Neurosurgery confronts a blind spot as transgender patient numbers climb

A narrative review published in Chinese Neurosurgical Journal argues that gender-affirming hormone therapy, the cornerstone of treatment for gender dysphoria, carries neurological and neurosurgical implications that clinicians can no longer afford to overlook.

The review, authored by Rajdeep Brahmachari and Chandrasekaran Kaliaperumal, draws together peer-reviewed articles, retrospective studies and case reports indexed in databases including PubMed, Google Scholar and EMBASE, alongside material from Psychiatry.org and the World Professional Association for Transgender Health. Its starting point is demographic. An estimated 25 million people worldwide are transgender, and the authors note that the prevalence of Americans identifying as transgender has doubled over the last decade, ranging between 0.3 and 0.76 percent of the total population. A retrospective study at a Dutch gender identity clinic likewise found a dramatic rise in people seeking professional help in recent decades, a trend echoed by epidemiological studies across several countries, with the sharpest increase reported among children and adolescents.

That growth, the authors argue, means neurosurgical departments will increasingly meet transgender patients before, during or after gender-affirming treatment. Yet surveys cited in the review indicate that neurosurgeons report lower confidence in treating LGBTQ patients because of limited knowledge and awareness of their condition. The paper sets out to close that gap by documenting neuroanatomical variations, neurological risk factors and perioperative considerations relevant to evidence-based care.

Part of the gap is biological. Neuroanatomical studies have shown that components of the brain in transgender individuals resemble the gender they identify with rather than the sex assigned at birth. Neuroimaging has revealed increased cortical thickness and weaker connections in regions known for processing one’s own body perception, and altered brain connection dynamics that track identified gender rather than assigned sex. Patients receiving gender-affirming hormone therapy show significant increases in gray matter density and volume compared with both male and female controls, specifically in the fusiform gyrus, cerebellum and lingual gyrus. The authors caution that more work is needed, but say current research suggests brain architecture and function play important roles in the pathophysiology of gender dysphoria.

The clinical stakes become clearer in the review’s survey of hormone-related neurological conditions. One major study found that transgender people may experience more disabling headaches than cisgender people, with an odds ratio of 1.76 and a 95 percent confidence interval of 1.34 to 2.32. In a retrospective study of 73 transgender individuals, 23.4 percent of transwomen treated developed worsening of chronic pain, including headache, after at least a year of hormone therapy, while 23.1 percent of transmen participants experienced improvement. Increased migraine frequency has also been reported in patients receiving high-dose estrogens.

Brain tumors add another layer of concern. A retrospective chart study found that hormone therapy is associated with a greater risk of meningioma and prolactinoma in transwomen, possibly linked to cyproterone acetate use, and with somatotropinomas in transmen. Meningioma incidence in transwomen exceeded that of the general European female population, with a standardized incidence ratio of 4.1, and the male population, at 11.9. Prolactinomas likewise occurred more often in transwomen than in general Dutch females, at 4.3, and males, at 26.5. Among transmen, two cases of somatotropinoma were observed, a standardized incidence ratio of 22.2 against a general European population. The review also highlights intracranial pressure dynamics: a case report and literature review identified 19 transmen with intracranial hypertension whose symptoms of headache, transient visual obscurations and blurred vision coincided with the onset of exogenous testosterone therapy in 89.5 percent of patients. The US Food and Drug Administration issued a safety label warning in 2022 that GnRH agonist use increases the risk of idiopathic intracranial hypertension.

Cerebrovascular risk features prominently. A large cohort study of 3,325 transwomen receiving hormone therapy found average ischemic stroke incidence rates of 9.4 cases per 1,000 person-years among those with six or more years of treatment, compared with 2.2 cases among those with less than six years. A 2021 meta-analysis of 14 studies including 109 transwomen reported that ischemic stroke was the most common stroke subtype in these patients, all of whom were on estradiol therapy. The authors note that gender minority social stressors and atypical stroke mechanisms may contribute, and that transgender individuals may have higher tobacco and alcohol use, lower diet quality and lower physical activity levels than cisgender people, though such data can be discrepant because of differing sampling techniques and methodology between studies. A retrospective cohort study of Medicare beneficiaries also reported a higher prevalence of epilepsy in transgender individuals, and some reports suggest drug interactions between antiseizure medications and hormone therapy agents.

