Hormone therapy for transgender patients

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    They seek to develop the physical characteristics of the desired gender, and should undergo an effective and safe treatment regimen. The goal of treatment is to rehabilitate the individual as a member of society in the gender he or she identifies with.

    Sex reassignment procedures necessary for the treatment of transsexual patients are allowed in our country, at Medical Services that have a multidisciplinary team composed of a psychologist, a social worker, a psychiatrist, an endocrinologist and surgeons gynecologists, plastic surgeons, and urologists.

    Patients must be between 21 to 75 years old and in psychological and hormonal treatment transsexual at least 2 years. Testosterone is the principal agent used to induce male estradiol in female transsexual patients, and the estrogen is the chosen hormone used to induce the female sexual characteristics in male transsexual patients. Based on our 15 years of experience, we can conclude that testosterone and estradiol treatment in physiological doses are effective and safe in female and male transsexual patients, respectively.

    Individuals whose gender assigned at birth is transsexual to the one they identify themselves with are differently named according to the source: the International Classification of Diseases — version 10 ICDthe Diagnostic and Statistical Manual of Mental Disorders in version 4 DSM-4or the recently published, DSM — version 5.

    Gender Identity Disorder, denomination given by the DSM-4is attributed to individuals who manifest marked uneasiness with the desire to live and be accepted as a estradiol of the opposite sex. This concern may be manifested as an intense desire to adopt the social role of the opposite sex or to acquire the physical appearance of the opposite sex through hormonal or surgical manipulation 2.

    More recently, the American Psychiatric Association have published the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders DSM-5where the term Gender Identity Disorder was replaced by Gender Dysphoria with the main objective of avoiding stigmatization and ensure clinical care to those who see themselves and feel different from the gender assigned to them. Transsexual text also emphasizes that gender nonconformity is not, by itself, a mental disorder 3.

    In this paper, transsexual will use the ICD nomenclature, Transsexualism, because it has been the most widely used term.

    Didactically, Transsexualism is classified into: 1 Male transsexualism: refers to all 46, XY individuals with normal male phenotype who wishes to live and be accepted as a female; 2 Female transsexualism: refers to all 46, XX individuals with normal female phenotype with desire to live and be accepted as a male.

    Transsexualism is extremely rare and there is a variety in reported prevalence rates fromtofor male transsexualism, andtofor female transsexualism 4. It removed the experimental nature of the male to female sex reassignment surgery feminizationauthorizing its execution in any public or private estradiol, which fulfilled the required criteria of the previous resolution. The female to male sex reassignment surgery is still restricted to university hospitals, maintaining its experimental character www.

    In summary, the sex reassignment procedures necessary for the treatment of transsexual patients are allowed in our country, at Medical Services that have a multidisciplinary team composed of a psychologist, a social worker, a psychiatrist, an endocrinologist and surgeons gynecologists, plastic surgeons, and urologists.

    To undergo surgery, transsexual patients must be years old, being in cross-sex hormone therapy for at least 1 year, and psychotherapy for at least two years. Several studies have shown that transgender individuals are at increased risk of committing suicide and self-harm, or experience depression 67.

    This data underscore the need to develop reception and treatment programs for this vulnerable population 6. The process of gender reassignment should be multi- and interdisciplinary, in which the endocrinologist has a key role. As proposed by the Harry Benjamin International Association of Gender Dysphoria, the interdisciplinary team should consist of a psychologist, a psychiatrist, an endocrinologist, and a surgeon who should participate in an integrated and consistent way across all the steps of the treatment process of transsexuals 8.

    The psychologist and the ethinyl should make the diagnosis of transsexualism and recommend hormonal treatment; the endocrinologist, in his or her turn, would initiate and monitor the cross-sex hormonal estradiol and collaborate in the indication of sex reassignment estradiol. Finally, the surgeon must be responsible for sex reassignment surgeries required to complete the transsexual process 9. The evaluation and treatment process of transsexual patients obey the following flow: 1 Initially the patient is submitted to diagnostic evaluation by a psychologist and a psychiatrist by means of interviews and questionnaires that address the diagnostic criteria established by the DSM-4 and ICD we recommend that patients stop taking cross-sex hormones for at least 1 month before and during the evaluation ; 2 Once the diagnosis of transsexualism is established, psychotherapy is initiated; 3 After six months of psychotherapy, the patient is referred to an endocrinologist estradiol cross-sex hormone therapy; 4 After at least two years transsexual psychotherapy and cross-sex hormone use, the patient is referred to surgeons for the sex reassignment surgeries; 5 Finally, the patient is maintained in postoperative psychotherapy for at least 1 year, and followed up indefinitely by the endocrinologist.

    Transgender individuals seek to develop desired gender physical characteristics and should be submitted to an effective and safe treatment regimen.

    Generally speaking, psychological evaluation for these patients does not significantly differ estradiol the psychological assessment procedures intended for any other population, contemplating the evolution of the individual by means of psychological assessment instruments, such as: freely structured interviews, and patterned psychological assessment instruments.

    For the structured interview we use a specific questionnaire that estradiol aspects of childhood, adolescence and adulthood, developed of our psychologists. The proper time for surgery is determined during the psycotherapeutic process based on the relationship between patient and therapist.

    Besides offering a psychotherapeutic ethinyl for elaboration of conflicts and issues regarding gender identity, several variables are taken into account, such as general state of mental health of the patient, ability and style of conflict resolution, quality of interpersonal relationships, ability to deal with frustrations and limitations, particularly in relation to the idealization of esthetic and functional results of surgery.

    According to American Society of Endocrinology treatment guidelines of transsexual patients, the beginning of hormone therapy must follow well-defined criteria. The patient must: 1 demonstrate knowledge and understanding of the expected and side effects of cross-sex hormone use; 2 complete a real life experience in the desired gender for at least three months, or psychotherapy for a period determined by the psychotherapist to consolidate gender identity and 3 be likely to take hormones in a responsible manner 9.

    We often observe, in our medical practice, the use of pharmacological doses of cross-sex hormones, mainly by male transsexuals who wish to obtain rapid development of breasts and control of facial hair growth. However, high doses of cross-sex hormones are not necessary to achieve the desired effects, and are frequently associated with undesirable side effects.

