Relationship Between Serum Estradiol Concentrations and Clinical Outcomes in Transgender Individuals Undergoing Feminizing Hormone Therapy: A Narrative Review

Abstract

Transgender, including gender diverse and nonbinary, individuals are treated with estradiol with or without antiandrogen to align their physical appearance with their gender identity, improve mental health and quality of life. Consensus guidelines give target ranges for serum estradiol concentration based on premenopausal female reference ranges. However, limited studies have evaluated the relationship between serum estradiol concentrations and clinical outcomes in transgender individuals undergoing feminizing hormone therapy. The available evidence has not found that higher serum estradiol concentrations, together with suppressed testosterone, enhance breast development, or produce more feminine changes to body composition. However, ensuring testosterone suppression appears to be an important factor to maximize these physical changes. Higher serum estradiol concentrations have been associated with higher areal bone mineral density. Although the resultant long-term clinical implications are yet to be determined, this could be a consideration for individuals with low bone mass. The precise serum estradiol concentration that results in adequate feminization without increasing the risk of complications (thromboembolic disease, cholelithiasis) remains unknown. Further prospective trials are required.

Effects of low-dose oral micronised progesterone on sleep, psychological distress, and breast development in transgender individuals undergoing feminising hormone therapy: a prospective controlled study

“…Limited studies have evaluated the influence of feminising hormone therapy regimens or sex steroid concentrations on breast development in trans individuals. Currently available data have not found a correlation with serum oestradiol concentration ( 39 ) but one study has reported a negative correlation between serum testosterone concentration and Tanner stage ( 37 ). There are currently no studies evaluating the influence of micronised progesterone on breast development.…”

Clinical features and prevalence of Klinefelter syndrome in transgender individuals: A systematic review

“…Menopausal hormone therapy has been shown to improve areal bone mineral density and reduce fracture risk 62 . Furthermore, several studies have demonstrated that feminizing gender‐affirming hormone therapy improves areal bone mineral density 63,64 . In general, higher serum estradiol concentrations correlate to higher areal bone mineral density 63 .…”

“…62 Furthermore, several studies have demonstrated that feminizing gender-affirming hormone therapy improves areal bone mineral density. 63,64 In general, higher serum estradiol concentrations correlate to higher areal bone mineral density. 63 Although there are no official guidelines, guidelines suggest monitoring bone mineral density with dual-energy X-ray absorptiometry every 24 months in people with Klinefelter syndrome.…”

“…63,64 In general, higher serum estradiol concentrations correlate to higher areal bone mineral density. 63 Although there are no official guidelines, guidelines suggest monitoring bone mineral density with dual-energy X-ray absorptiometry every 24 months in people with Klinefelter syndrome. Overall, the possible benefits of estradiol therapy for bone health should be balanced with the risks of thromboembolic disease in individuals with Klinefelter syndrome.…”

The problem of the use of hormonal therapy aimed for sex correction by transgender persons on their own initiative

“…Известно, что длительное нерациональное применение препаратов эстрадиола может приводить к гиперкоагуляции и развитию тромбозов [11], отекам [12], повышению пролактина и вторичным аденомам гипофиза [13], спорным остается вопрос о развитии онкологических заболеваний [14], в том числе рака груди [15,16]. Передозировка препаратами тестостерона, в свою очередь, ассоциирована с повышением гематокрита и тромбокрита [17], артериальной гипертонией [18], инсулинорезистентностью [19], акне [20], развитием поликистоза яичников и рака шейки матки [12,14].…”