Metabolic Response to Androgen Deprivation Therapy of Prostate Cancer

Prostate cancer (PC) stands as the most frequently diagnosed non-skin cancer and ranks as the second highest cause of cancer-related deaths among men in the United States. For those facing non-metastatic PC necessitating intervention, solely local treatments may not suffice, leading to a possible transition toward systemic therapies, including androgen deprivation therapy (ADT), chemotherapy, and therapies targeting androgen. Yet, these systemic treatments often bring about considerable adverse effects. Additionally, it is observed that overweight men are at a higher risk of developing aggressive forms of PC, advancing to metastatic stages, and succumbing to the disease. Consequently, there is a pressing demand for new treatment options that carry fewer side effects and enhance the current standard treatments, particularly for the majority of American men who are overweight or obese. In this article, we will review the metabolic response to ADT and how lifestyle modulation can mitigate these ADT-associated metabolic responses with a particular focus on the two clinical trials, Carbohydrate and Prostate Study 1 (CAPS1) and Carbohydrate and Prostate Study 2 (CAPS2), which tested the effects of low-carbohydrate diets on the metabolic side effects of ADT and PC progression, respectively. Furthermore, we will summarize the findings of serum metabolomic studies to elucidate the potential mechanisms by which ADT and low-carbohydrate diets can affect the metabolic response to mitigate the metabolic side effects while maximizing therapeutic efficacy.