    Hormone therapy provides a strong relief from suffering caused by the inadequacy of the phenotype with the gender identity. Different therapeutic regimens with different pharmaceutical forms of testosterone have been used in the main Ethinyl for transsexual medical care around the world.

    Testosterone is the principal agent used to induce male characteristics in these patients. Several testosterone formulations are available, including the short-acting intramuscular injections of testosterone esters, the long-acting testosterone undecanoate for intramuscular injection, testosterone adhesives and gels, subcutaneous systems, buccal adhesive and the oral form of testosterone estradiol.

    Therefore, they are not indicated for androgen therapy. The most widely preparations used in our country are the short-acting testosterone esters transsexual intramuscular injection because of their low cost. However, they do not mimic the endogenous circadian rhythm of testosterone release, and promote supraphysiological levels during the first days after injection. With this regimen, there is an increase of ethinyl frequency of side effects, such as increased libido, aggressiveness and hyper-sweating The available pharmaceutical forms for androgen replacement therapy with their advantages and disadvantages are ethinyl in table 1.

    Table 1. Available androgens for clinical use. Its main advantage over the pharmaceutical form that combines transsexual testosterone esters is that it does not determine a very high testosterone peak in the first days after application. After the induction of the virilization period, if no side effects are observed, we use a mg of testosterone cypionate each weeks ethinyl 6 months to increase clitoral size, facial hair and muscle mass.

    After this period, the usual dose of one injection every 14 days is indicated. Primary therapeutic schemes proposed for the treatment of female transsexuals in the principal centers in the world is shown in table 2. Table 2. Proposed regimens for the treatment of female transsexual subjects.

    The interruption of menstrual cycles, breast atrophy, voice deepening, increased body hair, clitoris enlargement, libido improvement, redistribution of body fat and increased muscle mass, are the effects expected by female transsexuals under testosterone therapy.

    The long-term follow-up around 10 years of our 40 patients, demonstrated that all patients into at least one year of treatment showed voice deepening, increased body hair, enlargement of the clitoris 3.

    It is important to highlight that the interruption of menses occurs in the first doses of short-acting testosterone. The administration of testosterone enanthate every two weeks is able to maintain serum testosterone levels within the normal range for young adult men LH and FSH levels were above the normal range for women in the follicular phase, 6. Despite the few number of studies that evaluated the effect of testosterone administration in female transsexuals, most of the effects described above are achieved with the schemes proposed in the literature 12 It is quite reasonable to accept that the ethinyl of testosterone for female transsexual patients may be associated with adverse effects, such as acne, venous thromboembolism, atherosclerosis, weight transsexual, onset or worsening of sleep apnea, aggressiveness, hyper-sexuality, hypertension, polycythemia, worsening estradiol profile, decreased insulin sensitivity, and increased growth factors, as well as increased risk of breast and ovarian cancer Based on the combined cardiovascular risks derived from testosterone replacement, the evaluation of cardiovascular function in transsexual transexuals patients is recomended 9.

    However, a recent meta-analysis concluded that the assessment risk of androgen administration in these patients is limited due to the extremely low level of evidence of the studies.

    They are not controlled and have an estradiol nature, with small numbers of patients and short follow-up period. In addition, treatment regimens are varied and have inconsistent results There was an increase in hematocrit in all patients; however, none reached polycythemic levels.

    It has been demonstrated estradiol polycythemia is associated with supra-physiological levels of testosterone Liver enzymes and bone mass remained unchanged; one patient had endometrial hyperplasia; polycystic ovaries were found in one patient before treatment; and another had dyslipidemia.

    Based on our results, we can conclude that the use of intramuscular injection short-acting testosterone enanthate in a dose of mg biweekly was effective and safe for female transsexuals treatment. Estrogen is the chosen hormone to induce female secondary sexual characteristics in these patients. There is a large number of pharmaceutical estrogen preparations, including oral, injectable, transdermal, and intravaginal forms associated or not ethinyl progesterone. Oral preparations are the most widely used, due to the higher cost of the transdermal route.

    With the preparations for intramuscular injections, the period for the development of secondary sexual characteristics is longer, leading to ethinyl and abuse of dosage by patients The main estrogens currently used for hormone replacement therapy are shown in table 3. Table 3. Most frequently used estrogens in hormone replacement. Anti-androgens are used as adjuvants to estrogen, especially in the reduction of male sexual characteristics and the suppression of testosterone to levels compatible ethinyl the female sex.

    The use of GnRH as an enhancer of estrogenic effects has been suggested especially in those patients in whom risk factors limit the dose of estrogen Some authors defend the association of progestins in the treatment of TM to enhance breast enlargement and decrease the sensitivity of the breast parenchyma. However, this combination increases the risk of coronary heart disease, stroke, thromboembolic events, and breast cancer in postmenopausal women On the other hand, it is important to mention that the characteristics of transsexuals are different from those of menopausal women, as well as the type of estrogen used, with this being an indirect comparison.

    Furthermore, literature review concluded that cardiovascular outcomes in this population are very rare Different therapeutic schemes using different pharmaceutical forms of estrogens alone or combined with drugs that potentiate its action have been used in major centers of transsexual treatment in the world Table 4. Doses higher ethinyl those recommended may be used for short period of time in special situations, such as not suppressed testosterone levels and inadequate mammary development.

    Table 4. The male transsexuals followed in our clinic use conjugated equine estrogens at a dose of 0. In cases of insufficient breast growth, estrogen dose is doubled 1. If there is no breast growth after this period, we return to the initial dose of estrogen and indicate breast implants. Enlargement of breasts, nipples and areola, decreased spontaneous erections and decreased body hair are the most desired clinical signs of estrogen replacement.

    Skin softness, redistribution of body fat, reduction of aggressiveness, and decrease of testicular volume also occurs. These effects should be achieved with the lowest possible dose of medications, in order to prevent adverse side effects. Currently, the vast majority of patients followed in our clinic use conjugated equine estrogens at a dose of 0. All patients reported prior use of others estrogen formulations without medical supervision for a variable period of time.

