Shoud I Continue to Take Antiandrogens After Srs
Lancet Diabetes Endocrinol. Author manuscript; available in PMC 2018 Apr 1.
Published in final edited form as:
PMCID: PMC5366074
NIHMSID: NIHMS835499
Oestrogen and anti-androgen therapy for transgender women
Vin Tangpricha
Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University School of Medicine and Atlanta VA Medical Center, Atlanta, GA, USA
Prof Martin den Heijer
Department of Endocrinology and Center of Expertise on Gender Dysphoria, VU University Medical Center, Amsterdam, Netherlands
Abstract
Transgender women experience lifelong gender dysphoria due to a gender assignment at birth that is incongruent with their gender identity. They often seek hormone therapy, with or without surgery, to improve their gender dysphoria and to better align their physical and psychological features with a more feminine gender role. Some of the desired physical changes from oestrogen and anti-androgen therapy include decreased body and facial hair, decreased muscle mass, breast growth, and redistribution of fat. Overall the risks of treatment are low, but include thromboembolism, the risk of which depends on the dose and route of oestrogen administration. Other associated conditions commonly seen in transgender women include increased risks of depression and osteoporosis. The risk of hormone-sensitive cancer seems to be low in transgender women, with no increased risk of breast cancer compared with women and no increase in prostate cancer when compared with men. The evidence base for the care of transgender women is limited by the paucity of high-quality research, and long-term longitudinal studies are needed to inform future guidelines.
Introduction
Transgender and gender-non-conforming people often seek hormone therapy, with or without surgery, to change their physical appearance to match their reaffirmed gender, and to alleviate the stress and discomfort associated with living in the incongruent gender.1 The uneasy feeling of living in an incongruent gender role is termed gender dysphoria. Transgender women, also referred to as transwomen or male-to-female transsexuals, are born with male genitalia and are typically assigned a male gender at birth. Gender dysphoria often presents in childhood. However, children often cannot articulate their discomfort or do not have a supportive family environment to seek medical attention, and thus present to health-care providers with gender dysophoria later in adulthood. Gender dysphoria can also present in adulthood without a clear start in childhood.
The prevalence of gender dysphoria or non-conforming gender identity is a topic of ongoing investigation. The precise number of transgender women estimated in a given population depends on the definition used. One early study in the Netherlands defined all patients who were treated with hormones and underwent surgery as transgender,2 and the investigators reported the prevalence of transgender women to be one in 11 900 people. A study from Ireland defined a transgender woman as a person assigned male gender at birth who is receiving oestrogen therapy,3 showing a similar prevalence of one in 10 154 people. Investigators of one of the largest cohort studies in the USA, which used US Veterans Health Administration data, reported a slightly higher prevalence of 3·29 in 10 000 people, based on codes in the ninth revision of the International Statistical Classification of Diseases used to charge for transgender services.4 Unfortunately, because of limitations of the study design, the researchers were unable to comment on whether these people were all transgender women; however, the veteran population tends to be predominantly men. In a 2016 systematic review of 29 studies,5 the prevalence of transgender women was roughly 5–20 per 100 000 when diagnostic codes or requests for medical treatment were used, or as high as 521 per 100 000 people if based on self-identification.
Hormonal therapy with gonadotropin-releasing hormone agonists can be started in early puberty (Tanner stage 2–3) to avoid the development of secondary sex characteristics in some individuals who have had appropriate mental health assessment, with the caveat that future fertility could be compromised. Oestrogen therapy follows treatment with gonadotropin-releasing hormone agonists in children, or can be combined with other testosterone-lowering drugs in adults. Several published guidelines exist to aid clinicians in the assessment, diagnosis, and medical treatment of adult transgender individuals. The World Professional Association for Transgender Health (WPATH) publishes comprehensive guidelines for health professionals that address all aspects of health care for gender-nonconforming people.1 The Endocrine Society publishes clinical practice guidelines that address the initiation and monitoring of hormone therapy for transgender children and adults.6 Other guidelines exist, including a clinical practice guideline published by the Royal College of Psychiatrists in the UK.7
In this Review, we provide an overview of the published literature on oestrogen and anti-androgen therapy in adult transgender women (ie, after puberty). The focus will be on the established treatment regimens, reported potential adverse events, long-term care and monitoring, and areas of uncertainty in the care of transgender women.
Oestrogen and anti-androgen therapy
An important goal for transgender women is to live as a woman in society and to have—as far as possible—a body that appears female (ie, to undergo feminisation). Secondary sex characteristics are formed under the influence of sex hormones, so an important factor in the male-to-female transition is to change the balance between oestrogens and androgens (ie, cross-sex hormone treatment). Important physical features in feminisation are breast growth, female body composition (ie, more adipose tissue on the hips and less in the abdominal region), and softer skin. Additionally, sex hormones affect the brain to change mood and have an effect on libido (figure).
Effects of oestrogen and anti-androgen therapy in transgender women
Supplementation with oestrogens lowers testosterone concentrations because of negative feedback on the hypothalamic–pituitary–gonadal axis. With the initiation of oestrogen therapy alone, testosterone concentrations decrease into the low-normal range for a man (200–300 ng/dL [6·9–10·4 nmol/L]), but are still above the normal range for a woman (<75 ng/dL [<2·6 nmol/L]).8 Most patients will require the addition of an anti-androgen medication to further inhibit testosterone production or to block the androgen receptor. Anti-androgen treatments such as spironolactone (in doses up to 400 mg daily) and cyproterone (in doses up to 100 mg daily) are effective adjunctive therapies, given in addition to oestrogen to lower testosterone concentrations into the female range.9–12 Spironolactone is better known as an aldosterone antagonist, but it also has antagonistic effects on the androgen receptor and can act as an oestrogen receptor agonist.13 Spironolactone could induce hyperkalaemia, especially in patients with impaired renal function. Prior and colleagues8 showed that the addition of spironolactone to oestrogen therapy is often necessary to lower testosterone values to the female range. In this study, high-dose oestrogen plus medroxyprogesterone led to a mean testosterone concentration of 169 ng/dL (5·9 nmol/L; SD 193 ng/dL [6·7 nmol/L]), whereas adding spironolactone to this regimen led to a mean testosterone concentration of 87 ng/dL (3 nmol/L; SD 111 ng/dL [3·8 nmol/L]).