Much of the review is practical. The authors call for a safe and welcoming clinical environment, noting that many transgender individuals postpone medical care because of stigma, social isolation and prejudice, and that some worry about a doctor’s reaction to their gender identity. They recommend inclusive language, careful documentation of the type and duration of hormone therapy, and attention to patients’ ideas, concerns and expectations. On consent, they point to WPATH Standards of Care version 8, which recommends patient autonomy while requiring evaluation of cognitive capability, attention to co-occurring mental health conditions and mental health professional advice before informed consent is given. Preoperative optimization should include recording preferred names, gender identities and pronouns, pregnancy testing, thromboprophylaxis for venous thromboembolism and multidisciplinary input from endocrinology, neuropsychiatry, anesthesia, neurology and gynecology. At least 80 percent of transgender patients are currently receiving or interested in receiving hormone therapy, and the review stresses that these regimens must not be stopped, since interruption can put patients at psychological and physical risk. General perioperative risks include elevated rates of HIV, human papillomavirus, hepatitis B and methicillin-resistant Staphylococcus aureus infections, higher rates of distress, anxiety and depression that may predispose to smoking, alcohol and drug use, and a suggested predisposition to diabetes and insulin resistance that the authors say requires further study.

In the operating room, the review flags drug interactions between feminizing hormone therapy and antiseizure medications, corticosteroids and neuromuscular blockers such as succinylcholine, with perioperative neuromuscular monitoring advised when blocking agents are used. HIV-positive patients on antiviral treatment may experience interactions with certain hypnotics, anxiolytics and antibiotics. Airway management deserves care: transmen who have not had gender-affirming surgery may wear breast binders that restrict respiration and cause severe respiratory complications, while transwomen who have undergone laryngeal procedures such as laryngoplasty may present intubation difficulties. Urinary catheterization in patients who have had gender-affirming surgery may require urological consultation, and standard precautions against HIV transmission remain essential. Blood transfusion should be considered cautiously because of hematological changes under hormone therapy, though the authors note no significant studies yet exist on this question.

After surgery, the review recommends offering a private room as an option without making it the only choice, consistently using patients’ preferred names and pronouns to avoid psychosocial stressors that can delay recovery, and prioritizing wound care, since keloid and hypertrophic scars carry significant psychosocial weight. Bone health generally improves with both masculinizing and feminizing hormone therapy, but patients on GnRH agonist regimens need endocrinological monitoring of bone mineral density with calcium and vitamin D supplementation to reduce vertebral fracture risk after spinal surgery. Pain management should be multidisciplinary, and estrogens in particular may have a neuroprotective effect on spinal cord injuries, reducing neuropathic pain. Spironolactone can cause orthostatic hypotension, and antiemetic and deep venous thrombosis prophylaxis should be considered. Because transgender patients are predisposed to anxiety and depression, prolonged hospital stays can worsen mental health. The authors conclude that evidence on transgender health remains largely confined to short retrospective studies, case reports and reviews, and call for improved education, inclusive clinical practices, multidisciplinary collaboration and further large-scale studies to guide standardized neurosurgical care.

Subject of Research: Neurosurgical implications of gender-affirming hormone therapy for transgender patients

Article Title: Gender reassignment and neurosurgical implications: a narrative review

Article References: Brahmachari, R., & Kaliaperumal, C. (2026). Gender reassignment and neurosurgical implications: a narrative review. Chinese Neurosurgical Journal, 12(1), Article 28. https://doi.org/10.1186/s41016-026-00447-5

Image Credits: AI Generated

DOI: 10.1186/s41016-026-00447-5

Keywords: transgender health, gender-affirming hormone therapy, neurosurgery, gender dysphoria, meningioma, stroke, intracranial hypertension, perioperative care, WPATH Standards of Care, neuroanatomy, epilepsy, patient consent