Evaluation of systemic and biochemical parameters in transgender men after hormone therapy

Transsexuality refers to the individual whose gender is not aligned with their biological sex, this is a condition that triggers a feeling of non-belonging, and has been increasing its incidence in recent years. It has an unknown origin, and current studies indicate that several biological factors may be linked to the occurrence of it. Trans male individuals are those who were born with the female biological sex, but do not identify with this designation. The therapy of choice is the administration of exogenous testosterone applied intramuscularly. The aim of this study was to describe the systemic and biochemical parameters of trans men after hormonal therapy, from the analysis of articles that highlight the systemic changes triggered by testosterone administration. The inversion of the reference values from female to male, in several systemic parameters, could be observed after the calculation of the means of the results reported in the literature, pointing out the mechanisms by which testosterone acts in the body.


ABOUT GENDER DYSPHORIA
Transsexuality, also called gender identity disorder (GID) or gender dysphoria (GD), is classified in ICD F64-0 ("ICD10 International Disease Code", 2020) and refers to the individual whose biological sex it does not align with his gender identity, that is, he witnesses a different gender than he was assigned at birth (BURKE et al., 2017;SARASWAT;WEINANDSAFER, 2015;UNGER, 2016). In the case of trans men, they are biologically born females, but identify with the male gender.
Biological sex, gender and sexual orientation are different things. Gender identity is about self-identification, as individually the person experiences their existence. Sexual orientation is about attraction to other genders, transgender individuals can be heterosexual, bisexual or homosexual, without this affecting their gender identity and, finally, biological sex is linked to the genital and chromosomal factor, which defines the entire physiological issue involved (GUPTA; IMBOREK; KRASOWSKI, 2016;ADRIAANSEN et al., 2017 In a study that analyzed neurological alterations in this population, it was found that some transgender men analyzed had the brain structure compatible with the structure of cis men Evaluation of systemic and biochemical parameters in transgender men after hormone therapy www.nucleodoconhecimento.com.br (who identify with their designated sex at birth), while others presented their brain structure different from both sexes of the control groups (BURKE et al., 2017). Other studies, such as that of Uribe et al. (2020), in individuals with GD reported that neurological alterations were found in places of the brain responsible for body perception, compared to the control group, composed of cisgender men (URIBE et al., 2020). Swaab et al. (2011) proposed that the incompatibility between gender and biological sex could occur due to the fact that the sexual differentiation of the brain occurs before the differentiation of sexual gonads at the beginning of fetal life (BAO; SWAAB, 2011). Still in the neurological sphere, Yokota et al. (2005) reported that the pattern of the callous body in people with GD is closer to people of the same gender than that of people of the same biological sex (YOKOTA; KAWAMURA; KAMEYA, 2005).

GENETIC FACTORS
As for the genetic factors that are being studied to understand the development of the condition, the most pointed is linked to the CYP17 gene (SARASWAT; WEINANDSAFER, 2015;BENTZ et al., 2008). The CYP17 gene is responsible for encoding the synthesis of a protein in the cytochrome P450 family, CYP17A1, which is linked to the synthesis of precursors of steroid hormones such as testosterone and estrogen, which are necessary for the normal development and reproduction of humans (BENTZ et al., 2008).
A control case study that counted on the participation of one hundred and fifty-one participants with DG pointed to a mutation in the CYP17 gene as a theoretical cause of the condition. CYP17 A2 T>C is a functional single nucleotide polymorphism, which is associated with elevation in serum and plasma of estradiol, progesterone and testosterone levels (BENTZ et al., 2008). The results of the research showed that of the 151 participants (49 of them being trans men), the mutant allus was statistically in greater association with trans male individuals and not with trans female participants (biologically assigned to males at birth). The allelic distribution in trans women was equivalent to male cis gender controls, while this distribution in the trans male portion did not follow a specific gender pattern, and its distribution was also equivalent to the group of cis men (SARASWAT; WEINANDSAFER, 2015;BENTZ et al., 2008).
Evaluation of systemic and biochemical parameters in transgender men after hormone therapy www.nucleodoconhecimento.com.br

PRE-NATAL EXPOSURE FACTORS
Prenatal exposure factors were also evaluated, studies were conducted in a sample of five hundred participants with GD, all of them exposed during fetal life to an estrogen iced drug for abortion prevention, Diethylstilbestrol (DES), of these 500 participants, 150 had severe gender dysphoria (SARASWAT; WEINANDSAFER, 2015).

EPIDEMIOLOGY
The number of patients with GD seeking help and treatment has been increasing over the decades (UNGER, 2016;GUPTA, IMBOREK;KRASOWSKI, 2016) and, according to a data survey, which was considered the largest recent study on the prevalence of transsexuality, it was reported that the prevalence is approximately 1 trans man for 40,000 cis people, and 1 trans woman for every 15,000 cis people (UNGER, 2016).
However, as many prevalence studies require a clinical database, and even with the increase in the number of individuals with GD a large number of them choose to perform hormone therapy at home, without attending health agencies, the accounting of the number of cases is complicated, thus leaving only a small portion of the true prevalence (UNGER , 2016).
The aim of this study was to describe the systemic and biochemical parameters of trans men after hormonal therapy. From a literature review, the following parameters were investigated: Red series (Hb, HTC, erythrocyte count), leukocyte count, creatinine, liver enzymes (ALT, ALT, GGT), lipid profile (total cholesterol, HDL, LDL, triglycerides) fasting glucose dosage and hormonal profile (total testosterone and estradiol). Based on these analyzed data, the mean of the obtained values was calculation, for the purpose of analyzing the profiles of this group.

