Replacement Hormone Therapy for Gender Dysphoria and Congenital Sexual Anomalies.

What is it about sexuality that makes it such a burning matter since the dawn of mankind? Much was lost of humankind heritage because of society's attitude toward sex and gender, but we've made progress. Medical knowledge progressed incredibly and so did social and cultural norms. In these days, on most places on the planet, there is acceptance. Still, gender issues take a center stage, often inflaming the social and political milieu everywhere. So how informed and prepared is the medical community to deal with these issues? Aside from medical treatments, gender dysphoric patients need mental health and social support throughout life. Do we have enough guidelines for treatments that have life-long effects? Do we actually know all of those effects? There are many issues to consider, like fertility preservation, puberty suppression with its adverse effects, and not in the least, the effects of the hormonal therapy on the target tissues.

Trastorno de identidad de género. Parte II: terapia endocrinológica en el proceso de readecuación corporal / Gender identity disorder. Part II: endocrine therapy in the process of body readjustment

Endocrinology step of transgender readjustment therapy is made according to previously published in the part 1 of article: “gender identity disorder in rev. chil. endocrinol. diabetes 2015, 8 (4): 167-173.During started puberty in Tanner stage 2-3, the persistence of the experience that their identity male or female gender is not coherent with its bodily, authorize to start the endocrinological therapy, as an important step of body readjusting. In the process of transition from male to female or female to male, should stop pubertal development, what we do with GNRH analogues: intramuscle leuprolideor triptorelin 11.25 mg. every 12 weeks or with medroxyprogesterone acetate 150 mg. monthly. This process continues until 16 years, adding antiandrogen, preferably spironolactone in the process of body readjusting of male to female. At 16 years old, starts the cross hormonal therapy to masculinizing or feminizing. Maintaining gonadotrophin suppression, female to male, testosterone undecanoate or other injectable testosterone esters is administered, customizing the date of administration and inMale to female, daily use of oral estradiol valerate or transdermal gel. Plasma levels of estradiol andtestosterone should not be located in high or supraphysiological range to avoid thromboembolism or polycythemia risk in those who receive testosterone. Should to be explained the time to obtain the bodily effects, achieving a realistic attitude of the goals and the need for regular checks. Attendance to emotional changes, mainly to meet the social gender role. The laboratory, metabolic, hormonal, hemogram and electrolytic changes are evaluated. To be indicated bone densitometry and study images of internal genitals and breasts are necesary...

Nuevas perspectivas en el tratamiento hormonal de la disforia de género en la adolescencia / New perspectives in the hormonal treatment of gender dysphoria in adolescence

En la última década se están aplicando tratamientos hormonales a adolescentes con disforia de género. Los profesionales de las unidades de tratamiento de la disforia de género no pueden hacer oídos sordos a esta nueva demanda. En este trabajo se expone cómo ha evolucionado la atención a estos adolescentes en las tres últimas versiones de los Estándares Asistenciales (EA) de la Asociación Mundial de Profesionales para la Salud Transgénero, en las que, a partir de la quinta versión de los EA, se empieza a contemplar que los adolescentes pueden ser subsidiarios de recibir tratamientos hormonales. También se analizan los recientes protocolos de intervención hormonal llevados a cabo por clínicas especializadas. Por último, se debate sobre los argumentos a favor y en contra de estos tratamientos hormonales. Estas intervenciones hormonales tienen importantes repercusiones en el desarrollo físico, social y psicosexual de los usuarios y conllevan implicaciones éticas y morales para los profesionales

Hormonal treatments have been used in adolescents with gender dysphoria in the last decade. The professionals working in gender dysphoria treatment units cannot ignore this new demand. The evolution of care for such adolescents according to the last three versions of the Standards of Care (SC) of the World Professional Association for Transgender Health is described. Starting with the fifth version of the SC, hormonal treatment of adolescents has been contemplated. Recent protocols for hormonal intervention carried out by specialized clinics are analyzed. Finally, the pros and cons of hormonal treatment are debated. These hormonal interventions have major impact on the physical, social, and psychosexual development of patients and have ethical and moral implications for professionals

Sexual functioning in patients with major depressive disorder in randomized placebo-controlled studies of extended release quetiapine fumarate.

