The FDA Knows the Drugs are Dangerous

Anabolic-androgenic steroid (AAS)/testosterone drugs and GnRHa (estrogen-blocking) drugs are used for gender transition in biological females. The FDA and other U.S. agencies have already indicated that AAS/testosterone treatments can have dangerous brain, behavioral, and other effects.

AAS/testosterone treatments raise testosterone dramatically in female-to-male transsexuals (FtMs) and suppress estrogen and estrogen receptors. GnRHa “puberty-blocking” treatments also suppress estrogen. These treatments are not FDA-approved for gender transition purposes in biological females (see FDA 2015; Scutti 2017; Smith 2017). In fact:

“There are no FDA-approved testosterone…therapies for women….There are also concerns about under- or overdosing as well as side effects from these treatments” (The Endocrine Society 2016).

AAS/testosterone or GnRHa drugs for gender transition purposes may pose many risks. Effects may include:

  • Abnormal brain development in adolescents
  • Mood swings, delusions, impaired judgment, and addiction
  • Altered self-related thinking and own-body perception
  • Self-harm and suicide
  • Impaired social functioning and autism
  • Impaired verbal abilities
  • Oxytocin problems
  • Attention deficit hyperactivity disorder (ADHD) symptoms
  • Aggression and anti-social or criminal behaviors
  • Schizophrenia, bipolar disorder, PTSD, borderline personality disorder, etc.
  • Dementia, cognition, memory, and neurological disorders
  • Mitochondrial dysfunction and oxidative stress
  • Altered gene expression and neurotransmitters
  • Altered sexual behaviors
  •  Changes in brain structures in adults

Abnormal Brain Development

National Institute on Drug Abuse (2018a) What are the risks of anabolic steroid use in teens?

“steroid use in teens is of concern, especially since the hormonal systems they interact with play a critical role in brain development during these years….[Medical research] suggests that pubertal steroid exposure could produce long-lasting structural changes in certain brain regions.

Mood Swings, Delusions, Impaired Judgment & Addiction

Food & Drug Administration (2013) Teens and steroids: A dangerous combo:

“[Anabolic-androgenic steroids] are drugs that mimic the actions of the male sex hormone testosterone….

They are known to have a range of serious adverse effects on many organ systems, and in many cases the damage is not reversible….

Both boys and girls may also experience mood swings and aggressive behavior ….

Mood swings are among the first side effects to show up, and steroid use may lead to mania or depression.”

National Institute on Drug Abuse (2016) Anabolic steroids:

“Anabolic steroids are synthetic variations of the male sex hormone testosterone….

Abuse of anabolic steroids may lead to mental problems, such as:

  • paranoid (extreme, unreasonable) jealousy
  • extreme irritability
  • delusions—false beliefs or ideas
  • impaired judgment

Extreme mood swings can also occur, including “roid rage”—angry feelings and behavior that may lead to violence.”

Food & Drug Administration (2017) Caution: Bodybuilding products can be risky:

“anabolic steroids have been associated with serious reactions such as severe acne, hair loss, altered mood, irritability, increased aggression, and depression….

If you’re taking any body building products that claim to contain steroids or steroid-like substances, FDA recommends that you stop taking them immediately.”

National Institute on Drug Abuse (2017) Anabolic steroids:

“Anabolic steroids affect a part of the brain called the limbic system, which controls mood. Long-term steroid abuse can lead to aggressive behavior and extreme mood swings. This is sometimes referred to as ‘roid rage’….

People who do become addicted keep using steroids despite bad effects on their bodies and lives. Also, people who misuse steroids typically spend a large amount of time and money obtaining the drugs, another sign they could be addicted.”

Self-Related Thinking & Own-Body Perception

Burke (2018) Testosterone effects on the brain in transgender men [female-to-male transsexuals]:

“[In female-to-male transsexuals], testosterone treatment resulted in functional and structural changes in self-referential and own body perception areas [of the brain].

Self-Harm & Suicide

Miller (2002) A comparison of health risk behavior in adolescent users of anabolic-androgenic steroids:

“Girls who used steroids scored…higher on suicide risk…than boys who used steroids….Although adolescent girls overall tend to use less alcohol or other illicit drugs than boys do (Johnston, O’Malley, & Bachman, 2001), among steroid users, the mean scores for girls and boys on each of the substance use risk scales were strikingly similar.”