MATERIALS AND METHODS
Evaluation of systemic and biochemical parameters in transgender men after hormone therapy www.nucleodoconhecimento.com.br

STUDY DESIGN
The present work is a Literature Review based on the research and analysis of bibliographic works and scientific articles related to the subject delimited, available and freely accessible in the scientific databases of the Indexers PubMed and Scientific Electronic Library Online (Scielo). In order to promote a broad review of the subject, national and international publications were selected preferably from the last ten years, which address the systemic changes that occur in trans male individuals after hormonal therapy.
The analyzed data were collected from a group of articles, 16 of them having been published within the period 2015-2020, using as keywords the following english terms: 17-

Hydroxysteroid Dehydrogenases, Transsexualism, Hormones and Hormone Replacement
Therapy. After collecting the results reported in the literature for biochemical and systemic parameters, a calculation of the mean of these data was performed for the purpose of analyzing the changes after hormonal therapy. From the three months, the physical changes become more evident, and this period is marked by the appearance of facial and body hair and voice alteration, which will begin to fail and will be hoarse until the definition of the vocal cords to a more serious and manly tone Individuals who start treatment with older age already have a higher degree of definitive Evaluation of systemic and biochemical parameters in transgender men after hormone therapy www.nucleodoconhecimento.com.br feminization that cannot be reversed with T, as a result, they may be lower (mean height difference up to 12 centimeters), present the pattern of fat distribution more feminine and may also have a hip wider than that of a cis man (ADRIAANSEN et al. , 2017;GOOREN, 2014).

HEMATOLOGICAL CHANGES
Erythropoiesis is one of the many mechanisms in the body that undergo changes because of exogenous administration of testosterone. Studies suggest that androgenics act indirectly as stimulants of erythropoietin production and directly in erythropoiesis in the bone marrow.
Higher testosterone levels in the blood plasma are constantly associated with higher hematocrit and hemoglobin values, but these values remain within the expected male reference values (cis men) (IRWIG, 2017;VELHO et al., 2017).
By calculating the mean data of the analyzed articles that reported changes in hemoglobin (Hb) and hematocrit (HTC), the results presented in Table 1 were obtained.
Taking into account the reference values for these parameters as the average of the adult Brazilian population ("MSD Manuals", 2020), the result of 14.09 g/dL for Hb found would be within the expected in both reference values, with no risk to health if the interpretation of the test was performed according to the female or male reference value, as well as the hematocrit result, which obtained an average compatible with both reference values.
Regarding the values related to the cell count of erythrocytes and leukocytes, the baseline and post-hormone therapy values of a studied group can also be seen in Table 1   Source: elaborated by the author himself.  Table 2.

Lipid Profile
Many studies that analyzed samples of male trans patients reported decreased HDL and increased LDL, as well as an unfavorable increase in triglyceride after one year of intramuscular testosterone administration (IRWIG, 2017;FERNANDEZ;TANNOCK, 2016). The average values found can be seen in Table 2. Even with the so-called increase in triglycerides and LDL cholesterol, the results are still within the reference values for these parameters.

Glycemic Profile
The glycemic profile presents a decrease in fasting glucose levels in trans men in HT, this decrease is accompanied by the reported decrease in insulin sensitivity, generating a compensatory increase of this hormone in plasma during fasting (GOOREN; Giltay; BUNCK, 2008). The mean values found related to fasting glucose in this group were from 81 to 93.6 mg/dL, and the reference value for this parameter was < 100 mg/dL ("SBD Guidelines 2019-2020", 2020).

Hormonal Profile
The changes found in the hormonal profile are the most relevant of this group and are directly linked to the administration of exogenous testosterone. Levels of sex hormones in the serum may change depending on the route of administration of the hormone. The dosages of the hormone may be adequate according to the laboratory tests of the patient, the excess testosterone causes the conversion of the same into estrogen by aromatization, generating an effect contrary to the desired (UNGER, 2016). The mean values of sex hormones (testosterone and estradiol) found in the literature can be seen in Table 3.  Systemic changes trigger morphophysiological and behavioral changes resulting from hormone replacement. In general, the values found show that in all parameters that use the binary system of division of reference values, the values were inversioned, going from female to male, with the continued administration of hormone therapy.
This study, therefore, brought evidence of changes in systemic parameters, contributing significantly to HT users, reporting the profound changes their bodies will undergo.
Evaluation of systemic and biochemical parameters in transgender men after hormone therapy www.nucleodoconhecimento.com.br Knowledge of these changes is very necessary, so that the bodily and systemic changes that occur are clear, serving support at the time of the decision to start the transition process or not. The results of the study may also be used in the future as a scientific support tool for health professionals who come across examinations of trans-male patients, thus giving greater safety and dignity in diagnoses of men in HT.