POLG and mitochondrial disease: Hypergonadotropic hypogonadism has also been reported in patients with mitochondrial diseases, including mtDNA depletion syndromes (C10orf2, POLG variants), mitochondrial neurogastrointestinal encephalomyopathy (MNGIE), primary coenzyme Q10 deficiency, and Leigh syndrome caused by LRPPRC variants (69, 70).