Polycystic Ovary Syndrome (PCOS): Effect Of Letrozole and Berberine

Letrozole and Berberine in Infertile PCOS Patients

Polycystic ovary syndrome (PCOS) is a heterogeneous disorder affecting almost4%-7% of the female population of reproductive age. Its heterogeneity is characterized by a wide spectrum of features, including ovulatory dysfunction and infertility, hyperandrogenism, hyperinsulinemia, insulin resistance (IR), and progression to type 2 diabetes.Since the Ming Dynasty in China,PCOS has been defined as "phlegm and wetness"infertility in traditional Chinese medicine ,namely "metabolic infertility".Chinese herbs have been used to treat PCOS for thousands of years with good effects.Berberine has also been used for diabetic patients in traditional Chinese medicine for hundreds of years. Recent studies have reported its effects on hyperglycemia and dyslipidemia.The purpose of this study is to determine whether Letrozole combined with berberine are effective in the treatment of infertile PCOS patients.

Study Overview

• Status: Unknown
• Conditions: Polycystic Ovary Syndrome
• Intervention / Treatment: Drug: Letrozole -Berberine; Drug: Letrozole; Drug: Berberine

• Study Type: Interventional
• Enrollment (Anticipated): 660
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yan Li, MD.PhD.; Email: liyantcm@163.com

Study Locations

• China
  • Harbin, China
    • Active, not recruiting
    • Second Affiliated Hospital of Heilongjiang University of Chinese Medicine
  • Anhui
    • Hefei, Anhui, China
      • Active, not recruiting
      • Affiliated Hospital of Anhui University of Chinese Medicine
  • Guangdong
    • Guangzhou, Guangdong, China
      • Active, not recruiting
      • Affiliated Hospital of Guangzhou Medical University
    • Guangzhou, Guangdong, China
      • Recruiting
      • Guangzhou Medical School First Affiliated Hospital
      • Principal Investigator: Hongxia Ma, MD
  • Heilongjiang
    • Daqing, Heilongjiang, China, 163000
      • Active, not recruiting
      • Daqing LongNa Hospital
    • Daqing, Heilongjiang, China
      • Active, not recruiting
      • Daqing Longnan hospital
    • Harbin, Heilongjiang, China, 150040
      • Recruiting
      • Obstetrics and Gynecology,Heilongjiang University of Chinese Medicine
      • Contact: Xiaoke Wu, MD.PhD.; Phone Number: 86-451-8213 0094; Email: xiaokewu2002@vip.sina.com
      • Contact: Lihui Hou, MD.; Phone Number: 86-451-8213 0094; Email: houlihui2007@sina.com
      • Principal Investigator: Lihui Hou, MD.
      • Principal Investigator: Xiaoke Wu, MD.PhD.
    • Harbin, Heilongjiang, China
      • Active, not recruiting
      • First Affliated Hospital of Harbin Medical University
    • Mudanjiang, Heilongjiang, China
      • Active, not recruiting
      • Mudanjiang maternal and children hospital
  • Henan
    • Zhengzhou, Henan, China
      • Active, not recruiting
      • 2nd Affiliated Hospital of Henan University of Chinese Medicine
  • Hunan
    • Changsha, Hunan, China
      • Active, not recruiting
      • First Affiliated Hospital of Hunan University of Chinese
  • Jiangsu
    • Suqian, Jiangsu, China
      • Active, not recruiting
      • SuqianMaternal and Child Health Hospital
  • Jiangxi
    • Nanchang, Jiangxi, China
      • Active, not recruiting
      • First Hospital, Jiangxi college of Chinese Medicine
  • Liaoning
    • Dalian, Liaoning, China
      • Active, not recruiting
      • Dalian Maternal and Child Health Hospital
  • Shanxi
    • Taiyuan, Shanxi, China
      • Active, not recruiting
      • Shanxi Hospital of Chinese Medicine
  • Tianjin
    • Tianjin, Tianjin, China
      • Active, not recruiting
      • First Affiliated Hospital of Tianjin University of Chinese Medicine
    • Tianjin, Tianjin, China
      • Active, not recruiting
      • Second Affiliated Hospital, Tianjin University of Chinese Medicine
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Active, not recruiting
      • Zhejiang province hospital of integrated traditional and western medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Chinese women
• Age between 20 and 40 years.

