Caring for transgender and gender-diverse patients with cancer presents unique challenges, making it essential for all members of the multidisciplinary team to be aware of and responsive to their needs. In this discussion, Mariachiara D’Elia, John Leggett and Dr Alison May Berner explore the critical role pharmacists play in ensuring that the care provided is inclusive and comprehensive. They also highlight the important advocacy role pharmacists can fulfil by offering evidence-based education for both the clinical team and the patient.
An estimated 0.5-1% of populations in the Global North identify as transgender, and up to 4.5% as gender diverse. A proportion of transgender and gender diverse (TGD) people will access gender-affirming hormone therapy (GAHT) to align their bodies with a sense of gender. Therefore, pharmacists need to be aware of the potential interactions between GAHT and a range of other medications.
This is particularly significant in cancer care, as up to one in two people will be diagnosed with cancer during their lifetime. Not only are some tumours sensitive to hormones, but there is also the potential for interactions between GAHT and cancer treatments, as well as adverse events such as abnormal liver function and venous thromboembolism (VTE).
How the care of TGD people is affected by cancer
The impact of cancer on TGD people extends far beyond medication interactions. Cultural competency and inclusive healthcare systems are often inadequate, and the transgender population continues to encounter discrimination throughout the cancer journey. Furthermore, specialist knowledge concerning the rights and practicalities of fertility preservation, as well as the potential effects of treatments on sexual function, remains limited.
Hormonal therapies
Common GAHT medications are shown in Table 1 below. GAHT can alter risk profiles for some hormone-responsive tumours, including breast, prostate and meningioma. However, there is a lack of prospective studies assessing the impact of GAHT on cancer outcomes.
There is ongoing speculation in both the literature and clinical settings regarding the potentially harmful role of GAHT, even in the absence of clear evidence of hormonal influences in cisgender populations. This may result in the withdrawal of GAHT when cancer is diagnosed, leading to a subsequent decline in quality of life and mental health during a time of significant vulnerability.
Table 1. Mode of delivery, dose and known effects on cancer incidence of gender-affirming hormonal drugs
IM, intramuscular; SC, subcutaneous.
Adapted from: Hembree W et al. Endocrine Treatment of Gender-Dysphoric/Gender Incongruent Persons: An Endocrine Society Clinical Practice Guideline. JCEM 2017;102:3869–903.
*While doses of 25–50 mg/day cyproterone acetate were recommended in the 2017 Endocrine Society Guidelines, subsequent evidence suggests that long-term doses of 25 mg/day or more are associated with an increased risk of meningioma. Studies have shown that doses of 10 mg/day achieve sufficient anti-androgenic effects with a lower risk of side effects.
Medicines reconciliation
TGD patients may take GAHT, whether it is prescribed or self-administered. Some individuals might not receive care from a gender identity clinic, but they may seek gender-affirming care from a private clinic. To attain a comprehensive reconciliation, consulting with multiple professionals and care providers is essential.
Drug-drug interactions
Drugs metabolised by the cytochrome P450 family of enzymes can affect the metabolism of oestrogen and progestins. Pharmacists can alert clinic teams to these potential interactions and suggest additional hormone monitoring as necessary.
Pain management in cancer
Pain can be a complication of a cancer diagnosis. The use of opiates necessitates special consideration for TGD individuals. Opiates can interfere with the central and peripheral hormone axes and, theoretically, this combination could diminish the gender-affirming effects of GAHT.
When patients have high opiate requirements or inadequately controlled pain, pharmacists may explore adjunctive analgesic options to minimise opiate use, thereby ensuring that GAHT remains as effective as intended.
Risk of thrombosis
A cancer diagnosis is associated with a higher risk of VTE. It is important to consider the relative thrombotic risk of each malignancy. Multiple myeloma is particularly associated with a high incidence of VTE, and this is increased when treated with immunomodulatory agents.
The use of exogenous oestrogen is an independent risk factor for VTE, but rates are far lower for transdermal formulations. Pharmacists can highlight a potential formulation switch in those experiencing, or at high risk of, VTE.
It is important to note that when a first VTE develops, anticoagulation should be initiated rather than discontinuing oestrogen. Pharmacists should advocate for a risk-managed approach, closely monitoring thrombotic risks and adjusting treatment protocols as necessary, while balancing the needs of both cancer therapies and hormone treatments.
