Comparing The Effect Of Estradiol Valerate And Conjugated Equine Estrogen In The Patients With Premature Ovarian Insufficiency A Randomized Control Trial

INTRODUCTION

Premature ovarian insufficiency is a condition where ovarian function declines significantly and irreversibly in women under 40, leading to elevated FSH levels and low serum estradiol. It affects about 1% of women under 40 and 0.1% under 30. Women with POI face increased risks of osteoporosis, cardiovascular disease and urogenital atrophy due to estrogen deficiency ,necessitating hormone replacement therapy(HRT) until the age of natural menopause. This study aims to compare the effects of two common estrogen formulations, oral estradiol valerate (2mg) and conjugated equine estrogen (0.625mg) , both combined with medroxyprogesterone acetate , on clinical radiological, and biochemical parameters in diagnosed POI  patients.

AIM : To compare the effect of estradiol valerate and conjugated equine estrogen in the patients with premature ovarian insufficiency.

OBJECTIVES:

PRIMARY OBJECTIVES:

1. To compare the changes in clinical parameters i.e., vasomotor symptoms, urogenital symptoms and psychological symptoms among group A and B.

2. To compare the changes in radiological parameters i.e., urogenital atrophy, breast density and uterine parameters among group A and B.

3. To compare the changes in biochemical parameters i.e., serum FSH, lipid profile and serum estradiol levels among group A and B.

SECONDARY OBJECTIVES:

To compare the side effects of HRT regimen including liver function test among group A and B.

STUDY SETTINGS : Department of Obstetrics and Gynecology, University College of Medical Sciences and Guru Teg Bahadur Hospital, Dilshad Garden, Delhi - 110095

STUDY DESIGN: Prospective international study

TIME FRAME : January 2024 to June 2025

SELECTION OF CASES: Diagnosis of POI will be based on the ESHRE guidelines : (1) Infrequent cycles or amenorrhea for at least 4 months before 40 years of age and (2) an elevated follicle stimulating hormone (FSH) level >25IU/L on two occasions >4 weeks apart. Patients with chromosomal anomalies and other known non-genetic causes of POI (including autoimmune diseases, ovarian surgery, chemotherapy and radiotherapy) were excluded.

INCLUSION CRITERIA: All the women below 40 years with newly diagnosed POI.

EXCLUSION CRITERIA :

1. Patient with chromosomal anomalies.

2. Already receiving or have received hormone therapy.

3. Hormone therapy is  contraindicated.

4. Have received non-hormonal treatment.

SAMPLE SIZE: Considering the available studies a sample of 375 subjects are required in each group. Which is not feasible in our step. Which is not feasible in our setup. Therefore keeping in view of the limitations of subject availability and time frame , we propose to take a convenient sample of 30 subjects in each group.

METHODLOGY: All the women visiting HRT clinic OPD of UCMS and GTBH Delhi, will be screened for primary ovarian insufficiency (POI) and a total of 60 women with diagnosis of POI, satisfying the inclusion and exclusion criteria will be recruited for the study. The recruited subjects will then be divided into two group: Group A and Group B by computer based randomization. After CTRI based randomization . After CTRI approval both groups will be started on respective drugs as mentioned.

Group A : Oral estradiol valerate 2mg along with oral medroxy progesterone acetate 10mg from day 15- day25

Group B: Conjugated equine estrogen 0.625 mg along with oral medroxy progesterone acetate 10mg from day 15 - day 25

OUTCOME MEASURES:

Primary Outcome:

1. Comparison between the changes in clinical parameters among two groups after 6 months of HRT .

2. Comparison between the changes in radiological parameters among two groups after 6 months of HRT.

3. Comparison between the changes biochemical parameters among two groups after 6 months of HRT .

Secondary Outcome:

Comparison of side effects of HRT among two group which will include liver function tests.

STATISTICAL ANALYSIS:

Quantitative parameters between and within the groups will be compared by Repeated Measure ANOVA followed by Tukey’s test at 5% level of significance . Qualitative parameters will be compared between the groups by Chi Square Test/ Fischer’s Exact Test and within the group by McNemar test at 5% level of signifiance.

CONFLICT OF INTEREST:None