Clinical trial NCT05463627: Effects of Metformin on Metabolic and Reproductive Outcomes in Chinese PCOS Patients
Official title: Effects of Metformin on Metabolic and Reproductive Outcomes in Chinese PCOS Patients
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Polycystic Ovary Syndrome
Metformin
Lead sponsor: RenJi Hospital
Sponsor class: OTHER
First posted: 2022-07-19
Enrollment: 1440
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Obese,overweight and normal-weight women aged 18-45 years (in childbearing age)with PCOS or/and IGR/DM were expected enrolled in our study

Brief summary: Polycystic ovary syndrome (PCOS) is a reproductive endocrine disease characterized by reproductive and metabolic abnormalities, which is a crucial cause of female infertility and an essential risk factor for type 2 diabetes. At present, there exist several clinical trials and studies on the usage of metformin in the treatment of PCOS patients in prediabetes, and the practical application of metformin in clinical practice has years of history. The treatment plan of metformin is of great significance in preventing type 2 diabetes in PCOS patients and assisting pregnancy in PCOS infertile patients.

Detailed description: The purpose of this study is to conduct a real world study on effects of metformin on the improvement of metabolism and reproductive outcome in Chinese prediabetic PCOS patients by collecting relevant medical system records from Renji Hospital affiliated to Shanghai Jiao Tong University School of Medicine as real world data and a significant supplement to clinical trial studies. At the same time, obese and non-obese PCOS patients may have different mechanisms of insulin resistance, so this study stratified PCOS patients to analyze whether metformin can improve treatment results for PCOS patients with prediabetes according to different body mass index (BMI).The investigator's study is the first real world study to investigate Chinese pre-diabetes PCOS patients treated by metformin and the metabolic and reproductive outcomes, which is innovative. The investigator's research also has a guiding significance for the practical application of metformin in improving glucose metabolism and reproductive outcomes in patients with different body weight in clinical practice, and has great relevance for PCOS patients to reduce long-term complications and improve quality of life.

Eligibility criteria: Inclusion Criteria:

1. Females at the age of 18-45years old;
2. Diagnosed with PCOS or/and impaired glucose regulation (IGR)/diabetes(DM)
3. Metformin regimens were used without other metabolic agents
4. The diagnosis of PCOS is based on the 2003 Rotterdam criteria and the diagnostic criteria for impaired glucose regulation (IGR) and type 2 diabetes are based on the 2021 American Diabetes Association(ADA) diagnosis criteria.

Exclusion Criteria:

1. Severe liver and kidney dysfunction (ALT is greater than 2.5 times the upper limit of normal, or Cr\>132umol/l, or eGFR \<60 mL/min/1.73m2), psychosis, accompanied by severe infection, severe anemia, neutropenia disease;
2. Participated in clinical trials of other drugs within 3 months;
3. In the past 5 years, there have been treated or untreated organ system tumors (except local skin basal cell carcinoma), regardless of whether there is evidence of local recurrence or metastasis;
4. A history of psychoactive substance abuse, including alcohol and a history of alcohol-related illnesses in the past 2 years;
5. Any conditions judged by the investigator that affect enrollment.

Primary outcomes:
measure: Reversed insulin resistance or restored glucose homeostasis in women with PCOS
timeFrame: 5 years
Secondary outcomes:
measure: change in the level of BMI
timeFrame: 5 years
measure: change in the level of glycated hemoglobin(HbA1c)
timeFrame: 5 years
measure: change in the level of 0'-180'Plasma Glucose(PG)
timeFrame: 5 years
measure: change in the level of 0'-180'insulin(ins)
timeFrame: 5 years
measure: change in the level of 0'-180'C-Peptide
timeFrame: 5 years
measure: change in the level of β cell homeostatic model assessment(HOMA-β)
timeFrame: 5 years
measure: change in the level of Matsuda Index(MI)
timeFrame: 5 years
measure: change in the level of deposition index(DI)
timeFrame: 5 years
measure: change in the level of waist-hip ratio(WHR)
timeFrame: 5 years
measure: change in the level of Luteinizing hormone(LH)
timeFrame: 5 years
measure: change in the level of Follicle stimulating hormone(FSH)
timeFrame: 5 years
measure: change in the level of Prolactin(PRL)
timeFrame: 5 years
measure: change in the level of estradiol(E2)
timeFrame: 5 years
measure: change in the level of testosterone(T)
timeFrame: 5 years
measure: change in the level of Sex hormone-binding globulin(SHBG)
timeFrame: 5 years
measure: change in the level of Dehydroepiandrosterone sulfate(DHEAS)
timeFrame: 5 years
measure: change in the level of Androstenedione(A2)
timeFrame: 5 years
measure: pregnancy rate
timeFrame: 5 years
measure: live birth rate
timeFrame: 5 years
measure: improvement rate of menstrual cycle
timeFrame: 5 years
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Renji Hospital Department of Endocrinology and Metabolism
state: Shanghai
Study officials:
affiliation: RenJi Hospital
name: Tao Tao, Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pedersen AJT, Stage TB, Glintborg D, Andersen M, Christensen MMH. The Pharmacogenetics of Metformin in Women with Polycystic Ovary Syndrome: A Randomized Trial. Basic Clin Pharmacol Toxicol. 2018 Feb;122(2):239-244. doi: 10.1111/bcpt.12874. Epub 2017 Sep 19.
citation: Li Y, Tan J, Wang Q, Duan C, Hu Y, Huang W. Comparing the individual effects of metformin and rosiglitazone and their combination in obese women with polycystic ovary syndrome: a randomized controlled trial. Fertil Steril. 2020 Jan;113(1):197-204. doi: 10.1016/j.fertnstert.2019.09.011. Epub 2019 Nov 9.
citation: Xiong F, Xiao J, Bai Y, Zhang Y, Li Q, Lishuang X. Metformin inhibits estradiol and progesterone-induced decidualization of endometrial stromal cells by regulating expression of progesterone receptor, cytokines and matrix metalloproteinases. Biomed Pharmacother. 2019 Jan;109:1578-1585. doi: 10.1016/j.biopha.2018.10.128. Epub 2018 Nov 15.