Symptoms and General Pathology

All Conditions

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Syndrome

Polycystic Ovary Syndrome

Cysts

Ovarian Cysts

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Gonadal Disorders

Endocrine System Diseases

Hypoglycemic Agents

All Drugs and Chemicals

Natriuretic Agents

Reproductive Control Agents

Metformin

Spironolactone

Ethinyl Estradiol

Contraceptive Agents

Contraceptives, Oral

Chlormadinone Acetate

Mineralocorticoid Receptor Antagonists

Mineralocorticoids

Hormones

Hormone Antagonists

Diuretics

Diuretics, Potassium Sparing

Contraceptive Agents, Female

This group will receive an oral contraceptive containing 0,03mg ethynylestradiol and 2mg chlormadinone acetate

The patient will receive an oral contraceptive (0,03mg ethynylestradiol and 2mg chlormadinone acetate) plus 100 mg spironolactone. One pill each once a day for twelve months.

The patient will receive an oral contraceptive (0,03mg ethynylestradiol and 2mg chlormadinone acetate) plus 850 mg metformin.

oral contraceptive (0,03mg ethynylestradiol and 2mg chlormadinone acetate)once a day for 12 months

oral contraceptive

Oral contraceptive plus spironolactone

Oral contraceptive (0,03mg ethynylestradiol and 2mg chlormadinone acetate) plus 850 mg of metformin

Oral contraceptive plus metformin

Rui A Ferriani, MD, PhD

Marcos Felipe S de Sa, MD, PhD

Carolina S Vieira, MD, PhD

The purpose of this study to assess early markers of cardiovascular disease in women with polycystic ovary syndrome in use of oral contraceptive containing ethynilestradiol and chlormadinone acetate alone or associated with Spironolactone.

Polycystic ovary syndrome (PCOS) is associated with comorbidities that may contribute to increased risk of cardiovascular disease (CVD). Oral contraceptives (OC) have been the mainstay of PCOS pharmacological therapy for decades. However, in non-hyperandrogenic women, OC use is associated with higher risk of cardiovascular disease, raising concern about a possible worsening of the unfavorable metabolic and cardiovascular profile of PCOS patients. There is lack of evidence about the impact of PCOS pharmacological therapies on cardiovascular risk markers and the long-term safety of these drugs in PCOS has not been established. The aim of this study is to compare the effect of an OC alone or associated with an anti-androgenic drug (spironolactone) on echografic cardiovascular risk markers, metabolic and hemostatic variables.

Safety of Hormonal Contraceptives Therapies in Polycystic Ovary Syndrome (PCOS) Women

Metabolic Effects of Multiple Therapies in Polycystic Ovary Syndrome (PCOS) Women

University of Sao Paulo

Rui Alberto Ferriani

Dysbiosis

Other Dietary Supplements

Drospirenone

Estradiol 17 beta-cypionate

Estradiol 3-benzoate

Estradiol

Polyestradiol phosphate

Drospirenone and ethinyl estradiol combination

Contraceptives, Oral, Hormonal

Contraceptive Agents, Hormonal

Estrogens

Acidophilus

Bifidobacterium

Participants are healthy women and there are no interventions.

Participants are PCOS patients and only will be given lifestyle interventions.

Participants are PCOS patients and will be given lifestyle interventions + Probiotic Agent interventions.

Participants are PCOS patients and will be given lifestyle intervention + Oral contraceptive interventions.

1. Balance the diet;
2. Limit high-calorie and high-fat food intake, reduce eating out, and establish regular eating habits;
3. Monitor body weight, avoid sedentary, get more sun and regular activities;
4. Mental health regulation.

Lifestyle intervention

Patients have to take a probiotic powder (product name: Tangwen Tai, lactobacillus plantarum LP45 + Lactobacillus acidophilus La28 + Bifidobacterium lactobacillus BAL531) twice a day for three months.

Probiotic Agent

The patient needs to take drospirenone ethinyl estradiol tablets (trade name: Yousi Yue) 1 tablet daily for 3 months.

Oral contraceptive

Rong Chen, Ph. D.