• Confirmed diagnosis of PCOS according to the Rotterdam 2003 criteria (2 out of 3):

  1. Oligo- or anovulation
  2. Clinical and/or biochemical signs of hyperandrogenism
  3. Polycystic ovaries and exclusion of other etiologies (congenital adrenal hyperplasia, androgen-secreting tumors, Cushing's syndrome)
• At least one patent tube and normal uterine cavity shown by hysterosalpingogram, HyCoSi or diagnostic laparoscopy within three years.
• Sperm concentration 20×106/mL and progressive motility (grades a and b) ≥50%.

Exclusion Criteria:

• Use of hormonal drugs or other medications including Chinese herbal prescriptions in the past 3 months.
• Patients with known sever organ dysfunction or mental illness.
• Pregnancy, post-abortion or postpartum within the past 6 weeks.
• Breastfeeding within the last 6 months.
• Not willing to give written consent to the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Letrozole -Berberine	Drug: Letrozole -Berberine; Letrozole 2.5 mg letrozole daily from day 5 of the menses for 5 days for month 1 to 3, 5.0 mg letrozole daily from day 5 of the menses for 5 days for month 4 to 6. Berberine 1.5g daily for 6 month.
Active Comparator: Letrozole	Drug: Letrozole; Letrozole 2.5 mg letrozole daily from day 5 of the menses for 5 days for month 1 to 3, 5.0 mg letrozole daily from day 5 of the menses for 5 days for month 4 to 6. Berberine Placebo 5 tablet tds for 6 months
Active Comparator: Berberine	Drug: Berberine; Berberine 1.5g daily for 6 month. Letrozole placebo 1 tablet daily from day 5 of the menses for 5 days for month 1 to 3, 2 tablets daily from day 5 of the menses for 5 days for month 4 to 6.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Live-birth rate	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Ovulation rate	Up to 1 year
Ongoing pregnancy rate at around gestation 8-10 weeks	Up to 1 year
Multiple pregnancy rate	Up to 1 year.
Miscarriage rate: loss of an intrauterine pregnancy before 20 completed weeks of gestation	Up to 1 year
Other pregnancy complications such as early pregnancy loss, gestational diabetes mellitus, pregnancy-induced hypertension and birth of small-for-gestational-age (SGA) babies.	Up to 1 year
Infant outcome	Up to 1 year
Changes in metabolic profile: glucose and insulin concentrations, cholesterol, triglycerides, high density lipoprotein (HDL-C) and low density lipoprotein (LDL-C)	Up to 1 year
Changes in hormonal profile: Follicle-stimulating hormone (FSH), Luteinizing hormone (LH), total testosterone (T), Sex hormone-binding globulin (SHBG) and Dehydroepiandrosterone sulfate (DHEAS)	Up to 1 year
Side effect.	Up to 1 year

Collaborators and Investigators

• Sponsor: Heilongjiang University of Chinese Medicine
• Collaborators: Ministry of Science and Technology of the People´s Republic of China
• Investigators: Study Chair: Lihui Hou, MD., The First Affliated Hospital,Heilongjiang University of Chinese Medicine .; Study Chair: Xiaoke Wu, MD.PhD., The First Affliated Hospital,Heilongjiang University of Chinese Medicine

Publications and helpful links

General Publications

• Zhou K, Zhang J, Xu L, Lim CED. Chinese herbal medicine for subfertile women with polycystic ovarian syndrome. Cochrane Database Syst Rev. 2021 Jun 4;6:CD007535. doi: 10.1002/14651858.CD007535.pub4.
• Li Y, Kuang H, Shen W, Ma H, Zhang Y, Stener-Victorin E, Hung E, Ng Y, Liu J, Kuang H, Hou L, Wu X. Letrozole, berberine, or their combination for anovulatory infertility in women with polycystic ovary syndrome: study design of a double-blind randomised controlled trial. BMJ Open. 2013 Nov 25;3(11):e003934. doi: 10.1136/bmjopen-2013-003934.

Study record dates

Study Major Dates

• Study Start: October 1, 2009
• Primary Completion (Anticipated): December 1, 2013
• Study Completion (Anticipated): December 1, 2013

Study Registration Dates

• First Submitted: April 27, 2010
• First Submitted That Met QC Criteria: May 3, 2010
• First Posted (Estimate): May 4, 2010

Study Record Updates

• Last Update Posted (Estimate): May 20, 2013
• Last Update Submitted That Met QC Criteria: May 17, 2013
• Last Verified: May 1, 2013

More Information

Terms related to this study

• Keywords: Polycystic Ovary Syndrome
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Endocrine System Diseases; Disease; Ovarian Cysts; Cysts; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Polycystic Ovary Syndrome; Syndrome; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Letrozole
• Other Study ID Numbers: you070316

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No