Drug adjustments according to renal function
Research has indicated that transgender individuals undergoing GAHT experience physiological changes within six to 12 months of commencing hormonal therapy. In transgender men, there is a rise in serum creatinine, which is a byproduct of muscle metabolism, deriving from increase in muscle mass. Transgender women will exhibit the opposite pattern.
The Cockroft-Gault equation is often used to estimate renal function, which requires a binary constant. When deciding which constant to use, it is important to consider when GAHT was initiated as changes are expected to be visible after a minimum of six months. If an accurate estimation of renal function is required, a nuclear medicine glomerular filtration rate test can be carried out.
Hormone-sensitive cancers
Cancers that are hormone-sensitive present a distinct challenge for transgender people, who may need to decide whether to cease or temporarily halt hormone therapy. In some instances, there will be clear evidence of poorer outcomes associated with continued therapy, such as the use of oestrogen in oestrogen receptor-positive breast cancers or cyproterone/other progestogens in meningioma. In other situations, this may remain more theoretical, such as the aromatisation of testosterone to oestrogen in certain gynaecological cancer histologies.
Pharmacists can assist clinical teams in appraising the evidence and facilitate shared decision-making about the use of hormonal treatments, remembering that transgender patients deserve the same level of choice as cis people in choosing whether to block endogenous hormones or take hormone replacement therapy.
In oestrogen receptor-positive breast cancer in transgender men, testosterone therapy and endocrine therapy can be carefully selected to minimise or mitigate the conversion of testosterone to oestradiol. Strategies may include the use of tamoxifen or fulvestrant to block oestrogen receptors, or the use of aromatase inhibitors alongside testosterone gel preparations to minimise spikes in conversion to oestradiol, with careful monitoring of serum oestradiol levels.
Formulation switching
TGD service users may hold strong preconceptions about the efficacy of various formulations in achieving desired gender-affirming effects. The use of transdermal preparations in hormone-sensitive cancers is often suggested to avoid the high serum peaks associated with parenteral preparations.
Transdermal formulations are frequently misunderstood as being less potent than their parenteral counterparts. Additionally, parenteral preparations are often more cost-effective. Pharmacists can reassure patients by offering clear information regarding proposed changes to GAHT, enabling patients to make informed decisions that align with their clinical objectives and financial circumstances.
UK Cancer and Transition Service and TRANS:CRIBING
The UK Cancer and Transition Service (UCATS) is a hybrid multidisciplinary team based at Chelsea and Westminster Hospital NHS Foundation Trust but operating nationally across the UK. It helps to coordinate and integrate cancer care and gender-affirming care by amassing knowledge and disseminating it to patients and their clinical teams, enabling shared decision-making.
The current team comprises medical oncology, sexual health specialists, pharmacy, palliative care and a dedicated specialist nurse. Anyone aged 18 or over who identifies as transgender or gender diverse and has cancer, either currently or historically, is eligible. Patients may self-refer or be referred by any member of their clinical team.
The above scenarios are just some of those that UCATS encounters, and where the UCATS pharmacist has played a vital role. Specialist advice can be found via UCATS if there is the need to temporarily stop or modify GAHT due to surgery, cancer diagnosis or other medical interventions, adjusting doses due to drug interactions or altered renal and liver function, or simply where patients feel they need further support.
The emerging insights from UCATS are shaping a world first-of-its-kind resource called TRANS:CRIBING, which guides and supports oncology healthcare professionals in caring for their transgender and non-binary patients by outlining clinical considerations for safe and inclusive prescribing. This initiative was developed by the national LGBTIQ+ cancer charity OUTpatients in partnership with the British Oncology Pharmacy Association.
Conclusion
As understanding of the intersection between cancer care and gender-affirming care increases, pharmacists remain a vital part of the multidisciplinary team.
At a time when transgender and gender diverse healthcare and rights are under threat, pharmacists can advocate for culturally sensitive and evidence-based care, as well as shared decision-making, to build trust and improve health equity.
Authors
Mariachiara D’Elia
Clinical rotational pharmacist, Royal Marsden NHS Foundation Trust
John Leggett MRPharmS
Specialist oncology pharmacist and non-medical prescriber, Barts Health NHS Trust and the UK Cancer and Transition Service, Chelsea and Westminster Hospital NHS Trust
Alison May Berner BA Hons MBBS MSc PhD MRCP
Academic clinical lecturer, honorary consultant in medical oncology and clinical lead for the UK Cancer and Transition Service, Chelsea and Westminster Hospital NHS Trust, Barts Health NHS Trust and Queen Mary University of London
