Ovarian health is essential for fertility, hormonal balance, and overall well-being. Conditions like Premature Ovarian Insufficiency (POI), Polycystic Ovary Syndrome (PCOS), and menopause can impair ovarian function, leading to irregular periods, infertility, and long-term health risks.

Fisetin, a plant-based compound, is currently gaining attention for its ability to support hormone balance and ovarian function. It's now a promising ingredient in ovarian health supplements, offering a natural alternative to conventional therapies.

This article explores how fisetin may help manage POI, relieve PCOS symptoms like insulin resistance, and ease menopause-related discomfort such as hot flashes and mood swings. It also explains what fisetin is and why it’s becoming a top choice in PCOS, hormonal balance, and ovarian health supplements.

What is Fisetin?

Fisetin is a distinctive flavonoid—a subgroup of polyphenols renowned for their health benefits. Naturally present in various fruits and vegetables, it’s most concentrated in strawberries, which provide about 100 mg of fisetin per 625 grams.

Other notable dietary sources include apples, persimmons, onions, cucumbers, and Emblica (Indian gooseberry).

Fisetin and Premature Ovarian Insufficiency (POI)

Premature Ovarian Insufficiency, or POI, occurs when ovarian function declines before the age of 40. Women with POI may experience irregular or absent periods, elevated follicle-stimulating hormone (FSH) levels, low estrogen, infertility, and menopausal symptoms like hot flashes and mood swings.

A recent 2024 study from Zhejiang University’s College of Animal Science demonstrated that dietary fisetin supplementation improved ovarian function in aged laying hens — a model often used to study ovarian aging. The study found that fisetin[1]:

• Increased egg production and eggshell quality
• Reduced follicular atresia (the degeneration of ovarian follicles)
• Promoted ovarian cell proliferation
• Raised serum estrogen and progesterone levels
• Restored antioxidant defenses in ovarian tissue
• Enhanced energy metabolism pathways

Mechanistically, fisetin upregulated SIRT1, a key protein that promotes cellular health and metabolism, and inhibited NF-κB, an inflammatory signaling pathway. It also activated AKT and JNK pathways, which support glucose metabolism and reduce apoptosis (cell death) in ovarian follicles. These actions collectively help balance ovarian energy metabolism and delay ovarian aging.

This research highlights the potential for fisetin to serve as a natural ovarian health supplement to support women facing POI and other ovarian aging conditions.

Fisetin’s Role in Delaying Oocyte Aging

The quality of oocytes (egg cells) after ovulation directly affects fertilization and embryo development. Unfortunately, oocytes age quickly after ovulation, especially in assisted reproductive technologies (ART), resulting in lower fertilization rates and impaired embryonic growth.

Research from South China Agricultural University found that fisetin delays aging in mouse oocytes by[2]:

• Enhancing antioxidant defenses through increased glutathione (GSH) and Sod2 gene expression
• Reducing reactive oxygen species (ROS) accumulation
• Improving spindle formation and mitochondrial function
• Decreasing apoptosis
• Regulating epigenetic markers like H3K9me3
• Upregulating mitochondrial genes (Tfam, Co2, Atp8) through increased Sirt1 expression

These findings suggest that fisetin supplement benefits include improving fisetin fertility potential by preserving egg cell quality and function, which is crucial for women experiencing fertility challenges or undergoing ART.

Fisetin Benefits for PCOS: A Natural Alternative to Metformin

PCOS is a common endocrine and metabolic disorder affecting up to 20% of women of reproductive age. It is characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology, often accompanied by insulin resistance. Metformin is the conventional treatment to improve insulin sensitivity and hormonal balance.

Several animal studies have demonstrated that fisetin can effectively target multiple pathological aspects of PCOS:

• In one rat model of letrozole-induced PCOS, fisetin (10 mg/kg) significantly normalized blood glucose, lipid profiles, insulin resistance (HOMA-IR), and hormone levels, including testosterone, estradiol, and progesterone. It also increased ovarian SIRT1 and AMPK expression and enhanced antioxidant enzyme activity (CAT, SOD, GPx), thereby providing ovarian-protective effects through modulation of the SIRT1/AMPK signaling pathway.
  Notably, these therapeutic effects were comparable to those of metformin (300 mg/kg), suggesting that fisetin may serve as a promising natural alternative to metformin in the management of PCOS[3].
• Another study showed high-dose fisetin reduced inflammation markers (TNF-α, IL-6), oxidative stress, and hormone imbalances, while increasing progesterone, follicle-stimulating hormone (FSH), GSH, and SOD activity. These benefits were reversed when AMPK was inhibited, indicating that fisetin acts via the AMPK/SIRT1 signaling pathway[4].

With its multi-targeted actions—from improving metabolic and hormonal balance to enhancing antioxidant defenses—fisetin offers a promising natural alternative to metformin, making it an appealing supplement-based approach for managing PCOS.

Supporting Hormonal Balance and Menopause with Fisetin

Hormonal fluctuations during PCOS and menopause can cause symptoms such as mood swings, hot flashes, and irregular cycles. Fisetin supports hormonal balance by:

• Raising estrogen and progesterone levels
• Reducing inflammation and oxidative stress in ovarian tissues
• Enhancing antioxidant defenses
• Regulating metabolic pathways involved in hormone production

This makes fisetin an attractive ingredient for hormonal balance supplements designed to ease symptoms related to both PCOS and menopause.

Why Consider Fisetin Supplements?

Although fisetin is found naturally in foods, typical dietary intake is relatively low. To obtain therapeutic effects as seen in studies, fisetin supplements provide concentrated and bioavailable forms.

Women looking to support ovarian health, improve fertility, manage PCOS symptoms, or maintain hormonal balance during menopause may benefit from fisetin supplementation.

Contact us to learn more about the benefits of Fisetin supplements.

References：
1. Zhaoyu Yang, Jiaxuan Zhang, et al. Flavonoid Fisetin Alleviates Ovarian Aging of Laying Chickens by Enhancing Antioxidant Capacity and Glucose Metabolic Homeostasis.  Antioxidants 2024, 13(12), 1432. doi: 10.3390/antiox13121432. PMID: 39765761
2.Xupeng Xing, Yalin Liang,et al. Fisetin Delays Postovulatory Oocyte Aging by Regulating Oxidative Stress and Mitochondrial Function through the Sirt1 Pathway. Molecules. 2023 Jul 20;28(14):5533. doi: 10.3390/molecules28145533. PMID: 37513404
3.Aynaz Mihanfara,Mohammad Nouri,et al. Ameliorative effects of fisetin in letrozole-induced rat model of polycystic ovary syndrome. The Journal of Steroid Biochemistry and Molecular Biology Volume 213, October 2021,105954. doi: 10.1016/j.jsbmb.2021.105954. Epub 2021 Jul 21. PMID: 34298098.
4.Simerjeet Kaur Chahal,Atul Kabra.Fisetin ameliorates polycystic ovary syndrome in rats via a mechanistic modulation of AMP-activated protein kinase and SIRT1 molecular pathway.Naunyn Schmiedebergs Arch Pharmacol. 2024 Dec;397(12):10017-10029. doi: 10.1007/s00210-024-03257-7. Epub 2024 Jul 4. PMID: 38963551