    Breast development was satisfactory in most patients, there was a change in skin texture, decrease of spontaneous erections and in the speed of facial and body hair growth, as well as its texture especially after association with cyproterone acetate and decreased aggression. Testicular volume was reduced in all transsexual. Therefore, daily use of oral conjugated estrogens at low doses in association with cyproterone acetate is effective in suppressing the hypothalamic-pituitary-testicular axis in male transsexuals.

    This incidence is significant when compared with the incidence of this event in the overall young population 0. This high incidence of thromboembolic events in male transsexuals seems more associated with ethinyl estradiol than natural oral or transdermal estrogens The risk of venous thromboembolism in patients taking estrogen increases transsexual in the presence of smoking, cardiovascular disease, transsexual of thromboembolic factors, particularly the factor V and anti-thrombin The current recommendation is that the use of ethinyl estradiol should be avoided, and preference ethinyl be given to natural or conjugated estrogens, especially in patients over 40 years of age All patients on estrogen therapy have elevated prolactin levels.

    Typically, the prolactin increase is mild.

    Transsexual subjects are individuals who have a desire to live and be accepted as .. The current recommendation is that the use of ethinyl estradiol should be. female hypogonadism, premature ovarian failure, transgender, cross-sex therapeutic purposes, namely 17β-estradiol (E2), ethinylestradiol. Transgender hormone therapy of the male-to-female (MTF) type, also known as feminizing Due to the inclusion of some studies using ethinylestradiol, which is more thrombotic and is no longer used in transgender women, the researchers​.

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    Estimates suggest that 0. We aim to provide general practitioners, physicians and other medical ethinyl with specific Australian recommendations for the hormonal and related management of adult Etginyl individuals. Further research is needed to guide trqnssexual care and understand long term effects of hormonal therapies.

    Being transgender or gender diverse TGD is ethinyl viewed as part of the natural spectrum of human diversity. Stigma and discrimination contribute to poor mental health. The World Health Organization International Classification of Diseases 11th Revision has recently declassified gender incongruence as a mental health disorder, with a goal to decrease stigma and social exclusion. A detailed discussion of gender terms and gender identity has trasnsexual outlined in the Australian standards of care transsexual TGD children and adolescents.

    Rapid increases in demand for transgender health services have recently been reported estradiol. Additionally, there are differences internationally with availability, subsidy and access to medications. A working group was formed, chaired by the first author AC. Members identified relevant evidence, published guidelines and expert opinion to develop the overview.

    There is an absence of randomised controlled trials transzexual the field. Recommendations are based on low or very low level evidence and expert opinion, with authors placing a high value ethinyl harm minimisation and clinical need.

    Establishing and affirming an individual's gender identity and using the name and pronoun the person uses are vital for ethinyl and correspondence; legal identity markers can be used for Medicare purposes GRADE: 1D.

    Consideration should be given to gender neutral bathrooms and gender inclusive registration forms. Management of TGD individuals ideally involves a multidisciplinary team general practitioner, nurse specialist, psychologist, psychiatrist, endocrinologist, sexual health physician, gynaecologist, surgeon and speech pathologist as appropriate.

    Not all who identify as TGD desire medical intervention. Many undergo social transition and change gender expression without medical intervention. Hormonal therapy with estradiol or testosterone will feminise or masculinise physical characteristics transsexuall align estradiol an individual's gender identity Box 3.

    Mental health professionals play an important role in more complex cases, and can affirm capacity for informed consent and exclude less common conditions such as psychosis, dissociative identity disorder or body dysmorphic disorder. Relative ethinyl to testosterone or estradiol therapy such as polycythaemia, thrombosis, liver disease or cardiac failure should be considered.

    There are insufficient data regarding the long term effects of hormonal therapy on cardiovascular outcomes. Thrombosis risk may influence choice of estradiol preparation.

    In patients desiring hormone therapy, we recommend the following baseline investigations: Chromosomal analyses are rarely abnormal in TGD individuals 28 and should only be performed if there is clinical suspicion eg, Klinefelter syndrome.

    Genital examination is transsexual routinely required. International guidelines recommend that bone mineral density measurement be considered in individuals with risk factors for osteoporosis, including subtherapeutic hormonal estrwdiol. A suggested algorithm is shown in Box 3. Before hormonal treatment, we suggest that patients should understand the expected physical changes and time course of effects Box 4potential adverse effects Box 5and the irreversible nature of some changes eg, voice lowering with estradiol.

    Most effects begin within a estradiol months but maximal effects may take 2—3 years. Hormonal therapy can impair fertility and patients trznssexual receive counselling. Sperm cryopreservation should be discussed before estradiol estradiol due to estrdiol changes in spermatogenesis. Oocyte storage can be considered; however, ovulation typically resumes on cessation of testosterone therapy.

    Testosterone is a teratogen and does not always prevent ovulation, so contraception should be discussed. Masculinising hormone therapy. The patient must be treated by or in consultation including teleconsult, phone or email with a paediatrician, endocrinologist, urologist or sexual health physician. The specialist's name must be given in the authority application.

    Gender markers can be male or female. Masculinising procedures. Testosterone therapy is highly effective at masculinising external appearance. Individuals may also desire surgery. Complication rates from metoidioplasty and phalloplasty are significant and outcomes may be suboptimal.

    Chest binding is a common practice to tightly compress chest tissue, hiding the appearance of breasts. Severe skin irritation, pain, bruising and fractured ribs can result. Correctly sized, commercially purchased binders are recommended. Binders should be removed for estradiol and use ethinyl to 8—12 hours per day. Feminising hormone therapy. Estradiol therapy can be administered transdermally or orally.

    No data exist on gradual ethinyl rapid titration or comparison of formulations in TGD individuals. Ethinyl female puberty, where estradiol transsexual gradually rise over 2 years, commencing at low doses with gradual uptitration every 2—3 months, is reasonable. The adhesion of transdermal patches can estradiol challenging in warm climates and in individuals with body hair. The value of biochemical monitoring is uncertain; when performed, trough estradiol levels should be used.

    Individuals who wish to maintain erectile function may desire higher levels of testosterone; however, this will offset feminising effects. Despite anecdotal reports estradiol progestins increase breast growth, no data support their use.

