A Multicenter Observational Study on the Development and Health Effects of Premature Ovarian Insufficiency

NCT06067529 | Recruiting

• 1 other identifier: ZDFY2022-4XA101
• Study Type: observational
• Target: 1,080
• Locations: 1 country
• Sites: 2

Brief Summary

Premature ovarian insufficiency (POI) refers to the occurrence of ovarian hypofunction in women before the age of 40, which seriously affects women's overall health and quality of life. However, there is currently insufficient understanding of the risk factors, pathogenesis, short-term and long-term health effects of POI, and the health effects of the disease, and there is a lack of high-quality evidence to support clinical diagnosis and treatment decisions. This study intends to construct a hospital-based multi-center POI case-control and prospective special disease cohort, after baseline assessment and follow-up monitoring, collect disease characteristics, lifestyle, social psychology, environmental and occupational exposure, biological samples and other data, aiming to observe POI The natural occurrence, progression and health impact of POI, clarify the risk factors of POI, evaluate the impact of POI on women's health and disease risk, and discuss the benefits, risks and options of HRT for POI patients. The results of this study will deepen and expand the understanding of the occurrence and development of POI and its short-term and long-term health effects, provide high-level evidence for optimizing POI prevention, diagnosis and treatment strategies, and establish a long-term management system, laying the foundation for interventional research.

Conditions

Premature Ovarian Insufficiency

Keywords

Premature Ovarian Insufficiency

Outcome Measures

Primary Outcomes (15)

• Bone density

  Measured by Dual Energy X-ray Unit: g/cm²

  Baseline, 12 months, 24 months, 36 months

• β-collagen degradation products

  Bone resorption marker , β-collagen degradation products, are measured in peripheral venous blood. Unit: pg/mL

  Baseline, 12 months, 24 months, 36 months

• Osteocalcin

  Bone formation markers, Osteocalcin, are measured in peripheral venous blood. Unit: ng/mL

  Baseline, 12 months, 24 months, 36 months

• Total type I collagen amino-terminal propeptide

  Bone formation markers, Total type I collagen amino-terminal propeptide, are measured in peripheral venous blood. Unit: μg/L

  Baseline, 12 months, 24 months, 36 months

• Reproductive hormones

  Reproductive hormones, including follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), progesterone (P), and testosterone (T), are measured in peripheral venous blood. These hormones are assessed together to evaluate female hormonal status.

  Baseline, 6 months, 12 months, 24 months, 36 months

• Thyroid function test

  Thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) are measured in peripheral venous blood. Results will be compared with reference ranges to evaluate thyroid function.

  Baseline, 12 months, 24 months, 36 months

• Symptoms related to low estrogen

  The symptoms related to low estrogen was quantified using the modified Kupperman Menopausal Index (mKMI). The total score is used to classify the symptom severity into four levels: asymptomatic (≤ 6), mild (7-15), moderate (16-30), and severe (≥ 31). A higher total score indicates more severe symptoms.

  Baseline, 6 months, 12 months, 24 months, 36 months

• Sexual life

  The assessment of Sexual life was conducted using the 6-item Female Sexual Function Index (FSFI-6). A total score ranging from 2 to 30, and a total score of 19 or less was defined as the diagnostic cutoff for identifying individuals with female sexual dysfunction.

  Baseline, 12 months, 24 months, 36 months

• Fasting blood glucose

  Fasting blood glucose is measured in peripheral venous blood. Results are compared with reference ranges to assess glucose metabolism. Unit: mmol/L

  Baseline, 6 months, 12 months, 24 months, 36 months

• Insulin

  Insulin is measured in peripheral venous blood. Results are compared with reference ranges to assess glucose metabolism. Unit: μU/mL

  Baseline, 6 months, 12 months, 24 months, 36 months

• Depressive symptoms

  Depressive symptoms were assessed using the 10-item Center for Epidemiologic Studies Depression Scale Revised (CES-D-10) . Total scores range from 0 to 30, and a cutoff score of ≥ 10 was utilized to identify individuals at risk for depression.

  Baseline, 6 months, 12 months, 24 months, 36 months

• Anxiety

  Anxiety was evaluated using the Generalized Anxiety Disorder-7 (GAD-7). Total scores were categorized into four levels consisting of minimal anxiety (0-4), mild anxiety (5-9), moderate anxiety (10-14) and severe anxiety (≥ 15).