Several other drugs can be used to lower testosterone including cyproterone and gonadotropin-releasing hormone agonists such as goserelin. Results of studies by Toorians and colleagues10 and Gava and colleagues11 showed that cyproterone, in combination with oestradiol, reduced testosterone to less than 30 ng/dL (1 nmol/L). However, there are no head-to-head studies that establish the superiority of one testosterone-lowering drug over another. Additionally, choices for one drug or another are primarily based on local regulations and reimbursement principles. Cyproterone seems to have a stronger anti-androgenic action than spiro nolactone,14 but depression is a potential side-effect.15 Cyproterone has anti-androgenic effects through antagonising the androgen receptor, but also has anti-gonadotropic effects. The gonadotropin-releasing hormone analogues such as leuprolide, histrelin, or goserelin work by reducing the secretion of luteinising hormone and follicle-stimulating hormone, which leads to decreased stimulation of testicular testosterone production. In 2016, the results of a small retrospective study showed similar anti-androgenic effects of both cyproterone and the gonadotropin-releasing hormone agonist leuprolide.11 Gonadotropin-releasing hormone analogues have relatively few effects other than lowering gonadal hormone concentrations. Gonadotropin-releasing hormone agonists are commonly prescribed in adolescents with gender dysphoria as a puberty blocker, to block the onset of puberty, but they might be used also in adult patients who have adverse drug reactions to anti-androgen therapy with spironolactone or cyproterone. The occurrence of (multiple) meningiomas has been reported in association with longer-term use (ie, use over several years) of cyproterone at doses of 25 mg daily or higher.16–19 As a result, in the UK, gonadotropin-releasing hormone agonists are prescribed as the only androgen-lowering agents used in conjunction with oestrogens in the treatment of transgender women in National Health Service gender identity clinics.20
Some patients request progesterone for enhanced breast growth. However, there have not been any well designed studies to assess the effectiveness of progesterone to improve breast development. Results of studies of progesterone combined with oestrogen in postmenopausal cis-gender women—ie, women who are not transgender—suggest that progesterone combined with oestrogen might be associated with an increased risk of cardiovascular disease.21 In fact, in a population-based study of premenopausal cis-gender women, taking oral contraceptives including progesterone with or without oestrogen was associated with increased risk of thromboembolism.22
Finasteride has been used in transgender women as an anti-androgen.23 This drug is a 5-α reductase inhibitor and might increase testosterone concentration by blocking synthesis of dihydrotestosterone from testosterone. However, this drug is not recommended as a first-line treatment because such drugs might lead to worsened depression.24
Treatment regimens and guidelines
WPATH and the Endocrine Society have released evidence-based guidelines for the treatment of transgender women (table 1).1,6 Both guidelines suggest that cross-sex hormone treatment be initiated in adults with well documented gender dysphoria and who are able to provide informed consent for treatment.1,6 Furthermore, the guidelines recommend assessment of medical and mental health issues that can be exacerbated by hormone therapy before initiation of cross-sex hormone treatment.1,6
Table 1
Recommendations from the Endocrine Society's clinical practice guidelines6
| Quality of evidence | |
|---|---|
| Before hormone therapy | |
| Confirm the diagnostic criteria of gender identity disorder or transsexualism and the eligibility and readiness criteria | Moderate |
| Evaluate and address medical conditions that can be exacerbated by hormone depletion and cross-sex hormone treatment | Moderate |
| | |
| During hormone therapy | |
| Maintain cross-sex hormone levels in the normal physiological range for the desired gender | Low |
| Review the onset and time course of physical changes induced by cross-sex hormone treatment | Low |
| Perform regular clinical and laboratory monitoring every 3 months during the first year and then once or twice yearly | Low |
| Monitor prolactin levels | Low |
| Screen for prostate cancer | Very low |
| Perform bone mineral density test if risk factors are present | Moderate |
| Screen for breast cancer by guidelines recommended for women | Low |
| Evaluate transsexual people treated with hormones for cardiovascular risk factors | Low |
| | |
| Before surgery | |
| Consider genital sex reassignment surgery only after both the physician responsible for endocrine transition therapy and the mental health professional find surgery advisable | Very low |
| Genital sex reassignment surgery recommended only after completion of at least 1 year of consistent and compliant hormone treatment | Very low |
| The physician responsible for endocrine treatment should medically clear transsexual individuals for sex reassignment surgery and collaborate with the surgeon regarding hormone use during and after surgery | Very low |
The hormonal regimens used for transgender women are not standardised across the world (table 2), partly because of regional differences in the availability of oestrogen and testosterone-lowering preparations, as well as cost considerations and differences in practices between countries and centres.25 For example, in some European countries (Belgium, Germany, Italy, Netherlands, and Norway) common regimens include oral oestradiol combined with cyproterone (50 mg daily).26 In the UK, oral oestradiol is combined with gonadotropin-releasing hormone agonists.7 In the USA, all forms of oestradiol are available (parenteral, oral, and patches or gels) and are combined with spironolactone. Conjugated oestrogens and synthetic oestrogens such as ethinylestradiol are not recommended because physicians are unable to monitor their concentrations in the blood, and because of the potential of these drugs to increase the risk of thromboembolism compared with other oestrogens.27 Because gonadotropin-releasing hormone agonists more effectively suppress endogenous sex steroids than other testosterone-lowering drugs, and could be associated with fewer short-term side-effects, the combination of oral oestradiol and gonadotropin-releasing hormone agonists might be regarded as the superior regimen; however, there are no published long-term studies apart from a small retrospective study in 40 patients, the results of which showed the equivalent effectiveness of cyproterone and leuprolide.11 Furthermore, the use of gonadotropin-releasing hormone agonists is limited in many countries because of their cost, which is greater than 1000 per year per patient in Europe, with even higher prices in the USA.