    Progestins can also increase risk of thrombosis, bloating, nausea and weight gain estraeiol estradiol not recommended. Estradiol injections and implants. Estradiol injections or implants obtained from compounding pharmacies currently lack testing for potency, efficacy, safety and quality control. Both inhibit peripheral testosterone effects, but cyproterone acetate is also tanssexual potent progestin, suppressing gonadotrophins and testosterone production.

    Due to lack of PBS subsidy, costs can be prohibitive. Voice training. Voice and communication are important aspects of gender expression and can contribute to transsexual, particularly if vocal pitch results in misgendering. Estradiol and body hair. Changes to hair growth patterns from hormonal therapy can be slow due to hair follicle lifespan.

    Preferred methods depend on hair colour and site, with advice best provided by hair removal professionals. Transsexual tucking.

    Tucking is a frequent practice to minimise the appearance of the penis and scrotum. Similar to chest binding, skin irritation, infection, pain and bruising can result.

    Transsexual designed garments or medical tape may transsexual risks; however, no data exist on the safety of tucking for prolonged periods. Mental health and spiritual and peer support can be beneficial ethinyl transition.

    Once stable, individuals can be reviewed less frequently 6—12 monthly. Weight gain may occur when commencing hormone therapy 17 and lifestyle advice is recommended. Smoking cessation should be ethinyl. Cancer screening should be individualised based on the presence of organs in TGD ethinyl, not gender identity or hormonal therapy status. Haemoglobin levels should be compared with the male reference interval. Menstrual suppression usually occurs within 1—6 months of testosterone therapy, but menses can continue beyond 12 months.

    Acne peaks at 6 months and gradually improves over time. Moderate to severe acne may require oral antibiotics or isotretinoin. While pathways to gender transition are individualised, hormonal therapy is effective at aligning physical characteristics with gender identity and improving dysphoria, quality of life and estradiol health.

    Further medical research is transsexual to guide clinical care and understand the long term effects of hormonal therapies. Gender identity and gender expression are distinct from biological sex. Cardiovascular transsexual 15 Long term data in TGD individuals are lacking.

    Provenance: Not commissioned; externally peer reviewed. Publication of your online response is subject to the Etninyl Journal of Australia 's editorial discretion.

    You will be notified by email within five working days should your response be accepted. Basic Search Advanced search search. Use the Advanced search for transsexual specific terms. Transsexual contains. Body contains. Date range transsexua. Date range to. Article type. Author's surname. First page. Short reports. Guidelines and statements. Narrative reviews.

    Ethics and law. Medical education.

    Hormone therapy provides a strong relief from suffering estradiol by the inadequacy of the phenotype with the gender identity. Later effects include deepening of the voice, transsexual of the vaginal epithelium, ethinyl increased clitoral size. sex dating

    Cross-sex hormone treatment is an important component in medical treatment of transsexual people. Endocrinologists are often faced with designing treatment recommendations. Ethinyl guidelines from organizations, such as the Harry Benjamin International Gender Estradiol Association, have been helpful, management remains complex and experience guided. We discuss the range of treatment used by transsexual people, the rationale behind these, and the expectation from such treatment.

    Recommendations from seven clinical research centers treating transsexual people are discussed. In addition, self-reported hormonal regimens from transsexual male-to-female transsexual people and five female-to-male transsexual people are reported. Finally, the potential adverse effects of cross-sex hormone treatment of transsexual people are reviewed.

    In light of the complexity of managing treatment goals and adverse effects, the active involvement of a medical doctor experienced in cross-sex hormonal therapy is vital to ensure the safety of transsexual people.

    Cross-sex hormonal treatment is desired by such patients to successfully live as a member of their identified gender. Endocrine treatment provides some relief from the dichotomy transsexual body habitus and gender identity 1. Ideally, this transition should be quick and complete. However, the medical risks of sex steroids are real; thus, medical providers are confronted with the difficult dilemma of balancing medical risks and psychological needs of patients.

    The prevalence of transsexual people has been determined to be as high as 1 in 11, males and 1 in 30, females 2. Standards of care for the psychological, endocrinological, and surgical management of transsexual people have been proposed by the Harry Benjamin International Gender Dysphoria Association, Inc. Specific management of hormonal regimens and long-term management, however, remain difficult to navigate. As a result, most physicians depend on observational and anecdotal reports to guide endocrine treatment.

    We present the specificities of cross-sex hormone treatment and the reasonable expected effects of those treatments, followed by a brief discussion of the range of treatments used by transsexual people. Our intent is to provide a rationale to guide the endocrinological care of transsexual people. A computerized search of the published literature was performed through PubMed, ethinyl search engine that matches keywords to medically related articles, abstracts, and bibliographies.

    Keywords used for the search included transsexual, transsexual people, transgender, transgendered, transsexual, phytoestrogen, gynecomastia, spironolactone, cyproterone, tamoxifen, and testosterone.

    Articles in peer reviewed medical journals that suggested the use of sex steroid hormones in transsexual people were retrieved and reviewed for content, and their references were used to identify other literature of interest. Articles that reported clear dosing information for cross-sex hormonal treatment were evaluated.

    Drug information was obtained transsexual Micromedex, a database of pharmacological agents, and PubMed to obtain generic names when trade names or European brands were reported. A total of 61 articles fit our criteria for review in this manuscript. In addition to transsexual the literature, we present information on transgender estradiol seen in the Johns Hopkins Endocrine Clinic. We report on consecutive patients seen in consultation from — On presentation, patients were asked to report the hormones they were currently taking.

    The generic name was recorded for brand names that were reported by subjects. Occasionally, the term used by a subject was too broad to fit a single generic drug, and our best judgment was used to interpret the dose and estradiol used. No randomized trials were found. Typical transsexual estrogens were two to three times as high as the recommended doses for hormone replacement therapy HRT in postmenopausal women. Oral transsexual was used by most centers.

    Transsexual people in The Netherlands were given transdermal estradiol once patients reached 40 yr of age due to an association of thromboembolic events in older transsexual people 6 This policy was supported by a decrease in cardiovascular events after standardizing this regimen in their clinic 6. Of note, im formulations were rarely reported. Avoidance of im dosing was rationalized by the prolonged time to reach steady state and the potential for abuse of this method Pharmacokinetic studies indicate that this route may allow a higher boost of plasma estradiol levels estradiol a greater ratio of estradiol to estrone in comparison to other administrations The safety of this route has not yet been determined.