OBJECTIVE: We evaluated sexual functioning from 6 acute, randomized, placebo-controlled studies (6-10 weeks) of once-daily extended release quetiapine fumarate (quetiapine XR) 50, 150, or 300 mg/day as monotherapy (Studies 1-4) or adjunct therapy (Studies 6-7) in major depressive disorder (MDD). METHODS: We present a pre-planned, non-inferiority analysis of quetiapine XR monotherapy versus placebo using Changes in Sexual Functioning Questionnaire (CSFQ) total score change (Studies 1-4). Post hoc analyses evaluated CSFQ total and domain scores for fixed-dose monotherapy (Studies 1-2), modified fixed-dose (Studies 3-4), and adjunct therapy studies (Studies 6-7). CSFQ data for active comparators (duloxetine [Study 2], escitalopram [Study 4]) are reported. RESULTS: Quetiapine XR monotherapy was non-inferior to placebo for sexual functioning (least squares mean [LSM] difference in CSFQ score change versus placebo, 0.16 [95% confidence interval: -0.59, 0.92]); LSM change in CSFQ score: 1.90, quetiapine XR (all doses) and 1.73, placebo. LSM differences versus placebo (95% confidence interval): 0.18 (-1.40, 1.75), duloxetine (Study 2); 0.16 (-1.77, 2.10), escitalopram (Study 4). LSM differences with adjunct quetiapine XR 150 mg/day (0.52; p = 0.338) or 300 mg/day (0.22; p = 0.679) were comparable with placebo plus antidepressants. Post hoc all-patient and gender-specific analyses were comparable for CSFQ total scores versus placebo with quetiapine XR 50, 150, or 300 mg/day, duloxetine, and escitalopram. Discussion Lack of negative effects on sexual functioning in patients with MDD may improve treatment acceptability. CONCLUSION: Quetiapine XR (monotherapy or adjunct therapy) had an impact on sexual function that was comparable with placebo.

[Adolescents with gender identity disorder: reconsideration of the age limits for endocrine treatment and surgery].

The third versions of the guideline for treatment of people with gender identity disorder (GID) of the Japanese Society of Psychiatry and Neurology does not include puberty-delaying hormone therapy. It is recommended that feminizing/masculinizing hormone therapy and genital surgery should not be carried out until 18 year old and 20 year old, respectively. On the other hand, the sixth (2001) and the seventh (2011) versions of the standards of care for the health of transsexual, transgender, and gender nonconforming people of World Professional Association for Transgender Health (WPATH) recommend that transsexual adolescents (Tanner stage 2, [mainly 12-13 years of age]) are treated by the endocrinologists to suppress puberty with gonadotropin-releasing hormone (GnRH) agonists until age 16 years old, after which cross-sex hormones may be given. A questionnairing on 181 people with GID diagnosed in the Okayama University Hospital (Japan) showed that female to male (FTM) transsexuals hoped to begin masculinizing hormone therapy at age of 15.6 +/- 4.0 (mean +/- S.D.) whereas male to female (MTF) transsexuals hoped to begin feminizing hormone therapy as early as age 12.5 +/- 4.0, before presenting secondary sex characters. After confirmation of strong and persistent cross-gender identification, adolescents with GID should be treated with cross-gender hormone or puberty-delaying hormone to prevent developing undesired sex characters. These treatments may prevent transsexual adolescents from attempting suicide, being depressive, and refusing to attend school. Subsequent early breast and genital surgery may help being employed in desired sexuality.

Hormonal therapy and sex reassignment: a systematic review and meta-analysis of quality of life and psychosocial outcomes.

OBJECTIVE: To assess the prognosis of individuals with gender identity disorder (GID) receiving hormonal therapy as a part of sex reassignment in terms of quality of life and other self-reported psychosocial outcomes. METHODS: We searched electronic databases, bibliography of included studies and expert files. All study designs were included with no language restrictions. Reviewers working independently and in pairs selected studies using predetermined inclusion and exclusion criteria, extracted outcome and quality data. We used a random-effects meta-analysis to pool proportions and estimate the 95% confidence intervals (CIs). We estimated the proportion of between-study heterogeneity not attributable to chance using the I(2) statistic. RESULTS: We identified 28 eligible studies. These studies enrolled 1833 participants with GID (1093 male-to-female, 801 female-to-male) who underwent sex reassignment that included hormonal therapies. All the studies were observational and most lacked controls. Pooling across studies shows that after sex reassignment, 80% of individuals with GID reported significant improvement in gender dysphoria (95% CI = 68-89%; 8 studies; I(2) = 82%); 78% reported significant improvement in psychological symptoms (95% CI = 56-94%; 7 studies; I(2) = 86%); 80% reported significant improvement in quality of life (95% CI = 72-88%; 16 studies; I(2) = 78%); and 72% reported significant improvement in sexual function (95% CI = 60-81%; 15 studies; I(2) = 78%). CONCLUSIONS: Very low quality evidence suggests that sex reassignment that includes hormonal interventions in individuals with GID likely improves gender dysphoria, psychological functioning and comorbidities, sexual function and overall quality of life.

Dehydroepiandrosterone replacement therapy.