Table 2
Oestrogen and anti-androgen preparations for transgender women
| Route | Dose | Advantages | Disadvantages | |
|---|---|---|---|---|
| Oestrogens | ||||
| Oestradiol | Oral | 1–6 mg daily | Inexpensive Oestradiol levels can be monitored | Might be associated with increased risk of thromboembolism in older patients (age >40 years) |
| Conjugated oestrogens | Oral | 1·25–5 mg daily | Inexpensive | Might be associated with increased risk of thromboembolism in older patients (age >40 years) Oestradiol levels cannot be monitored |
| Oestradiol valerate or oestradiol cypionate | Intramuscular | 10– 20 mg intramuscularly every 1–2 weeks | Avoids liver first-pass effect Does not depend on intestinal absorption | Requires intramuscular injections, which can cause pain for some Can result in supraphysiological levels of oestradiol if not properly given |
| Oestrogen patch or gel | Topical | Varies depending on preparation | Least associated with risk of thromboembolism Avoids liver first-pass effect | Expensive Patches can be difficult to adhere to the skin Patches can cause skin irritation Risk of skin-to-skin transference of oestradiolto others |
| | ||||
| Anti-androgens | ||||
| Spironolactone | Oral | 50–400 mg in divided doses twice a day | Inexpensive | Requires monitoring of potassium Has diuretic and antihypertensive effect |
| Cyproterone | Oral | 50–100 mg daily | Inexpensive | Hepatotoxic at high doses Can suppress the hypothalamic–pituitary–adrenal axis Can cause depression Not widely available in the USA |
| Gonadotropin-releasing hormone agonists | Intramuscular or subcutaneous implant | Varies depending on preparation | Suppression of entire pituitary gonadal axism Few side-effects | Expensive Not widely available in some countries Limited long-term safety data |
Concentrations of oestradiol and testosterone should be monitored every 3–6 months in the first 2 years of therapy, then annually to ensure that they are in the physiological range for a woman, and especially to ensure that oestradiol concentrations do not exceed peak levels (<400 pg/mL [13·9 nmol/L]) seen in women.6 The precise concentration of oestradiol that results in adequate feminisation with the lowest risk of complications is not known.28 For transgender women taking spironolactone, it is advisable to measure serum potassium concentrations every 3–4 months in the first 2 years, then annually, since the potassium concentrations could increase during spironolactone therapy.6 After gonadectomy, testosterone concentrations drop to nearly zero—only a small amount is still produced by the adrenal glands—and thus, after surgery, anti-androgens can be discontinued. Serum testosterone can be measured within a month after surgery to confirm that testosterone concentrations are low (ie, <50 pg/mL [1·7 nmol/L]) and that testosterone-lowering medications are not needed. It is important to keep the dose of oestrogen at a level that not only maintains sex characteristics and relieves gender dysphoria, but is also adequate to prevent osteoporosis, hot flashes, and mood disorders.29
We recommend that hormones be prescribed under medical supervision to allow monitoring of hormone levels and screening for potential adverse events. However, many transgender women have inadequate access to health-care providers who have experience with transgender medicine.30 Other barriers to care include the financial costs of medical care, discrimination against transgender patients, and other socioeconomic and cultural barriers .31 As a result, up to 50% of transgender women might self-medicate with hormones before seeking the advice of a physician .15,32,33 Transgender women who self-prescribe often have a poor understanding of potential side-effects and safe doses of oestrogens, and can report inadequate breast growth.40 Although less is known about transgender women who self-medicate with cross-hormone therapy, oestrogen and anti-androgen treatment taken under medical supervision seems to be associated with few adverse events.42
Expected time course and physical changes
The Endocrine Society guidelines for endocrine treatment of transsexual people presents an overview of the feminising physical effects of cross-sex hormone treatment in transgender women, most of which start within a few months and progress for 2–3 years.6 However, there is a shortage of high-quality evidence about the precise time course and effect-modifiers of these feminising effects, which is partly because these changes cannot be easily measured. Clinically, the most compelling effects of cross-sex hormone treatment are softening of the skin, mood changes, a decrease in libido and erections, fat redistribution at the hips, and growth of breast tissue. Results of studies that focused on bodyweight and composition indicate an increase in bodyweight of 1–3 kg per year, with an increase in fat mass (2–4 kg) and a decrease in lean body mass (2–4 kg) after 1 year of cross-sex hormone treatment.9,12,36 The fat mass increases are apparent as both visceral and subcutaneous fat depots.37,38
An important issue for many transgender women is breast development. But despite its importance, only a few low-quality studies have been done to investigate the effect of cross-sex hormone therapy on this outcome.39 Breast development starts within 2–3 months after initiation of combined oestrogen and anti-androgen treatment, and takes up to 2 years to complete. In a longitudinal study by Meyer and colleagues,34 breast hemi-circumference increased by 14 cm after 3 years of oestrogen therapy. The response to oestrogen can vary from individual to individual. Up to two-thirds of transgender women are unsatisfied with their breast development and apply for breast augmentation surgery .40 No evidence exists that the addition of progesterone improves breast development.39 Cross-sex hormone treatment has also been reported to lead to softening of the skin and feminine hair growth, but systematic studies have not been done.35,41
Comorbidities and pitfalls
Overview
Although cross-sex hormone treatment is now regarded as fairly safe when taken under medical supervision, several associated comorbid conditions can occur with hormone therapy.42 Since oestrogen and testosterone-lowering drugs are often taken in combination and the specific drugs used vary by country and region, it can be difficult to attribute comorbid conditions specifically to oestrogen or testosterone-lowering drugs.
Thromboembolic disease
Oestrogen use is associated with an increased risk of venous thrombosis, as has been reported in many studies of oral contraceptives and postmenopausal hormonal replacement in women.43 The risk of venous thrombosis in the general population of non-transgender women and men who are not taking oestrogen ranges from one to two events annually per 1000 individuals; incidence increases with age.44 Bell and colleagues45 reported the remaining lifetime risk of thromboembolism to be 8·1% (95% CI 7·1–8·7) in a cohort of non-transgender, middle-aged adults (aged 45–64 years) living in the USA. Oestrogen is believed to be the key component in the causation of venous thrombosis, which might be modified by the route of administration of oestrogen or whether it is taken with progestogens.46
The lifetime risk of venous thrombosis in transgender women has been reported to range between 1% and 5%. However, many of the studies were small and very short in follow-up time.47 Furthermore, many venous thrombotic events are likely to be under-reported. Data from early studies in transgender women in the Netherlands suggested a high lifetime prevalence (about 5% over a mean of 10 years of follow-up) of thromboembolic disease.48 However, subsequent studies indicate that the risk of thromboembolic disease is much lower, and that the cause of the increased risk of thromboembolic disease in the earlier cohort was due to the use of ethinylestradiol.49 Indeed, reports from several European centres have suggested that the lifetime risk of thromboembolism is very low (about 1%).9,50,51 In one study from Belgium, the investigators reported that three of 50 transgender women had a thromboembolic event.52 In a retrospective chart review of 165 transgender women, the prevalence of thromboembolism was 1·2%, and was more frequent with the use of conjugated oestrogens, compared with other oestrogen preparations.40
The risks of thromboembolism can also be modified by the route of drug administration. A meta-analysis and systematic review of oestrogen replacement therapies in cis-gender women showed that oral oestrogen, but not transdermal oestrogens, increased the risk of venous thromboembolism.53 A transgender clinic in Amsterdam, Netherlands, noted a 50% reduction in risk of venous thromboembolism after recommending that all trans-gender women older than 40 years change from oral to transdermal oestrogen.48 Additionally, Ott and colleagues50 identified no cases of venous thromboembolism 162 transgender women treated with transdermal oestrogen and followed up for a mean of 5 years, lending support to the belief that transdermal preparations could be less thrombogenic than oral oestrogen.
Although the lifetime risk of thromboembolic disease seems to be low in patients followed up in multispecialty gender clinics, providers should inform patients about the potential risk of thromboembolic disease due to oestrogen treatment, and which factors modify this risk. Modifiers in transgender women include the oestrogen preparation used (ethinylestradiol or conjugated oestrogens vs 17–β oestradiol), dosing method (oral vs transdermal), age (older than 50 years is associated with increased risk), obesity (body-mass index >27),54 and postoperative state (with prophylaxis for deep venous thrombosis vs without).27 We believe that transgender women who continue to smoke should be switched to transdermal oestrogens, although there are few data to suggest that this reduces risk of thromboembolism.
