Svetlana Vujović1 , M. Ivović1, M. Tančić Gajić1, L. J. Marina1, Z. Arizanović1, M. Barać1, S. Popovic1, B. Barać2, D. Duišin3, A. Milošević4, M. Djordjević5 and D. Micić1
(1)
Department of Gonadal Endocrinology, University of Belgrade, Clinic of Endocrinology, Diabetes and Diseases of Metabolism, Clinical Center of Serbia, Belgrade, Serbia
(2)
Institute of Rheumatology, Belgrade, Serbia
(3)
Clinic of Psychiatry, Department of Transgenderism, Clinical Center of Serbia, University of Belgrade, Belgrade, Serbia
(4)
Gradska Bolnica, Department of Urology, University of Belgrade, Belgrade, Serbia
(5)
Department of Urology, Children’s Hospital, University of Belgrade, Belgrade, Serbia
Svetlana Vujović
Email: prof.svetlana.vujovic@gmail.com
Harry Benjamin, the father and establisher of transsexualism, tried to describe this phenomenon as terra incognita or noli me tangere (1966), trying to explain that many doctors were blinded in the presence of a new undescribed and undiagnosed disorder [1]. Ira Pauly described one hundred transsexuals from 13 countries [2].
6.1 Definition
In everyday practice two sexes are mentioned: male and female. However, there are four different types of sex:
· Gonadal (presence of ovaries or testis)
· Chromosomal (46,XX or 46,XY)
· Phenotype (female or male)
· Psychic (feeling of being woman or man)
In a case of transsexualism, gonadal, chromosomal, and phenotype sex are of one type, and, psychic sex is the opposite. In such a situation, transsexualism can be classified under pseudohermaphroditism.
Male-to-female transsexuals (MFTs) have testis, a 46,XY karyotype, a male phenotype and a feeling of being female. Female-to-male transsexuals (FMTs) have ovaries, a 46,XX karyotype, a female phenotype and a feeling of being male.
Gender dysphoria is characterized by suffering from a strong, persistent discomfort between the biological sex and the experienced expressed gender with significant impairment in interpersonal, familial, social, professional and other important areas of functioning [3].
Persons with gender dysphoria want to have the secondary sexual characteristics of the opposite sex. Transsexual identification is permanently present. The disorder is not a part of some other disorder or disease.
6.2 Etiology
Until now, the etiology of transsexualism has been unknown. There are some hypotheses (Table 6.1) and many scientific centers in the world are working on the discovery of an etiological cause of transsexualism.
Table 6.1
Some etiological hypotheses of transsexualism
|
Effects of gonadal steroids on the hypothalamus during gonadal formation [4] |
|
Disorders of androgen to estrogen conversion [5] |
|
Receptor disorders |
|
Aromatase changes [6] |
Gender identity is developed as a result of the interaction between the developing brain and gonadal steroids from the 8th to 12th gestational week. Swaab and Hofman [7] found a gender-specific difference between the volume of the suprachiasmatic nucleus and the nuclei striae terminalis. The latest studies from Prince Henry’s Institute in Australia implied a longer androgen receptor gene, leading to less effective circulating testosterone, undermasculinization and a brain more similar to a female brain in MFTs. This study was criticized by the fact that in some other disorders with changes in androgen receptors no similar changes in psychic gender were found. Trying to make a contribution to examining the etiology of transsexualism, our team provided data on finger lengths in transsexuals [8].
6.3 Incidence
Since 1966, many studies have referred to the incidence of transsexualism. The ratio between MFTs and FMTs has varied, depending on surgeons’ willingness to perform the operation. Because male-to-female surgery is less complicated, there have been more MFTs. In countries with highly specialized surgeons, such as Serbia, the number of transsexuals has been the same (male-to-female and female-to-male) [9]. In Table 6.2, the incidence of transsexualism is shown.