Dhejne (2011) Long-term follow-up of transsexual persons undergoing sex reassignment surgery:

“The overall mortality for sex-reassigned persons was higher during follow-up…than for controls of the same birth sex, particularly death from suicide….Sex-reassigned persons also had an increased risk for suicide attempts…and psychiatric inpatient care ….Persons with transsexualism, after sex reassignment, have considerably higher risks for mortality, suicidal behaviour, and psychiatric morbidity than the general population.”

Darke (2014) Sudden or unnatural deaths involving anabolic‐androgenic steroids:

“To determine causes of death, characteristics, toxicology, and pathology of AAS positive cases, all cases…were retrieved. All were male, and the mean age was 31.7 years. Deaths were mainly due to accidental drug toxicity (62.5%), then suicide (16.7%) and homicide (12.5%).”

Thiblin (1999) Cause and manner of death among users of anabolic androgenic steroids:

“Homicides, suicides, and poisonings determined accidental or indeterminate in manner were related to impulsive, disinhibited behavior characterized by violent rages, mood swings, and/or uncontrolled drug intake [in male AAS users].

The observations in the present study indicate an increased risk of violent death from impulsive, aggressive behavior, or depressive symptoms associated with use of AAS….Finally, the observations indicate that use of AAS may be the gateway of approach to abuse of other psychotropic drugs.”

Måsson (2008) Women with polycystic ovary syndrome:

“Polycystic ovary syndrome (PCOS) is a common hyperandrogenic [high testosterone] endocrine disorder affecting women of fertile age….Suicide attempts were seven times more common in the PCOS group than in the controls. Current as well as lifetime use of antidepressants and anxiolytic drugs were more common in the PCOS group.”

Sher (2014) Association of testosterone levels and future suicide attempts in females with bipolar disorder:

“At baseline, testosterone levels positively correlated with the number of previous major depressive episodes and suicide attempts. Cox proportional hazards regression analysis found that higher baseline testosterone levels predicted suicide attempts during the follow-up period…

Testosterone levels may predict suicidal behavior in women with bipolar disorder.”

Rice (2015) Adolescent suicide and testosterone:

“Completed suicide is much more common in men than in women….One biological hypothesis that accounts for the increased frequency of completed suicide in men is that the male sex hormone testosterone partially mediates the observed increase in suicide frequency….Specifically, we propose that the impairment wrought by…high levels of testosterone in the adolescent upon the emotion regulation system contribute to an account for these findings.”

Impaired Social Functioning & Autism

Ye (2011) Androgens modulate brain networks of empathy in female-to-male transsexuals:

“functional magnetic resonance imaging was used in a group of female-to-male transsexuals before and during androgen therapy….Long-term androgen administration reduced the pSTS [posterior superior temporal sulcus] activity in response to emotional stimuli as well as its response to social relation. More importantly, the functional connectivity among frontal, temporal and striatal regions was weakened while the connectivity among limbic regions was strengthened as the androgen level increased during hormone therapy…..[Androgen therapy] not only reduced the activity of a core neural hub but also markedly altered the organization of the brain network supporting emotional and social cognitive processes related to empathy and mentalizing.”

van Honk (2011) Testosterone administration impairs cognitive empathy in women depending on second-to-fourth digit ratio:

“Here, we show that administration of testosterone in 16 young women led to a significant impairment in their cognitive empathy, and that this effect is powerfully predicted by a proxy of fetal testosterone: the right-hand second digit-to-fourth digit ratio. Our data thus not only demonstrate down-regulatory effects of current testosterone on cognitive empathy, but also suggest these are preprogrammed by the very same hormone prenatally.”

Olsson (2016) Testosterone and estrogen impact social evaluations and vicarious emotions:

“In the present double-blind placebo-controlled study, we administered an acute exogenous dose of testosterone…to healthy female…volunteers….Our results showed that testosterone administration to females…diminished their accuracy in inferring mental states….Taken together, these results suggest that sex hormones affect social–cognitive and emotional functions at several levels, linking our results to neuropsychiatric disorders in which these functions are impaired.”

