Hormone fluctuations are known to contribute to the severity of symptoms in patients with mitochondrial disease or mental illness. However, a precise picture of the mechanisms for volatile processes involved can be elusive. Using the Creighton Model Fertility Care SystemTM, a noteworthy progesterone deficiency in a patient with mitochondrial dysfunction was identified during the perimenopause and a unique targeted progesterone therapy for treatment was used yielding some positive outcomes. The case history involves miscarriage, endometriosis, and bipolar. This case stimulates discussion about the feedback loops in female patients, involving life stressors, hormone levels, mitochondrial interaction, and potential considerations for measurement and treatment to improve patient outcomes.