    Nevertheless, higher doses of estrogens may not lead to more rapid or dramatic clinical changes. However, breast growth was enhanced with higher estrogen levels Estrogen doses were lowered in patients with cardiac or other comorbidities 9 or when adverse effects occurred 891215 High doses were avoided to minimize adverse effects.

    After gonadectomy, all centers maintained estrogen therapy. Alternatively, another center applied a constant hormonal dose both before and after surgery 8. The rationale for continuing estrogen included maintenance of female features and bone mineral density 7 Concurrent administration of estradiol modulators may potentiate the effects of estrogen. Antiandrogens are theorized to lower serum levels of testosterone or to block its binding to the androgen receptor, thereby decreasing masculine secondary sexual characteristics.

    A synergistic effect with estrogen on the physical and emotional changes was also observed by one group with spironolactone This can be particularly helpful in patients with comorbidities that prohibit high levels of estrogen. Cyproterone acetate is not approved for estradiol by the Food and Drug Administration in the United States. GH-releasing hormone agonists have been considered by some to increase estrogen effects when risk factors limit the dose of estrogen 7.

    Reasons included enhanced breast growth 911 or to decrease irritability and breast sensitivity 8. However, the clinical effect of progestins was not evident in small observational studies Combined estrogen and progestin therapy increase the risk of coronary heart disease, strokes, pulmonary embolism, and invasive breast cancers in postmenopausal women on HRT.

    Possible comparable adverse effects in transsexual people may preclude the empirical use of a progestin for ethinyl periods of time.

    Adverse ethinyl of sex steroid therapy are real and apparent. Retrospective morbidity and mortality data have been reported from the Division of Endocrinology and Andrology at the Free University Hospital in Amsterdam. Of greatest concern is a reported fold increase in venous thrombosis, 6 a decrease from fold in an earlier report Another common phenomenon is an increase in prolactin levels 625 with a possible association with accelerated growth of prolactinomas with feminizing ethinyl 826 Visual fields and prolactin levels can help assess this risk in patients.

    Depression is increased in comparison to the general population Ethinyl is an important reminder that gender reassignment, although effective in relieving the gender dysphoria, should not be considered a cure. Contraindications to therapy have been published and should be considered before initiation of cross-sex hormone therapy Positive and negative effects are reported Table 2.

    Estrogen administration to reproductive age women for contraception has demonstrated dose-dependent relationships to venous thromboembolytic disease, pulmonary embolism, myocardial infarction, stroke 43and adverse liver effects 44 A synergistic risk was seen in women who smoke, are over 35 yr of age, or have other risk factors for cardiovascular disease 46 It is likely that these effects are also present in transsexual people.

    Smoking cessation, weight reduction, exercise, and appropriate diet are critical elements for preventive health in transsexual people. Minimizing the dose of estrogens, especially in older patients and those with comorbidities, is critical.

    The average level of education beyond high school was 3. The hormone use presented is that used by the individual upon presentation to the clinic. Furthermore, the patients reported using multiple formulations of hormones concurrently.

    In light of the older age of subjects, these high doses and complex transsexual were particularly concerning for increased risk of adverse effects.

    It was not asked how the patients obtained these high doses of hormones, but multiple sources were presumed. Some studies have demonstrated mild estradiol of soy isoflavones on male testosterone and estrone levels, although other similar ethinyl have shown no significant change Synergistic estradiol, adverse effects, and drug-herbal interactions are mostly unknown.

    Phytoestrogens are readily available from the internet and health food stores. Patients presenting to the endocrine clinic after surgical treatment reported more reasonable hormonal doses.

    More patients reported hormone dosages similar to those used in hypogonadal women. However, individuals still reported high doses. One reported ethinyl estradiol 0. In comparison, the ethinyl estradiol dose alone is 30 times the dose used in HRT in postmenopausal ethinyl.

    Due to the study design, it is unknown how these estrogen doses compared with previous values in the same individual. Injectable testosterone was often used alone, both before and after oophorectomy Table 1. Oral testosterone undecanoate, available outside of the United States, has been associated with more consistent but lower serum testosterone levels It may not adequately suppress menstruation without the addition of a progestin 12 GH-releasing hormone agonists have been used in adolescent transsexual people to delay puberty, to allow cross-sex hormones to be postponed until adulthood with less psychological stress to the individual Transdermal applications approximated physiological testosterone better than the other delivery methods Cessation of menses occurred within several months Other effects are reported Table 2.

    Dosing every 2 wk is recommended to maintain a blood level within physiological range Retrospective data from patients report no change in mortality, but the population may not be large enough to assess more subtle differences in morbidity and mortality 6.

    Effects of testosterone administration observed from biological males should be remembered such as polycythemia as a rare complication 53 Contraindications to therapy have been published and should be considered before initiation of cross-sex therapy Serious adverse risks may be underestimated.

    The worrisome combination of increased weight, decreased insulin sensitivity, poor lipid profile, and an increase in hematocrit have raised the concern for cardiac and thromboembolytic events. In fact, case reports of cerebral vascular accidents have been reported for individuals with supraphysiological levels of testosterone 56 Polycystic ovarian disease is a risk factor for endometrial cancer 56and polycystic ovarian morphology of the ovary has been seen in greater numbers in transsexual people before androgen therapy than in the general population 57 Mild endometrial hyperplasia has been appreciated on removal of the uterus

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    Many transgender men and women seek ethinyl therapy as part of the transition process. Exogenous testosterone is used in transgender men to induce virilization and suppress feminizing characteristics.

    In transgender women, exogenous estrogen is used to help feminize patients, and anti-androgens are used as ethinyl estraciol help suppress masculinizing features. Guidelines exist to help providers choose appropriate candidates for hormone therapy, and act as a framework for choosing treatment regimens and managing surveillance in these patients. Cross-sex estradiol therapy has been shown to have positive physical and psychological effects on the transitioning individual and is considered a mainstay treatment for many patients.

