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

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.

Study Overview

• Status: Recruiting
• Conditions: Premature Ovarian Insufficiency
• Intervention / Treatment: Drug: hormone replacement therapy

• Study Type: Observational
• Enrollment (Estimated): 1080

Contacts and Locations

• Study Contact: Name: Jianhong Zhou, Doctor of Medicine(M.D.); Phone Number: 86 15990008569; Email: zhoujh1117@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • Recruiting
      • Women's Hospital School of Medicine Zhejiang University
      • Contact: Jianhong Zhou, Doctor of Medicine(M.D.); Phone Number: 86 15990008569; Email: zhoujh1117@zju.edu.cn
      • Contact: Yizhou Huang, Doctor of Medicine(M.D.); Phone Number: 86 15267073860; Email: cchhkkxx@126.com
      • Principal Investigator: Jianhong Zhou, Doctor of Medicine(M.D.)
      • Sub-Investigator: Yizhou Huang, Doctor of Medicine(M.D.)
      • Sub-Investigator: Zheng Lou, Master of Medicine
    • Hangzhou, Zhejiang, China, 310000
      • Not yet recruiting
      • Women's Hospital School of Medicine Zhejiang University
      • Contact: Jianhong Zhou, MD,PhD; Phone Number: 15990008569; Email: zhoujh1117@zju.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

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

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
Women with POI; 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.; 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; 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.; 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; 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.; 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; 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.; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Affected Complete Blood Count After Treatment	Complete blood count (CBC) parameters are measured in peripheral venous blood. A participant is considered to have affected CBC if any of the following parameters falls outside the established reference range listed below. The number of participants with at least one affected test result after treatment will be reported. Parameters and reference ranges: White blood cell count: 3.5-9.5 × 10⁹/L Red blood cell count: 3.80-5.10 × 10¹²/L Hemoglobin: 115-150 g/L Platelet count: 125-350 × 10⁹/L	Baseline, 6 months, 12 months, 24 months, 36 months
Ultrasound examination of pelvic	Ultrasound examination of pelvic is performed. Results are compared with reference imaging standards to assess and monitor participants' pelvic health.	Baseline, 6 months, 12 months, 24 months, 36 months
Ultrasound examination of breast	Ultrasound examination of breast is performed. Results are compared with reference imaging standards to assess and monitor participants' breast health.	Baseline, 6 months, 12 months, 24 months, 36 months

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2023
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: July 6, 2023
• First Submitted That Met QC Criteria: September 27, 2023
• First Posted (Actual): October 5, 2023

Study Record Updates

• Last Update Posted (Actual): May 28, 2026
• Last Update Submitted That Met QC Criteria: May 25, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Premature Ovarian Insufficiency
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Genital Diseases, Female; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Primary Ovarian Insufficiency; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormones
• Other Study ID Numbers: ZDFY2022-4XA101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No