Bos (2016) Testosterone reduces functional connectivity during the ‘Reading the Mind in the Eyes’ Test:

“we found that a single administration of testosterone in 16 young women significantly altered connectivity of the left IFG [inferior frontal gyrus] with the anterior cingulate cortex (ACC) and the supplementary motor area (SMA) during RMET [performance on the ‘Reading the Mind in Eyes’ Test,’ in which emotions have to be inferred from the eye-region of a face]….Our findings thus reveal a neural mechanism by which testosterone can impair emotion-recognition ability, and may link to the symptomatology of ASC [autism], in which the same neural network is implicated.”

(2018) Male susceptibility to autism linked to male hormones in early-stage brain development:

“Exposure to androgens (male hormones) during brain development alters genes related to autism spectrum disorder (ASD), according to a new study published in Biological Psychiatry.

Schwarz (2011) Sex-specific serum biomarker patterns in adults with Asperger’s syndrome:

“free testosterone levels were elevated in adults with AS [Asperger syndrome]….This effect was specific for females [with Asperger syndrome].”

Bejerot (2012) The extreme male brain revisited:

“Women with ASD [autism] had higher total and bioactive testosterone levels.”

Cesta (2016) Polycystic ovary syndrome and psychiatric disorders:

“Following adjustment for comorbid psychiatric disorders, women with PCOS [polycystic ovary syndrome, a chronic excess testosterone condition] were still at a significantly increased risk for bulimia, schizophrenia, bipolar disorder, depressive and anxiety disorders, personality disorders, with the highest…[adjusted odds] for ASD [autism].”

Neuroscience News (2014) Estrogen receptor expression may help explain why more males have autism

Estrogen is known to be neuroprotective, but nobody has looked at whether its function is impaired in the brain of individuals with autism. We found that the children with autism didn’t have sufficient estrogen receptor beta expression.”

Impaired Verbal Abilities

van Goozen (1995) Activating effects of cross-sex hormones:

“The administration of androgens to [female-to-male transsexuals]…had a deteriorating effect on verbal fluency tasks.”

ECNP (2015) Testosterone changes brain structures in female-to-male transsexuals:

“with testosterone treatment [in female-to-male transsexuals] the volume of grey matter decreased in two specific regions of the brain, the Broca’s and Wernicke’s areas, which are mainly responsible for language processing.”

Worsley (2014) Higher testosterone levels are correlated with poorer verbal memory in women with chronic schizophrenia

“in women with chronic schizophrenia, higher testosterone levels are associated with poorer cognition, in particular, verbal memory.”

Baskaran (2017) Estrogen replacement improves verbal memory:

“young [female] athletes [whose menstrual periods have stopped]…with estrogen deficiency have not been evaluated for cognitive deficits…..We hypothesized that estrogen replacement would improve verbal memory and executive control….[The athletes] show improvements in verbal memory and executive control following 6 months of estrogen replacement. These findings in athletes, who are in their prime of neurocognitive development, underscore the need for future studies.”

Oxytocin Problems

Okabe (2013) Testosterone inhibits…oxytocin neural system in mice:

“Testosterone suppressed the oxytocin (OT) system in both sexes.”

Rissman (2008) Roles of oestrogen receptors α and β in behavioural neuroendocrinology:

“ERβ [estrogen receptor beta] increases the amount of oxytocin peptide produced, and ERα [estrogen receptor alpha] increases expression of its receptor.”

Acevedo-Rodriguez (2015) Oxytocin and estrogen receptor β in the brain:

estrogen receptor β [beta] activation has been found to both reduce anxiety-related behaviors and increase OT peptide transcription, suggesting a role for OT in this estrogen receptor β-mediated anxiolytic effect.

Estrogens can act in a synergistic manner with OT, not only by enhancing its anxiolytic effects but also by increasing OTR [oxytocin receptor] levels.”

Attention Deficit Hyperactivity Disorder (ADHD) Symptoms

National Institute on Drug Abuse (2018a) What are the risks of anabolic steroid use in teens?