Osteoporosis
Cross-sex hormone treatment with oestrogens should be protective of bone density, since oestrogens are the major sex steroid hormone that prevents bone loss in both men and women.55 Low bone density is common after gonadectomy if oestrogen is not prescribed at adequate doses to prevent oestrogen concentrations from dropping into a menopausal range.56 Some study findings suggest that low bone density can be present initially in transgender women. Up to 16% of transgender women have T-scores less than –2·5 at the hip or spine bones at initial presentation, indicating that osteoporosis might occur even before initiation of oestrogen treatment, and can be present in transgender women in their 20s or 30s.57,58 The cause of low bone density in transgender women before the initiation of cross-sex hormone treatment is unclear. Potential causative factors might include poor nutrition and vitamin D status, and low levels of physical activity and exercise.48 Although there are no established guidelines about when bone mineral density testing should be done, it might be prudent to check an initial screening dual energy x-ray absorptiometry after age 40 years if risk factors are present, or if there is a personal history of fracture. Despite reports of low bone density occurring in transgender women, there are very few reports of fragility fractures occurring in transgender women.59
Liver disease
Liver disease was a concern in initial cohort studies, wherein abnormal liver function tests were reported to occur in up to 15% of transgender women .60 However, it was subsequently determined that the cause of the abnormal findings was not the use of oestrogen; rather the liver function abnormalities identified were secondary to alcohol misuse or viral hepatitis.48 In a longitudinal cohort study of transgender women in Europe, roughly 5% of study participants had transient increases in liver enzyme concentrations to greater than twice the normal range, but values returned to the normal range after 12 months.36 Another study conducted in the USA found that measurements of aspartate aminotransferase and alanine aminotransferase in transgender women did not differ from either the male or female reference range.61 These data suggest that oestradiol might not be hepatotoxic, as previously believed on the basis of data from earlier cohort studies.60 The alterations in liver function tests reported in earlier studies might have been due to the older age of the early Dutch cohort compared with recent cohorts, differences in alcohol intake, and the formulation of oestrogen treatment used. The risk of oestrogen therapy with respect to liver function remains an area of uncertainty, and the Endocrine Society guidelines recommend periodic measurement of liver function tests.
Lipid abnormalities
Treatment of postmenopausal women with oestrogen, with or without progesterone, has been associated with an increase in triglycerides and HDL cholesterol and a decrease in total and LDL cholesterol.62,63 In premenopausal women, oral contraceptive pills containing oestrogen and progesterone also seem to be associated with increased total cholesterol, triglyceride, and HDL cholesterol concentrations.64 Results of one of the largest studies examining the effect of oestrogen (given as conjugated equine oestrogen, 0·625 mg daily) and progesterone compared with placebo, in postmenopausal women, showed increases in HDL cholesterol and triglycerides, and decreases in LDL and total cholesterol.62
Specific to transgender women, data from several longitudinal cohort studies15,38,65 suggest that oestrogen (with or without progesterone) increases triglyceride concentrations. In a meta-analysis of 23 studies including 3231 transgender women, Maraka and colleagues66 reported that oral oestrogen increased serum triglyceride concentrations by about 30 mg/dL (0·34 nmol/L) after 24 months from initiation of oestrogen therapy, with no changes in other lipid parameters, including HDL and LDL cholesterol. However, the oestrogen regimens included in this meta-analysis included different anti-androgen preparations including cyproterone, gonadotropin-releasing hormone agonists, and spironolactone, making it difficult to attribute the changes in lipids caused by oestrogen treatment alone. Only 14 of 1073 transgender women were reported to have had a myocardial infarction in this meta-analysis. It is difficult to interpret whether this represents an increased risk of myocardial infarction without a control group of transgender women who are not being treated with oestrogen therapy. Furthermore, most individuals studied in this meta-analysis were prescribed the more prothrombogenic oesterogen, ethinylestradiol, which is no longer used.
Mental health and depression
The prevalence of psychiatric and mood disturbances is high among transgender people.67 Several reports suggest that cross-sex hormone treatment improves quality of life and depressive mood symptoms.68–71 In a systematic review and meta-analysis of 28 studies including more than 1800 transgender people (with about 1100 transgender women), hormone treatment, with or without surgery, improved gender dysphoria and quality of life in 80% (95% CI 72–88; 16 studies; I 3=78%) of patients.72 However, suicide rates remain high in transgender people after hormone therapy, with or without gender reaffirming surgery.73–76 Blosnich and colleagues73 reported that the crude rate of suicide among transgender military veterans was 82 per 100 000 person-years, which is higher than the rates in non-transgender veterans and the US population, but similar to suicide rates seen in veterans with depression, schizophrenia, and substance misuse.77,78 It is important that clinicians screen for signs of depression and suicidal ideation at each visit, and to refer patients for counselling and psychiatric treatment when needed.
Breast cancer
Several reports have suggested an increased risk of breast cancer in transgender women.79 In one of the largest cohorts of transgender women and transgender men, the overall prevalence of breast cancer was 20·0 per 100 000 patient-years of cross-sex hormone treatment.80 For transgender women specifically, the standardised incidence ratio was 0·7 (95% CI 0·03–5·57) compared with natal women, but 33·3 (21·89–45·17) compared with biological men.81 There are no clear guidelines for when mammogram screening for breast cancer should start. In the absence of any evidence, in our opinion, it could be reasonable to start mammogram screening in transgender women at the same age recommended for cis-gender women, or earlier if known risk factors are present, such as a family history of breast cancer.81
Prostate cancer
Since castration—either surgical or medical—is the primary treatment in prostate cancer, it might be expected that the incidence of prostate cancer is low in transgender women. Indeed, reports of prostate cancer have been limited to a few case reports.82 In a review of more than 1000 transgender women followed up by the Amsterdam clinic, only one case of prostate cancer was discovered.83 On the basis of the low overall prevalence of prostate cancer, these authors suggest screening for prostate cancer only after age 50 years.
Special considerations
Gender-reaffirming surgery
Cross-sex hormone treatment affects secondary sex characteristics of transgender women, making them more feminine in appearance; however, it has little effect on the primary sex organs except to cause some testicular atrophy.6 Therefore, many transgender women will seek gender reaffirming surgeries to remove the testes and to create a neovagina.84 Breast development under cross-sex hormone treatment can often be unsatisfactory and thus many transgender women might choose to have breast augmentation surgery.85 In transgender women who initiate cross-sex hormone treatment after puberty, secondary male sex characteristics might require surgery such as chondrolaryngoplasty (the so-called tracheal shave) for a prominent larynx or facial feminisation for frontal bossing.86,87 Laryngoplasty can also be done to change the pitch of the voice.88 Before laryngoplasty, transgender women can benefit from undergoing voice assessment, conditioning, and therapy by a voice and communication professional.89
There is debate about whether cross-sex hormone treatment, particularly oestrogen, should be interrupted before surgical procedures given the potential thromboembolic risk of oestrogen (and possibly of anti-androgens). Many centres advise transgender women to cease oestrogen use at least 2–4 weeks before any major surgery and do not re-initiate oestrogen treatment until the postoperative patient is fully ambulatory.25 It is important that transgender women undergo postoperative prophylaxis for deep vein thrombosis.25 Furthermore, transgender women should reduce the risk of postoperative deep vein thrombosis before surgery by modifying lifestyle factors as bodyweight, smoking, and drug misuse, which can affect the outcome of surgery and the risk of complications.90 This recommendation is especially true for plastic surgery procedures in which microcirculation is involved.
