We [27, 58] and others have observed increase in the occurrence of fatigue and obesity related to the significant changes in serum estradiol and SHBG concentrations, potentially related to breast cancer patients receiving anti-estrogen tamoxifen (TAM) or with the different types of estrogens diethylstilbestrol (DES), ethinyl estradiol (EE), estradiol (E2) and in studies reporting acute as well as chronic adverse effects, including general fatigue, due to the use of ethinylestradiol in postmenopausal patients with heavily pre-treated metastatic breast cancer. The gene discussed is SHBG; the disease is obesity due to melanocortin 4 receptor deficiency.