Dehydroepiandrosterone (DHEA) replacement therapy has attracted considerable attention over recent years. Significant beneficial effects of DHEA replacement have been reported in patients representing the pathophysiological model of complete DHEA deficiency, in other words, adrenal insufficiency (AI). This includes effects on well-being, energy levels, mood, and libido, which is usually impaired in AI, particularly in female patients. DHEA exerts its action mainly indirectly via downstream metabolism to sex steroids, and conversion to active androgens is likely to play a major role. In addition, DHEA has well-described neurosteroidal properties, and by exerting anti-gamma aminobutyric acid(GABA)ergic action it may have antidepressive potential. Other patient groups that may benefit from DHEA replacement are patients receiving chronic exogenous glucocorticoid treatment, which invariably leads to persistent suppression of DHEA production. In patients with systemic lupus erythematosus, DHEA has been shown to reduce disease activity and has a glucocorticoid-sparing effect. However, caution is required regarding DHEA treatment in individuals with only a relative decline in circulating DHEA levels. This particularly includes the physiological decline of DHEA and its sulfate ester observed with aging. Even the elderly maintain circulating levels of DHEA that are orders of magnitude higher than what is observed in AI. Even physiological menopause does not necessarily lead to a decrease in circulating androgens while estrogen production invariably ceases. Current evidence from randomized, controlled trials in healthy elderly persons including several cohorts of postmenopausal women does not justify the use of DHEA. However, DHEA may be a suitable option for androgen replacement in women with established androgen deficiency, for example, bilateral oophorectomy and premature menopause.

Tadalafil, a further innovation in the treatment of sexual dysfunction.

In recognition of the large number of sufferers of sexual dysfunction worldwide, and the variety of etiologies of the condition, investigation into effective pharmacological agents has been expanded. One method of intervention is inhibition of the phosphodiesterase type 5 (PDE5) enzyme, which has already been exploited with a considerable degree--though not complete--success. A number of new agents that inhibit PDE5 are under development. Notable among these is tadalafil, which has demonstrated a high level of selectivity for PDE5 over the other phosphodiesterases and has shown efficacy in improving erectile function and sexual satisfaction in phase III trials. Throughout the clinical development program for tadalafil, the drug has been well tolerated and without serious side effects. The manufacturer, Lilly ICOS, received an approvable letter from the US Food and Drug Administration for use of the drug as a treatment for erectile dysfunction on April 30, 2002. Lilly ICOS hopes to market tadalafil, with the trade name Cialis, in the USA in 2003.

Changes in anthropometry with testosterone therapy in a female with gender identity disorder.

A 31-year-old regularly menstruating Japanese female was referred to our outpatient clinic by a psychiatrist. She had been diagnosed as having gender identity disorder by detailed counseling and clinical intervention 3 years earlier. After obtaining fully informed written consent, we treated her with 125 mg of testosterone enanthate, intramuscularly, every 2 weeks for 4 months. Serum testosterone levels increased to the normal male value (from 28 to 432 ng/dL). Although menstrual cycle remained regular, her voice became lower after 4 months of therapy. Body weight, body mass index, and lean body mass increased, while body fat mass and percentage of body fat decreased. However, trunk-leg fat ratio did not change during the observation period. During testosterone therapy, a disproportionate increase in lean body mass and decrease in body fat mass are early onset events, while the shift toward upper body fat distribution may be a late onset event along with increase in BMD.

An open trial of oral sildenafilin antidepressant-induced sexual dysfunction.

BACKGROUND: Sildenafil is a selective inhibitor of cyclic GMP-specific phosphodiesterase type 5 that has been associated with greater improvement of erectile function compared to placebo among men with erectile dysfunction. The goal of our study was to evaluate its efficacy in a small sample of outpatients with antidepressant-induced sexual dysfunction. METHODS: We studied the first 14 depressed outpatients (9 men and 5 women; mean age: 46.4 +/- 8.4) who were consecutively treated with oral sildenafil. Twelve of the 14 patients were treated with an SSRI and 2 with mirtazapine. All patients were prescribed oral sildenafil tablets at the initial dose of 50 mg q.d. p.r.n., with the possibility of increasing the dose to 100 mg q.d. p.r.n., if clinically indicated. We administered a sexual functioning questionnaire derived from the Guided Interview Questionnaire for females and males and from the Arizona Sexual Experience Scale to all patients before and after at least 4 weeks of treatment with oral sildenafil. The mean sildenafil dose in our 14 patients was 57 +/- 18 mg/day. RESULTS: All 14 subjects completed the follow-up assessments and no subjects discontinued the drug prematurely. We observed statistically significant improvements in all domains of sexual functioning, including libido, arousal, orgasm, sexual satisfaction, and (in males only) erectile function, with a 69% rate of patients reporting themselves as much or very much improved. Oral sildenafil treatment appeared to be very well tolerated, with only 1 out of 14 (7%) patients reporting an adverse event (hot flashes). CONCLUSIONS: Our findings of statistically significant improvements in all domains of sexual functioning in a sample of 14 men and women with antidepressant-induced sexual dysfunction suggest that this agent may represent an efficacious approach to this population.