# Potential association between endocrine disrupting chemicals (EDCs) and gynecomastia: a systematic review based on partial experimental evidenceendocrine-disrupting chemicals

**Authors:** Haobo Wang, Mengdie Wang, Cuihong Fan, Yueyao Sun, Jianping Feng, Meng He, Ning Li, Fangjian Shang, Bo Liu

PMC · DOI: 10.3389/fendo.2026.1734644 · 2026-02-03

## TL;DR

This paper reviews how endocrine-disrupting chemicals may contribute to gynecomastia in men by disrupting hormone balance.

## Contribution

It systematically reviews EDCs like bisphenols and phthalates and highlights gaps in understanding their role in male breast development.

## Key findings

- EDCs disrupt hormonal balance, potentially leading to gynecomastia.
- Bisphenols, phthalates, and polycyclic aromatic hydrocarbons are linked to male breast development.
- Current research lacks clarity on mechanisms and mixed exposure effects.

## Abstract

Gynecomastia (GYN), the most prevalent benign breast condition in men, is primarily driven by an estrogen-androgen imbalance, which induces glandular proliferation and adipose hypertrophy. This imbalance leads to the proliferation of mammary gland tissue and hypertrophy of adipose tissue. Endocrine-disrupting chemicals (EDCs), as a class of exogenous substances widely distributed in the environment, can disrupt hormonal homeostasis by mimicking estrogen, antagonizing androgens, or interfering with hormone metabolism. Consequently, they represent a significant environmental risk factor for inducing male breast development. Some evidence also suggests that gynecomastia may represent a chronic, non-infectious inflammatory response to estrogenic stimulation, which could further alter the tissue’s hormonal sensitivity. This paper systematically reviews typical EDCs associated with male breast development, including bisphenols, phthalates, and polycyclic aromatic hydrocarbons. It examines their exposure pathways and mechanisms of action, analyzes the clinical characteristics, public health implications, and current prevention and control status of gynecomastia. The review highlights existing issues in current research, such as unclear mechanisms and the complexity of mixed exposure effects. It proposes that future efforts should focus on strengthening research into the molecular mechanisms linking EDCs to male breast development, improving population exposure monitoring systems, and refining prevention and control strategies. This will provide a theoretical basis for the scientific prevention and clinical management of the condition. Furthermore, the paper emphasizes the critical importance of strictly controlling the environmental release of EDCs to protect public health.

## Linked entities

- **Chemicals:** bisphenols (PubChem CID 6626)

