Polycystic Ovary Syndrome (PCOS)
Conditions
Keywords
Polycystic Ovary Syndrome, Dihydroartemisinin
Brief summary
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
Dihydroartemisinin tablets 40mg tid po for 90 days
DRUGPlacebo
Identical placebo tid for 90 days
Sponsors
Shanghai Zhongshan Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 40 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The occurrence of a regular menstrual cycle | From the start of treatment to the end of follow-up at 26 weeks | The occurrence of a regular menstrual cycle is defined as at least three consecutive spontaneous vaginal bleedings lasting for 2-7 days, with intervals between the start of each cycle of 21 and 35 days (inclusive), during the 26-week period after initiating treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The number of bilateral antral follicles | Before and immediately after 90-day treatment | This will be measured by transvaginal/transanal ultrasound before and immediately after 90-day treatment. Antral follicles are defined as follicles measuring 2-9 mm in diameter in the ovary. |
| Serum AMH | Before and immediately after 90-day treatment | This will be measured before and immediately after 90-day treatment. |
| Serum total testosterone | Before and immediately after 90-day treatment | This will be measured before and immediately after 90-day treatment. |
| The presence of a dominant follicle | From the start of treatment to the end of follow-up at 26 weeks | This will be verified by transvaginal/transanal ultrasound before predicted ovulation, or testing serum progesterone in the predicted mid-luteal phase (A progesterone level\>16nmol/L or 5ng/ml is suggestive of ovulation) in those with at least two consecutive spontaneous bleedings. |
| free androgen index (FAI) | Before and immediately after 90-day treatment | This will be calculated before and immediately after 90-day treatment. FAI is calculated from measurable values for total testosterone and SHBG, using the following equation: FAI = (Total testosterone in nmol/L / SHBG in nmol/L) × 100. |
| HOMA-IR | Before and immediately after 90-day treatment | HOMA-IR will be calculated before and immediately after 90-day treatment. HOMA-IR is calculated using the following equation: HOMA-IR = fasting plasma glucose in mmol/L×fasting insulin in μU/ml/22.5. |
| Serum sex hormone binding globulin (SHBG) | Before and immediately after 90-day treatment | This will be measured before and immediately after 90-day treatment. |
Countries
China
Contacts
Primary ContactLiangshan Mu, MD, PhD
Outcome results
None listed