Fertility
Cross-sex hormone treatment in transgender women reduces sperm quantity and quality, and eventually results in irreversible infertility, even after cross-sex hormone treatment is stopped.91 The time course, doses of oestrogen and testosterone-lowering drugs, and risk factors that lead to irreversible infertility are not known. Many transgender women desire the opportunity to have their own biological children in the future, and seek cryopreservation of their sperm.92 Results of a case series of 29 transgender women showed a high rate of abnormalities in sperm characteristics, even before the initiation of oestrogen therapy, including oligo-azoospermia (27%, eight of 29), teratozoospermia (31%, nine of 29), and asthenozoospermia (31%, nine of 29).93 Why sperm characteristics are altered in transgender women even before initiation of hormone therapy is not clear. Because cross-sex hormone treatment can reduce sperm number and quality, it is important to discuss fertility issues before the start of hormonal treatment.1,94 Transgender women should be offered sperm banking before the initiation of cross-sex hormone treatment, since it is more difficult to retrieve sperm after cross-sex hormone treatment has been initiated.1 There are no published longitudinal data for the effect of hormone therapy on sperm quality and the time course over which sperm quality is permanently altered. Physicians should also remind transgender women that cross-sex hormone treatment is not an effective contraceptive.
Ageing
Concentrations of sex hormones vary with age. Whereas sex hormone concentrations increase during puberty in both sexes, there is a difference between men and women in the decline of circulating sex hormones. In men, there is a gradual decline of circulating testosterone, whereas in women there is a sudden decrease in circulating oestrogen after menopause. There is compelling evidence in cis-women that an earlier start of menopause is associated with an increased risk of osteoporosis and cardiovascular disease, whereas a later start is associated with an increased risk of uterine and breast cancer.95 Results of the Women's Health Initiative study21,96,97 showed that hormone replacement therapy (oestrogen plus progestogen [medroxyprogesterone]) increased the incidence of breast cancer, coronary heart disease, and ischaemic stroke. The increased risk of breast cancer and coronary heart disease was not seen in women receiving oestrogen alone, without progestogens.98
Data from transgender women at older ages (>50 years) are completely absent, and it is difficult to attempt to apply the existing evidence from natal women to transgender women because of physiological differences; for example, transgender women do not have a uterus, and breast cancer might have a different histopathology. So, although there are no compelling data about whether or not to stop oestrogen treatment in transgender women at age 50 years, the Women's Health Initiative study provides evidence that full oestrogen replacement in late menopause might not be safe. In our opinion, it seems prudent to discuss with the patient the possibility of gradually tapering their oestrogen dose at an advanced age, as is done in some transgender health clinics (eg, in the Netherlands).29 This topic is an important area of uncertainty that should be addressed in future research.
Conclusions
Transgender women seek treatments to better align their gender identity with their physical characteristics. Endocrine treatment remains a key component of care for transgender women. Although no randomised trials are available, hormonal and surgical treatment has been shown in several cohort studies to lead to a clear improvement in psychological wellbeing and quality of life. Health-care providers should understand that there is a wide spectrum of gender non-conforming conditions and that hormonal therapy is only one aspect of medical care. Health professionals should be aware of the WPATH standards of care and the Endocrine Society guidelines, both of which provide guidance on how to initiate and monitor hormone treatment. The recommendations are based on the currently available published evidence; however, most of the available evidence comes from low-quality studies. It might be difficult to conduct randomised controlled studies with sufficient power to answer specific questions related to transgender women. Results of large cohort studies have shown that, generally, when oestrogens are taken under medical supervision, the risks of adverse events are low.42 The establishment of large, long-term cohort studies from different regions of the world, where different hormone regimens are used in clinical practice, will help advance our understanding and determine whether hormone therapy is associated with any long-term health risks.99 For now, key treatment goals are to avoid supraphysiological dosing of oestrogen and to reduce modifiable risks associated with oestrogen therapy.
Acknowledgments
We are partly supported by the National Center for Advancing Translational Sciences of the US National Institutes of Health (NIH; award number UL1TR000454). The content of this Review is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. We thank Walter Pierre Bouman from the Nottingham Centre for Gender Dysphoria (Nottingham, UK) for his critical review of this manuscript.
Footnotes
Contributors
VT and MdH drafted and edited the manuscript.
Declaration of interests
We declare no competing interests.
Contributor Information
Vin Tangpricha, Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University School of Medicine and Atlanta VA Medical Center, Atlanta, GA, USA.
Prof Martin den Heijer, Department of Endocrinology and Center of Expertise on Gender Dysphoria, VU University Medical Center, Amsterdam, Netherlands.
