Abstract
Gender dysphoria describes the distress associated with having a gender identity that differs from one’s birth-assigned sex. To relieve this distress, transgender, and gender diverse (henceforth, trans) individuals commonly undergo medical transition involving hormonal treatments. Current hormonal treatment guidelines cater almost exclusively for those who wish to transition from male to female or vice versa. In contrast, there is a dearth of hormonal options for those trans individuals who identify as non-binary and seek an androgynous appearance that is neither overtly male nor female. Though prolonged puberty suppression with gonadotrophin releasing hormone agonists (GnRHa) could in theory be gender-affirming by preventing the development of unwanted secondary sex characteristics, this treatment option would be limited to pre- or peri-pubertal adolescents and likely have harmful effects. Here, we discuss the theoretical use of Selective Estrogen Receptor Modulators (SERMs) for non-binary people assigned male at birth (AMAB) who are seeking an androgynous appearance through partial feminization without breast growth. Given their unique range of pharmacodynamic effects, SERMs may represent a potential gender-affirming treatment for this population, but there is a lack of knowledge regarding their use and potentially adverse effects in this context.
Highlights
Trans individuals have a gender identity that is different from the sex they were assigned at birth, as opposed to cisgender people, whose gender identity corresponds with their assigned sex [1]
A recent study of >8000 60-80 year-old post-menopausal cisgender women receiving daily lasofoxifene showed a 32% reduction in major coronary events over five years compared to hypogonadal postmenopausal cisgender women [45]. While these findings suggest that selective estrogen receptor modulator (SERM) might promote cardiovascular health, such effects again cannot be directly extrapolated to non-binary people assigned male at birth (AMAB), given likely different mechanisms underlying their cardiovascular risk profile
In the clinical setting, increasing numbers of non-binary individuals are seeking gender-affirming hormone therapy, and some desire androgynous physical characteristics to align with their gender identity
Summary
Trans individuals have a gender identity that is different from the sex they were assigned at birth, as opposed to cisgender people, whose gender identity corresponds with their assigned sex [1]. Lasofoxifene has been approved in the EU for both osteoporosis and vaginal atrophy [45] and is currently being reviewed by the FDA as a treatment for breast cancer [48] Given their tissue-specific antagonistic and agonistic effects, SERMs could potentially be suitable either as an independent or combined treatment modality for the gender-affirming care of non-binary individuals AMAB who desire partial feminization without breast growth. A recent study of >8000 60-80 year-old post-menopausal cisgender women receiving daily lasofoxifene showed a 32% reduction in major coronary events over five years compared to hypogonadal postmenopausal cisgender women [45] While these findings suggest that SERMs might promote cardiovascular health, such effects again cannot be directly extrapolated to non-binary people AMAB, given likely different mechanisms underlying their cardiovascular risk profile. Consistent with this, clinical trials – ideally across multiple centers to aid in patient recruitment – are required to provide greater evidence regarding the potential benefits and harms of using SERMs in non-binary individuals
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