“Teens who use anabolic steroids may also be at increased risk for some cognitive side effects compared with adults. For example, males who begin using anabolic steroids during the teen years show increased impulsivity and decreased attention, compared to men who began using steroids in their adult years.98 In adolescent rats, anabolic steroid exposure is associated with electrolytic imbalances, hyperactivity, anxiety, and increased sympathetic autonomic modulation (e.g., fight or flight response) during adulthood, even when steroid use was discontinued during adolescence.99

Roberts (2016) Ovarian hormones, ADHD, risk-taking, & impulsivity:

ADHD symptoms were most pronounced [in women] when estrogen was low; this association manifested (1) between women, with lower average estrogen across the entire cycle predicting higher ADHD symptoms, and (2) within women, with lower-than-average levels of estrogen during periods of higher-than-average progesterone predicting higher ADHD symptoms two days later….[W]ithin-person effects of ovarian hormones were significant only among women with high negative or positive urgency (emotion-related impulsivity) or high sensation seeking.”

Aggression & Anti-Social or Criminal Behaviors

van Goozen (1995) Activating effects of cross-sex hormones:

“In a group of 35 female-to-male transsexuals…a large battery of tests on aggression, sexual motivation and cognitive functioning was administered twice: shortly before and three months after the start of cross-sex hormone treatment. The administration of androgens to females was clearly associated with an increase in aggression proneness.”

Dhejne (2011) Long-term follow-up of transsexual persons undergoing sex reassignment surgery:

“Female-to-males, but not male-to-females, had a higher risk for criminal convictions than their respective birth sex controls.”

Lundhold (2010) Use of anabolic androgenic steroids in substance abusers arrested for crime:

“findings also suggest that AAS use is highly overrepresented in women who commit crimes.”

Dabbs (1997) Age, testosterone, and behavior among female prison inmates:

“Testosterone is related to criminal violence and aggressive dominance in prison among women.”

Ohlsson Gotby (2015) Congenital adrenal hyperplasia, polycystic ovary syndrome and criminal behavior:

“Our findings indicate that female hyperandrogenism in adulthood, but not prenatal hyperandrogenism, is associated with risk for criminal behavior.”

Probst (2018) Reactive aggression tracks within‐participant changes in women’s salivary testosterone:

“This study is the first to demonstrate that women react more aggressively in response to provocation when their testosterone level is high than when their testosterone is low, suggesting that testosterone plays an important role in the regulation of women’s aggressive behavior following social provocation.”

Hermans (2008) Exogenous testosterone enhances responsiveness to social threat in the neural circuitry of social aggression:

“These data demonstrate that testosterone enhances responsiveness in neural circuits of social aggression [in female subjects].”

Choi (2011) Violence toward women and illicit androgenic-anabolic steroid use:

“Substantial evidence now suggests that increased aggression is associated with illicit use of anabolic-androgenic steroids (AAS) by athletes….AAS users reported significantly more fights, verbal aggression, and violence toward their significant others when using AAS than when not using AAS…but AAS users off-drug did not significantly differ from nonusers. These findings support the anecdotal evidence that wives and girlfriends of AAS users may be at risk of serious injury from users while they are on-drug.”

Hallgren (2015) Anti-social behaviors associated with anabolic-androgenic steroid use among male adolescents:

“we compared the prevalence of anti-social behaviors among adolescent AAS [anabolic-androgenic steroid] users, non-AAS illicit drug users, and drug non-users….Across all survey years, the risk ratios for virtually all measured anti-social behaviors were significantly higher among AAS users compared to non-AAS illicit drug users and to drug non-users.”

Klötz (2007) Violent crime and substance abuse:

“the incidence of violent crime among users of AAS without signs of other drug abuse was comparable to the corresponding incidences for drug addicts without AAS use. This observation suggests that the violent criminality observed among AAS users is not confounded in any systematic fashion by abuse of other drugs. The findings also indicate that use of AAS in certain predisposed individuals might cause a high rate of violent crimes, especially if the use of AAS is combined with the use of other illegal substances.”

Skårber (2010) Is there an association between the use of anabolic-androgenic steroids and criminality?

“The results suggest that there is an association between the use of AAS and criminality, especially with regard to crimes of violence and weapon offences, and that this criminality may be enhanced when AAS are combined with other drugs of abuse.”

National Institute on Drug Abuse (2018a) What are the risks of anabolic steroid use in teens?

“adolescent male hamsters given anabolic steroids show increased aggression, even after steroid use is discontinued. These aggressive effects are paralleled by changes in levels of serotonin100,101 and androgen receptors in the rodent brain.102

Welker (2014) Testosterone, cortisol, and psychopathic traits in men and women

“The relationships between testosterone cortisol and psychopathy were examined [in women and men].

