Research of Integrated Traditional Chinese and Western Medicine on Precocious Puberty

Precocious puberty is characterized by the premature appearance of secondary sexual characteristics. Globally, the timing of puberty onset in children has shown a certain tendency to advance. In China, the incidence of precocious puberty has been increasing year by year. Precocious puberty exerts long-term and systemic impacts on children's health: advanced bone age leads to short stature; earlier sexual development than peers may induce emotional problems such as anxiety and inferiority; it may increase the risk of obesity and type 2 diabetes, posing long-term hazards to cardiovascular health; it may also result in irregular menstruation or dysmenorrhea, exerting indirect effects on reproductive health.

Modern traditional Chinese medicine (TCM) holds that: various factors lead to liver-kidney yin deficiency, hyperactivity of ministerial fire, and early arrival of tian gui (the substance responsible for promoting growth, development and reproduction), thereby triggering premature sexual development. The main syndrome types identified in clinical practice include yin deficiency with fire hyperactivity syndrome, liver stagnation transforming into fire syndrome, and phlegm-dampness internal accumulation syndrome.

Since the late 1970s, the investigators' department has taken the lead in treating precocious puberty with TCM diagnostic methods, proposing that the pathogenesis of precocious puberty lies in "kidney yin deficiency and hyperactivity of ministerial fire", and adopting the therapy of nourishing yin and purging fire for its treatment. A number of studies have confirmed that TCM medicines with the effects of nourishing yin and purging fire can effectively alleviate the yin deficiency with fire hyperactivity syndrome in children, delay the development of secondary sexual characteristics and bone age.

At present, central precocious puberty is mostly treated with gonadotropin-releasing hormone analogs (GnRHa). However, this treatment has the drawback of inhibiting the growth axis, yielding limited benefits for children with advanced bone age, overweight or obesity, and may even affect glucose and lipid metabolism. Moreover, some children with precocious puberty complicated with obesity may be intolerant to this therapy. In contrast, TCM therapy and integrated TCM-Western medicine therapy can effectively delay the development of secondary sexual characteristics and advanced bone age, and improve final adult height, thus being widely applied in China.

Although a large number of relevant studies have been reported in recent years and TCM diagnosis and treatment guidelines for precocious puberty have been formulated, there is still a lack of high-quality evidence-based medical research to support the advantageous aspects of integrated TCM-Western medicine diagnosis and treatment. Additionally, the underlying mechanisms of diagnosis and treatment for different syndrome types of precocious puberty remain insufficiently studied.

In this study, the investigators will conduct a multicenter, randomized, double-blind, placebo-controlled clinical trial to evaluate the effects of Sanghe Jianghuo Granules on the regulation of the hypothalamic-pituitary-gonadal (HPG) axis, metabolic homeostasis and inflammatory microenvironment, so as to verify its efficacy and safety. Furthermore, combined with transcriptomics, proteomics and network pharmacology, the investigators will identify the key targets and action pathways of Sanghe Jianghuo Granules, and verify its regulatory effect on the HPG axis through in vivo and in vitro experiments.

Study Overview

• Status: Not yet recruiting
• Conditions: Puberty, Precocious
• Intervention / Treatment: Combination product: 10% drug-containing placebo, for a period of 3 months.; Drug: administered "Mulberry and Lotus Leaf Heat-Clearing Granules," with the following drug composition: mulberry leaves, lotus leaves, fresh rehmannia, anemarrhena, scutellaria, atractylodes, etc.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Jian Yu, Doctor; Phone Number: 8613816881206; Email: yuj@shmu.edu.cn
• Study Contact Backup: Name: Teng Fan; Phone Number: 8619921314120; Email: fanteng@fudan.edu.cn

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 201102
      • Children's Hospital of Fudan University
      • Contact: na Wang, Doctor; Phone Number: 8618203638814; Email: 18203638814@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• pediatric patients clinically diagnosed with precocious puberty: girls who exhibit secondary sexual characteristics or gonadal development before the age of 8, accompanied by obesity (BMI ≥ P85), and classified as having a syndrome of yin deficiency with hyperactivity of fire complicated by phlegm-dampness. Inclusion age: girls aged 5 years to 9 years, all of whom are initial cases and have not received any drug treatment related to precocious puberty.

Exclusion Criteria:

• Secondary precocious puberty, associated with diabetes, thyroid dysfunction, other endocrine disorders, and severe underlying conditions.

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
Placebo Comparator: Control group; 10% drug-containing placebo, for a period of 3 months.	Combination product: 10% drug-containing placebo, for a period of 3 months.; 10% drug-containing placebo, for a period of 3 months. The drug was Mulberry and Lotus Leaf Heat-Clearing Granules.
Active Comparator: Intervention group; administered "Mulberry and Lotus Leaf Heat-Clearing Granules," with the following drug composition: mulberry leaves, lotus leaves, fresh rehmannia, anemarrhena, scutellaria, atractylodes, etc., for an intervention period of 3 months..	Drug: administered "Mulberry and Lotus Leaf Heat-Clearing Granules," with the following drug composition: mulberry leaves, lotus leaves, fresh rehmannia, anemarrhena, scutellaria, atractylodes, etc.; administered "Mulberry and Lotus Leaf Heat-Clearing Granules," with the following drug composition: mulberry leaves, lotus leaves, fresh rehmannia, anemarrhena, scutellaria, atractylodes, etc., for an intervention period of 3 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Breast Tanner Stages	Measured by the attending physician	The measurement times are before the start of the experiment and the 3rd month after the start

