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Researchers carried out a review of adult gender transition medications and their pharmacogenomic implications.

Gender dysphoria, characterized by the incongruity between an individual’s experienced gender and their assigned gender at birth, often leads to gender transition, a process involving the modification of sexual characteristics to align with one’s identity. Hormone therapy plays a critical role in the transition, serving to diminish existing characteristics of the birth-assigned gender while fostering the development of the desired gender’s traits. An increasing number of adults in the LGBTQ community of both genders are seeking hormone therapy. 

Pharmacogenomics in Gender Dysphoria 

The review, published in the journal Frontiers in Endocrinology, focuses on an area often overlooked in gender dysphoria pharmacotherapy: pharmacogenomics. The pharmacodynamic objectives of hormonal therapy are twofold: first, to decrease endogenous sex hormone levels, thereby diminishing secondary sex characteristics; and second, to introduce exogenous sex hormones that align with the affirmed gender. 

Transgender and gender-nonconforming pharmacotherapy is complex, involving hormone agonists and antagonists that elicit both desired and adverse effects. Hormone therapy aims to align physical characteristics with gender identity, necessitating careful administration of estradiol and testosterone. 

For feminizing therapy, estradiol levels often exceed those in cisgender women’s hormone therapies by more than four times, and spironolactone dosing levels akin to those used for edema treatment are frequently used.

Testosterone therapy for transgender men surpasses dosages for male hypogonadism. Despite their therapeutic benefits, these elevated hormone levels raise concerns, necessitating further investigation into their long-term physiological and pathological impacts.

Both estradiol and testosterone elevate the risk of thromboembolic events in transgender patients while preserving bone density. Longterm monitoring for transgender individuals includes prostate and breast cancer screening, lipid profiling, liver function assays, hematocrit assessment for erythrocytosis, and screenings for hypertension and coronary artery disease. 

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Existing gaps in transgender pharmacology literature, such as optimal routes of administration and dosing adjustments for aging transgender individuals, call for in-depth surveys and case-control or cohort trials. Also, further studies could help define the presence of pharmacogenetic responses to estradiol due to ESR1 genomic variants.

Current literature reveals limited evidence regarding the efficacy and safety of hormonal treatment for transgender women, emphasizing the need for comprehensive studies encompassing antiandrogens and estradiol, focusing on dosages, routes of administration, and outcomes related to quality of life and adverse responses. 

Concerns arise about the impact of prolonged hormone therapies on malignancies. Addressing breast cancer risks in transgender males undergoing testosterone therapy presents a unique challenge. While cisgender females with breast cancer sometimes resort to testosterone therapy, transgender males face uncertainties due to potential estrogenic breast cancer growth. Ongoing research is imperative to establish informed guidelines for transgender males.

Conclusion 

The field of transgender and gender-nonconforming pharmacotherapy is expanding, offering opportunities for robust studies. Healthcare professionals, including physicians, pharmacists, nurse practitioners, and physician assistants, must stay abreast of best practices, monitoring protocols, and emerging research. 

While primary care providers can handle certain aspects, consultation with transgender healthcare specialists is advisable. Integrating transgender pharmacology education into professional curricula can ensure that all practitioners possess the requisite knowledge for optimal patient care.

Source: 

Sehgal, I. (2023). Review of adult gender transition medications: mechanisms, efficacy measures, and pharmacogenomic considerations. Frontiers in Endocrinology, 14. https://doi.org/10.3389/fendo.2023.1184024