Xu Zhang, master

Rong Chen, Ph. D

Xu Zhang, Master

Polycystic ovary syndrome (PCOS) has a significant impact on women's health, but its pathogenesis is not yet clear. Dysbiosis of gut microbiota may play a role in the pathological change of PCOS. Most of the current researches are still limited to the use of amplicon sequencing to compare the basic taxonomic differences of gut microbiota between PCOS patients and normal controls. Overall analysis of microbiome species, genes, function, metabolism, and immunity in PCOS is still lacked. In this research, we would perform metagenomic sequencing to find the characteristics of gut microbiota of PCOS and to explore their correlations with metabolic, immune, and clinical symptoms. Finally, different interventions (lifestyle interventions, lifestyle interventions + oral probiotic, lifestyle interventions+ compound oral contraceptives) would be used to explore the change of gut microbiome in PCOS patients. This research will not only help the understanding of the pathophysiology of PCOS, but also provide a reference for the selection of clinical treatment options.

1. Data quality assurance: ① all inspections and measurements will be performed by either the hospital or the sequencing company personnel according to standard operating procedures (SOPs), except for saliva and stool samples, which will be self-collected by patients. For sample collection, we will provide text descriptions of the SOPs as well as video instruction. Designated staff will be assigned for support and can be contacted if participants have any queries concerning sample collection; ② a case report form (CRF) will be prepared according to the current SOPs, and detailed instructions will be provided to ensure consistency in data collection. At the same time, each CRF will be properly stored at least 5 years for verification and backtracking; ③ all experimental data will be logged into the database to ensure information accuracy based on the existing data; ④ we will keep the contact information of each participant, remind them of precautions during participation, and conduct regular follow-ups.
2. Sample size determination: The number of participants is based on comparable sample sizes in the literature. In this trial, there will be 50 healthy individuals (control group) and 150 PCOS (polycystic ovary syndrome) patients. The 150 PCOS patients will be randomly assigned to three intervention groups. This sample size accounts for a plausible insufficiency of data caused by patient dropouts and withdrawals before the study is completed. The participation cycle is of approximately four months, followed by a 2-year follow-up.
3. Metagenomic sequencing technology Metagenomic sequencing is the main technique used in this study. Metagenomics, also known as economics, was first proposed by Handelman and studies the molecular composition of microbial populations, their interactions, and gene functions.

   In medicine, metagenomics compares the structural and functional changes of human microbial communities under normal and disease states. It can analyze the diversity and the functional differences of microbial communities from healthy individuals and from patients with diseases, thus determine how diseases relate to changes in the microbial communities and in their respective metabolic networks. Therefore, metagenomics provides theoretical evidence for disease prevention, detection, and treatment. At present, the internationally renowned Human Microbiome Project (HMP, http://www.hmpdacc.org/) and the Metagenomics of the Human Intestinal Tract (MetaHIT) are typical applications of metagenomics in medicine.

   \[Metagenomic species, genes, and functional annotation\]

   ① Data quality control: the sequenced raw data will contain a certain amount of low-quality data, so quality control must be performed. Only high-quality data can correctly reflect the actual occurrence of microorganisms in the sample.

   ② Metagenome assembly: based on Clean Data, individual samples will be assembled separately at first, then reads that do not participate in the assembling above will be combined and mixed for assembly. This will increase the sequencing depth of low-abundance species in each sample and provide more sequencing information for each species.

   ③ Gene prediction: MetaGeneMark will be used for gene prediction based on single samples and mixed-assembled scaftigs. The redundancy of all predicted genes will be reduced to obtain a Uniq gene set. Then, the Clean Data of each sample will be compared to the gene set and the abundance of the gene set will be determined for each sample.

   ④ Species annotation: Clean Data will be used for quality control. It will be compared with an annotated according to reference genome databases of bacteria, archaea, viruses, and fungi from NCBI. A species abundance table will be obtained for each sample at different classification levels.

   ⑤ Functional annotation: functional annotation and abundance statistics will be based on the Uniq gene set and the KEGG database.

This study will collect 50 healthy participants and 150 PCOS participants. At the same time, 150 patients with PCOS will be randomly divided into the lifestyle intervention group, lifestyle interventions + Probiotic Agent group, lifestyle intervention + oral contraceptive group by random number table method.

Polycystic ovary syndrome (PCOS) is a syndrome of endocrine disorders characterized by sparse ovulation or anovulation, high androgen or insulin resistance, and polycystic ovary. PCOS is a woman-specific disease, so participants must be women.

The Role of Dysbiosis of Gut Microbiota in the Pathogenesis of PCOS.

The Role of Dysbiosis of Gut Microbiota in the Pathogenesis of Polycystic Ovary Syndrome.

