# Bridging tradition and innovation: electroacupuncture’s impact on premature ovarian insufficiency

**Authors:** Sining He, Lele Ling, Yaran Sheng, Xue Zhao, Long Yuan, Peng Liu, Bingrong Li, Bimeng Zhang

PMC · DOI: 10.3389/fendo.2025.1685306 · Frontiers in Endocrinology · 2026-02-19

## TL;DR

This paper reviews how electroacupuncture may help treat premature ovarian insufficiency by regulating biological pathways and improving ovarian function.

## Contribution

The paper systematically reviews the mechanisms and clinical progress of electroacupuncture in treating POI, integrating traditional and modern scientific approaches.

## Key findings

- Electroacupuncture shows potential in regulating the HPO axis and neuroendocrine-immune network in POI.
- EA may improve ovarian function by modulating pathways like PI3K/Akt and reducing oxidative stress.
- EA treatment regimens have demonstrated efficacy and safety in recent clinical studies.

## Abstract

Premature ovarian insufficiency (POI) refers to the decline in ovarian function in women before the age of 40, which can lead to premature ovarian failure and ultimately lead to infertility. In recent years, the incidence of POI has continued to rise, posing a serious threat to women’s reproductive health and mental well-being. Although hormone replacement therapy (HRT) is currently the most widely used Western medical treatment method, its long-term use may carry risks such as thrombosis and breast cancer, and it is not yet an ideal treatment option. Electroacupuncture(EA), as an important intervention method in complementary and alternative medicine (CAM), has been shown to exert multisystem regulatory effects, particularly showing promising prospects in the intervention of POI. This review focuses on the mechanism of action of EA in the treatment of POI. First, the advantages and disadvantages of common animal modeling methods were analyzed. The effects of EA have been studied in terms of improving ovarian function, regulating the hypothalamic–pituitary–ovarian (HPO) axis, balancing the neuroendocrine–immune network, alleviating inflammatory responses, regulating local ovarian blood flow, activating mesenchymal stem cell function, and regulating the intestinal microbiota. Research on the mechanism of EA regulation of POI focused on analyzing the phospholipid 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway, Hippo signaling pathway, cell apoptosis, and oxidative stress factors. In addition, this paper summarizes the clinical research progress of different EA treatment regimens in recent years, further verifying their efficacy and safety. Looking ahead, research on EA for POI is expected to achieve breakthroughs with the help of cutting-edge technologies, such as establishing personalized and standardized treatment plans; integrating multidimensional technologies such as genomics, transcriptomics, metabolomics, and tissue clearing; and conducting systematic research on the temporal and spatial dynamic changes in ovarian function. Through the interdisciplinary integration of traditional acupuncture theory and modern life science technology, it is hoped that the underlying mechanisms of EA treatment for POI can be further elucidated, thereby providing a solid theoretical foundation and practical guidance for its clinical application.

## Linked entities

- **Proteins:** PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha), AKT1 (AKT serine/threonine kinase 1)
- **Diseases:** thrombosis (MONDO:0000831), breast cancer (MONDO:0004989)

