Intracranial Hypertension in a Transgender Man

Abstract

Objective

Case description of recurrent idiopathic intracranial hypertension (IIH) in a transgender man on gender-affirming hormone therapy.

Methods

Case report.

Results

A 24-year-old transmasculine patient (assigned female at birth), with a body mass index (BMI) of 37.3, presented with headaches, transient visual obscurations (TVOs), pulsatile tinnitus, Frisén 5 papilledema, and scotomas. He was diagnosed with IIH after normal magnetic resonance imaging (MRI) and magnetic resonance venogram (MRV), an elevated opening pressure of 27 cm water, and normal cerebrospinal fluid studies. IIH resolved with acetazolamide and optic nerve sheath fenestration (ONSF). He then started gender-affirming testosterone therapy and was on this for 20 months when his headaches, pulsatile tinnitus, TVOs, and Frisén 3 papilledema recurred at a BMI of 31. Brain MRI and MRV were normal. Opening pressure was elevated at 31 cm. water. Acetazolamide 4 g/day did not improve the papilledema, thus a left ONSF was repeated resulting in eventual resolution of the IIH.

Discussion

Several reports have been published of IIH development in patients receiving testosterone therapy. Hormone prescribers for gender affirmation may wish to screen for visual loss and optic nerve edema in patients undergoing testosterone therapy, which may also stimulate appetite weight gain.

PRACTICAL IMPLICATIONS

Consider idiopathic intracranial hypertension in the differential diagnosis for patients undergoing hormonal therapy presenting with headaches and transient visual obscurations.

Idiopathic intracranial hypertension (IIH) is frequently encountered in the neuro-ophthalmology clinic, but there have been few advances in treatment. To some degree, this may be due to its poorly understood pathophysiology because discovery of more precise mechanisms could provide potential therapeutic targets. Alterations in CSF flow dynamics form the fundamental basis and are the target of current therapies, namely, carbonic anhydrase inhibition and surgical intervention. In a review article by Hornby et al.,¹ the authors posited the role of the adipose/gut/brain metabolism axis in IIH. These theories describe variations in metabolic cytokine profiles and have been investigated because of the close association of IIH with obesity. Other theories of hormonal changes stem from IIH being more common in females and its association with polycystic ovarian syndrome, an androgen-driven process.² In addition to these established associations, we bring attention to recently published reports of IIH in patients receiving exogenous testosterone for gender-affirming hormone therapy.³ We describe a case of IIH recurrence in a patient undergoing gender-affirming hormone therapy and review the evidence for an androgen-mediated basis to IIH.

Case Description

A 24-year-old transmasculine patient (assigned female at birth) on gender-affirming hormone therapy with a body mass index (BMI) of 37 kg/m² presented with headaches, transient visual obscurations, and pulsatile tinnitus. The patient reports the use of “he/his” pronouns, which will be adopted in this study. Evaluation revealed bilateral Frisén grade 5 papilledema (Figure 1, A and B) and scotomas, with corresponding nerve fiber layer elevation (Figure 1, C and D). There were an inferotemporal defect in the right eye (Figure 1F) and a central scotoma in the left eye (Figure 1E) on Humphrey perimetry. Opening pressure on lumbar puncture was 27 cm of water. CSF studies, as well as brain MRI and head magnetic resonance venogram (MRV), were normal. IIH resolved (Figure 1, G–L) with acetazolamide 4 g daily and a left optic nerve sheath fenestration. The patient then began gender-affirming intramuscular (IM) testosterone therapy. His testosterone level was 212.4 pg/mL on initiation of testosterone treatment, which was 100 mg IM biweekly and then increased to 150 mg IM biweekly after 18 months. During the twentieth month of therapy, the patient had recurrence of IIH symptoms at a BMI of 31 kg/m². Frisén grade 2–3 papilledema was demonstrated bilaterally (Figure 2, A and B), with recurrence of retinal nerve fiber layer elevation (Figure 2, C and D). There was a worse scotoma of the left eye on Humphrey perimetry that extended into the inferotemporal quadrant (Figure 2E). Total testosterone was 689.1 pg/mL. Brain MRI and head MRV were normal. Repeat lumbar puncture revealed elevated opening pressure at 31 cm water with normal CSF studies. Acetazolamide at 4 g/d was restarted but was ineffective; thus, a nerve sheath fenestration was performed again resulting in eventual resolution of the IIH (Figure 2, G–L). The patient was able to safely continue IM testosterone.

Figure 1. Photo, Perimetry, and Optical Coherence Tomography Before and After the First Optic Nerve Sheath Fenestration.

Top row: Frisén 5 papilledema of the right (A) and left (B) eyes, correlating with retinal nerve fiber layer (RNFL) elevation of the right (C) and left (D) eyes on optical coherence tomography (OCT). Inferonasal defect in the right eye (F) and a central/paracentral defect in the left eye (E). Bottom row: Resolved papilledema (G and H) with residual optic neuropathy (I and J) after acetazolamide and left optic nerve sheath fenestration. Visual field defects improved (K and L).

Figure 2. Photo, Perimetry, and Optical Coherence Tomography Before and After the Second Optic Nerve Sheath Fenestration.

Top row: Frisén 2–3 papilledema recurrence of the right (A) and left (B) eyes 18 months into gender-affirming testosterone therapy, with increased RNFL of both eyes (C and D). Worse visual field defect in the left eye (E). Stable enlarged blind spot of the right eye (F and L). Bottom row: Resolved papilledema (G–J) after acetazolamide and repeat left optic nerve sheath fenestration. Left eye scotoma improved (K).

Discussion

IIH has several established associations, but no unifying pathophysiologic mechanism. We described a case of IIH in a patient receiving gender-affirming testosterone therapy, whose IIH recurred after increasing his testosterone dose. Reports of similar cases have been previously published, resulting in a proposed androgen-driven basis to IIH.^3,4 Evidence to support this hypothesis includes a testosterone-mediated increase of choroid plexus CSF production and unique androgen profiles in persons assigned female at birth with IIH compared with age-matched controls with obesity and polycystic ovarian syndrome.⁵ Interestingly, there are also cases of IIH in patients undergoing gender-affirming hormonal therapy with estrogen.^6,7 Although these cases seem contradictory, they may be explained by different effects exerted by androgens, as hypogonadism in those assigned male at birth and androgen excess in those assigned female at birth both result in similar adverse metabolic phenotypes.⁵ To the best of our knowledge, there are no published cases of IIH in intersex individuals. Although there are few studies investigating these mechanisms, their findings coupled with cases of transgender patients warrant further attention. Hormone prescribers for gender affirmation may wish to screen for visual loss and optic nerve edema in patients undergoing testosterone therapy, which may also stimulate appetite, leading to weight gain.

Clinical and bench studies provide evidence for an androgen-driven basis for IIH. Recent reports of IIH in patients receiving gender-affirming testosterone therapy may be due to these mechanisms. Further studies on understanding the neurohormonal mechanism of CSF regulation and IIH pathophysiology may help target future intracranial hypertension therapies.

Appendix. Authors

Study Funding

The authors report no targeted funding.

Disclosure

The authors report no disclosures relevant to the manuscript. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp.