Estrogen and Memory in a Transsexual Population

doi:10.1006/hbeh.1998.1478

Hormones and Behavior

Volume 34, Issue 2, October 1998, Pages 199-208

https://doi.org/10.1006/hbeh.1998.1478 Get rights and content

Abstract

The association between administered estrogen and performance on verbal memory and other cognitive tasks was examined. Male-to-female transsexuals undergoing estrogen treatment for sex reassignment (n= 29) scored higher on Paired Associate Learning (PAL) compared to a similar transsexual control group, awaiting estrogen treatment (n= 30) (P< 0.05). No differences between groups receiving and not receiving estrogen were detected on a control memory task (Digit Span) or on other cognitive tasks including Mental Rotations and Controlled Associations. There were no group differences in age. Group differences in mood or in general intellectual ability also did not explain the findings. Results suggest a specific influence of estrogen in men on verbal memory tasks, similar to that seen in prior studies of women. They are discussed in terms of differential processing demands of the two memory tasks and possible differences between estrogenic influences on Mental Rotations and Controlled Associations in men versus women.

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Gender-affirming hormone treatment and cognitive function in transgender young adults: a systematic review and meta-analysis
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Citation Excerpt :
The descriptive characteristics of the eligible studies are summarized in Table 1. Briefly, eight studies were conducted in Europe (Burke et al., 2016a; Gomez-Gil et al., 2009; Miles et al., 2006; Miles et al., 1998; Schoning et al., 2010; Slabbekoorn et al., 1999; Van Goozen et al., 1994; Van Goozen et al., 2002), one in the USA (Friedman, 2000) and one in both Europe and the USA (Haraldsen et al., 2005). Six studies were cohort (Burke et al., 2016a; Haraldsen et al., 2005; Miles et al., 2006; Slabbekoorn et al., 1999; Van Goozen et al., 1994; Van Goozen et al., 2002) and three cross-sectional (Friedman, 2000; Miles et al., 1998; Schoning et al., 2010), whereas one study presented both a longitudinal and a cross-sectional analysis (Gomez-Gil et al., 2009).
Previous studies have examined whether steroid hormone treatment in transgender individuals may affect cognitive function; yet, their limited power does not allow firm conclusions to be drawn. We leveraged data from to-date literature aiming to explore the effect of gender-affirming hormone administration on cognitive function in transgender individuals.
A search strategy of MEDLINE was developed (through June 1, 2019) using the key terms transgender, hormone therapy and cognitive function. Eligible were (i) cohort studies examining the longitudinal effect of hormone therapy on cognition, and (ii) cross-sectional studies comparing the cognitive function between treated and non-treated individuals. Standardized mean differences (Hedges’ g) were pooled using random-effects models. Study quality was evaluated using the Newcastle-Ottawa Scale.
Ten studies (seven cohort and three cross-sectional) were eligible representing 234 birth-assigned males (aM) and 150 birth-assigned females (aF). The synthesis of cohort studies (n = 5) for visuospatial ability following hormone treatment showed a statistically significant enhancement among aF (g = 0.55, 95% confidence intervals [CI]: 0.29, 0.82) and an improvement with a trend towards statistical significance among aM (g = 0.28, 95%CI: -0.01, 0.58). By contrast, no adverse effects of hormone administration were shown. No heterogeneity was evident in most meta-analyses.
Current evidence does not support an adverse impact of hormone therapy on cognitive function, whereas a statistically significant enhancing effect on visuospatial ability was shown in aF. New longitudinal studies with longer follow-up should explore the long-term effects of hormone therapy, especially the effects on younger individuals, where there is greater scarcity of data.
Explorative Prospective Evaluation of Short-Term Subjective Effects of Hormonal Treatment in Trans People—Results from the European Network for the Investigation of Gender Incongruence
2019, Journal of Sexual Medicine
Citation Excerpt :
Literature on the cognitive effects of HT is limited and often suffers from methodologic limitations, such as small sample sizes or a lack of pretreatment data.31 Some studies in trans women using estrogens show an improvement in (aspects of) short-term memory, whereas others did not find consistent effects.16,32,33 In our study, no change was observed in loss of concentration or memory loss scores for both trans women and trans men.
Although many studies on the short- and long-term effects of hormonal treatment (HT) in trans people focus on objective changes such as body composition or bone density, few studies have evaluated self-reported effects of HT.
To evaluate self-reported symptoms during the first year of HT in trans people.
This study is part of the European Network for the Investigation of Gender Incongruence, a multicenter prospective cohort study. For this study, 205 trans women and 193 trans men from the gender clinics of Amsterdam, Ghent, and Florence, who were >18 years of age and started hormonal treatment were included. Questionnaires, self-developed based on the Menopause Rating scale and clinical experiences, were completed, and changes in symptom scores were analyzed using linear mixed models.
Self-reported psycho vegetative symptoms, as well as physical, cognitive, emotional, sexual and genital complaints, and pain were evaluated at baseline and after 3, 6, and 12 months of HT using a 4-point Likert scale (no, mild, moderate, or severe complaints).
In trans men, with a median age of 23, transient increases were reported in night sweats, weight gain, and clitoral pain. Persistent increases were reported for hot flashes, balding, voice instability, acne, and increase in sexual desire, whereas emotional instability, fear, and menses decreased. For trans women, with a median age of 29, hot flashes, night sweats, fatigue, weight gain, changes in olfactory sense, brittle nails, emotional instability, mood swings, and breast tenderness increased persistently during 12 months of HT, whereas a decrease was observed for balding and sexual desire. Sleeping difficulties decreased temporarily. No changes were observed in palpitations, dizziness, abdominal complaints, anxiety, panic attacks, cognition, and pain, except for clitoral and breast pain.
Knowledge on the occurrence of these self-reported, subjective effects and their course over time may help physicians informing trans people starting with and during HT.
This study was performed in a large cohort of trans people. The follow-up period was limited to 12 months.
Changes in self-reported symptoms were mentioned in all investigated areas, except cognition. Most symptoms were as expected and even desired, whereas others may be considered unpleasant by some trans people.
van Dijk D, Dekker MJHJ, Conemans EB, et al. Explorative Prospective Evaluation of Short-Term Subjective Effects of Hormonal Treatment in Trans People—Results from the European Network for the Investigation of Gender Incongruence. J Sex Med 2019;16:1297–1309.
The transsexual brain - A review of findings on the neural basis of transsexualism
2015, Neuroscience and Biobehavioral Reviews