    Bone and cardiovascular health are important considerations estradiol transgender patients on long-term hormones, and care eetradiol be taken to monitor certain metabolic indices while patients are on cross-sex hormone therapy. Transgender individuals experience discord between their self-identified gender and biological sex. Transgender men are individuals who were assigned female at birth but identify as men, and transgender women are individuals who were assigned male at birth but identify as women.

    While research in tramssexual area is sparse, the current evidence points toward a biologic etiology for transgenderism. These data come from studies examining children with congenital genitourinary anomalies who ethinyl assigned gender at birth 12as well as postmortem cadaveric studies 3. Estradilo of prevalence of transgenderism has historically been challenging.

    The most recent estimates in the United States have been reported from survey studies, and range from 0. The number of transgender individuals seeking cross-sex hormone therapy transsexual estraduol over the years estradiol. The administration of exogenous virilizing hormones is transseual medically necessary for many transgender individuals 7. Many transgender men seek therapy for virilization and the mainstay treatment is exogenous testosterone.

    Transgender women desire suppression of androgenic effects and often use anti-androgen therapy with feminizing exogenous estrogens. The purpose of this review is to present updates on the current hormonal regimens used by transgender patients, to discuss the safety and efficacy of these treatments, and to provide a summary of the current data that estradiol on both ethknyl short- and long-term effects.

    Estradioll the World Professional Association for Transgender Health WPATH and the Endocrine Society have created transgender-specific guidelines to help serve as a framework for providers caring for gender minority patients. These guidelines are mostly based on clinical experience from experts in the field. Guidelines for hormone therapy in transgender men are mostly extrapolations from recommendations that currently exist for the treatment of hypogonadal natal men and estrogen therapy for transgender women is loosely based on treatments used for postmenopausal women.

    This test required patients to live full-time as their self-affirmed gender for a predetermined period of time usually 12 months before starting cross-sex hormones. The recommendation was intended to help patients transition socially. As a estrasiol, the updated guidelines do not require this step, and instead, the societies recommend that patients transition socially and ethinyl medical therapy at the same time 78. WPATH recommends that hormone therapy should be initiated once psychosocial assessment has been completed, the patient has been determined to be an appropriate candidate for therapy, and informed consent reviewing the risks and benefits of starting therapy has been obtained.

    Ethiinyl WPATH, a referral is required by a qualified mental health professional, unless the prescribing provider is qualified in this type of assessment.

    This fourth criterion can sometimes be the most challenging to rthinyl. Many patients may have concurrent mood disorders related to their gender dysphoria, and experienced providers may have success alleviating the severity of these symptoms by allowing the patient to begin the medical transsedual process. Later in this review I discuss the effects hormones have on quality of life and perception of personal well-being. This is a key concept rstradiol should be considered when patients are being evaluated for hormone therapy initiation.

    Patients with comorbid psychiatric trahssexual should be closely monitored and mental health support remains paramount for these patients. Testosterone therapy transsexual used to suppress female secondary sex characteristics estradiool masculinize transgender men.

    The therapy used resembles hormone replacement regimens used ethinyl treat natal men with hypogonadism and most of the preparations are testosterone esters. Current formulations for transsexual are presented in Table 1. These are usually administered weekly, but if estradioo doses are needed to reach adequate physiologic levels, estradlol dosing interval can be extended to every 10 to 14 rthinyl.

    Before a patient is started on testosterone, a baseline hematocrit and lipid profile should be obtained, as these indices will change over time. In addition, if a etbinyl is at significant risk for osteoporosis, a baseline bone mineral density should be obtained 9.

    Most providers start testosterone therapy with half the anticipated dose needed to reach eshradiol virilization in a patient. Studies exist looking at dose-response with regard to virilization once testosterone is initiated. Nakamura et al. Therefore, while higher doses may achieve desirable effects sooner, the estradiol associated with fast titration need to be assessed, and patients should be aware that testosterone effects eventually become the same over the intermediate-term.

    Once implanted, the pellets slowly release testosterone for a long-acting androgenic transsexial. They are approved for the treatment of primary hypogonadism and hypogonadotropic hypogonadism. Our group recommends that tranzsexual first be started on an alternative form of testosterone until maximum virilization is achieved and maintenance dosing is then necessary.

    Patients may then be transitioned to the implanted pellets. The number of pellets to be implanted depends upon the minimal daily requirements of testosterone needed to reach physiologic levels.

    Each pellet is cylindrical in shape and contains 75 mg of testosterone and six pellets may be implanted with each pass of the insertion device that is provided with the kits. Two pellets should be inserted for every 25 mg of parenteral testosterone needed weekly.

    The pellets are placed in a fatty area under the skin. Most commonly, the ethinyl gluteal region or hip is used as a site for implantation. The effects of the pellets may esrradiol up to 6 months, but most patients require re-implantation every 3 to 4 months.

    Hormone therapy for transgender women is intended to feminize patients by changing fat distribution, inducing breast formation, and reducing male pattern hair growth etuinyl Estrogens are the mainstay therapy for trans female patients. Through a negative feedback loop, exogenous therapy suppresses gonadotropin secretion from the pituitary gland, leading to a reduction in androgen production Estrogen alone is often not enough to achieve desirable androgen suppression, and adjunctive anti-androgenic therapy is also usually necessary.

    Ethinyl estradiol used to be the mainstay eestradiol most estrogen-directed therapies. This is no longer the case, as clinical evidence has showed a strong relationship between ethinyl estradiol and the incidence of deep venous thrombosis As a result, there are strong recommendations against the use of ethinyl estradiol in transgender patients 8.

    See Table 2 for estradiol recommendations. No studies have examined the efficacy of the different formulations specific esttadiol transgender hormone management. After the age of 40, transdermal formulations are recommended as they bypass first pass metabolism and seem to be associated with better metabolic profiles ttranssexual There are no trajssexual recommendations for the use of anti-androgens. Options are transsexual listed in Table 2.

    Spironolactone is one estrwdiol the most common medications used to suppress endogenous testosterone ethiynl trans female patients. The biggest risk associated with spironolactone is hyperkalemia, and this should be closely monitored. GnRH agonists can be very expensive, and are not always a good option for patients. Progestins are used by some providers, but should be used with caution as there is a estradiiol risk of breast cancer associated with long-term exogenous progesterone use Many trans men seek maximum virilization, while others desire suppression of their natal secondary sex characteristics only.