According to national laws and regulations, human genetic resources may not be provided abroad.

Based on the gene and species composition of each sample, the Chao1 and Shannon indexes, as well as the observed OTUs (operational taxonomic units), will be calculated in order to identify the differences in gene and species diversity for each group.

The Spearman correlation coefficient between genes will be calculated, and genes with strong correlation will be grouped into one cluster, as a CAG. The abundance of CAGs in each sample will be determined Furthermore, the significantly enriched species in the control and PCOS groups will be enumerated for network display.

The LEfSe discriminant analysis will be used to screen for significant differences between groups. The dimensionality reduction will be implemented by LDA, and the impact of function difference will be evaluated to obtain the LDA score and identify significantly different functions between groups.

For the obtained species, genes, or functions with significant difference, the correlation between them and clinical indicators will be calculated, and key biomarkers with significant and strong correlation will be identified.

Use glucose tolerance and insulin test (75gOGTT+insulin) to assess whether the patient has insulin resistance, as well as the level of insulin resistance.

Six-sex-hormone tests, one of the clinical examination items, will be performed to measure androgen levels in the subjects.

Peking Union Medical College

Peking Union Medical College Hospital

Micronutrients

Vitamins

Vitamin B 6

Pyridoxal

Pyridoxine

Vitamin B Complex

Antioxidants

Vitamin B6

Drospirenone 4 mg once a day for 6 months

Drospirenone 4 mg once a day and Metionac twice daily (200 mg S-adenosylmethionine, 100 mg N-acetylcisteine, 75 mg alpha lipoid acid and 0,65 Vitamin B6) for 6 months

Metionac twice daily (200 mg S-adenosylmethionine, 100 mg N-acetylcisteine, 75 mg alpha lipoid acid and 0,65 Vitamin B6) for 6 months

Metionac is a food suplement composed by 200 mg of SAMe, 100 mg of NAC, 75 mg of ALA and 0,65 mg of vitamin B6 per tablet for 6 months

Metionac

Evaluate the efficacy of the combination of antioxidants ALA, NAC, Vit. B6 and SAMe as a dietary supplement, in the improvement of metabolic and endocrine parameters and clinical manifestations of PCOS.

The investigators will explain the study to all patients who meet the inclusion and exclusion criteria during the study period. After signing the informed consent patients will be randomized 1:1 to oral contraceptive 4 mg drospirenone once daily or oral contraceptive 4 mg drospirenone + combination of 200 mg S-adenosylmethionine, 100 mg N-acetylcisteine, 75 mg Alpha lipoid acid and 0,65 mg vitamin B6 (Metionac) twice daily. Patients for whom oral contraceptive is not indicated will be enrolled in third study group of Metionac twice daily. 2 study visits will be carried out, Baseline (Visit 0) and after 6 months therapy (Visit 1).

Evaluation of Metionac for the Modulation of Metabolic and Endocrine Parameters in Patients With PCOS.

Evaluation of the Efficacy of the Combination of Antioxidants Metionac for the Modulation of Metabolic and Endocrine Parameters in Patients With Polycystic Ovary Syndrome: A Prospective Randomized Study.

Evolution of Body Mass Index in patients with PCOS after 6 months therapy

Evolution of Insuline level in patients with PCOS after 6 months therapy

Evolution of Glucose level in patients with PCOS after 6 months therapy

Evolution of Triglycerides level in patients with PCOS after 6 months therapy

Evolution of high-density lipoprotein (HDL) cholesterol level in patients with PCOS after 6 months therapy.

Evolution of low-density lipoprotein (LDL) level in patients with PCOS after 6 months therapy

Evolution of aspartate aminotransferase (AST) level in patients with PCOS after 6 months therapy

Evolution of alanine aminotransferase (ALT) level in patients with PCOS after 6 months therapy

Evolution of gamma glutamyltransferase (GGT) level in patients with PCOS after 6 months therapy

Evolution of total and free bilirubin level in patients with PCOS after 6 months therapy

Evolution of 17 beta estradiol level in patients with PCOS after 6 months therapy

Evolution of 17 hydroxy progesterone level in patients with PCOS after 6 months therapy

Evolution of luteinizing hormone (LH) level in patients with PCOS after 6 months therapy

Evolution of follicle-stimulating hormone (FSH) level in patients with PCOS after 6 months therapy

Evolution of testosterone level in patients with PCOS after 6 months therapy

Evolution of androstenedione level in patients with PCOS after 6 months therapy

Evolution of Dehydroepiandrosterone (DHEA) level in patients with PCOS after 6 months therapy

Evolution of thyroid stimulating hormone (TSH) level in patients with PCOS after 6 months therapy.