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bone age	Bone age is determined by radiologists in our hospital who take a posteroanterior radiograph of the left hand and judge the bone age according to the Greulich-Pyle (GP) atlas method.	The measurement times are before the start of the experiment and the 3rd month after the start
Traditional Chinese Medicine syndrome score	Based on the Guidelines for Integrated Traditional Chinese and Western Medicine Diagnosis and Treatment of Pediatric Precocious Puberty (2023 Edition) and clinical experience, the Traditional Chinese Medicine (TCM) syndrome scores were screened and determined.	The measurement times are before the start of the experiment and the 3rd month after the start

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Testosterone	Testosterone(nmol/L, detected from the blood) Blood samples are collected from all patients in the morning after an overnight fast. Hormone levels are measured using chemiluminescent immunoassay.	The measurement times are before the start of the experiment and the 3rd month after the start
PRL	Prolactin(mIU/L, detected from the blood) Blood samples are collected from all patients in the morning after an overnight fast. Hormone levels are measured using chemiluminescent immunoassay.	The measurement times are before the start of the experiment and the 3rd month after the start
Estradiol	Estradiol(pmol/L, detected from the blood) Blood samples are collected from all patients in the morning after an overnight fast. Hormone levels are measured using chemiluminescent immunoassay.	The measurement times are before the start of the experiment and the 3rd month after the start
FSH	Follicle-Stimulating Hormone(U/L, detected from the blood) Blood samples are collected from all patients in the morning after an overnight fast. Hormone levels are measured using chemiluminescent immunoassay.	The measurement times are before the start of the experiment and the 3rd month after the start
LH	Luteinizing Hormone(U/L, detected from the blood) Blood samples are collected from all patients in the morning after an overnight fast. Hormone levels are measured using chemiluminescent immunoassay.	The measurement times are before the start of the experiment and the 3rd month after the start
Height	The height is measured and obtained by the physician. Place the mechanical height measuring device horizontally on a flat surface, against a wall, and calibrate the height measuring device reading. Instruct the examinee to stand barefoot on the base plate of the height measuring device, facing away from the pillar. When the doctor moves the height measuring device, he holds the handle of the height measuring device, moves horizontally, tries to keep the head upright, and keeps the body and limbs naturally straight. For hair knots and braids that are not convenient to measure height, they should be untied and headwear should be removed. The horizontal pressure plate should be in contact with the head, and the tightness should be moderate. The data is read in cm units and is accurate to 0.1.	The measurement times are before the start of the experiment and the 3rd month after the start
Weight	The weight is measured and obtained by the physician. Place the electronic scale flat on the ground, calibrate the scale reading, instruct the examinee to empty their bowels and bladder, wear light clothing and stand barefoot naturally in the center of the electronic scale pedal, keep the body stable, record the data, the unit is kg, and the value is accurate to 0.1.	The measurement times are before the start of the experiment and the 3rd month after the start
Uterine volume	Uterine volume obtained through ultrasound measurement; The size and shape of the organs are measured by a professional ultrasound physician from our hospital. The volume is calculated using the formula: V=(π /6)lengthanteroposterior diameter*transverse diameter, with the unit being cubic centimeters (cm³).	The measurement times are before the start of the experiment and the 3rd month after the start
Waist-Hip Ratio	Use a flexible, non-elastic anthropometric tape (mm-scale) and have the subject stand upright (feet shoulder-width apart, arms relaxed, abdomen relaxed) in lightweight, form-fitting clothing. For waist circumference: Mark the midpoint between the costal arch's inferior margin and iliac crest's superior border (umbilicus as alternative if unclear). Wrap the tape horizontally here-level, skin-adherent, no subcutaneous compression. Record to 0.1 cm at end of normal expiration; average 2-3 readings. For hip circumference: Locate the gluteal region's widest transverse diameter (confirmed posteriorly/laterally). Wrap tape horizontally here (level, flat). Record to 0.1 cm; average 2-3 readings. Compute WHR as mean waist ÷ mean hip (decimal, e.g., 85.2 cm ÷ 102.5 cm ≈ 0.83). Trained personnel must conduct measurements to reduce inter-observer variation.	The measurement times are before the start of the experiment and the 3rd month after the start
ovarian volume	Ovarian volume obtained through ultrasound measurement The size and shape of the organs are measured by a professional ultrasound physician from our hospital. The volume is calculated using the formula: V=(π /6)lengthanteroposterior diameter*transverse diameter, with the unit being cubic centimeters (cm³).	The measurement times are before the start of the experiment and the 3rd month after the start
follicle diameter	Follicle diameter obtained through ultrasound measurement The size and shape of the organs are measured by a professional ultrasound physician from our hospital.	The measurement times are before the start of the experiment and the 3rd month after the start
Serum levels of various steroid hormones	Serum metabolomics sequencing:Liquid Chromatography-Mass Spectrometry (LC-MS) technology for non-targeted metabolomics detection of small-molecule metabolites in serum, and simultaneously using a targeted steroid hormone panel for profiling.	The measurement times are before the start of the experiment and the 3rd month after the start
Fecal sample gut microbiota	Analysis of gut microbiota detection: detection of gut microbiota in fecal samples (16sRNA, gut microbiome metagenomics, metabolomics).	The measurement times are before the start of the experiment and the 3rd month after the start

Collaborators and Investigators

• Sponsor: Children's Hospital of Fudan University

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: December 25, 2025
• First Submitted That Met QC Criteria: December 25, 2025
• First Posted (Actual): January 8, 2026

Study Record Updates

• Last Update Posted (Actual): March 19, 2026
• Last Update Submitted That Met QC Criteria: March 17, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: RCT; precocious puberty; Sanghe Jianghuo Granules
• Additional Relevant MeSH Terms: Endocrine System Diseases; Gonadal Disorders; Puberty, Precocious
• Other Study ID Numbers: FDCH-ZY-2025402

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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