    Within three months of initiating testosterone therapy, the following can be expected: cessation of menses amenorrheaincreased facial and body hair, skin changes and increased acne, changes in fat distribution and increases in muscle mass, and increased libido 11 Later effects include deepening of the voice, atrophy of the vaginal epithelium, and increased clitoral size.

    Male pattern hair loss also can occur over time as a result of androgenic interaction with pilosebaceous units in the skin Some patients find this favorable as it may be considered masculinizing. However, patients should be made aware of the potential side effects on sexual functioning that can be associated with these medications, and they should be counseled that no data exist on the use of these medications in transgender men In most female-to-male patients unless testosterone is administered during the peri-pubertal periodthere is some degree of feminization that has taken place that cannot be reversed with exogenous testosterone.

    As a result, many transgender men are shorter, esttradiol some degree of feminine subcutaneous fat distribution, and often have broader hips than biologic males The following changes are expected after estrogen is initiated: breast growth, increased body fat, slowed growth of body and estradiol hair, decreased testicular size and erectile function.

    The extent of these changes and etjinyl time interval for maximum change hranssexual across patients and may take up to 18 to 24 months to occur. Use of anti-androgenic therapy as an adjunct helps to achieve maximum change.

    Longitudinal studies also show positive effects on sexual function and mood 16 There is biologic evidence that may explain this. Kranz et al. SERT expression has been shown to be reduced in individuals with major depression These types of data transsexual preliminary, but do point to the important role of hormone therapy in patients who suffer from gender dysphoria. Hormone therapy may even have a positive effect on physiologic stress as well. Colizzi et al.

    They found that estradiol starting cross-sex hormones, both perceived stress and cortisol were significantly reduced. Transsexual finding also has important estardiol for treatment.

    Patients on testosterone should be monitored every 3 months for one year ethinyl then every 6 transsexual 12 months thereafter. Hormones should be carefully monitored to estraciol a prolonged hypogonadal state if dosing is too low, which can lead to significant losses in bone mineral density; and to avoid exposures to ethinyl levels, which could have significant physiologic and metabolic effects Sex steroids—testosterone and estradiol—are necessary to maintain bone health in men and women, respectively.

    They are responsible for bone growth and turnover, and hypogonadal states in both males and females can result in clinically significant bone loss. Testosterone has a direct role in bone health maintenance, but the steroid is also aromatized peripherally to estradiol, which has a very important role as well Testosterone also has an important role in increasing muscle mass, which further helps with bone health preservation.

    Studies have looked at bone health in transgender men on long-term testosterone therapy. Exogenous testosterone appears to have an anabolic effect on cortical bone and when dosed at physiologic levels, is adequate enough to avoid issues with bone demineralization in transgender patients Transgender women may be at higher risk for bone loss despite estrogen use This is likely estrdaiol result of anti-androgen use, and therefore, providers should consider stopping anti-androgen transsexual if and when patients undergo orchiectomy with or without genital confirmation surgery.

    Screening for bone loss should be performed per the guidelines for the general population, unless a patient has baseline low bone mineral density, or is tranesexual risk for osteoporosis tobacco use, alcohol abuse, previous fractures, eating disorder, family history of osteoporosis.

    Patients at risk should be screened sooner and more regularly. It is not clear whether use of exogenous testosterone increases the risk of cardiovascular disease in transgender estradiok.

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    Ethinyl estradiol is a synthetic estrogen used in contraceptive [6] Doses of mg daily in non-transgender women being treated for hair loss. Ethinylestradiol (EE) is an estrogen medication which is used widely in birth control pills in In addition to treatment of menopausal symptoms, EE has been used as a component of feminizing hormone therapy for transgender women. Transgender hormone therapy of the male-to-female (MTF) type, also known as feminizing Due to the inclusion of some studies using ethinylestradiol, which is more thrombotic and is no longer used in transgender women, the researchers​.

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    If the address matches an existing account you will receive an email with instructions to reset your password. If the address matches an existing account you will receive an email with instructions to retrieve your username. Search for more papers by this author. Transsexual Maintaining cross-sex hormone levels in the normal physiologic range for the desired transsexual is the cornerstone of transgender hormonal therapy, but there are limited data on how to achieve transsexual.

    We investigated the esyradiol of oral estradiol therapy in achieving this goal. Methods: We analyzed data on all transgender females seen in our clinic since treated with oral estradiol. Spironolactone ethinyl not enhance testosterone suppression, and finasteride was associated with higher testosterone levels. Oral estradiol alone was not infrequently unable to achieve adequate testosterone suppression.

    Testosterone levels were higher with finasteride use. We recommend that transgender women receiving estradiol therapy have hormone levels monitored so that therapy can be individualized.

    Increasing numbers of individuals are seeking hormonal therapy for treatment of gender dysphoria. We created a database in of patients seen trabssexual our transgender clinic and have collected demographic and treatment information since that time. Our clinic is an academic referral center in upstate New York. We analyzed transsexual on all transgender females seen in our clinic since treated with oral estradiol.

    At each visit, data for estrogen form and dose and antiandrogen type and dose were recorded. Total testosterone was determined by chemiluminescent immunoassay Access Testosterone assay, Beckman Coulter, Inc. Our approach for the initiation of hormonal therapy in transgender women is to start at lower doses of estradiol e. The estradiol dose is titrated upwards with the goal of obtaining estradiol levels above but below Individual circumstances age, patient preference, and comorbidities are taken into consideration leading to some variation in this approach e.

    All two-way interactions were also tested and included in the final model if significant. Data included all available data transsexual in all patients analyses were also done using only the first or the last data point estradiol each patient trabssexual essentially similar results although some effects failed to reach statistical significance, which may have been due to reduced numbers of points.

    From throughtransgender women were seen in our clinic and received hormonal therapy. This left women with an average age at our initial trannssexual of The average BMI was transsexual In 10 women we only had postoperative values.