Evolution of homocysteine (HC) level in patients with PCOS after 6 months therapy.

Evolution of HOMA insulin resistance level in patients with PCOS after 6 months therapy.

Evolution of hemoglobin A1c in patients with PCOS after 6 months therapy.

Evolution of sex hormone binding globulin in patients with PCOS after 6 months therapy.

Evolution of hirsutism score measured by Ferriman - Gallwey scale in patients with PCOS after 6 months therapy. The Ferriman-Gallwey scale for hirsutism. A score of 1 to 4 is given for nine areas of the body. A total score less than 8 is considered normal, a score of 8 to 15 indicates mild hirsutism, and a score greater than 15 indicates moderate or severe hirsutism. A score of 0 indicates absence of terminal hair.

Evolution of acne self assessed from 1 to 10 (1 minimum severity, 10 maximum severity) in acne severity level in 3 areas: face, neck, back in patients with PCOS after 6 months therapy.

Evolution of alopecia using Ludwig scale in patients with PCOS after 6 months therapy. The Ludwig hair loss scale illustrates progressive hair loss patterns in women. It ranges from I to III. Stage I begins with thinning on the top of the head. In stage II the scalp starts to show. All of the hair at the crown of the head may be lost when the hair loss progresses to stage III.Stage I begins with thinning on the top of the head. In stage II the scalp starts to show. All of the hair at the crown of the head may be lost when the hair loss progresses to stage III.

Regularization of irregular menstrual cycle in patients with PCOS after 6 months therapy

Evolution of migraine score using Migraine Disability Assessment test (MIDAS) in patients with PCOS after 6 months. The MIDAS score is derived as the sum of missed days due to a headache over a 3-month period in the three domains: school work or work for pay; household work or chores; and family, social, and leisure activities. The four-point grading system for the MIDAS questionnaire is as follows:

• Grade 1 (scores ranging from 0 to 5): little or no disability Grade 2 (scores ranging from 6 to 10): mild disability Grade 3 (scores ranging from 11 to 20): moderate disability Grade 4 (21 or greater): severe disability.

Evolution of quality of life score using Health-Related Quality of Life Questionnaire for women with Polycystic Ovary Syndrome (adapted from PCOSQ qustionnaire) in patients with PCOS after 6 months therapy. The PCOS HRQL questionnaire represents a new measure for women with PCOS and includes five domains: emotional, body hair, infertility, weight, and menstrual problems. A shorten version with 19 questions was used. It ranges from 0 (no impact on quality of life to 114 maximum negative impact in the patient´s quality of life.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Safety of Hormonal Contraceptives Therapies in Polycystic Ovary Syndrome (PCOS) Women	NCT00842140	Polycystic Ovar...	oral contracept... Oral contracept... Oral contracept...	18 Years - 35 Years	University of Sao Paulo
The Role of Dysbiosis of Gut Microbiota in the Pathogenesis of PCOS.	NCT03843736	Polycystic Ovar...	Lifestyle inter... Probiotic Agent Oral contracept...	18 Years - 45 Years	Peking Union Medical College Hospital
Safety of Hormonal Contraceptives Therapies in Polycystic Ovary Syndrome (PCOS) Women	NCT00842140	Polycystic Ovar...	oral contracept... Oral contracept... Oral contracept...	18 Years - 35 Years	University of Sao Paulo
The Role of Dysbiosis of Gut Microbiota in the Pathogenesis of PCOS.	NCT03843736	Polycystic Ovar...	Lifestyle inter... Probiotic Agent Oral contracept...	18 Years - 45 Years	Peking Union Medical College Hospital
Safety of Hormonal Contraceptives Therapies in Polycystic Ovary Syndrome (PCOS) Women	NCT00842140	Polycystic Ovar...	oral contracept... Oral contracept... Oral contracept...	18 Years - 35 Years	University of Sao Paulo
Evaluation of Metionac for the Modulation of Metabolic and Endocrine Parameters in Patients With PCOS.	NCT05340634	Polycystic Ovar...	Metionac Oral contracept...	18 Years -	Margan Biotech

Spots Global Cancer Trial Database for oral contraceptive