“Testosterone was positively related to psychopathy.”

van Honk (2004) Testosterone shifts the balance between sensitivity for punishment and reward in healthy young women

“[Healthy young women] showed a more disadvantageous pattern of decision-making after testosterone compared to placebo administration. These findings not only provide the first direct evidence for the effects of testosterone on punishment–reward contingencies in humans, but they also give further insights into the hypothetical link between testosterone and psychopathy.”

van Wingen (2010) Testosterone reduces amygdala–orbitofrontal cortex coupling

“Healthy middle-aged women received a single nasal testosterone dose in a randomized, placebo-controlled, crossover manner….The results show that testosterone rapidly reduced functional coupling of the amygdala with the orbitofrontal cortex, and enhanced amygdala coupling with the thalamus. This suggests that testosterone may reduce the regulatory control over the amygdala, or that testosterone shifts amygdala output away from the orbitofrontal cortex towards the thalamus. Testosterone also reduced functional coupling with the contralateral amygdala.”

Westlye (2017) Brain connectivity aberrations in anabolic-androgenic steroid users

“Sustained anabolic-androgenic steroid (AAS) use has adverse behavioral consequences, including aggression, violence and impulsivity….Here, we tested the effects of AAS on resting-state functional brain connectivity in the largest sample of AAS-users to date. ….In line with the emotional and behavioral consequences of AAS, current users exhibited reduced functional connectivity between key nodes involved in emotional and cognitive regulation.

Bipolar Disorder, Schizophrenia, PTSD, & Other Psychiatric Disorders

Wooderson (2015) An exploration of testosterone levels in patients with bipolar disorder:

“Women with bipolar disorder had significantly higher testosterone levels than female controls.”

Meinhard (2013) The role of estrogen in bipolar disorder:

“studies showed very low levels of estrogen in [bipolar] women with postpartum psychosis and significant improvement of symptoms after treatment with estrogen.”

Tan (2017) Borderline personality disorder and polycystic ovary syndrome:

“Overall, the literature shows women with borderline personality disorder to have higher than expected serum androgen levels.”

Matevosyan (2011) Schizophrenia and Stein–Leventhal syndrome: comorbidity features:

“Insulin resistance and elevated testosterone in women contribute in shared pathogenesis of schizophrenia and PCOS.”

Cesta (2016) Polycystic ovary syndrome and psychiatric disorders:

“Women with PCOS had a 50% increased odds of having a psychiatric disorder.

Including schizophrenia, bipolar disorder, bulimia, ASD, tics, and personality, anxiety and depressive disorders.”

Worsley (2014) Higher testosterone levels are correlated with poorer verbal memory in women with chronic schizophrenia:

“in women with chronic schizophrenia, higher testosterone levels are associated with poorer cognition, in particular, verbal memory.”

Newton-Mann (2017) Estrogen receptors: Mechanism of action and relevance to schizophrenia:

“Sex differences are observed in schizophrenia, with women exhibiting an overall better disease outcome, leading to the estrogen hypothesis of schizophrenia that postulates a protective role of estrogen against the development and severity of the disorder.”

Sandoiu (2017) Estrogen regulates the brain’s fear response, protecting against PTSD:

“[Study results suggest] that estrogen can protect against the formation of PTSD [posttraumatic stress disorder]. The authors add that in addition to its role in modulating the fear response, previous studies have also suggested that estrogen alters pain perception.”

Cooney (2017) Depression and anxiety in polycystic ovary syndrome:

“Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive age women and is associated with an increased prevalence of depression and anxiety symptoms….Obesity, insulin resistance, and elevated androgens may partly contribute to this association.”

(2018) PCOS linked to increased risk of mental health disorders:

“PCOS patients were more likely to be diagnosed with mental health disorders, including depression, anxiety, bipolar disorder and eating disorders.”

Dementia, Cognition, Memory & Neurological Disorders

Heffernan (2015) Everyday memory deficits associated with anabolic-androgenic steroid use in regular gymnasium users:

“AAS use in a recreational sports context is associated with RM [retrospective memory], EF [executive function] and PM [prospective memory] deficits, indicating that AAS use may damage everyday remembering.”

