of Releasing Myofascial Chain in Patients with Patellofemoral Pain Syndrome - A Randomized Clinical Trial" is awarded best article for  Vol 12 issue 08
A Study by Virendra Atam et. al. entitled "Clinical Profile and Short - Term Mortality Predictors in Acute Stroke with Emphasis on Stress Hyperglycemia and THRIVE Score : An Observational Study" is awarded best article for  Vol 12 issue 07
A Study by K. Krupashree et. al. entitled "Protective Effects of Picrorhizakurroa Against Fumonisin B1 Induced Hepatotoxicity in Mice" is awarded best article for issue Vol 10 issue 20
A study by Mithun K.P. et al "Larvicidal Activity of Crude Solanum Nigrum Leaf and Berries Extract Against Dengue Vector-Aedesaegypti" is awarded Best Article for Vol 10 issue 14 of IJCRR
A study by Asha Menon "Women in Child Care and Early Education: Truly Nontraditional Work" is awarded Best Article for Vol 10 issue 13
A study by Deep J. M. "Prevalence of Molar-Incisor Hypomineralization in 7-13 Years Old Children of Biratnagar, Nepal: A Cross Sectional Study" is awarded Best Article for Vol 10 issue 11 of IJCRR
A review by Chitra et al to analyse relation between Obesity and Type 2 diabetes is awarded 'Best Article' for Vol 10 issue 10 by IJCRR. 
A study by Karanpreet et al "Pregnancy Induced Hypertension: A Study on Its Multisystem Involvement" is given Best Paper Award for Vol 10 issue 09

List of Awardees

A Study by Ese Anibor et al. "Evaluation of Temporomandibular Joint Disorders Among Delta State University Students in Abraka, Nigeria" from Vol 13 issue 16 received Emerging Researcher Award


A Study by Alkhansa Mahmoud et al. entitled "mRNA Expression of Somatostatin Receptors (1-5) in MCF7 and MDA-MB231 Breast Cancer Cells" from Vol 13 issue 06 received Emerging Researcher Award


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International Journal of Current Research and Review (IJCRR) provides platform for researchers to publish and discuss their original research and review work. IJCRR can not be held responsible for views, opinions and written statements of researchers published in this journal

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