Nuances of gender affirming therapy for transgender women with spinal cord injury

Abstract

Case Description

56-year-old transgender woman with new spinal cord injury (SCI) on gender affirming hormonal therapy (GAHT) with estrogen and spironolactone.

Findings

After her injury, estrogen and spironolactone were discontinued, for blood clots and hypotension, respectively. Alternative options were explored.

Clinical Relevance

Little is known about GAHT in SCI for transgender women. Shared decision making should be used to navigate risks, benefits, and alternative options.

Case Description: A 56-year-old transgender woman on gender affirming hormonal therapy (GAHT) sustained new complete paraplegia from a fall with concomitant cervical spondylotic myelopathy. Her examination was consistent with a C6 American Spinal Injury Association Impairment Scale (AIS) A complete tetraplegia from these separate injuries to the spinal cord.

Findings: This patient had identified as transgender for many years, deriving much personal meaning from engagement with the Lesbian, Gay, Bisexual, Transgender, Queer, and/or related identity (LGBTQ+) community. She began GAHT with oral estrogen and spironolactone four years before her spinal cord injury (SCI), with positive effects on mood and sense of gender congruence. After her injury, these medications were continued in acute care. She received appropriate deep venous thrombosis (DVT) prophylaxis during this time. One month after injury, she was found to have a deep peroneal DVT and placed on therapeutic anticoagulation with apixaban. Two days later, she developed hypoxia and was found to have a subsegmental pulmonary embolus. After the discovery of multiple venous thromboemboli (VTE), using shared decision making, her estrogen was discontinued. Later, during her inpatient rehabilitation admission, she experienced orthostatic hypotension (OH), limiting tolerance and progress with her therapies. Her anti-testosterone medication, spironolactone, was held as it was thought to be contributing to her OH. She prioritized her medical stability in order to maximize rehabilitation goals. However, she also expressed desire to resume GAHT as soon as possible.

She experienced depressed mood related to adjustment to her life with SCI, as well as sadness and loss of identity at feeling that she was “detransitioning” in the absence of GAHT. This was exacerbated by the inpatient rehabilitation setting, where bowel, bladder, and skin cares involved vulnerability, including exposure of genitals and being seen without her typical means of gender expression (e.g. makeup, wig, own clothes). The predominance of male patients on the unit, many of whom also saw her without gender expression markers, further contributed to difficulty expressing and experiencing femininity. Depressed mood was a significant factor in rehabilitation setbacks. Mental health supports included a psychologist, her established community therapist, and pharmacotherapy. She also received gender affirming speech therapy and connection to the hospital LGBTQ+Care Coordinator.

After three months of treatment with therapeutic anticoagulation for her VTE, Endocrinology and Hematology were consulted to assist with safely restarting GAHT. Balancing increased gender congruence with the risks of blood clots, she elected to start an estrogen transdermal patch and leuprorelin, along with indefinite therapeutic anticoagulation while on estrogen therapy given her history of VTE, SCI, and prior nicotine use. After resuming GAHT, her mood and therapy engagement improved, and no further VTE were identified.

Discussion

Over 16,000 individuals with SCI that identify as LGBTQ+ are estimated to live in the United States (1). Unfortunately, many health care providers do not consider patients’ gender or sexuality and lack the knowledge and confidence to adapt care for LGBTQ+ patients with SCI (2). Transgender individuals with SCI are particularly underrepresented in the literature, despite having unique physiological and rehabilitation needs and experiences (1). In particular, the risks and nuances of GAHT use for patients with SCI have not been explored.

Transgender individuals experience a different gender identity than the sex they are assigned at birth. They may choose to use GAHT, including feminizing or masculinizing hormones, to align their physical appearance more closely with gender identity (1,3). Gender affirming care improves quality of life (3,4), improves anxiety and depression (1,3), and is considered medically necessary for transgender people who desire it (4). Feminizing therapy includes estrogen, commonly in conjunction with anti-testosterone medications, such as spironolactone, cyproheptadine acetate, gonadotropin-releasing hormone (GnRH) agonists like leuprorelin, or 5α-reductase inhibitors like finasteride (5,6). As demonstrated in this case study, these medications are associated with risks, many of which are already elevated after an acute SCI, like VTE and OH.

Rates of VTE are higher among transfeminine individuals on GAHT compared to cisgender men and women (5,7). This can be affected by hormone formulation, dosing, route, and duration of therapy. Transdermal estrogens are associated with the lowest risk of VTE (7). If a VTE occurs while on GAHT, it should be treated with the same anticoagulation recommendations as in cisgender individuals (8). Some clinicians would additionally recommend discontinuation or decrease of estrogen after an acute VTE (5). However, withholding GAHT can lead to adverse mental health consequences (3,8), as in this case. If GAHT is stopped, psychological intervention can be beneficial, though not all care systems have robust support from providers trained in concerns specific to transgender individuals. Shared decision-making with the patient should be used to weigh the risks and benefits of resumption (8). Continuation of therapeutic anticoagulation is a consideration, which has been shown to prevent recurrent VTE in cisgender women on hormone therapy for osteoporosis or menopause (8).

Little is known about the rates of blood clots with the combination of GAHT and SCI, which is already an independent risk factor for VTE. One study noted that GAHT could further increase risk of VTE in patients with SCI, but no studies have yet characterized or evaluated that risk (9). The patient in this case study was taking oral estrogen prior to her injury and during acute care, but it is difficult to determine the degree that the oral estrogen increased her VTE risk.

Estrogen therapy may be associated with an increased risk of cardiovascular events for transgender women (5,6); SCI also increases the risk of cardiovascular disease, including heart disease and stroke.

Similarly, little data is available to weigh risks and benefits of different anti-testosterone medications in the context of SCI. The risk of VTE is less with spironolactone compared to other anti-testosterone medications (7). However, spironolactone can cause OH, among other side effects like hyperkalemia or acute kidney injury (5,6), and the diuretic effect is a consideration for patients managing a neurogenic bladder. The patient in this case study was unable to tolerate rehabilitation therapies while taking spironolactone due to hypotension. Switching to leuprorelin resolved this side effect, but could decrease bone mineral density over time, another problem associated with SCI (5,6). Other options for anti-testosterone treatment also have the potential of worsening SCI sequelae. For example, finasteride is associated with OH and sexual dysfunction, while cyproheptadine can be associated with VTE or hepatotoxicity.

SCI providers need to be well-equipped to treat transgender individuals. Transgender persons experience disparate care within the health care system, often reporting providers’ lack of knowledge about transgender health concerns (4,10). Over 20% of patients report they have avoided seeking health care due to fear of discrimination or poor treatment (5). Improving the knowledge base regarding GAHT for transgender patients with SCI is important so providers can adequately discuss and manage these medications and their side effects, facilitating gender-affirming care.

Clinical relevance/conclusions

Little is known about safety of GAHT for patients with SCI. This case report demonstrates the dearth of available data to weigh the risks and benefits of GAHT after SCI, especially in the context of blood clots. The nature of SCI rehabilitation presents additional psychological and interpersonal challenges for transgender individuals. Shared decision making resulted in changing her route of estrogen therapy, continuing therapeutic anticoagulation, and switching to an alternative anti-testosterone agent to mitigate side effects while promoting psychosocial wellbeing. Further research is needed to more strongly support recommendations.

Disclaimer statements

Contributors None.

Funding None.

Declaration of interest None.

Conflicts of interest Authors have no conflict of interests to declare.