References
1. Coleman E, Bockting W, Botzer M, et al. Standards of care for the health of transsexual, transgender, and gender-nonconforming people, version 7. Int J Transgend. 2012;13:165–232. [Google Scholar]
2. Bakker A, van Kesteren PJ, Gooren LJ, Bezemer PD. The prevalence of transsexualism in the Netherlands. Acta Psychiatr Scand. 1993;87:237–38. [PubMed] [Google Scholar]
3. Judge C, O'Donovan C, Callaghan G, Gaoatswe G, O'Shea D. Gender dysphoria—prevalence and co-morbidities in an Irish adult population. Front Endocrinol (Lausanne) 2014;5:87. [PMC free article] [PubMed] [Google Scholar]
4. Kauth MR, Shipherd JC, Lindsay J, Blosnich JR, Brown GR, Jones KT. Access to care for transgender veterans in the Veterans Health Administration: 2006–2013. Am J Public Health. 2014;104(suppl 4):S532–34. [PMC free article] [PubMed] [Google Scholar]
5. Collin L, Reisner SL, Tangpricha V, Goodman M. Prevalence of transgender depends on the case definition. J Sex Med. 2016;13:613–26. [PMC free article] [PubMed] [Google Scholar]
6. Hembree WC, Cohen-Kettenis P, Delemarre-van de Waal HA, et al. Endocrine treatment of transsexual persons: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2009;94:3132–54. [PubMed] [Google Scholar]
8. Prior JC, Vigna YM, Watson D. Spironolactone with physiological female steroids for presurgical therapy of male-to-female transsexualism. Arch Sex Behav. 1989;18:49–57. [PubMed] [Google Scholar]
9. Deutsch MB, Bhakri V, Kubicek K. Effects of cross-sex hormone treatment on transgender women and men. Obstet Gynecol. 2015;125:605–10. [PMC free article] [PubMed] [Google Scholar]
10. Toorians AW, Thomassen MC, Zweegman S, et al. Venous thrombosis and changes of hemostatic variables during cross-sex hormone treatment in transsexual people. J Clin Endocrinol Metab. 2003;88:5723–29. [PubMed] [Google Scholar]
11. Gava G, Cerpolini S, Martelli V, Battista G, Seracchioli R, Meriggiola MC. Cyproterone acetate versus leuprolide acetate in combination with transdermal oestradiol in transwomen: a comparison of safety and effectiveness. Clin Endocrinol (Oxf) 2016;85:239–46. [PubMed] [Google Scholar]
12. Mueller A, Zollver H, Kronawitter D, et al. Body composition and bone mineral density in male-to-female transsexuals during cross-sex hormone therapy using gonadotrophin-releasing hormone agonist. Exp Clin Endocrinol Diabetes. 2011;119:95–100. [PubMed] [Google Scholar]
13. Braunstein GD. Gynecomastia. N Engl J Med. 2007;357:1229–37. [PubMed] [Google Scholar]
14. Yamasaki K, Sawaki M, Noda S, et al. Comparison of the Hershberger assay and androgen receptor binding assay of twelve chemicals. Toxicology. 2004;195:177–86. [PubMed] [Google Scholar]
15. Moore E, Wisniewski A, Dobs A. Endocrine treatment of transsexual people: a review of treatment regimens, outcomes, and adverse effects. J Clin Endocrinol Metab. 2003;88:3467–73. [PubMed] [Google Scholar]
16. Gil M, Oliva B, Timoner J, Macia MA, Bryant V, de Abajo FJ. Risk of meningioma among users of high doses of cyproterone acetate as compared with the general population: evidence from a population-based cohort study. Br J Clin Pharmacol. 2011;72:965–68. [PMC free article] [PubMed] [Google Scholar]
18. Ter Wengel PV, Martin E, Gooren L, Den Heijer M, Peerdeman SM. Meningiomas in three male-to-female transgender subjects using oestrogens/progestogens and review of the literature. Andrologia. 2016 doi: 10.1111/and.12550. published online Feb 16. [PubMed] [CrossRef] [Google Scholar]
19. Gazzeri R, Galarza M, Gazzeri G. Growth of a meningioma in a transsexual patient after estrogen-progestin therapy. N Engl J Med. 2007;357:2411–12. [PubMed] [Google Scholar]
20. Ahmad S, Barrett J, Beaini A, et al. Gender dysphoria services: a guide for general practitioners and other healthcare staff. Sex Relation Ther. 2013;28:173–86. [Google Scholar]
21. Manson JE, Hsia J, Johnson KC, et al. for the Women's Health Initiative Investigators. Estrogen plus progestin and the risk of coronary heart disease. N Engl J Med. 2003;349:523–34. [PubMed] [Google Scholar]
22. Barsoum MK, Heit JA, Ashrani AA, Leibson CL, Petterson TM, Bailey KR. Is progestin an independent risk factor for incident venous thromboembolism? A population-based case-control study. Thromb Res. 2010;126:373–78. [PMC free article] [PubMed] [Google Scholar]
23. Spack NP. Management of transgenderism. JAMA. 2013;309:478–84. [PubMed] [Google Scholar]
24. Irwig MS. Safety concerns regarding 5α reductase inhibitors for the treatment of androgenetic alopecia. Curr Opin Endocrinol Diabetes Obes. 2015;22:248–53. [PubMed] [Google Scholar]
25. Wylie K, Knudson G, Khan SI, Bonierbale MB, Watanyusakul S, Baral S. Serving transgender people: clinical care considerations and service delivery models in transgender health. Lancet. 2016;388:401–11. [PubMed] [Google Scholar]
26. Dekker MJ, Wierckx K, Van Caenegem E, et al. A European Network for the Investigation of Gender Incongruence: Endocrine Part. J Sex Med. 2016;13:994–99. [PubMed] [Google Scholar]
27. Asscheman H, T'Sjoen G, Lemaire A, et al. Venous thrombo-embolism as a complication of cross-sex hormone treatment of male-to-female transsexual subjects: a review. Andrologia. 2014;46:791–95. [PubMed] [Google Scholar]
28. Feldman J, Brown GR, Deutsch MB, et al. Priorities for transgender medical and healthcare research. Curr Opin Endocrinol Diabetes Obes. 2016;23:180–87. [PMC free article] [PubMed] [Google Scholar]
29. Gooren L, Lips P. Conjectures concerning cross-sex hormone treatment of aging transsexual persons. J Sex Med. 2014;11:2012–19. [PubMed] [Google Scholar]
30. Irwig MS. Transgender care by endocrinologists in the United States. Endocr Pract. 2016;22:832–36. [PubMed] [Google Scholar]
31. Safer JD, Coleman E, Feldman J, et al. Barriers to healthcare for transgender individuals. Curr Opin Endocrinol Diabetes Obes. 2016;23:168–71. [PMC free article] [PubMed] [Google Scholar]
32. Mepham N, Bouman WP, Arcelus J, Hayter M, Wylie KR. People with gender dysphoria who self-prescribe cross-sex hormones: prevalence, sources, and side effects knowledge. J Sex Med. 2014;11:2995–3001. [PubMed] [Google Scholar]
33. Rotondi NK, Bauer GR, Scanlon K, Kaay M, Travers R, Travers A. Nonprescribed hormone use and self-performed surgeries: "do-it-yourself" transitions in transgender communities in Ontario, Canada. Am J Public Health. 2013;103:1830–36. [PMC free article] [PubMed] [Google Scholar]