Kanayama (2008) Long-term psychiatric and medical consequences of anabolic–androgenic steroid abuse:

“High concentrations of AAS [anabolic-androgenic steroids], comparable to those likely sustained by many AAS abusers, produce apoptotic [cell death] effects on various cell types, including neuronal cells—raising the specter of possibly irreversible neuropsychiatric toxicity.”

Kanayama (2018) Public health impact of androgens:

“Emerging evidence now also suggests that long-term androgen exposure may cause neurotoxicity, raising the possibility that aging androgen abusers may be at increased risk for dementia.

Kaufman (2016) Brain and cognition abnormalities in long-term anabolic-androgenic steroid users:

“Long-term AAS use is associated with right amygdala enlargement and reduced right amygdala rsFC with brain areas involved in cognitive control and spatial memory, which could contribute to the psychiatric effects and cognitive dysfunction associated with AAS use. The MRS abnormalities we detected could reflect enhanced glutamate turnover and increased vulnerability to neurotoxic or neurodegenerative processes, which could contribute to AAS-associated cognitive dysfunction.”

Namjoshi (2016) Chronic exposure to androgenic-anabolic steroids exacerbates axonal injury and microgliosis in the CHIMERA mouse model of repetitive concussion:

“AAS-treated mice exhibited significantly exacerbated axonal injury and microgliosis, indicating that AAS exposure can alter neuronal and innate immune responses to concussive TBI [traumatic brain injury].

Pomara (2015) Neurotoxicity by synthetic androgen steroids:

“Mounting evidence exists suggesting that in addition to psychiatric and behavioral effects, non-medical use of AAS carries neurodegenerative potential. Although, the nature of this association remains largely unexplored, recent animal studies have shown the recurrence of this AAS effect, ranging from neurotrophin unbalance to increased neuronal susceptibility to apoptotic stimuli.

Experimental and animal studies strongly suggest that apoptotic mechanisms are at least in part involved in AAS-induced neurotoxicity. Furthermore, a great body of evidence is emerging suggesting that increased susceptibility to cellular oxidative stress could play a pivotal role in the pathogenesis of many neurodegenerative disorders and cognitive impairment….Supplementary to abandoning the drug abuse that represents the first step in reducing the possibility of irreversible brain damage in AAS abusers, neuroprotective strategies have to be developed and implemented in future.”

Pope (2017) Long-term anabolic-androgenic steroid (AAS) Use: A possible new risk factor for early dementia:

“We have recently demonstrated marked visuospatial memory deficits, which can predict dementia onset, in long-term AAS users. Our neuroimaging data have also shown white matter abnormalities in AAS users. Additionally, on magnetic resonance spectroscopy, AAS users exhibited markedly reduced brain scyllo-inositol levels compared to non-users.”

Seitz (2017) White matter abnormalities in long-term anabolic-androgenic steroid users:

“Recent studies of long-term anabolic-androgenic steroid (AAS) users reported amygdala structural and functional connectivity abnormalities. We assessed white matter microstructure in the inferior-fronto-occipital fasciculus (IFOF), a major associative bundle of the amygdala network….Our results suggest that long-term AAS use alters IFOF white matter organization and integrity, which in turn might affect amygdala-related processes such as reward system function.”

Soleman (2016) Does polycystic ovary syndrome affect cognition?

“Objective: To study effects of overexposure to androgens…during working memory processes in women with polycystic ovary syndrome (PCOS) [a chronic high-testosterone condition]….

Women with PCOS may need additional neural resources during a working memory task compared with women without PCOS, suggesting less efficient executive functioning. This inefficiency may have effects on daily life functioning of women with PCOS. Antiandrogenic treatment appears to have a beneficial effect on this area of cognitive functioning.”

Endocrine Society (2016) Estrogen-deficient female athletes’ memory improves with estrogen:

“In young female athletes who stop having their menstrual periods because of excessive exercise, estrogen replacement appears to improve their memory….

The estrogen recipients had greater improvement in both immediate recall of words and in their ability to flexibly switch back and forth between tasks, even when the researchers controlled for patient age and pre-treatment test scores.”