## Full-text entities

- **Genes:** Jun (Jun proto-oncogene, AP-1 transcription factor subunit) [NCBI Gene 24516], FOXO3 (forkhead box O3) [NCBI Gene 2309] {aka AF6q21, FKHRL1, FKHRL1P2, FOXO2, FOXO3A}, Tgfb1 (transforming growth factor, beta 1) [NCBI Gene 59086] {aka Tgfb}, Akt1 (Akt serine/threonine kinase 1) [NCBI Gene 11651] {aka Akt, LTR-akt, PKB, PKB/Akt, PKBalpha, Rac}, Prkaca (protein kinase cAMP-activated catalytic subunit alpha) [NCBI Gene 25636] {aka Cs-PKA, PKCA1}, BECN1 (beclin 1) [NCBI Gene 8678] {aka ATG6, VPS30, beclin1}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, HMOX1 (heme oxygenase 1) [NCBI Gene 3162] {aka HMOX1D, HO-1, HSP32, bK286B10}, Ptgs2 (prostaglandin-endoperoxide synthase 2) [NCBI Gene 29527] {aka COX-2, Cox2, PGHS-2, PHS II, Pghs2}, NR5A1 (nuclear receptor subfamily 5 group A member 1) [NCBI Gene 2516] {aka AD4BP, ELP, FTZ1, FTZF1, POF7, SF-1}, Kitlg (KIT ligand) [NCBI Gene 60427] {aka Kitl, Mgf, SCF}, Cyp19a1 (cytochrome P450, family 19, subfamily a, polypeptide 1) [NCBI Gene 25147] {aka Aromatase, Cyp19, Cyp19a, p450arom}, Mtor (mechanistic target of rapamycin kinase) [NCBI Gene 56718] {aka Frap1, RAFT1}, CXCR4 (C-X-C motif chemokine receptor 4) [NCBI Gene 7852] {aka CD184, D2S201E, FB22, HM89, HSY3RR, LCR1}, FOXL2 (forkhead box L2) [NCBI Gene 668] {aka BPES, BPES1, PFRK, PINTO, POF3}, Kit (KIT proto-oncogene receptor tyrosine kinase) [NCBI Gene 64030], Bax (BCL2 associated X, apoptosis regulator) [NCBI Gene 24887], Il4 (interleukin 4) [NCBI Gene 287287] {aka Il4e12}, Pgr (progesterone receptor) [NCBI Gene 25154], Nfe2l2 (NFE2 like bZIP transcription factor 2) [NCBI Gene 83619], PTEN (phosphatase and tensin homolog) [NCBI Gene 5728] {aka 10q23del, BZS, CWS1, DEC, GLM2, MHAM}, Foxo3 (forkhead box O3) [NCBI Gene 56484] {aka 1110048B16Rik, 2010203A17Rik, FKHRL1, Fkhr2, Foxo3a}, Pik3r1 (phosphoinositide-3-kinase regulatory subunit 1) [NCBI Gene 18708] {aka PI3K, p50alpha, p55alpha, p85alpha}, Bcl2 (BCL2, apoptosis regulator) [NCBI Gene 24224] {aka Bcl-2}, PTK2B (protein tyrosine kinase 2 beta) [NCBI Gene 2185] {aka CADTK, CAKB, FADK2, FAK2, PKB, PTK}, Areg (amphiregulin) [NCBI Gene 29183], PDPK1 (3-phosphoinositide dependent protein kinase 1) [NCBI Gene 5170] {aka PDK1, PRO0461}, CXCL12 (C-X-C motif chemokine ligand 12) [NCBI Gene 6387] {aka IRH, PBSF, SCYB12, SDF1, TLSF, TPAR1}, MAP1LC3A (microtubule associated protein 1 light chain 3 alpha) [NCBI Gene 84557] {aka ATG8E, LC3, LC3A, MAP1ALC3, MAP1BLC3}, Eif4ebp1 (eukaryotic translation initiation factor 4E binding protein 1) [NCBI Gene 116636] {aka PHAS-I}, Yap1 (Yes1 associated transcriptional regulator) [NCBI Gene 363014] {aka YAP65, Yap}, IGF1R (insulin like growth factor 1 receptor) [NCBI Gene 3480] {aka CD221, IGFIR, IGFR, JTK13}, PIK3R1 (phosphoinositide-3-kinase regulatory subunit 1) [NCBI Gene 5295] {aka AGM7, GRB1, IMD36, p85, p85-ALPHA, p85alpha}, Ppargc1a (PPARG coactivator 1 alpha) [NCBI Gene 83516] {aka LRPGC1, PGC-1v, PGCvf, PGCvf-1, PGCvf1, Ppargc1}, KEAP1 (kelch like ECH associated protein 1) [NCBI Gene 9817] {aka INrf2, KLHL19}, SIRT5 (sirtuin 5) [NCBI Gene 23408] {aka SIR2L5}, Prl (prolactin) [NCBI Gene 24683] {aka Gha1, PRLB, PRLSD1, Prl1a1, Prol, RATPRLSD1}, Gnrh1 (gonadotropin releasing hormone 1) [NCBI Gene 25194] {aka Gnrh, Gnrha, Lhrh, Rgnrhg1, SH-4}, FMR1 (fragile X messenger ribonucleoprotein 1) [NCBI Gene 2332] {aka FMRP, FRAXA, POF, POF1}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, Sirt1 (sirtuin 1) [NCBI Gene 309757] {aka Sir2}, Tafazzin (tafazzin, phospholipid-lysophospholipid transacylase) [NCBI Gene 363521] {aka Taz}, BAX (BCL2 associated X, apoptosis regulator) [NCBI Gene 581] {aka BCL2L4}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, Notch1 (notch receptor 1) [NCBI Gene 25496] {aka NOTCH, TAN1}, AMH (anti-Mullerian hormone) [NCBI Gene 268] {aka MIF, MIS}, Creb1 (cAMP responsive element binding protein 1) [NCBI Gene 81646] {aka Creb}, PDK1 (pyruvate dehydrogenase kinase 1) [NCBI Gene 5163], BCL2 (BCL2 apoptosis regulator) [NCBI Gene 596] {aka Bcl-2, PPP1R50}, Amh (anti-Mullerian hormone) [NCBI Gene 25378] {aka