## Full-text entities

- **Genes:** PRL (prolactin) [NCBI Gene 5617] {aka GHA1, pPRL}, JUNB (JunB proto-oncogene, AP-1 transcription factor subunit) [NCBI Gene 3726] {aka AP-1}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, Fgf9 (fibroblast growth factor 9) [NCBI Gene 14180] {aka Eks, FGF-9, Fgf4b, GAF, HBGF-9}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, NR0B1 (nuclear receptor subfamily 0 group B member 1) [NCBI Gene 190] {aka AHC, AHCH, AHX, DAX-1, DAX1, DSS}, ARNT (aryl hydrocarbon receptor nuclear translocator) [NCBI Gene 405] {aka ARNT1, HIF-1-beta, HIF-1beta, HIF1-beta, HIF1B, HIF1BETA}, ESR1 (estrogen receptor 1) [NCBI Gene 2099] {aka ER, ESR, ESRA, ESTRR, Era, NR3A1}, Gja1 (gap junction protein, alpha 1) [NCBI Gene 14609] {aka Cnx43, Cx43, Cx43alpha1, Cxnk1, Gja-1, Npm1}, IGF1R (insulin like growth factor 1 receptor) [NCBI Gene 3480] {aka CD221, IGFIR, IGFR, JTK13}, CGB5 (chorionic gonadotropin subunit beta 5) [NCBI Gene 93659] {aka CGB, HCG}, Esr1 (estrogen receptor 1 (alpha)) [NCBI Gene 13982] {aka ER, ER-alpha, ERa, ERalpha, ESR, Estr}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, Ccn1 (cellular communication network factor 1) [NCBI Gene 16007] {aka Cyr61, Igfbp10}, UGT1A (UDP glucuronosyltransferase family 1 member A complex locus) [NCBI Gene 7361] {aka GNT1, UGT, UGT1, UGT1A@}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, Epas1 (endothelial PAS domain protein 1) [NCBI Gene 13819] {aka HIF-2alpha, HIF2A, HLF, HRF, MOP2, bHLHe73}, PRLR (prolactin receptor) [NCBI Gene 5618] {aka HPRL, MFAB, RI-PRLR, hPRLrI}, SHBG (sex hormone binding globulin) [NCBI Gene 6462] {aka ABP, SBP, TEBG}, CYP19A1 (cytochrome P450 family 19 subfamily A member 1) [NCBI Gene 1588] {aka ARO, ARO1, CPV1, CYAR, CYP19, CYPXIX}, CYP4F3 (cytochrome P450 family 4 subfamily F member 3) [NCBI Gene 4051] {aka CPF3, CYP4F, CYPIVF3, LTB4H}, KISS1 (KiSS-1 metastasis suppressor) [NCBI Gene 3814] {aka HH13, KiSS-1}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, SRD5A1 (steroid 5 alpha-reductase 1) [NCBI Gene 6715] {aka S5AR 1}, EREG (epiregulin) [NCBI Gene 2069] {aka EPR, ER, Ep}, NR1I2 (nuclear receptor subfamily 1 group I member 2) [NCBI Gene 8856] {aka BXR, ONR1, PAR, PAR1, PAR2, PARq}, CYP17A1 (cytochrome P450 family 17 subfamily A member 1) [NCBI Gene 1586] {aka CPT7, CYP17, P450C17, S17AH}, PPIG (peptidylprolyl isomerase G) [NCBI Gene 9360] {aka CARS-Cyp, CYP, SCAF10, SRCyp}, AR (androgen receptor) [NCBI Gene 367] {aka AIS, AR8, DHTR, HPCX3, HUMARA, HYSP1}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, Muc1 (mucin 1, transmembrane) [NCBI Gene 17829] {aka CD227, EMA, Muc-1}, AHR (aryl hydrocarbon receptor) [NCBI Gene 196] {aka FVH3, RP85, bHLHe76}, IGF1 (insulin like growth factor 1) [NCBI Gene 3479] {aka IGF, IGF-I, IGFI, MGF}
- **Diseases:** androgen deficiency (MESH:D014770), miscarriage (MESH:D000022), endometrial hyperplasia (MESH:D004714), Male pseudohermaphroditism (MESH:D058490), adjustment disorder (MESH:D000275), depression (MESH:D003866), breast and prostate cancer (MESH:D001943), sleep deprivation (MESH:D012892), estrogenic (MESH:D056828), stillbirths (MESH:D050497), social phobia (MESH:D000072861), tenderness (MESH:D063806), type 1 diabetes (MESH:D003922), aggressive behavior (MESH:D010554), eating disorders (MESH:D001068), liver dysfunction (MESH:D017093), dysthymia (MESH:D019263), mammary hyperplasia (MESH:D006965), ovarian dysfunction (MESH:D010049), malaria (MESH:D008288), cryptorchidism (MESH:D003456), emotional and cognitive disorders (MESH:D003072), chromosomal disorder (MESH:D025063), tissue (MESH:D017695), leprosy (MESH:D007918), Symptom (MESH:D012816), metastasis (MESH:D009362), birth defects (MESH:D000014), secondary testicular failure (MESH:C543092), thyroid cancer (MESH:D013964), polycystic ovary syndrome (MESH:D011085), hyperinsulinemia (MESH:D006946), carcinogenic (MESH:D011230), abnormal breast development (MESH:D061325), male breast disorder (MESH:D018567), chronic renal failure (MESH:D007676), abortions (MESH:D000026), adipose hypertrophy (MESH:D006984), infertility (MESH:D007246), Endocrine disorders (MESH:D004700), steroid hormone metabolism disorders (MESH:D043202), preterm birth (MESH:D047928), cardiovascular disease (MESH:D002318), insulin resistance (MESH:D007333), weight loss (MESH:D015431), toxicity (MESH:D064420), Morris syndrome (MESH:D008114), GYN (MESH:D006177), obese (MESH:D009765), suicidal ideation (MESH:D001072), weight gain (MESH:D015430), mammary tumors (MESH:D015674), prolactinomas (MESH:D015175), hyperprolactinemia (MESH:D006966), Hyperthyroidism (MESH:D006980), carcinogenesis (MESH:D063646), testicular cancer (MESH:D013736), Germ cell tumors (MESH:D009373), glands (MESH:D000307), Adrenal cortical tumors (MESH:D000314)
- **Chemicals:** GSH (MESH:D005978), steroid (MESH:D013256), BPAF (MESH:C583074), sesquiterpenes (MESH:D012717), tea tree oil (MESH:D020947), lipid (MESH:D008055), cypermethrin (MESH:C017160), 5alpha-dihydrotestosterone (MESH:D013196), glucose (MESH:D005947), NP (MESH:D009405), Bisphenol (MESH:C543008), NP7 (-), Phthalates (MESH:C032279), PCB (MESH:D011078), Lin (MESH:C018584), DDT (MESH:D003634), BkF (MESH:C022921), tetrabromobisphenol (MESH:C000708656), thiamethoxam (MESH:D000077922), imidacloprid (MESH:C082359), epoxy resins (MESH:D004853), monoterpenes (MESH:D039821), PVC (MESH:D011143), NPEO (MESH:C025256), chlorine (MESH:D002713), Essential oils (MESH:D009822), DDVP (MESH:D004006), BPA (MESH:C006780), ATZ (MESH:D001280), TT (MESH:D013739), progesterone (MESH:D011374), DEHP (MESH:D004051), BPC (MESH:C000705689), MEHP (MESH:C016599), PAH (MESH:D011084), neonicotinoids (MESH:D000073943), B[a]P (MESH:D001564), T (MESH:D014316), benzo[a]anthracene (MESH:C030935), BPF (MESH:C000611646), androstenedione (MESH:D000735), LinAc (MESH:C074463), pyrethroid insecticides (MESH:D011722), 17beta-estradiol (MESH:D004958), organochlorine (MESH:D006843), fluoranthene (MESH:C007738), octylphenol (MESH:C474055), lavender oil (MESH:C045718)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606], Glycine max (soybean, species) [taxon 3847], Mus musculus (house mouse, species) [taxon 10090]
- **Cell lines:** CD-1 — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_5731)

## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12909171/full.md

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Source: https://tomesphere.com/paper/PMC12909171