  Baseline, 6 months, 12 months, 24 months, 36 months

• Subjective psychological well-being

  Subjective psychological well-being over the preceding two weeks was quantified through the World Health Organization Five Well-Being Index (WHO-5).A total raw score of \< 13 was considered indicative of potential psychological health issues.

  Baseline, 6 months, 12 months, 24 months, 36 months

• Number of Participants with Affected Hepatic Function Tests After Treatment

  Hepatic function parameters are measured in peripheral venous blood. Affected is defined as any value outside the reference ranges below. The number of participants with at least one affected result attributed to HRT will be reported. Parameters and reference ranges: Total protein: 65.0-85.0 g/L Albumin: 40.0-55.0 g/L Albumin/Globulin ratio: 1.20-2.40 (unitless) Alanine aminotransferase (ALT): 7-40 U/L Aspartate aminotransferase (AST): 13-35 U/L Total bilirubin: ≤23.0 μmol/L Direct bilirubin: ≤4.0 μmol/L Indirect bilirubin: ≤19.0 μmol/L Alkaline phosphatase (ALP): 35-100 U/L Gamma-glutamyl transferase (GGT): 7-45 U/L

  Baseline, 6 months, 12 months, 24 months, 36 months

• Number of Participants with Affected Renal Function Tests After Treatment

  Renal function parameters are measured in peripheral venous blood. Affected is defined as any value outside the reference ranges below. The number of participants with at least one abnormal result attributed to HRT will be reported. Parameters and reference ranges: Creatinine: 41-73 μmol/L Urea: 2.60-7.50 mmol/L Uric acid: 155-357 μmol/L

  Baseline, 6 months, 12 months, 24 months, 36 months

Secondary Outcomes (3)

• Number of Participants with Affected Complete Blood Count After Treatment

  Baseline, 6 months, 12 months, 24 months, 36 months

• Ultrasound examination of pelvic

  Baseline, 6 months, 12 months, 24 months, 36 months

• Ultrasound examination of breast

  Baseline, 6 months, 12 months, 24 months, 36 months

Study Arms (4)

Women with POI

1. Inclusion Criteria 1.1 Age at Diagnosis: Less than 40 years of age. 1.2 Diagnosis of POI: Met one of the following diagnostic criteria based on ESHRE guidelines: Spontaneous POI: Oligomenorrhea or amenorrhea for at least 4 months, combined with elevated FSH levels (\> 25 IU/L) on two occasions at least 4 weeks apart. Iatrogenic POI: Documented history of bilateral oophorectomy, or ovarian failure resulting from chemotherapy or radiotherapy. 1.3 Informed Consent: Willing to participate in the study, provide biological samples, and complete long-term follow-up assessments. 2. Exclusion Criteria 2.1 Current Pregnancy or Lactation: Women who were pregnant or breastfeeding at the time of enrollment. 2.2 Severe Systemic Conditions: Presence of severe somatic or psychiatric diseases (e.g., active malignancy not related to POI, severe heart/renal failure, or cognitive impairment) that would preclude adherence to the study protocol or long-term follow-up.

Control

1. Inclusion Criteria: 1.1 Age: 18-50 years. 1.2 Menstrual History: Regular menstrual cycles (21-35 days) for the past 12 months. 1.3 Consent: Willingness to participate, provide biological samples, and provide written informed consent. 2. Exclusion Criteria: 2.1 Physiological Status: Pregnancy, breastfeeding, or clinical perimenopause/postmenopause. 2.2 Reproductive Disorders: History of PCOS, endometriosis, or other reproductive pathologies. 2.3 Iatrogenic \& Toxic Factors: Prior ovarian surgery (e.g., cystectomy), chemotherapy, or radiotherapy. 2.4 Systemic Diseases: History of endocrine (e.g., thyroid dysfunction), autoimmune, cardiovascular, liver, kidney, or hematological diseases, or malignancy. 2.5 Genetic \& Familial Background: First-degree relatives with POI or early menopause (\< 45 years). Family history of hereditary diseases. 2.6 Medication: Use of hormonal drugs or contraceptives within the last 6 months.

Ovarian Surgery group

1. Inclusion Criteria: 1.1 Age: 18-60 years. 1.2 Patients with ovarian surgery: women scheduled to undergo ovarian surgery for gynecological disease. 1.3 Informed Consent: Willing to participate in the study, provide biological samples, and sign the informed consent. 2. Exclusion Criteria: 2.1 Reproductive Disorders: History of PCOS, endometriosis, or other reproductive pathologies. 2.2 Medication: Use of hormonal drugs or contraceptives within the last 6 months. 2.3 Genetic or chromosomal abnormalities: Turner syndrome, or other genetic disease. 2.4 Physiological Status: Pregnancy, breastfeeding, or seeking the help of assisted reproductive technology. 2.5 Severe systemic Diseases: History of endocrine (e.g., thyroid dysfunction), autoimmune, cardiovascular, liver, kidney, hematological diseases, malignancy, or cognitive impairment.

