Acupuncture for Insulin Resistance in Women With Polycystic Ovary Syndrome

Effects of Acupuncture on Homeostatic Model Assessment of Insulin Resistance in Women With Polycystic Ovary Syndrome: Study Protocol for a Randomized Controlled Trial

This two-stage clinical research programme aims to evaluate the preliminary effectiveness and safety of acupuncture for improving insulin resistance in women with polycystic ovary syndrome (PCOS). Phase I will be a prospective, single-centre, open-label, single-arm exploratory trial involving 20 participants, all of whom will receive active acupuncture plus lifestyle management. Acupuncture will be administered three times per week for 12 weeks, followed by a 12-week follow-up period. The study will primarily assess safety, tolerability, feasibility, and the preliminary change in the homeostatic model assessment of insulin resistance (HOMA-IR) from baseline to Week 12. The effect size and variability of HOMA-IR change, together with safety, adherence, and dropout data obtained from Phase I, will be used to determine the sample size and finalize the design of Phase II. Phase II is planned as a prospective, multicentre, parallel, randomized, participant- and outcome assessor-blinded, sham-controlled trial comparing active acupuncture plus lifestyle management with sham acupuncture plus lifestyle management to confirm the effectiveness and safety of the intervention.

Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder among women of reproductive age. Insulin resistance is considered an important pathogenic feature of PCOS and is associated with hyperandrogenism, ovulatory dysfunction, infertility, and an increased long-term risk of type 2 diabetes and cardiovascular disease. Although acupuncture has been used for reproductive and metabolic disorders, evidence regarding its effects on insulin resistance in women with PCOS remains limited.

This clinical research programme consists of two sequential phases. Phase I is a prospective, single-centre, open-label, single-arm exploratory clinical trial. A total of 20 women with PCOS will be enrolled, and all participants will receive active acupuncture plus lifestyle management. The objectives of Phase I are to evaluate the safety, tolerability, and feasibility of the intervention and to explore its preliminary effects on insulin resistance in women with PCOS.

Participants will receive 30-minute acupuncture sessions three times per week for 12 consecutive weeks, for a maximum of 36 treatment sessions. Active acupuncture will be performed using two standardized sets of acupuncture points that will be used alternately. Needles will be inserted to an appropriate depth and manually stimulated to elicit de qi. Selected acupuncture points will receive low-frequency electrical stimulation at 2 Hz. Acupuncture points not connected to the electrical stimulator will be manually stimulated at regular intervals during each treatment session.

All participants will receive individualized lifestyle management beginning at baseline. The lifestyle programme combines nutritional consultation, dietary and physical activity guidance, a web- and mobile-based PCOS management platform, and a wearable step counter. Participants will record their dietary intake and physical activity and will receive regular feedback from the research team.

The Phase I treatment period will last 12 weeks, followed by a 12-week post-treatment follow-up period. Outcomes will be assessed at baseline, Week 12, and Week 24. Safety outcomes will include adverse events, treatment-related adverse events, serious adverse events, and treatment discontinuations. Preliminary effectiveness will be assessed primarily by the change in the homeostatic model assessment of insulin resistance (HOMA-IR) from baseline to Week 12. Outcomes at Week 24 will be used to explore the durability of the intervention effects.

Secondary and exploratory outcomes will include anthropometric measurements and body composition; glucose metabolism and insulin resistance parameters; reproductive endocrine parameters; lipid profiles; menstrual frequency; ovarian morphology and ovulation status; health-related quality of life; anxiety and depression symptoms; traditional Chinese medicine constitution characteristics; treatment adherence; and participant retention. Adverse events will be monitored throughout the treatment and follow-up periods.

The magnitude and variability of the change in HOMA-IR, together with the safety, feasibility, recruitment, adherence, and dropout findings obtained from Phase I, will be used to determine whether the clinical research programme should proceed to Phase II. These Phase I data will also be used to calculate the required sample size and finalize the detailed design of the Phase II trial. Therefore, the Phase II sample size has not yet been fixed and may change according to the Phase I results.

If the Phase I findings support progression, Phase II will be conducted as a prospective, multicentre, parallel, randomized, participant- and outcome assessor-blinded, sham-controlled clinical trial. Eligible participants will be randomly allocated in a 1:1 ratio to one of the following groups:

Active acupuncture plus lifestyle management.

Sham acupuncture plus lifestyle management.

Participants in both Phase II groups will receive 30-minute active or sham acupuncture sessions three times per week for 12 consecutive weeks, followed by a 12-week follow-up period. Active acupuncture will follow the standardized protocol used and evaluated in Phase I. Sham acupuncture will involve superficial needle insertion at non-acupuncture and non-meridian points without manual stimulation. Electrodes will be attached, but the electrical stimulator will be set to zero intensity.

All Phase II participants will receive the same standardized lifestyle-management programme. Outcomes are planned to be assessed at baseline, Week 12, and Week 24. The principal Phase II efficacy outcome is expected to be the between-group difference in the change in HOMA-IR from baseline to Week 12. Phase II will confirm the effectiveness and safety of active acupuncture plus lifestyle management compared with sham acupuncture plus lifestyle management. The final Phase II protocol, outcome hierarchy, statistical analysis plan, and sample size will be specified after the Phase I results have been reviewed and before Phase II recruitment begins.

Inclusion Criteria:

• Age 20 to 40 years
• BMI ≥ 24 and <40
• PCOS diagnosis according to Rotterdam criteria 2003 [23] with at least two of the following three symptoms: (1) infrequent ovulation or anovulation; (2) hyperandrogenism or clinical manifestations of high blood androgen; (3) ultrasound findings of polycystic ovaries in 1 or 2 ovaries, or ≥12 follicles measuring 2 to 9 mm in diameter, and/or ovarian volume ≥10 mL
• Voluntarily participate in this research project and sign the informed consent form

Exclusion Criteria:

• Exclusion of other endocrine disorders such as androgen secreting tumors, suspected Cushing's syndrome and non-classic congenital adrenal hyperplasia, thyroid dysfunction and hyperprolactinemia
• Type I diabetes or not well controlled type II diabetes
• Pharmacological or acupuncture treatment within past 3 months
• Pregnancy or breastfeeding in the last 6 months
• Blood pressure >160/100mmHg
• Daily smoking and alcoholic intake
• Mental problems
• Language or mental disorders, or inability to understand the experimental content