Study Summary

This clinical trial aims to evaluate the efficacy and safety of the traditional Chinese herbal formula Huanjingjian decoction in women with premature ovarian insufficiency (POI). The study is designed to address the following key questions:

1. Does Huanjingjian decoction improve clinical symptoms in patients with POI?
2. What adverse medical events, if any, occur during the treatment with Huanjingjian decoction? To answer these questions, researchers will compare Huanjingjian decoction plus hormone replacement therapy (HRT) with placebo plus HRT, in order to determine whether Huanjingjian decoction provides additional therapeutic benefits in the management of POI.

Participants will:

Receiving either Huanjingjian decoction plus HRT, or placebo plus HRT. Attending monthly clinic visits over a 6-month period for clinical assessments and laboratory testing.

Keeping a detailed diary to record symptoms, treatment adherence, and menstrual flow, as measured by the number of sanitary pads used.

This study is a prospective, randomized, controlled clinical trial designed to evaluate the efficacy of the traditional Chinese herbal formula Huanjingjian decoction in combination with hormone replacement therapy for the treatment of premature ovarian insufficiency. The primary objective is to determine whether the addition of Huanjingjian decoction to hormone replacement therapy provides greater improvement in clinical symptoms compared with placebo combined with hormone replacement therapy. It is hypothesized that, at 12 weeks, treatment with Huanjingjian decoction in combination with hormone replacement therapy will result in superior clinical outcomes relative to placebo combined with hormone replacement therapy.

Inclusion Criteria:

• Age between 18 and 39 years
• Meet the diagnostic criteria for Premature Ovarian Insufficiency (POI) according to the 2024 ESHRE Guideline on Premature Ovarian Insufficiency

Exclusion Criteria:

• Menstrual disorders attributable to congenital gonadal dysgenesis or acquired structural pathologies;
• Menstrual irregularities secondary to endocrine disorders, including polycystic ovary syndrome (PCOS), hyperprolactinemia, dysfunctional uterine bleeding (DUB), gonadal hormone deficiency, hyperthyroidism, and other related endocrine conditions;
• Oligomenorrhea or amenorrhea induced by surgical or medical interventions, such as chemotherapy, pelvic radiotherapy, ovarian cystectomy, ovarian drilling, ovarian wedge resection, salpingectomy, tubal ligation, pelvic abscess surgery, or uterine artery embolization;
• History of abnormal vaginal bleeding accompanied by clinically significant findings on endometrial biopsy, or unexplained irregular vaginal bleeding within the preceding 12 months;
• Suspected cervical malignancy or precancerous cervical lesions, suspected malignant breast tumors, or a known or suspected history of hormone-dependent tumors or malignancies;
• Previous or current history of deep vein thrombosis (DVT), pulmonary embolism, thrombotic disorders, or cerebrovascular events (stroke);
• Presence of uncontrolled and/or undiagnosed systemic diseases that could confound study results or compromise patient safety, including severe hepatic, renal, cardiac, or neurological disorders;
• Known hypersensitivity or allergy to any study-related medications;
• Pregnancy or lactation;
• Participation in other clinical trials within the last 3 months;
• Failure or refusal to provide written informed consent.

Primary outcome data under request

From publication until the third year after publication

Research scope

Participants, care providers, investigators, and outcome assessors will remain blinded to the treatment allocation throughout the trial. Randomisation codes will be generated by an independent statistician who is not involved in participant recruitment. Study medications (Huanjingjian decoction and placebo) will be manufactured and packaged to be identical in appearance, taste, and packaging. Sealed envelopes containing the randomisation codes will be kept securely by the clinical trial unit and may only be opened in case of a medical emergency or a serious adverse event requiring unblinding. Furthermore, the statisticians conducting the data analysis will maintain blinding during the analysis phase, with datasets identified solely as Group A and Group B to ensure unbiased evaluation.