Abnormalities of the Endometrium Persist Despite Adequate Progesterone Supplementation in the Polycystic Ovary Syndrome
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 36
- 主要终点
- Endometrial biopsy
研究概览
简要总结
Objective: To study the influence of metabolic factors on the action of progesterone on the endometrium of women with PCOS.
Design: A prospective open-label clinical trial. Setting: Participants were recruited from an outpatient reproductive endocrinology clinic at an academic tertiary medical care center from 2014 to 2019.
Subjects: To assess the sole effect of progesterone (P4) on the endometrium we studied amenorrheic (cycles> 90 days) women with PCOS (n=23), comparing them to healthy eumenorrheic control women ( n=13).
Intervention(s): All subjects underwent an endometrial biopsy (EB) in the follicular phase of the first study cycle. They were then treated with micronized P4 (400 mg/day x 10 days intravaginally) from days 14-28 of the cycle, and a second EB was performed between days 20-24 of the cycle (second phase).
Main Outcome Measure(s): EB samples were analyzed under light microscopy for histomorphometric analysis.
详细描述
PATIENTS AND METHODS
Subjects Inclusion criteria for PCOS women will be: a) ages 18 to 35 years, and b) PCOS was defined by the Rotterdam criteria, which includes two of the following three features: a) oligo-amenorrhea; b) clinical or biochemical signs of hyperandrogenism; and c) polycystic ovaries (6). These criteria yield four PCOS phenotypes (A thru D) (1-3). Controls were recruited from the family planning outpatient office. All participants will be healthy women ages 18 to 35 years with regular menstrual cycles, no evidence of hirsutism, no comorbidities, and not using hormone medications in the previous 3 months.
Exclusion criteria are as follows: a) use of any hormone treatment in the previous 3 months; b) other causes of anovulation as evidenced by abnormal levels of prolactin, cortisol, dehydroepiandrosterone sulphate (DHEAS), 17-hydroxyprogesterone (17-OHP), androstenedione, thyroid-stimulating hormone (TSH), and free T4, in blood samples obtained between days 2 and 5 of the cycle in cycling subjects or on any other day in amenorrheic subjects; c) gynecologic disorders or other associated diseases, such as endometriosis, hypertension, or diabetes mellitus; d) follicle-stimulating hormone (FSH) >15 UI/L (cycle days 2-5); or e) a positive β-subunit of human chorionic gonadotropin (β-HCG).
Study Protocol
This trial was previously approved by the Research Ethics Committee (#21253613.6.0000.0068) of the Faculdade de Medicina, Hospital das Clínicas, Universidade de São Paulo (FMUSP), São Paulo, Brazil. The patients will be evaluated at Gynecology Outpatient office. The patients will be divided into two groups: a) PCOS and b) controls. All subjects will be cared for at the Endocrinology Gynecology Section and the Human Reproductive Center of the Gynecology Division, Hospital das Clínicas, FMUSP. After signing the informed consent will be written in accordance with Resolution 196/96 of the National Health Board (Resolução 196/96 do Conselho Nacional de Saúde), all subjects will be included in the study and evaluated as follows:
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 35 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Diagnosis of Polycystic ovarian syndrome (defined by the Rotterdam criteria, which includes two of the following three features: a) oligo-amenorrhea; b) clinical or biochemical signs of hyperandrogenism; and c) polycystic ovaries) ages 18 to 35 years; must be able to swallow tables
- •Controls - the family planning outpatient office and healthy women ages 18 to 35 years with regular menstrual cycles, no evidence of hirsutism; must be able to swallow tables
排除标准
- •: a) use of any hormone treatment in the previous 3 months; b) other causes of anovulation as evidenced by abnormal levels of prolactin, cortisol, dehydroepiandrosterone sulphate (DHEAS), 17-hydroxyprogesterone (17-OHP), androstenedione, thyroid-stimulating hormone (TSH), and free T4, in blood samples obtained between days 2 and 5 of the cycle in cycling subjects or on any other day in amenorrheic subjects; c) gynecologic disorders or other associated diseases, such as endometriosis, hypertension, or diabetes mellitus; d) follicle-stimulating hormone (FSH) >15 UI/L (cycle days 2-5); or e) a positive β-subunit of human chorionic gonadotropin (β-HCG); Clinical diagnosis of Alzheimer´s disease; ; insulin dependent diabetes; thryoid diasease.
研究组 & 干预措施
Morphological analysis of endometrium
PCOS: Seventeen PCOS subjects underwent two endometrial biopsies after the first P4-treated cycle, the first between days 5-9 of the cycle and the other between days 20-22 (i.e., under P4 treatment) of the cycle.
Controls: Thirteen ovulatory control women under two endometrial biopsies, performed after the first month of luteal P4 treatment, the first between days 5-9 and the second between days 20-22 of the cycle To quantify the parameters of interest, images were captured using a high-resolution camera (AxioCam-MCR, Carl Zeiss) adapted to a light microscope (Axiolab, Carl Zeiss) and adjusted with 40× objective lenses. The images were transmitted to a computer with AxioVision Rel 4.2 software (Carl Zeiss). For assessment of glandular and surface epithelial thickness, cell count, and counting newly formed blood vessels, ten images of each endometrial sample were made for each patient. For VEGF-C determination, the numerical density of blood vessels per mm2 was established
干预措施: Progesterone 400 Mg Vaginal Suppository on PCOS (Drug)
结局指标
主要结局
Endometrial biopsy
时间窗: 3 months
Number of patients with adequate changes of endometrium similar to luteal phase.
次要结局
未报告次要终点
研究者
Edmund Baracat
Full Professor and head of Discipline
University of Sao Paulo General Hospital