Table 6.2
Incidence of transsexualism around the world
|
Author |
Year |
Country |
Ratio MF:FM |
|
Benjamin |
1966 |
USA |
6:1 |
|
Eklund |
1988 |
Netherlands |
3:1 |
|
Godienski |
1988 |
Poland |
1:5.5 |
|
Ross |
1981 |
Australia |
9:1 |
|
Garrels |
2000 |
Germany |
1.2:1 |
|
Vujovic |
2009 |
Serbia |
1:1 |
In some studies, the number of patients was too small. In human biology the incidence of many disorders is the same in males and females and it would be difficult to explain such a high difference in ratio, except with some technical details regarding the operations.
6.4 Diagnosis
A team of three highly educated psychiatrists in the field of sexual disorders confirm the diagnosis after 1 year or more of follow-up. They have to exclude many psychiatric disorders such as transvestitism, homosexuality etc. After that the endocrinologist examines the patient, detects the karyotype and carries out hormonal analysis. It is necessary to take blood samples in MFTs for follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, estradiol, progesterone, testosterone, SHBG, 17 OH progesterone, free thyroxine, thyroid-stimulating hormone (TSH), and cortisol. In FMTs on day 7 of the menstrual cycle (for those younger than 30 years of age) blood samples are taken for FSH, LH, prolactin, estradiol, testosterone, androstenedione, dehydroepiandrosterone sulfate (DHEAS), 17 OH progesterone (to exclude congenital adrenal hyperplasia), fT4, TSH, cortisol and on day 21 progesterone is measured. According to these results endocrine diseases mimicking transsexualism can be excluded such as androgen-secreting tumors, congenital adrenal hyperplasia, pseudohermaphroditism of other different origins, and some other endocrine diseases, such as thyroid and adrenal gland diseases. A complete internal examination and an ultrasound of the gonads (ovaries or testis) and breasts are obligatory.
After confirming diagnosis from the endocrine point of view therapy regarding the characteristics of the opposite sex can be initiated. Sperm of MFTs can be frozen if desired and FMTs can store their follicles in case they want to have a biological child later on.
6.5 Therapy
The aim of the therapy is to help a patient to look like a person they feel that they can depend upon to provide normal sexual function and work abilities, and to determine the dosage of the therapy individually.
6.5.1 Male to Female Therapy
Before the operation and 6 months later oestradiol ampoules at 10 mg are given intramuscularly within a 7- to 10-day interval with ciproterone acetate (50 mg daily orally). Micronized progesterone is added 7 days a month (100 mg) after 6 months of therapy. From 6 months after the operation estroprogestagen therapy is initiated orally and it is necessary to continue throughout life. Ciproterone acetate is reduced to 25 mg, according to hirsutism status. The effects of estrogen, progestogen and antiandrogen therapy on body shape is shown in Table 6.3. There are many reasons for adding progesterone (Table 6.4).
Table 6.3
Changes in symptoms and signs during therapy for male to female transsexuals (MFTs)
|
Month |
Symptoms and signs |
|
1 |
Breast enlargement, areola pigmentation, higher pitch voice |
|
3 |
Loss of erection and ejaculation, softer skin, strength decrease, more sensitive, loss of typical male libido |
|
6 |
Sex hair loss, changes in waist to hip ratio |
|
12 |
Significant reduction of sex hair, more prominent female sex characteristics |
Table 6.4
Progesterone effects in MFTs
|
Decreases the number of estradiol receptors |
|
Higher affinity for androgens receptors |
|
Stimulates 17 beta dehydrogenase (conversion of estradiol to estrone) |
|
Antimineralocorticoid effects |
|
Sedative and anxiolytic effect |
|
Stops spermatogenesis at the level of spermatogonia |
|
Seminal tubule atrophy |
|
Decreases Leydig cell number |
6.5.2 Therapy for FM Transsexuals
Testosterone ampoules are initiated in a dose of 250 mg every 2 weeks. It is safer than the oral route because it is lifelong therapy. Testosterone can also be advised in the form of transdermal and sublingual implants. Alkalizing forms are contraindicated. Dihydrotestosterone gel (non-aromatizable to estradiol) is advised for local treatment on the clitoris (Table 6.5). After 12 months of therapy the expert team of psychiatrist, endocrinologist and surgeon gives a final conclusion and suggestion regarding the operation. Later on, transsexuals have twice-yearly endocrinological checkups. Our team follows up transsexuals for 20 years.
