At the same time, estrogen can negatively feedback on the hypothalamic-pituitary (HP) axis, inhibiting gonadotropin-releasing hormone (GnRH) and subsequently luteinizing hormone (LH), which leads to a decrease in testosterone levels, and this creates a negative obesity-hypogonadism cycle [46]. Here, PLOD1 is linked to obesity due to melanocortin 4 receptor deficiency.