34. Meyer WJ, 3rd, Webb A, Stuart CA, Finkelstein JW, Lawrence B, Walker PA. Physical and hormonal evaluation of transsexual patients: a longitudinal study. Arch Sex Behav. 1986;15:121–38. [PubMed] [Google Scholar]
35. Giltay EJ, Gooren LJ. Effects of sex steroid deprivation/administration on hair growth and skin sebum production in transsexual males and females. J Clin Endocrinol Metab. 2000;85:2913–21. [PubMed] [Google Scholar]
36. Wierckx K, Van Caenegem E, Schreiner T, et al. Cross-sex hormone therapy in trans persons is safe and effective at short-time follow-up: results from the European network for the investigation of gender incongruence. Sex Med. 2014;11:1999–011. [PubMed] [Google Scholar]
37. Giltay EJ, Elbers JM, Gooren LJ, et al. Visceral fat accumulation is an important determinant of PAI-1 levels in young, nonobese men and women: modulation by cross-sex hormone administration. Arterioscler Thromb Vasc Biol. 1998;18:1716–22. [PubMed] [Google Scholar]
38. Elbers JM, Giltay EJ, Teerlink T, et al. Effects of sex steroids on components of the insulin resistance syndrome in transsexual subjects. Clin Endocrinol (Oxf) 2003;58:562–71. [PubMed] [Google Scholar]
39. Wierckx K, Gooren L, T'Sjoen G. Clinical review: breast development in trans women receiving cross-sex hormones. J Sex Med. 2014;11:1240–47. [PubMed] [Google Scholar]
40. Seal LJ, Franklin S, Richards C, Shishkareva A, Sinclaire C, Barrett J. Predictive markers for mammoplasty and a comparison of side effect profiles in transwomen taking various hormonal regimens. J Clin Endocrinol Metab. 2012;97:4422–28. [PubMed] [Google Scholar]
41. Thornton MJ. Human skin: a mirror for estrogen action? Menopause. 2016;23:119–20. [PubMed] [Google Scholar]
42. Weinand JD, Safer JD. Hormone therapy in transgender adults is safe with provider supervision; a review of hormone therapy sequelae for transgender individuals. J Clin Transl Endocrinol. 2015;2:55–60. [PMC free article] [PubMed] [Google Scholar]
43. Rosendaal FR, Van Hylckama Vlieg A, Tanis BC, Helmerhorst FM. Estrogens, progestogens and thrombosis. J Thromb Haemost. 2003;1:1371–80. [PubMed] [Google Scholar]
44. Beckman MG, Hooper WC, Critchley SE, Ortel TL. Venous thromboembolism: a public health concern. Am J Prev Med. 2010;38(suppl 4):S495–501. [PubMed] [Google Scholar]
45. Bell EJ, Lutsey PL, Basu S, et al. Lifetime risk of venous thromboembolism in two cohort studies. Am J Med. 2016;129:339, e19–26. [PMC free article] [PubMed] [Google Scholar]
46. Sandset PM. Mechanisms of hormonal therapy related thrombosis. Thromb Res. 2013;131(suppl 1):S4–7. [PubMed] [Google Scholar]
47. Shatzell JJ, Connelly KJ, DeLoughery TG. Thrombotic issues in transgender medicine: a review. Am J Hematol. doi: 10.1002/ajh.24593. published online Oct 25. [PubMed] [CrossRef] [Google Scholar]
48. van Kesteren PJ, Asscheman H, Megens JA, Gooren LJ. Mortality and morbidity in transsexual subjects treated with cross-sex hormones. Clin Endocrinol (Oxf) 1997;47:337–42. [PubMed] [Google Scholar]
49. Gooren LJ, Giltay EJ, Bunck MC. Long-term treatment of transsexuals with cross-sex hormones: extensive personal experience. J Clin Endocrinol Metab. 2008;93:19–25. [PubMed] [Google Scholar]
50. Ott J, Kaufmann U, Bentz EK, Huber JC, Tempfer CB. Incidence of thrombophilia and venous thrombosis in transsexuals under cross-sex hormone therapy. Fertil Steril. 2010;93:1267–72. [PubMed] [Google Scholar]
51. Dittrich R, Binder H, Cupisti S, Hoffmann I, Beckmann MW, Mueller A. Endocrine treatment of male-to-female transsexuals using gonadotropin-releasing hormone agonist. Exp Clin Endocrinol Diabetes. 2005;113:586–92. [PubMed] [Google Scholar]
52. Wierckx K, Mueller S, Weyers S, et al. Long-term evaluation of cross-sex hormone treatment in transsexual persons. J Sex Med. 2012;9:2641–51. [PubMed] [Google Scholar]
53. Canonico M, Plu-Bureau G, Lowe GD, Scarabin PY. Hormone replacement therapy and risk of venous thromboembolism in postmenopausal women: systematic review and meta-analysis. BMJ. 2008;336:1227–31. [PMC free article] [PubMed] [Google Scholar]
54. Ribeiro DD, Lijfering WM, Rosendaal FR, Cannegieter SC. Risk of venous thrombosis in persons with increased body mass index and interactions with other genetic and acquired risk factors. J Thromb Haemost. 2016;14:1572–78. [PubMed] [Google Scholar]
55. Cauley JA. Estrogen and bone health in men and women. Steroids. 2015;99(part A):11–15. [PubMed] [Google Scholar]
56. van Kesteren P, Lips P, Gooren LJ, Asscheman H, Megens J. Long-term follow-up of bone mineral density and bone metabolism in transsexuals treated with cross-sex hormones. Clin Endocrinol (Oxf) 1998;48:347–54. [PubMed] [Google Scholar]
57. Van Caenegem E, Taes Y, Wierckx K, et al. Low bone mass is prevalent in male-to-female transsexual persons before the start of cross-sex hormonal therapy and gonadectomy. Bone. 2013;54:92–97. [PubMed] [Google Scholar]
58. Van Caenegem E, Wierckx K, Taes Y, et al. Preservation of volumetric bone density and geometry in trans women during cross-sex hormonal therapy: a prospective observational study. Osteoporos Int. 2015;26:35–47. [PubMed] [Google Scholar]
59. Fischer EM, Patsch J, Muschitz C, Becker S, Resch H. Severe osteoporosis with multiple vertebral fractures after gender reassignment therapy—is it male or female osteoporosis? Gynecol Endocrinol. 2011;27:341–44. [PubMed] [Google Scholar]
60. Asscheman H, Gooren LJ, Eklund PL. Mortality and morbidity in transsexual patients with cross-gender hormone treatment. Metabolism. 1989;38:869–73. [PubMed] [Google Scholar]
61. Roberts T, Kraft C, French D, et al. Interpreting laboratory results in transgender patients on hormone therapy. Am J Med. 2014;127:159–62. [PubMed] [Google Scholar]
62. Rossouw JE, Cushman M, Greenland P, et al. Inflammatory, lipid, thrombotic, and genetic markers of coronary heart disease risk in the Women's Health Initiative trials of hormone therapy. Arch Intern Med. 2008;168:2245–53. [PMC free article] [PubMed] [Google Scholar]
63. Miller VT, LaRosa J, Barnabei V, et al. Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women. The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial. JAMA. 1995;273:199–208. [PubMed] [Google Scholar]
