Gender-affirming hormone treatment and cognitive function in transgender young adults: a systematic review and meta-analysis

Karalexi, Maria A.; Georgakis, Marios K.; Dimitriou, Nikolaos G.; Vichos, Theodoros; Katsimpris, Andreas; Petridou, Eleni; Papadopoulos, Fotios C.

doi:10.1016/j.psyneuen.2020.104721

Cited by 28 publications

(32 citation statements)

References 74 publications

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“…Evidence for negative effects of same-sex hormone deprivation on cognitive aging and AD risk begs the question of whether GHT impacts cognitive functioning in transgender individuals. While neuropsychological research on this topic is limited, meta-analysis indicates no adverse effects of GHT in young adult transgender men or women ( Karalexi et al, 2020 ). Rather, young transgender men exhibited a significant enhancement of visuospatial ability following testosterone treatment ( Karalexi et al, 2020 ).…”

Section: Exogenous Estrogen Exposuresmentioning

confidence: 99%

Endogenous and Exogenous Estrogen Exposures: How Women’s Reproductive Health Can Drive Brain Aging and Inform Alzheimer’s Prevention

Jett

Malviya

Schelbaum

et al. 2022

Front. Aging Neurosci.

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After advanced age, female sex is the major risk factor for late-onset Alzheimer’s disease (AD), the most common cause of dementia affecting over 24 million people worldwide. The prevalence of AD is higher in women than in men, with postmenopausal women accounting for over 60% of all those affected. While most research has focused on gender-combined risk, emerging data indicate sex and gender differences in AD pathophysiology, onset, and progression, which may help account for the higher prevalence in women. Notably, AD-related brain changes develop during a 10–20 year prodromal phase originating in midlife, thus proximate with the hormonal transitions of endocrine aging characteristic of the menopause transition in women. Preclinical evidence for neuroprotective effects of gonadal sex steroid hormones, especially 17β-estradiol, strongly argue for associations between female fertility, reproductive history, and AD risk. The level of gonadal hormones to which the female brain is exposed changes considerably across the lifespan, with relevance to AD risk. However, the neurobiological consequences of hormonal fluctuations, as well as that of hormone therapies, are yet to be fully understood. Epidemiological studies have yielded contrasting results of protective, deleterious and null effects of estrogen exposure on dementia risk. In contrast, brain imaging studies provide encouraging evidence for positive associations between greater cumulative lifetime estrogen exposure and lower AD risk in women, whereas estrogen deprivation is associated with negative consequences on brain structure, function, and biochemistry. Herein, we review the existing literature and evaluate the strength of observed associations between female-specific reproductive health factors and AD risk in women, with a focus on the role of endogenous and exogenous estrogen exposures as a key underlying mechanism. Chief among these variables are reproductive lifespan, menopause status, type of menopause (spontaneous vs. induced), number of pregnancies, and exposure to hormonal therapy, including hormonal contraceptives, hormonal therapy for menopause, and anti-estrogen treatment. As aging is the greatest risk factor for AD followed by female sex, understanding sex-specific biological pathways through which reproductive history modulates brain aging is crucial to inform preventative and therapeutic strategies for AD.

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Section: Exogenous Estrogen Exposuresmentioning

confidence: 99%

Endogenous and Exogenous Estrogen Exposures: How Women’s Reproductive Health Can Drive Brain Aging and Inform Alzheimer’s Prevention

Jett

Malviya

Schelbaum

et al. 2022

Front. Aging Neurosci.

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“…Couple this with the data already showing that oxygen-carrying haemoglobin levels are reduced in transwomen to female norms levels [45], it is a sports performance proxy that is urgently needing investigation due to the importance of the cardiovascular system during aerobic exercise. Low testosterone concentrations have been reported in transwomen undergoing hormone replacement therapy (HRT) [46] and in a recent meta-analysis, HRT was found not to affect the motor coordination or visuospatial abilities of transwomen [47]. In a study of 50 non-athlete transwomen who had undergone gender-affirming surgery (GAS) coupled with HRT, a reduction in muscle mass and bone mineral density was reported together with an increase in fat mass following HRT initially and 1 year after GAS [48].…”

Section: The Challengementioning

confidence: 99%

Integrating Transwomen and Female Athletes with Differences of Sex Development (DSD) into Elite Competition: The FIMS 2021 Consensus Statement

et al. 2021

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Sport is historically designated by the binary categorization of male and female that conflicts with modern society. Sport's governing bodies should consider reviewing rules determining the eligibility of athletes in the female category as there may be lasting advantages of previously high testosterone concentrations for transwomen athletes and currently high testosterone concentrations in differences in sex development (DSD) athletes. The use of serum testosterone concentrations to regulate the inclusion of such athletes into the elite female category is currently the objective biomarker that is supported by most available scientific literature, but it has limitations due to the lack of sports performance data before, during or after testosterone suppression. Innovative research studies are needed to identify other biomarkers of testosterone sensitivity/responsiveness, including molecular tools to determine the functional status of androgen receptors. The scientific community also needs to conduct longitudinal studies with specific control groups to generate the biological and sports performance data for individual sports to inform the fair inclusion or exclusion of these athletes. Eligibility of each athlete to a sport-specific policy needs to be based on peer-reviewed scientific evidence made available to policymakers from all scientific communities. However, even the most evidence-based regulations are unlikely to eliminate all differences in performance between cisgender women with and without DSD and transwomen athletes. Any remaining advantage held by transwomen or DSD women could be considered as part of the athlete's unique makeup.

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“…Available data have not demonstrated any adverse impact of PS on executive function in TGD youth; however, the sample size of this study was small and likely underpowered ( 93 ). A recent systematic review and meta-analysis of data in postpubertal TGD young adults reported no adverse impact of GAH on any cognitive domain assessed and significant improvement in visuospatial abilities following testosterone treatment ( 94 ).…”

Section: Potential Side Effects Of Hormonal Interventionmentioning

confidence: 99%

Approach to the Patient: Pharmacological Management of Trans and Gender-Diverse Adolescents

O’Connell

Nguyen

Ahler

et al. 2021

The Journal of Clinical Endocrinology &Amp; Metabolism

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Internationally, increasing numbers of children and adolescents with gender dysphoria are presenting for care. In response, gender affirming therapeutic interventions that seek to align bodily characteristics with an individual’s gender identity are more commonly being employed. Depending on a young person’s circumstances and goals, hormonal interventions may aim to achieve full pubertal suppression, modulation of endogenous pubertal sex hormone effects and/or development of secondary sex characteristics congruent with their affirmed gender. This is a relatively novel therapeutic area and, while short-term outcomes are encouraging, longer-term data from prospective longitudinal adolescent cohorts are still lacking, which may create clinical and ethical decision-making challenges. Here we review current treatment options, reported outcomes, and clinical challenges in the pharmacological management of trans and gender diverse adolescents.

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Gender-affirming hormone treatment and cognitive function in transgender young adults: a systematic review and meta-analysis

Cited by 28 publications

References 74 publications

Endogenous and Exogenous Estrogen Exposures: How Women’s Reproductive Health Can Drive Brain Aging and Inform Alzheimer’s Prevention

Endogenous and Exogenous Estrogen Exposures: How Women’s Reproductive Health Can Drive Brain Aging and Inform Alzheimer’s Prevention

Integrating Transwomen and Female Athletes with Differences of Sex Development (DSD) into Elite Competition: The FIMS 2021 Consensus Statement

Approach to the Patient: Pharmacological Management of Trans and Gender-Diverse Adolescents

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