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This activating effect of androgens corresponds to the observation, that tests of visual memory generally favour males. On the other hand, the treatment with oestrogen in MtF transsexuals has been observed to improve verbal memory abilities (Miles et al., 1998). Despite several lines of evidence supporting the assumption that, in the case of mental rotation, the transsexuals’ performance adjusts towards the performance of people sharing the desired sex, there is also evidence challenging this view.
Transsexualism describes the condition when a person's psychological gender differs from his or her biological sex and is commonly thought to arise from a discrepant cerebral and genital sexual differentiation. This review intends to give an extensive overview of structural and functional neurobiological correlates of transsexualism and their course under cross-sex hormonal treatment. Research in this field enables insight into the stability or variability of gender differences and their relation to hormonal status. For a number of sexually dimorphic brain structures or processes, signs of feminisation or masculinisation are observable in transsexual individuals, which, during hormonal treatment, partly seem to further adjust to characteristics of the desired sex. Still, it appears the data are quite inhomogeneous, mostly not replicated and in many cases available for male-to-female transsexuals only. As the prevalence of homosexuality is markedly higher among transsexuals than among the general population, disentangling correlates of sexual orientation and gender identity is a major problem. To resolve such deficiencies, the implementation of specific research standards is proposed.
Prolonged androgen deprivation may influence the autoregulation of estrogen receptors in the brain and pelvic floor muscles of male rats
2015, Behavioural Brain Research
Androgen deprivation in males has detrimental effects on various tissues and bodily functions, some of which can be restored by estradiol (E2) administration. We investigated how the duration of androgen deprivation affects the autoregulation of estrogen receptors (ERs) levels in core brain areas associated with sexual behavior and cognition, as well as in pelvic floor muscles (PFM). We also measured c-Fos levels in brain areas associated with sexual behavior shortly after the rats mated.
Prolonged castration increases ERα levels in the preoptic area (POA) and E2 treatment reverses these effects. In the POA, c-Fos levels after mating are not affected by the duration of androgen deprivation and/or E2 treatment. ERβ levels in the POA as well as c-Fos levels in the POA and the core area of nucleus accumbens correlate with the mounting frequency for E2-treated Short-Term castrates. Additionally, ERβ levels in the medial amygdala are positively correlated with the mounting frequency of Long-Term castrates that received E2 treatment. In the hippocampus, ERs are downregulated only when E2 is administered early after castration, whereas downregulation of ERα in the prefrontal cortex only occurs with delayed E2 treatment. Early, but not delayed, E2 treatment after castration increases ERβ levels in the bulbocavernosus and ERα levels in the levator ani of male rats.
Our data suggest that the duration of androgen deprivation may influence the autoregulation of ERs by E2 treatment in select brain areas and pelvic floor muscles of male rats.
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Citation Excerpt :
However, the observed mood changes in hormone-treated patients might also be due to hormones-induced external physical modifications that in turn produces better self-confidence and social skills, as they reinforces gender affirmation. Regarding cognition, behavioral studies have shown that high doses of E2 during transition improve verbal fluency (Van Goozen et al., 1995) and verbal memory (Miles et al., 1998), but deteriorate mental rotations ability (Van Goozen et al., 1995). Neurofunctional imaging studies provided partially support for these behavioral studies, as they reported different brain activation patterns before and after CSHT in MtF patients during cognitive tasks (Carrillo et al., 2010; Schoning et al., 2010; Sommer et al., 2008).
Ovarian hormones are pivotal for the physiological maintenance of the brain function as well as its response to environmental stimuli. There is mounting evidence attesting the relevance of endogenous ovarian hormones as well as exogenous estradiol and progesterone for emotional and cognitive processing.
The present review systematically summarized current knowledge on sex steroid hormonal modulation of neural substrates of emotion and cognition revealed by functional magnetic resonance imaging (fMRI). Twenty-four studies of healthy naturally cycling and combined oral contraceptives (COC) user women, or women undergoing experimental manipulations, during their reproductive age, were included. Furthermore, six studies of premenstrual dysphoric disorder (PMDD), a hormonally based mood disorder, and three of gender dysphoria (GD), which provides an intriguing opportunity to examine the effect of high-dose cross-sex hormone therapy (CSHT) on brain functioning, were included. Globally, low (early follicular and the entire follicular phase for estrogen and progesterone, respectively) and high (COC, CSHT, late follicular and luteal phase for estrogen; COC, mid- and late-luteal phase for progesterone) hormonal milieu diversely affected the response of several brain regions including the amygdala, anterior cingulate cortex, and inferior frontal gyrus, but their functional recruitment across groups and domains was scattered.
The constellation of findings provides initial evidence of the influence of sex steroid hormones on cortical and subcortical regions implicated in emotional and cognitive processing. Further well-powered and multimodal neuroimaging studies will be needed to identify the neural mechanism of functional brain alterations induced by sex steroid hormones.
The effect of estrogen on the sexual interest of castrated males: Implications to prostate cancer patients on androgen-deprivation therapy
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Citation Excerpt :
One study showed that E treatment improved at least one cognitive domain in PCa patients on ADT [7]. Similar data are available for MtFs [131,132]. However, these findings were not supported in two other studies [133,134].
Androgen deprivation therapy (ADT) for prostate cancer (PCa) treatment causes sexual dysfunction. We review here the effects of estrogen on the sexual performance of androgen-deprived males. The major findings are:
- 1.
  Estrogen receptors are present in brain centers that are important for sexual behavior; as well as in male reproductive organs, in a pattern suggesting that estrogen may have some role in orgasmic function and genital skin sensitivity.
- 2.
  Estrogen restores sexual interest above castrate levels in many vertebrates including reptiles, birds and mammals; but multiple factors contribute to the magnitude of this effect.
- 3.
  Data from castrated men, aromatase-deficient men, male-to-female transsexuals, and men on antiandrogens all suggest that estrogen can maintain some libido in androgen-deprived men.
We discuss the general benefits of estrogen therapy to quality of life of men on ADT, the potential risks of this treatment, and possible treatment regimes for estrogen therapy in males. Unless contraindicated, we propose that PCa patients on ADT would benefit from supplemental parenteral estrogen.