Oophorectomy group

1. Inclusion Criteria: 1.1 Age: 45-65 years. 1.2 Patients with oophorectomy: women scheduled to undergo oophorectomy due to gynecological diseases and met criteria for being menopausal. 1.3 Menopausal status: at least 12 consecutive months of amenorrhea without other medical causes. 1.3 Informed Consent: Willing to participate in the study, provide biological samples, and sign the informed consent. 2. Exclusion Criteria: 2.1 Reproductive Disorders: History of PCOS, endometriosis, or other reproductive pathologies. 2.2 Medication: Use of hormonal drugs or contraceptives within the last 6 months. 2.3 Genetic or chromosomal abnormalities: Turner syndrome, or other genetic disease 2.4 Physiological Status: Pregnancy, breastfeeding, or seeking the help of assisted reproductive technology. 2.5 Severe systemic Diseases: History of endocrine (e.g., thyroid dysfunction), autoimmune, cardiovascular, liver, kidney, hematological diseases, malignancy, or cognitive impairment.

Interventions

hormone replacement therapy

Eligibility Criteria

• Age: 10 Years - 65 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Women with POI; Control; Ovarian Surgery group; Oophorectomy group

You may qualify if:

• Iatrogenic POI: Documented history of bilateral oophorectomy, or ovarian failure resulting from chemotherapy or radiotherapy.
• Informed Consent: Willing to participate in the study, provide biological samples, and complete long-term follow-up assessments.

You may not qualify if:

• Severe Systemic Conditions: Presence of severe somatic or psychiatric diseases (e.g., active malignancy not related to POI, severe heart/renal failure, or cognitive impairment) that would preclude adherence to the study protocol or long-term follow-up.
• Control
• Age: 18-50 years. 1.2 Menstrual History: Regular menstrual cycles (21-35 days) for the past 12 months.
• Consent: Willingness to participate, provide biological samples, and provide written informed consent.
• Physiological Status: Pregnancy, breastfeeding, or clinical perimenopause/postmenopause.
• Reproductive Disorders: History of PCOS, endometriosis, or other reproductive pathologies.
• Iatrogenic \& Toxic Factors: Prior ovarian surgery (e.g., cystectomy), chemotherapy, or radiotherapy.
• Systemic Diseases: History of endocrine (e.g., thyroid dysfunction), autoimmune, cardiovascular, liver, kidney, or hematological diseases, or malignancy.
• Genetic \& Familial Background: First-degree relatives with POI or early menopause (\< 45 years). Family history of hereditary diseases. 2.6 Medication: Use of hormonal drugs or contraceptives within the last 6 months.
• Ovarian Surgery group
• Age: 18-60 years. 1.2 Patients with ovarian surgery: women scheduled to undergo ovarian surgery for gynecological disease.
• Informed Consent: Willing to participate in the study, provide biological samples, and sign the informed consent.
• Reproductive Disorders: History of PCOS, endometriosis, or other reproductive pathologies.
• Medication: Use of hormonal drugs or contraceptives within the last 6 months.
• Genetic or chromosomal abnormalities: Turner syndrome, or other genetic disease.

Sponsors & Collaborators

• Women's Hospital School Of Medicine Zhejiang University: lead

Study Sites (2)

Women's Hospital School of Medicine Zhejiang University

Hangzhou, Zhejiang, 310000, China

RECRUITING

Women's Hospital School of Medicine Zhejiang University

Hangzhou, Zhejiang, 310000, China

NOT YET RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Peripheral venous blood, female vaginal secretions, and ovarian tissue

MeSH Terms

Conditions

Primary Ovarian Insufficiency

Condition Hierarchy (Ancestors)

Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gonadal Disorders; Endocrine System Diseases

Central Study Contacts

Jianhong Zhou, Doctor of Medicine(M.D.)

CONTACT

86 15990008569; zhoujh1117@zju.edu.cn

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Department director

Study Record Dates

• First Submitted: July 6, 2023
• First Posted: October 5, 2023
• Study Start: October 10, 2023
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: May 28, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)