Written by Tabish Mehraj, PhD. In this study, crocin significantly improved Follicle-stimulating hormone levels (P = 0.048) and reduced hirsutism, as measured by the Ferriman–Gallwey score (P = 0.042), by day 90. It also significantly improved acne severity (P = 0.03), with no patients in the crocin group having severe acne at the end of the study. However, crocin did not significantly improve fasting blood sugar.

Polycystic ovary syndrome (PCOS) is a common metabolic disorder associated with menstrual irregularity, hirsutism, acne, and insulin resistance. Metformin remains a central treatment, but its benefits may be incomplete, and gastrointestinal intolerance is common. Crocin is a major bioactive component of saffron (Crocus sativus L.), which has antioxidant and anti-inflammatory properties and could be beneficial for reducing insulin sensitivity and supporting reproductive hormone balance. This study evaluated whether adding crocin to metformin improves biochemical and clinical aspects of PCOS compared to metformin alone.

This randomized, double-blind, placebo-controlled clinical trial was conducted at a university-affiliated obstetrics and gynecology clinic in Yazd, Iran. Women aged 18–44 years with PCOS were grouped in a 1:1 ratio to receive either crocin 15 mg once daily plus metformin 500 mg twice daily or a matching placebo plus metformin 500 mg twice daily for 12 weeks, corresponding to three menstrual cycles. Serum fasting blood sugar (FBS), dehydroepiandrosterone sulfate (DHEA-S), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were measured at baseline and study completion. Clinical outcomes included Ferriman–Gallwey hirsutism score, acne severity, menstrual pattern, blood pressure, and Dermatology Life Quality Index (DLQI). Statistical analyses used between-group and within-group comparisons, with statistical significance defined as p<0.05.

Results/Key Findings

• Out of 86 women screened, 50 were randomized to crocin (n=25) or placebo (n=25); after 10 exclusions, 40 participants completed the study (crocin, n=19; placebo, n=21). Baseline characteristics were generally similar between groups.
• By day 90, crocin significantly increased serum FSH compared with placebo (p=0.048) and produced greater improvements in hirsutism, as measured by the Ferriman–Gallwey score (p=0.042), and in acne severity (p=0.029). No participants in the crocin group had severe acne at the final assessment.
• Crocin did not significantly differ from placebo in LH, fasting blood glucose, DHEA-S, blood pressure, quality of life, or menstrual-pattern distribution (all p>0.05), although menstrual cycles normalized in 90.5% of the crocin group versus 68.4% of the placebo group.
• Mild sleep disturbances, nausea, and vomiting were reported, but no participants discontinued treatment because of adverse effects.

There are a few important strengths to the study, including the randomized, double-blind design, use of a matched placebo, concurrent metformin treatment in both groups, trial registration, standardized assessment of hirsutism using the Ferriman–Gallwey scale, and evaluation of both biochemical markers and patient-relevant dermatological outcomes. The study also addresses a meaningful gap by examining crocin as an adjunctive treatment for symptoms that substantially affect women with PCOS. A few limitations are the final sample size, attrition related to the COVID-19 pandemic, irregular follow-up, and metformin intolerance, which reduced the analyzable population. The reported statistical power for the primary LH outcome was only 0.55, limiting the ability to detect clinically relevant differences in LH. The 12-week duration was insufficient to establish long-term efficacy, safety, fertility effects, or sustained changes in menstrual function. Important PCOS-related variables, including insulin, body weight, lipid profile, inflammatory markers, cardiometabolic indices, and fertility status, were not assessed. The study used a relatively low crocin dose of 15 mg/day, so the dose-response relationship remains unknown.

In women with PCOS receiving metformin, adjunctive crocin 15 mg daily for 12 weeks was associated with improvements in FSH, hirsutism, and acne, without apparent treatment-limiting toxicity. However, it did not significantly improve LH, glycemic status, DHEA-S, blood pressure, quality of life, or menstrual-pattern distribution compared with metformin alone. These findings suggest a possible benefit for selected hyperandrogenic dermatological manifestations but do not establish crocin as a comprehensive PCOS treatment. Larger, adequately powered, longer-term trials with higher, standardized doses, intention-to-treat analyses, broader metabolic and reproductive outcomes, and systematic safety monitoring are warranted.

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Posted October 8, 2026.

Dr. Tabish Mehraj is a pharmaceutical scientist with expertise in pharmaceutics, drug delivery, and formulation development. She earned her PhD in Pharmaceutical Sciences from the University of Mississippi, where her research focused on the formulation, optimization, and characterization of lipid-based nanocarriers for targeted liver delivery of antimalarial therapeutics. Dr. Mehraj has also served as an ORISE Fellow at the U.S. Food and Drug Administration (FDA), where she evaluated the effects of formulation and process design on the quality and performance of intravaginal drug delivery systems and developed bio-relevant in vitro drug release testing methods. She has teaching experience in pharmaceutical and life sciences courses and has authored peer-reviewed publications, book chapters, and conference presentations. Dr. Mehraj is an active member of the American Association of Pharmaceutical Scientists and has been recognized by honor societies including Rho Chi and Gamma Beta Phi.

Reference:

1. Saghafi, F., Javaheri, A., Mohammadi, F., Hatamizadeh, N., Khanizadeh, F., Safakish, M., & Sahebnasagh, A. (2025). Evaluation of therapeutic effects of Crocin in patients with polycystic ovary syndrome: A randomized Double-Blind clinical trial. Journal of Pharmaceutical Health Care and Sciences, 11(1), 69.