Table 6.5
Dynamic of clinical changes during testosterone therapy for female to male transsexuals (FMTs)
|
Month |
Symptoms or signs |
|
1 |
Acne, tenderness in the inguinal, increased libido, increased strength |
|
6 |
Menstruation loss, deepening voice, clitoral enlargement |
|
9 |
Increase of bitrochanteric circumference 4–7 cm, clitoris length 4 cm |
|
12 |
Decreased breast volume, spread of sexual hair, more typical masculine phenotype |
There was an equal number of MFTs and FMTs. FMTs were not smaller than control women, which is consistent with other studies [10, 11]. Males were 12 cm taller on average. Mostly, they finished secondary school. By profession MFTs are usually models, musicians, dancers, or waiters, while FMTs may be want to be hairdressers. Their mother’s average age was 20–25 years and their father’s 26–30 years. Mothers were mostly housewives and fathers were soldiers or policemen. In our group 12 MFTs and 18 % FMTs refused the operation. Of all of them, 16.6 % of MFTs and 16.4 % FMTs were married.
6.5.3 Possible Unwanted Effects of Therapy
In the literature unwanted effects of hormone therapy have been described in cases in which dosages were higher or in which it was given to patients who had previously had other diseases for which hormone therapy was contraindicated, such as liver or renal insufficiency, thromboembolism, undiagnosed bleeding, carcinomas, porphyria, pregnancy, meningioma etc. Sometimes, wanting to obtain a typical characteristic of the opposite sex, patients multiply the doses themselves for a longer period. In the world of endocrinology the most important thing is to achieve the appropriate dosage of hormone therapy (Table 6.6).
Table 6.6
Possible unwanted effects of hormone therapy in transsexuals
|
Male to female transsexual |
Female to male transsexual |
|
Thromboembolism |
Hypercholesterolemia |
|
Hyperprolactinemia |
Hepatocyte hyperplasia |
|
Depression |
Liver adenoma |
|
Hypertrophy of the prostate |
Liver carcinoma |
|
Myocardial infarction |
Calculous cholecystitis |
|
Breast carcinoma |
6.6 Conclusion
Special expert gender teams have to be formed throughout the world in order to help transsexuals to have much better quality of life.
References
1.
Benjamin H (1966) The transsexual phenomenon. Julian Press, New York
2.
Pauly IB (1968) The current status of changes of sex operations. J Nerv Ment Dis 147:460–471PubMedCrossRef
3.
American Psychiatrists Association (2013) Diagnostic and statistical manual of mental disorders, 5th edn. American Psychiatric Association Press, Washington, DC
4.
Dorner G (1988) Neuroendocrine response to estrogens and brain differentiation in heterosexuals, homosexuals and transsexuals. Arch Sex Behav 17:57–75PubMedCrossRef
5.
Mac Lusky NJ, Naftolin F (1981) Sexual differentiation of the central nervous system. Science 211:1294–1302CrossRef
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Slijepčević D, Vujović S (1992) Transseksualizam-endokrini aspekti. Orthomedica, Beograd
7.
Zhou JN, Hofman N, Gooren LJG, Swaab D (1995) A sex differentiation in the human brain and its relation to transsexuality. Nature 378:68–70PubMedCrossRef
8.
Vujović S, Popović S, Mrvošević Marojevic L, Ivović M, Tančić Gajić M et al (2014) Finger length ratio in Serbian transsexuals. Sci World J 2014:763563, fingers
9.
Vujović S, Popović S, Sbutega Milošević G, Djordjević M, Gooren LJG (2009) Transsexualism in Serbia: a twenty years follow up study. J Sex Med 6:1018–1023PubMedCrossRef
10.
van Kasteren PJ, Gooren LJ, Megens JA (1996) An epidemiological and demographic study of transsexualism in the Netherlands. Arch Sex Behav 25:589–595CrossRef
11.
Gooren LJG (1990) The endocrinology of transsexualism: a review and commentary. Psychoneuroendocrinology 15:3–14PubMedCrossRef