Dihydroartemisinin for the Treatment of Polycystic Ovary Syndrome

Official title

Dihydroartemisinin for the Treatment of Polycystic Ovary Syndrome: a Multi-centre Placebo-controlled Randomized Clinical Trial

Overview

Polycystic ovarian syndrome (PCOS) is the most frequent endocrine disorder affecting women of reproductive age, with a prevalence of 10 to 13%. PCOS is characterized by irregular menstrual cylcles/ovulatory dysfunction, hyperandrogenism, and polycystic ovarian morphology. For infertile patients seeking ovulation induction, letrozole is the drug of first choice. For PCOS patients not seeking pregnancy, there exists a variety of treatments to alleviate symptoms. It has been demonstrated that artemisinin derivatives can promote energy expenditures and insulin sensitivity by activating thermogenic adipocytes, thereby protecting against diet-induced obesity and metabolic disorders in rodents. Recently, we showed in a single arm pilot study including 19 PCOS-patients, that dihydroartemisinin ameliorated hyperandrogenemia reduced antral follicle count and normalized menstrual cycles. Based on these findings, we aim to evaluate the efficacy of dihydroartemisinin in women with PCOS in a placebo controlled randomized clinical trial. The primary outcome is return of regular menstrual cycles within 6 months after start of treatment, with antral follicle count and metabolic profile being secondary outcomes. The results will potentially impact the standard of care for patients diagnosed with PCOS.

Interventions

• Drug Dihydroartemisinin
  Dihydroartemisinin tablets 40mg tid po for 90 days
• Drug Placebo
  Identical placebo tid for 90 days

Primary outcome measures

• The occurrence of a regular menstrual cycle [Time frame: From the start of treatment to the end of follow-up at 26 weeks]

Secondary outcome measures (7)

• The presence of a dominant follicle [Time frame: From the start of treatment to the end of follow-up at 26 weeks]
• The number of bilateral antral follicles [Time frame: Before and immediately after 90-day treatment]
• Serum AMH [Time frame: Before and immediately after 90-day treatment]
• Serum total testosterone [Time frame: Before and immediately after 90-day treatment]
• Serum sex hormone binding globulin (SHBG) [Time frame: Before and immediately after 90-day treatment]
• free androgen index (FAI) [Time frame: Before and immediately after 90-day treatment]
• HOMA-IR [Time frame: Before and immediately after 90-day treatment]

Eligibility criteria

Inclusion criteria

• Women with PCOS defined as having irregular menstrual cycles and hyperandrogenism. Irregular menstrual cycles are defined as < 21 or > 35 days or < 8 cycles per year. Hyperandrogenism refers to either hyperandrogenemia or hirsutism. Hyperandrogenemia will be defined as an elevated total testosterone >1.67 nmol/L measured by Elecsys Testosterone II (Roche Diagnostics). Hirsutism is determined by a modified Ferriman-Gallwey Score >4 at screening exam.
• Body Mass Index (BMI) between 18.5 and 28 kg/M2
• Negative pregnancy test
• No plan for pregnancy in the coming 6 months

Exclusion criteria

• Patients on oral contraceptives. A two-month washout period will be required prior to screening for patients on these agents. A one-month washout will be required for patients on oral cyclic progestins. Patients on depo-progestins or hormonal implants are excluded.
• Patients with liver disease defined as ALT or AST above normal range of each participating center, or total bilirubin>30umol/L. Metabolic dysfunction-associated steatotic liver disease (MASLD) with normal ALT and AST can be included.
• Patients with anemia (Hemoglobin < 12 g/dL) or neutropenia (neutrocyte <1.8×10\^9/L).
• Patients with renal disease defined as serum creatinine> 115umol/L.
• Patients diagnosed with other endocrine diseases that are known to cause secondary polycystic ovary morphology, e.g., Cushing's syndrome, hyperprolactinemia, congenital adrenal hyperplasia (21-hydroxylase deficiency or other enzyme deficiency), hypothyroidism, etc.
• Patients diagnosed with Type 1 or Type 2 diabetes.
• Patients with known heart disease, like heart failure, atrial fibrillation, coronary heart disease, etc.
• Patients with a history of any type of cancer.
• Patients taking other medications known to affect reproductive function or metabolism. These medications include GnRH agonists and antagonists, antiandrogens, gonadotropins, GLP-1 receptor agonist, SGLT2i, metformin and thiazolidinediones. The washout period on all these medications will be two months.
• Patients who have undergone a bariatric surgery procedure within the past 12 months.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

China · 4 centers

• The First Affiliated Hospital of Xiamen University — Xiamen
• Women and Children's Hospital, School of Medicine, Xiamen University — Xiamen
• Zhongshan Hospital Fudan University — Shanghai
• The First Affiliated Hospital of Wenzhou Medical University — Wenzhou

Publications

• Mu L, Shen Y, Wang G, Liu C, Yang H, Li W, Mol BW, Li X, Dong X, Jiang J. Dihydroartemisinin for the treatment of polycystic ovary syndrome: study protocol for a multi-centre placebo-controlled randomised clinical trial. BMJ Open. 2026 Jun 19;16(6):e108980. doi: 10.1136/bmjopen-2025-108980. PMID 42320967

Identifiers

NCT: NCT06842524 · B2024-417(2)

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