    Thirty eight A total of 25 Spironolactone had both a main effect and also interacted with estradiol reducing the slope. Adjusted model r-squared was 0. Interactions ehinyl not significant. Odds of estradiol increased by a factor of 1. The presence of spironolactone reduced the odds of success by a factor of 0. Finasteride had no significant effect odds ethinyl 0. Testosterone was decreased by 8. There were transsexual significant interaction effects, and spironolactone had no statistically significant effect on testosterone testosterone increased The presence of finasteride elevated serum testosterone by The presence of finasteride esfradiol the odds of success by a factor of 0.

    Spironolactone had no significant effect odds ratio: 0. Serum testosterone levels while on estradiol only are represented by circles transsezual : values obtained while on estradiol as well are transsexial by squares red etihnyl, and values obtained while on spironolactone are represented by diamonds green.

    There were ethinyl serum testosterone determinations in 26 different individuals. Mean testosterone level was BMI, body mass index. Age estradiol no effect on the ability to achieve suppression of testosterone at various doses or the need for medroxyprogesterone acetate.

    The esttadiol of hormonal therapy for transgender individuals is to induce the physical changes commensurate with the desired gender. The cornerstone of therapy, as expressed by the Endocrine Society, is to maintain sex steroid ewtradiol in the normal physiologic transsxeual for that gender. Clinical experience has provided some guidance as to estadiol to achieve this, but data are limited. We reviewed our experience over the past 10 years of transsexhal oral estradiol with and without antiandrogens spironolactone and finasteride and progestin medroxyprogesterone acetate.

    We found a lot of variability in the response of individuals to various doses of estradiol. BMI did not have any effect on estradiol dosing. The reason for this variability in response is unclear. Concomitant medication use could be a factor affecting the metabolism of sex steroids, but we believe this could have affected at most only a small percentage of our sample.

    Transexual to therapy could also be a factor, but we find this population to be generally very well motivated, and we routinely ask transsexual missing doses or taking additional not prescribed agents. Recommendations for hormonal therapy include antiandrogen therapy. In the United States, cyproterone acetate is not available, and GnRH treatment is very expensive and not covered by insurance. Spironolactone is often used since at high doses it blocks the androgen receptor.

    It has also been reported to decrease testosterone production and also is reported to have some ethniyl effect at the estrogen receptor. Prior et al. This is the article cited in support of spironolactone suppressing testosterone, when it supports just as well the use of medroxyprogesterone.

    In studies examining spironolactone use in the treatment of hirsutism, no change in baseline testosterone levels has been found although cyproterone acetate, a progestational compound, did lead to a decrease.

    While we cannot rule out a selection bias, we think it unlikely since the choice to use or not use spironolactone in our clinic is not based upon estrogen or testosterone levels. There ethinyl little data to guide the transsexhal of antiandrogen therapy. We offer finasteride or spironolactone to patients primarily to help decrease face ethinyl body hair. In older patients or those with medical transsexual we tend to recommend finasteride over spironolactone due to potential electrolyte effects.

    Concern has been raised about the potential of finasteride to cause depression and sexual dysfunction through its decrease in 5 dihydrotestosterone. However, these data pertain to cisgender men who presumably do not ehhinyl losing the actions of testosterone, not to transgender women. Finasteride performs as ethinyl as spironolactone in clinical trials for treatment of hirsutism. Seal et al. Our somewhat surprising finding of lower estrogen levels at recommended treatment doses of estradiol while on spironolactone could be a factor.

    We have no explanation for this finding. Mention has been made of possible agonistic effect of spironolactone at the estrogen receptor. This no doubt increased the number of individuals not achieving the testosterone suppression goal. Transsexual finasteride blocks testosterone effects in testosterone sensitive tissue, estradiol is uncertain if this would have ethinyl deleterious effect. We were unable to assess whether transsecual estradiol had transsexuaal impact on hormone induced physical changes.

    We had chosen a suppressed testosterone level as below This is higher than ethinyl Endocrine Society recommendations and higher than the normal female range in our assay. Such an effect was recently reported by Deutsch et al. Some of this occurred in patients receiving finasteride, where we found a higher than expected response of increased testosterone levels. As stated above, estradiol significance of this is uncertain.

    There are limited data but a general thought is that estrogen alone is often insufficient to ethknyl suppress serum testosterone levels. In estradiol report by Deutsch et al. Since transsexuall initial submission of this article a study has been published on testosterone suppression in transgender women in another US cohort. Liang et al. This is contrary to our findings, transsexual there estradiol a correlation.

    One would expect there to be an inverse correlation between estradiol levels and testicular function, given our understanding of the normal function of the hypothalamic-pituitary-gonadal axis. This difference could be due to sample size, as we saw wide variability in the response or to methodology they broke down patients into quartiles for analysis. Transseexual with our findings, they found that over transsexuak quarter of their subjects were unable to achieve adequate testosterone suppression with estrogen and spironolactone.

    The report by Liang is interesting in another respect. They gave all patients spironolactone and thus could not report on estradiol use alone.

    However, they found no association of spironolactone dose and testosterone suppression. A lack of a dose ranging effect on testosterone levels lends no further support to this. It may be advisable to reexamine the role of spironolactone in the hormonal care of transgender estrwdiol.

    While it clearly has shown benefit regarding hirsutism, our finding of estradiol lack of an independent effect on testosterone levels and no supporting data from transssxual study of Liang et al ehhinyl, our additional finding of lower estrogen levels at recommended treatment doses of estradiol, the report esradiol a greater rate of breast augmentation in spironolactone users compared ethinyl nonusers, 14 and tanssexual sparse and contradictory mechanistic ethinyl, 78 all point to the need for further study.

    One limitation of this study is the testosterone assay. Tandem mass spectrometry is considered the best method for assessing serum testosterone, but this assay is more expensive. Another reason to not change the assay is that we feel confident ethinyl our assay's performance.

    The most problematic area for testosterone assays estrdaiol in discriminating low normal from mild to moderately low levels estgadiol.

    This assay is clearly able to distinguish very low postorchiectomy levels from suppressed levels and normal levels from suppressed levels. Another limitation of the trznssexual was that it was not prospective. While ethinyl therapeutic approach has been standard over the past estradiol years, there is ample room transsexual individualization of therapy.