Abstract
Idiopathic intracranial hypertension (IIH) is a condition of unknown etiology, characterized by elevated intracranial pressure frequently manifesting with chronic headaches and visual loss. Similar to polycystic ovary syndrome (PCOS), IIH predominantly affects obese women of reproductive age. In this study, we comprehensively examined the systemic and cerebrospinal fluid (CSF) androgen metabolome in women with IIH in comparison with sex-, BMI-, and age-matched control groups with either simple obesity or PCOS (i.e., obesity and androgen excess). Women with IIH showed a pattern of androgen excess distinct to that observed in PCOS and simple obesity, with increased serum testosterone and increased CSF testosterone and androstenedione. Human choroid plexus expressed the androgen receptor, alongside the androgen-activating enzyme aldoketoreductase type 1C3. We show that in a rat choroid plexus cell line, testosterone significantly enhanced the activity of Na+/K+-ATPase, a surrogate of CSF secretion. We demonstrate that IIH patients have a unique signature of androgen excess and provide evidence that androgens can modulate CSF secretion via the choroid plexus. These findings implicate androgen excess as a potential causal driver and therapeutic target in IIH.
Highlights
Idiopathic intracranial hypertension (IIH) is a chronic and disabling condition characterized by elevated intracranial pressure (ICP) [1]
Women with IIH have a distinct androgen excess profile compared with polycystic ovary syndrome (PCOS) and simple obesity
We provide potentially novel insights into potential mechanisms relating to the pathogenesis of IIH
Summary
Idiopathic intracranial hypertension (IIH) is a chronic and disabling condition characterized by elevated intracranial pressure (ICP) [1]. Patients have reduced quality of life due to chronic headaches and papilledema-induced visual loss (permanent in 25% of patients) [2, 3]. Occurring in areas of socioeconomic deprivation, IIH incidence is rising rapidly in line with the global epidemic of obesity (2 per 100,000 in 2002 to 5 per 100,000 in 2016), driving escalating health care costs (predicted at ≤450 million dollars per year by 2030) [4]. IIH is overwhelmingly a disease of obese women of reproductive age [5, 6], and endocrine disturbances have been hypothesized to play a pathogenic role [7, 8]. IIH etiology remains unexplained [3]; identifying the cause of IIH was determined as the most important research ques-
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