ESR1 and polycystic ovary syndrome: Walters et al. reinforced the importance of direct AR-mediated androgen actions, while also highlighting a potential indirect role for ER signaling in the development of reproductive features of PCOS [8], suggesting that, in the absence of AR, aromatizable androgens may act via ER pathways to induce reproductive dysfunction, a hypothesis supported by clinical evidence that anti-estrogens such as letrozole and clomiphene are effective ovulation induction therapies in PCOS [30,31,32].