Context: Estrogens, dopaminergic neural network and brain-derived growth factor (BDNF) play a cardinal role in female sexual activity. Objective: This is the first study to investigate the interaction between genetic polymorphisms of ERα (rs2234693), DRD4 (7R-48bp VNTR), BDNF (rs6265) genes and sexuality parameters of young healthy women. Methods: Sexual function was evaluated by the Greek version of the Female Sexual Function Index questionnaire (FSFI). Detection of polymorphisms was conducted by amplification of genetic sequence using the method of polymerase chain reaction (PCR). Patients: One hundred thirty three Greek heterosexual women aged 20-25 years, higher education students, voluntarily participated in the study. All women were sexually active, with ovulatory menstrual cycles (28-35 days), without biochemical hyperandrogenemia. Results: Among non-carriers of 7R allele of 48bp-VNTR polymorphism (DRD4), increased arousal (p=0.033, r=0.22, medium effect) and lubrication levels (p=0.019, r=0.24, medium effect) were reported in women with T allele (wild-type) of rs2234693 (ERα) polymorphism compared to women with CC genotype. Among carriers of GG genotype (wild-type) of rs6265 polymorphism (BDNF), increased arousal levels (p=0.032, r=0.26, medium effect) were reported in carriers of T allele (wild-type) of rs2234693 (ERα) polymorphism compared to women with CC genotype. Conclusions: DRD4 gene and BDNF gene polymorphisms seem to enhance the impact of ERα gene polymorphism on female sexuality. Dopaminergic activity is reduced by the decreased binding affinity of ERα that is related to CC genotype of rs2234693. The synergistic effect of genotypes GG (BDNF) and T (ERα) could be associated with elevated sexual response markers, given that GG genotype of rs6265 is associated with increased release of BDNF, while BDNF release is increased in response to ERα activity.