Letrozole Versus Chinese Herbal Medicine on Polycystic Ovary Syndrome (PCOS)

The Effects of Chinese Herbal Medicine and Letrozole on Live Birth in Infertile Women With Polycystic Ovary Syndrome:A Double-blind Randomized Controlled Trial

This is a multicenter double-blind randomized controlled trial. A total of 420 anovulatory Chinese women with PCOS will be recruited, and the randomization will be stratified by each participating site. Participants will be randomized into one of the two treatment arms: letrozole and CHMG or letrozole and CHMG placebo. CHMG or its placebo will be taken twice a day for up to six months. Letrozole (2.5 mg daily) was given on days 3-7 of the menstrual cycle after a spontaneous period or withdrawal bleeding, and the dose will be increased to 5.0 mg daily during the last three months for non-pregnant women in both groups.The aim of the present study is to determine the efficacy of combined treatment with letrozole and CHMG on improving live birth rates in infertile Chinese women with PCOS. Our hypothesis is that the combination of letrozole and CHMG is more likely to increase the ovulation rate and decrease the miscarriage rate and result in a higher live birth rate in PCOS women than letrozole alone.

Study Overview

• Status: Unknown
• Conditions: Polycystic Ovary Syndrome
• Intervention / Treatment: Drug: Letrozole; Drug: Chinese herbal medicine granules or Chinese herbal medicine granules placebo

• Study Type: Interventional
• Enrollment (Anticipated): 420
• Phase: Not Applicable

Contacts and Locations

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
      • Guangzhou Medical School First Affiliated Hospital
  • Heilongjiang
    • Daqing, Heilongjiang, China
      • Active, not recruiting
      • Daqing Longnan Hospital
    • Daqing, Heilongjiang, China
      • Active, not recruiting
      • Daqing Oilfield General Hospital
    • Harbin, Heilongjiang, China, 150001
      • Recruiting
      • First Affliated Hospital of Harbin Medical University
      • Contact: Muer An, MD
      • Principal Investigator: Muer An, MD
    • Herbin, Heilongjiang, China, 150040
      • Recruiting
      • Dept Obs & Gyn, First Affiliated Hospital National Key Discipline and Trial Base Heilongjiang University of Chinese Medicine
      • Principal Investigator: Lihui Hou, MD.
      • Contact: Lihui Hou, MD.; Phone Number: 86-451-82130094
    • 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
    • Xuzhou, Jiangsu, China
      • Active, not recruiting
      • Maternal and Child Health Hospital of Xuzhou
  • Jiangxi
    • Nanchang, Jiangxi, China
      • Active, not recruiting
      • First Hospital, Jiangxi college of Chinese Medicine
  • Liaoning
    • Dalian, Liaoning, China
      • Recruiting
      • Dalian Maternal and Child Health Hospital
      • Principal Investigator: Xiaoguang Shao, MD
  • 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
      • Recruiting
      • Zhejiang province hospital of integrated traditional and western medicine
      • Contact: Xin Sun, MD
      • Principal Investigator: Xin Sun, MD

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

1. Chinese women with PCOS. PCOS must have been diagnosed based on the presence of two of the following three Rotterdam criteria : (1) oligomenorrhea, anovulation; (2) hyperandrogenism; and (3) the observation of polycystic ovaries by sonography. Oligomenorrhea is defined as an intermenstrual interval >35 days or <8 menstrual bleedings in the past year. Amenorrhea is defined as an intermenstrual interval >90 days.
2. History of at least one year of infertility.
3. Age between 20 and 40 years old.
4. Normal semen analysis based on World Health Organization criteria (2010). The husband did not need to sign the consent form because semen analysis is part of the clinical assessment at the sites. A sperm concentration ≥15 × 106/mL and total motility ≥40% in the semen analysis of the husband was required for the woman to be included.
5. Normal uterine cavity and at least one tube patent upon hysterosalpingography or HyCoSy.

Exclusion criteria

1. History of significant system diseases such as heart, lung, or kidney diseases.
2. History of other endocrine disorders.
3. Use of hormonal therapy, including metformin, in the past 3 months.
4. Previous sterilization procedures (vasectomy or tubal ligation) that have been reversed.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Letrozole+ Chinese herbal medicine granules	Drug: 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.; Drug: Chinese herbal medicine granules or Chinese herbal medicine granules placebo; twice a day for 6 month
Placebo Comparator: Letrozole+ Chinese herbal medicine granules placebo	Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Live birth rate	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ovulation rate		Up to 1 year
Miscarriage rate		Up to 1 year
Change in hormonal profile	Follicle-stimulating hormone, luteinizing hormone, total testosterone, sex hormone binding globulin, and dehydroepiandrosterone sulphate.	Up to 1 year
Change in metabolic profile	glucose and insulin concentrations, cholesterol, triglycerides, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol.	Up to 1 year
Change in physical measurements	weight, vital signs, and hip and waist measurements.	Up to 1 year
Pregnancy complications	gestational diabetes, pregnancy-induced hypertension, intrauterine growth retardation, ectopic pregnancy, congenital anomaly, preeclampsia, preterm labor, HELLP syndrome, preterm premature rupture of membranes, placental abruption, placenta accreta, placenta previa, postpartum hemorrhage, and others.	Up to 1 year
Birth defects		Up to 1 year
Safety parameters	renal and liver function tests and complete blood count.	Up to 1 year
Side effect profile	The major risks to the subject are side effects from letrozole and CHMG and the risks associated with pregnancy.	Up to 1 year

Collaborators and Investigators

• Sponsor: Heilongjiang University of Chinese Medicine

Study record dates

Study Major Dates

• Study Start: September 1, 2009
• Primary Completion (Anticipated): August 1, 2014
• Study Completion (Anticipated): August 1, 2014

Study Registration Dates

• First Submitted: September 6, 2011
• First Submitted That Met QC Criteria: September 8, 2011
• First Posted (Estimate): September 9, 2011

Study Record Updates

• Last Update Posted (Estimate): November 5, 2013
• Last Update Submitted That Met QC Criteria: November 4, 2013
• Last Verified: November 1, 2013

More Information

Terms related to this study

• Keywords: Randomized controlled trial; Polycystic ovary syndrome; Chinese herbal medicine; Letrozole; Chinese herbal medicine granules; Live birth
• 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: letrozole