MIS}, Tnf (tumor necrosis factor) [NCBI Gene 24835] {aka RATTNF, TNF-alpha, Tnfa}, Kl (Klotho) [NCBI Gene 83504], BMP15 (bone morphogenetic protein 15) [NCBI Gene 9210] {aka GDF9B, ODG2, POF4}, CAT (catalase) [NCBI Gene 847], NFE2L2 (NFE2 like bZIP transcription factor 2) [NCBI Gene 4780] {aka IMDDHH, NRF2, Nrf-2}, Wwtr1 (WW domain containing transcription regulator 1) [NCBI Gene 295062], CTNNB1 (catenin beta 1) [NCBI Gene 1499] {aka CTNNB, EVR7, MRD19, NEDSDV, armadillo}, Ace2 (angiotensin converting enzyme 2) [NCBI Gene 302668], Ifng (interferon gamma) [NCBI Gene 25712] {aka IFNG2, If2f}, NUP62 (nucleoporin 62) [NCBI Gene 23636] {aka IBSN, SNDI, p62}
- **Diseases:** estrogen deficiency (MESH:D056828), inflammatory cytokines (MESH:D000080424), amenorrhoea (MESH:C537962), rash (MESH:D005076), spleen deficiency (MESH:D013160), AITD (MESH:D013967), endometrial hyperplasia (MESH:D004714), autoimmune attacks (MESH:D001327), nausea (MESH:D009325), chronic pain (MESH:D059350), depression (MESH:D003866), breast cancer (MESH:D001943), CMV (MESH:D003586), gynecological diseases (MESH:D005831), fatigue (MESH:D005221), stress urinary incontinence (MESH:D014550), Addison's disease (MESH:D000224), ovulatory dysfunctions (MESH:D006331), blood stasis (MESH:D014647), liver depression (MESH:D017093), vaginal dryness (MESH:D014627), decline in ovarian function (MESH:D010051), tuberculosis (MESH:D014376), HIV (MESH:D015658), immune dysregulation (OMIM:614878), metabolic abnormalities (MESH:D008659), fragile X syndrome (MESH:D005600), TS (MESH:D014424), kidney deficiency (MESH:D007680), DOR (MESH:D010049), cognitive decline (MESH:D003072), SLE (MESH:D008180), amenorrhea (MESH:D000568), radiation damage (MESH:D011832), Infectious (MESH:D003141), POF (MESH:D016649), Emotional injury (MESH:D014947), headaches (MESH:D006261), Chronic inflammation (MESH:D007249), pituitary dysfunction (MESH:D010900), fibrosis (MESH:D005355), rheumatoid arthritis (MESH:D001172), hematomas (MESH:D006406), abnormal (MESH:D000014), thrombosis (MESH:D013927), PCOS (MESH:D011085), ovarian failure (MESH:C564499), blood deficiency (MESH:D006402), breast tenderness (MESH:D061325), lipid metabolism abnormalities (MESH:D052439), malnourished (MESH:D044342), Congenital deficiency (MESH:D007153), venous thromboembolism (MESH:D054556), hot flashes (MESH:D019584), Parkinson's disease (MESH:D010300), viral infections (MESH:D014777), follicular (MESH:D005497), mitochondrial damage (MESH:D028361), menstrual disorders (MESH:D004412), irritability (MESH:D001523)
- **Chemicals:** taurine (MESH:D013654), phospholipids (MESH:D010743), GSH (MESH:D005978), steroid (MESH:D013256), lipid (MESH:D008055), paeoniflorin (MESH:C015423), phosphatidylinositol 3-phosphate (MESH:C055525), 4-vinylcyclohexene dioxide (MESH:C012606), BPA (MESH:C006780), LH (MESH:D007986), cadmium (MESH:D002104), glutamate (MESH:D018698), glucose (MESH:D005947), malic acid (MESH:C030298), glycine (MESH:D005998), hydroxyl radicals (MESH:D017665), heavy metal (MESH:D019216), cAMP (MESH:D000242), cyclophosphamide (MESH:D003520), GV20 (-), cisplatin (MESH:D002945), T (MESH:D014316), vitamin D (MESH:D014807), P (MESH:D010758), Phthalates (MESH:C032279), NO2 (MESH:D009585), E2 (MESH:D004958), phosphatidylcholine (MESH:D010713), Nicotine (MESH:D009538), MDA (MESH:D008315)
- **Species:** Brucella (genus) [taxon 234], Severe acute respiratory syndrome coronavirus 2 (no rank) [taxon 2697049], gut metagenome (species) [taxon 749906], Faecalibacterium (genus) [taxon 216851], mumps virus [taxon 1979165], Rattus norvegicus (brown rat, species) [taxon 10116], Bacteroides (genus) [taxon 816], Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** C57BL/6J — Mus musculus (Mouse), Transformed cell line (CVCL_C0MW)

## Full text

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## Figures

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## References

165 references — full list in the complete paper: https://tomesphere.com/paper/PMC12960178/full.md

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Source: https://tomesphere.com/paper/PMC12960178