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The effective clinical study of HRT-GD regimens is hampered by barriers to trust and information sharing between physicians and transgender patients who have historically suffered from significant disparities in access to healthcare. Studies have shown that these drugs cause a drop in serum levels of SHBG and LH, but significantly increase free testosterone. This drug has a stronger anti-androgenic effect than spironolactone but carries a significantly greater risk of adverse effects including depression and meningioma (at doses exceeding 25mg/day) (51,55). The application to fragile subjects such as the elderly, those with a history of mental disorder, eating behaviour or substance abuse must benefit from an appropriate support in the daily routine for the KD to be potentially considered as a feasible treatment for concomitant conditions. Finally, abuse of alcohol and some substances increase the risk of metabolic acidosis under certain circumstances.97 The concomitant consumption of a KD exacerbates the risk, and it is therefore to be recommend against the prescription of a KD to those with a history of alcohol and substance abuse where relapse seems possible, especially in the absence of adequate support. However, it has been proposed that the KD might be a possible bridge treatment for those with AN in order to avoid starvation and increase patient compliance,9 although no clinical evidence has been reported to support this hypothesis to date. Severe mental illness, similar to impaired cognitive ability and aging, may lead to reduced compliance in adequate water consumption and constant use of prescribed electrolyte and vitamin supplement crucial to maintain a good safety profile especially during a VLCKD among all KDs, thus increasing the risk of side effects. 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