The Effect of Dihydroartemisinin in PCOS

Phase 4

Completed

• Conditions: Polycystic Ovary Syndrome
• Interventions: Drug: Dihydroartemisinin

• Registration Number: NCT05465135
• Lead Sponsor: Shanghai Zhongshan Hospital

Brief Summary

Artemisinin has been widely used as a first-line antimalarial drug in routine clinical practice. In recent years, it has been reported that Artemisinin also has some significant anti-inflammatory, anti-tumor and immune-modulating effects. The investigators' previous studies discovered that Artemisinin dramatically reduced serum androgen levels and improved poly-cystic ovary syndrome(PCOS) in animals. Preliminary study by the investigators found that artemisinin derivatives are capable of reducing both androgen levels and improving insulin resistance, two clinical characteristics of PCOS. Thus artemisinin derivatives has the potential effect to alleviate PCOS symptoms. The current study aims to investigate the effect of artemisinin on improving PCOS and serum androgen levels in PCOS subjects.

Detailed Description

Polycystic ovary syndrome (PCOS) is a common reproductive endocrine metabolic disorder caused by a combination of genetic and environmental factors. The pathogenesis of PCOS remains unclear. Artemisinin has been widely used as a first-line antimalarial drug in routine clinical practice. In recent years, it has been reported that Artemisinin has significant anti-inflammatory, anti-tumor and immune-modulating effects. The investigator's previous studies found that artemisinin and its derivatives could significantly promote uncoupling protein 1 (UCP1) transcription and the conversion of white fat to brown fat. Artemisinin derivatives upregulated the levels of genes critical for brown fat differentiation and function, accompanied by enhanced mitochondrial biosynthesis, demonstrating their potential to promote white fat browning and improve metabolism in rodent models. The investigators also observed that androgen levels in drug-induced PCOS rats were reduced, when treated with artemether analogs for prophylactic and therapeutic purposes, respectively. It is believed that the two core mechanisms in the pathogenesis of PCOS are excessive androgen synthesis and insulin resistance. Preliminary study by the investigators found that artemisinin derivatives are capable of reducing both serum androgen levels and improving insulin resistance, two clinical characteristics of PCOS. Thus artemisinin derivatives has the potential effect to alleviate PCOS symptoms and control or even reverse the disease progression. The current study aims to investigate the effect of artemisinin on improving PCOS and serum androgen levels in PCOS subjects.

Study Timeline

• Study Start: 2022-07-01
• Study First Submitted: 2022-07-10
• Study First Submitted QC: 2022-07-15
• Study First Posted: 2022-07-19
• Primary Completion: 2023-03-23
• Study Completion: 2023-04-23
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-17
• Last Update Posted: 2024-05-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 19

Inclusion Criteria

• BMI 23-30kg/M2

• No plan for pregnancy in the coming 6 months

• Newly diagnosed PCOS, or PCOS without any medication for the past three months.

• Patients should meet all the three following criteria:

  1. Oligomenorrhea or amenorrhea: Oligomenorrhea is defined as more than 35 days between menstrual periods and less than 8 menstrual bleedings in the past year; amenorrhea is defined as more than 90 days between two menstrual bleedings.
  2. Polycystic ovaries: ≥12 follicles in both ovaries (diameter<10mm), confirmed by ultrasound.
  3. Elevated androgen levels: testosterone>1.67 nmol/L.

Exclusion Criteria

• Previously treated with steroids or other medications for PCOS in the past 3 months.
• Patients with other endocrine diseases that can cause secondary PCOS, including but not limited to: 21 hydroxylase deficiency, prolactinoma, hypothyroidism, Cushing's syndrome, etc.
• Pregnancy.
• Patients with other serious diseases affecting heart, liver, kidney, or other major organs.
• Patients with any type of cancer.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Dihydroartemisinin Group	Dihydroartemisinin	The subjects take Dihydroartemisinin, 40mg tid for 12 weeks

Primary Outcome Measures

Name	Time	Method
Recovery of regular menses by questionnaire	12 weeks	Periodical vaginal bleeding by questionnaire
Bilateral ovary volume	12 weeks	Length, width and height of bilateral ovaries measured by B type ultrasound
Number of immature follicles	12 weeks	Total number of follicles with diameters \<10 mm measured by B type ultrasound
Serum testosterone levels	12 weeks	Measurement of serum total testosterone

Secondary Outcome Measures

Name	Time	Method
Sex hormone binding globulin (SHBG)	12 weeks	Measurement of serum SHBG
Serum anti-Mullerian hormone	12 weeks	Measurement of serum AMH
Serum dehydroepiandrosterone sulfate	12 weeks after drug intervention	Measurement of serum DHEA

Trial Locations

Locations (1)

Zhongshan Hospital Fudan University; 🇨🇳 Shanghai, China