View all citing articles on Scopus

^☆: G. H. Bower

¹: To whom correspondence should be addressed at Department of Psychology, City University, London, EC1V OHB, UK. E-mail:C. L. [email protected].

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Regular ArticleEstrogen and Memory in a Transsexual Population☆

Abstract

Intelligence

Arch. Clin. Neuropsychol.

Behav. Neural Biol.

Psychoneuroendocrinology

Psychoneuroendocrinology

Learning Individual Differ.

Psychoneuroendocrinology

Brain Cogn.

J. Exp. Child. Psychol.

Horm. Behav.

Dev. Brain Res.

Exp. Neurol.

Personal. Individual Differ.

Personal. Individual Differ.

Neuropsychologia

Psychoneuroendocrinology

Psychoneuroendocrinology

Psychoneuroendocrinology

Diagnostic and Statistical Manual of mental Disorders

The control of short-term memory

Sci. Am.

Working memory

The Psychology of Learning and Motivation

Estrogen replacement therapy and cognitive function in older women

J. Am. Med. Assoc.

Working memory and secondary memory deficits in Alzheimer' Disease

J. Clin. Exp. Neuropsychol.

Age related sex differences in verbal memory

J. Clin. Psychol.

Intellectual changes and sex differences in octogenarians: A 20 year longitudinal study of aging

Dev. Psychol.

An evaluation of psychologic effects of sex hormone administration in aged women. Results of therapy after six months

J. Gerontol.

Effects of test anxiety and sex of subject on neuropsychological test performance: Finger tapping, trail making, digit span and digit symbol tests

Percept. Mot. Skills.

Human behavioral sex differences: A role for gonadal hormones during early development?

Psychol. Bull.

Manual for Kit of Factor-Referenced Cognitive Tests

The Pharmacological Basis of Therapeutics

Regular Article
Estrogen and Memory in a Transsexual Population☆