This study aimed to evaluate the comparative efficacy of Myo-inositol (MI) and D-chiro-inositol (DCI) with metformin in enhancing ovarian function, promoting ovulation, and reducing perceived stress in patients with polycystic ovary syndrome (PCOS). Women with PCOS were identified using the Androgen Excess Society's criteria, and 60 participants were enrolled and divided equally into two groups. One group received a 40:1 ratio of MI plus DCI, while the other received metformin for a 12-week period. Endocrine and metabolic parameters, insulin-resistance, stress levels, and quality of life were assessed pre- and post-treatment. Both MI plus DCI and metformin significantly improved insulin sensitivity (HOMA-IR, p < 0.001), SHBG levels (p = 0.021), ovarian volume (p < 0.001), and menstrual regularity (p = 0.002), along with BMI, quality of life, and PSS scores (p < 0.001). Metformin showed slightly better outcomes in certain parameters, such as insulin sensitivity and endocrine markers, probably due to a higher representation of Phenotype A. In contrast, we hypothesize that MI plus DCI may be more effective for Phenotypes C and D. Our findings support both MI plus DCI and metformin as effective treatments for PCOS, with each treatment offering specific benefits. These results highlight the potential for a phenotype-specific tailored therapeutic approach to better manage the complex metabolic, endocrine, and stress-related challenges of PCOS. Trial Registration: clinicalTrial.gov NCT05767515. Registered 3 February, 2023.
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