Reproductive steroids such as androgens and estrogens fuel the growth of prostate cancer and of hormone receptor positive breast cancer. Therapies that block their bioactivity improve cancer-specific outcomes, but lead to hypogonadism. The degree of reproductive steroid deprivation achieved by contemporary therapeutic strategies -such as global androgen deprivation in prostate cancer or ovarian ablation combined with aromatase inhibition in premenopausal breast cancer- is more profound compared to hypogonadism occurring as a consequence of conventional gonadal axis pathology. Given the widespread expression of androgen and estrogen receptors it is not surprising that hormonal deprivation has multiple adverse constitutional and somatic adverse consequences. Patients exposed to these treatments offer a unique clinical model to study the effects of profound untreated hypogonadism over an extended period. In addition, given their overall good prognosis, these patients need dedicated care to mitigate adverse clinical outcomes. In this talk, I will discuss new insights into biological mechanisms of sex steroid action that we have learned from these patients. In addition, I will examine the evidence informing the provision of endocrine care to optimize clinical outcomes.