Mitochondrial Dysfunction & Oxidative Stress

Victor (2013) Mitochondrial impairment and oxidative stress in leukocytes after testosterone administration to female‐to‐male transsexuals:

 “Treatment of FtMs [female-to-male transsexuals] with T [testosterone] can induce impairment of mitochondrial function and a state of oxidative stress. This effect should be taken into account in order to modulate possible comorbidities in these patients.

Gene Expression & Neurotransmitters

National Institute on Drug Abuse (2016) Anabolic steroids:

“Continued steroid abuse can act on some of the same brain pathways and chemicals—including dopamine, serotonin, and opioid systems—that are affected by other drugs.”

National Institute on Drug Abuse (2018b) How do anabolic steroids work in the brain?

“Anabolic steroids act at androgen receptors to influence cellular functioning and gene expression….

Research with human cells demonstrates that anabolic steroids also interact with certain types of GABAA receptors, which could mediate the increased anxiety reported by steroid users.105,106 In addition, animal studies show that anabolic steroids increase serotonin levels in brain regions involved in mood107 and dopamine levels in reward-related brain regions.107,108 Chronic use of anabolic steroids has also been shown to cause dysfunction of these reward pathways in animals.”

Kranz (2015) High-dose testosterone treatment increases serotonin transporter binding in transgender people

“One and 4 months of androgen treatment in female-to-male transsexuals increased SERT [serotonin reuptake transporter] binding in amygdala, caudate, putamen, and median raphe nucleus. SERT  binding increases correlated with treatment-induced increases in testosterone levels, suggesting that testosterone increases SERT expression on the cell surface.”

Altered Sexual Behaviors

Ye (2018) Androgene verändern die Hirnantworten auf sexuelle Stimuli bei Frau-zu-Mann-Transsexuellen:

“In order to assess the effects of chronic hormonal treatment, we used functional magnetic resonance imaging in a group of female-to-male transsexuals before and during androgen therapy…A broad network of cortical and subcortical regions were activated during the processing of erotic stimuli (nude vs. dressed), including the insula, amygdala, and hypothalamus. The insula activity in response to erotic male stimuli decreased over the initial 4 months of hormonal therapy. In the following 8 months, the insula response to erotic female stimuli increased. In other words, long-term androgen administration makes the brain more ‘male’ by reducing the sexual arousal caused by male stimuli and amplifying that caused by female stimuli.”

Structural Changes in Adult Brains

Pol (2006) Changing your sex changes your brain:

“Compared with controls…androgen treatment in female-to-male [adult transsexual] subjects increased total brain and hypothalamus volumes towards male proportions.

Prior to cross-sex hormone treatment, no differences in brain volumes between transsexuals and comparison subjects were found.”

Kranz (2018) Effects of testosterone treatment on hypothalamic neuroplasticity in female-to-male transgender individuals:

“ testosterone replacement therapy in FtMs [female-to-male transsexuals] changes hypothalamic microstructure towards male proportions.”

Rametti (2012) Effects of androgenization on the white matter microstructure of female-to-male transsexuals:

“testosterone acts on the white matter microstructure ordering its coherence and axonal organization. Moreover, the size of this effect depends on the bio-availability of testosterone before beginning the hormone treatment. ” [Females with higher testosterone before transition treatments had stronger brain changes in response to transition treatments.]

Note: Many female patients may have high testosterone before transition treatments (Auer; Baba; Becerra-Fernández; Bosinski; Futterweit; Mueller), and may therefore experience especially strong brain changes in response to treatments. However, researchers say that female-to-male transsexuals “are biologically and endocrinologically female” even though they may have elevated testosterone.

(ECNP 2015) Testosterone changes brain structures in female-to-male transsexuals:

“with testosterone treatment the volume of grey matter decreased in two specific regions of the brain, the Broca’s and Wernicke’s areas, which are mainly responsible for language processing. At the same time, the neuronal pathway (white matter) connecting these two regions via the extreme capsule got stronger.”

Nuruddin (2014)  Effects of gonadotropin-releasing hormone agonist on brain development:

“[a study investigated] the effect of GnRHa treatment on structural development of the ovine brain….Analysis revealed highly significant GnRHa treatment effects on the volume of the left and right amygdalae, indicating larger amygdalae in treated animals….Additionally, we observed a significant interaction between sex and treatment on left amygdala volume, indicating stronger effects of treatment in female compared to male animals.

*Emphasis added in all studies above.