64. Berenson AB, Rahman M, Wilkinson G. Effect of injectable and oral contraceptives on serum lipids. Obstet Gynecol. 2009;114:786–94. [PMC free article] [PubMed] [Google Scholar]
65. Ott J, Aust S, Promberger R, Huber JC, Kaufmann U. Cross-sex hormone therapy alters the serum lipid profile: a retrospective cohort study in 169 transsexuals. J Sex Med. 2011;8:2361–69. [PubMed] [Google Scholar]
66. Maraka S, Ospina NS, Rodriguez-Gutierrez R, et al. Effect of sex steroids on lipids, venous thromboembolism, cardiovascular disease and mortality in transgender individuals: a systematic review and meta-analysis. Endocrine Society Annual Meeting 2016; Boston, MA, USA. April 1–4, 2016; FRI–136. [Google Scholar]
67. Dhejne C, Van Vlerken R, Heylens G, Arcelus J. Mental health and gender dysphoria: a review of the literature. Int Rev Psychiatry. 2016;28:44–57. [PubMed] [Google Scholar]
68. Gorin-Lazard A, Baumstarck K, Boyer L, et al. Hormonal therapy is associated with better self-esteem, mood, and quality of life in transsexuals. J Nerv Ment Dis. 2013;201:996–1000. [PubMed] [Google Scholar]
69. Gómez-Gil E, Zubiaurre-Elorza L, Esteva I, et al. Hormone-treated transsexuals report less social distress, anxiety and depression. Psychoneuroendocrinology. 2012;37:662–70. [PubMed] [Google Scholar]
70. Gorin-Lazard A, Baumstarck K, Boyer L, et al. Is hormonal therapy associated with better quality of life in transsexuals? A cross-sectional study. J Sex Med. 2012;9:531–41. [PubMed] [Google Scholar]
71. White Hughto JM, Reisner SL. A systematic review of the effects of hormone therapy on psychological functioning and quality of life in transgender individuals. Transgend Health. 2016;1:21–31. [PMC free article] [PubMed] [Google Scholar]
72. Murad MH, Elamin MB, Garcia MZ, et al. Hormonal therapy and sex reassignment: a systematic review and meta-analysis of quality of life and psychosocial outcomes. Clin Endocrinol (Oxf) 2010;72:214–31. [PubMed] [Google Scholar]
73. Blosnich JR, Brown GR, Wojcio S, Jones KT, Bossarte RM. Mortality among veterans with transgender-related diagnoses in the Veterans Health Administration, FY2000–2009. LGBT Health. 2014;1:269–76. [PubMed] [Google Scholar]
74. Guzmán-Parra J, Sánchez-Álvarez N, de Diego-Otero Y, et al. Sociodemographic characteristics and psychological adjustment among transsexuals in Spain. Arch Sex Behav. 2016;45:587–96. [PubMed] [Google Scholar]
75. Dhejne C, Lichtenstein P, Boman M, Johansson AL, Långström N, Landén M. Long-term follow-up of transsexual persons undergoing sex reassignment surgery: cohort study in Sweden. PLoS One. 2011;6:e16885. [PMC free article] [PubMed] [Google Scholar]
76. Asscheman H, Giltay EJ, Megens JA, de Ronde WP, van Trotsenburg MA, Gooren LJ. A long-term follow-up study of mortality in transsexuals receiving treatment with cross-sex hormones. Eur J Endocrinol. 2011;164:635–42. [PubMed] [Google Scholar]
77. CDC. Injury prevention and control: data & statistics (WISQARSTM): fatal injury reports, national and regional, 1999–2010, 2013. US Centers for Disease Control and Prevention; 2014. [accessed Dec 12, 2013]. www.cdc.gov/injury/wisqars/index.html. [Google Scholar]
78. Ilgen MA, Bohnert AS, Ignacio RV, et al. Psychiatric diagnoses and risk of suicide in veterans. Arch Gen Psychiatry. 2010;67:1152–58. [PubMed] [Google Scholar]
79. Gooren L, Bowers M, Lips P, Konings IR. Five new cases of breast cancer in transsexual persons. Andrologia. 2015;47:1202–05. [PubMed] [Google Scholar]
80. Brown GR, Jones KT. Incidence of breast cancer in a cohort of 5 135 transgender veterans. Breast Cancer Res Treat. 2015;149:191–98. [PubMed] [Google Scholar]
81. Maglione KD, Margolies L, Jaffer S, et al. Breast cancer in male-to-female transsexuals: use of breast imaging for detection. AJR Am J Roentgenol. 2014;203:W735–40. [PubMed] [Google Scholar]
82. Turo R, Jallad S, Prescott S, Cross WR. Metastatic prostate cancer in transsexual diagnosed after three decades of estrogen therapy. Can Urol Assoc J. 2013;7:E544–46. [PMC free article] [PubMed] [Google Scholar]
83. Gooren L, Morgentaler A. Prostate cancer incidence in orchidectomised male-to-female transsexual persons treated with oestrogens. Andrologia. 2014;46:1156–60. [PubMed] [Google Scholar]
84. Horbach SE, Bouman MB, Smit JM, Özer M, Buncamper ME, Mullender MG. Outcome of vaginoplasty in male-to-female transgenders: a systematic review of surgical techniques. J Sex Med. 2015;12:1499–512. [PubMed] [Google Scholar]
85. Weigert R, Frison E, Sessiecq Q, Al Mutairi K, Casoli V. Patient satisfaction with breasts and psychosocial, sexual, and physical well-being after breast augmentation in male-to-female transsexuals. Plast Reconstr Surg. 2013;132:1421–29. [PubMed] [Google Scholar]
86. Wolfort FG, Dejerine ES, Ramos DJ, Parry RG. Chondrolaryngoplasty for appearance. Plast Reconstr Surg. 1990;86:464–69. [PubMed] [Google Scholar]
87. Altman K. Facial feminization surgery: current state of the art. Int J Oral Maxillofac Surg. 2012;41:885–94. [PubMed] [Google Scholar]
88. Thomas JP, Macmillan C. Feminization laryngoplasty: assessment of surgical pitch elevation. Eur Arch Otorhinolaryngol. 2013;270:2695–700. [PubMed] [Google Scholar]
89. Davies S, Papp VG, Antoni C. Voice and communication change for gender nonconforming individuals: giving voice to the person inside. Int J Transgend. 2015;16:117–59. [Google Scholar]
90. Sieffert MR, Fox JP, Abbott LE, Johnson RM. Obesity is associated with increased health care charges in patients undergoing outpatient plastic surgery. Plast Reconstr Surg. 2015;135:1396–404. [PubMed] [Google Scholar]
91. De Roo C, Tilleman K, T'Sjoen G, De Sutter P. Fertility options in transgender people. Int Rev Psychiatry. 2016;28:112–19. [PubMed] [Google Scholar]
92. T'Sjoen G, Van Caenegem E, Wierckx K. Transgenderism and reproduction. Curr Opin Endocrinol Diabetes Obes. 2013;20:575–79. [PubMed] [Google Scholar]
93. Hamada A, Kingsberg S, Wierckx K, et al. Semen characteristics of transwomen referred for sperm banking before sex transition: a case series. Andrologia. 2015;47:832–38. [PubMed] [Google Scholar]
94. Richards C, Seal L. Trans people's reproductive options and outcomes. J Fam Plann Reprod Health Care. 2014;40:245–47. [PubMed] [Google Scholar]
95. Ossewaarde ME, Bots ML, Verbeek AL, et al. Age at menopause, cause-specific mortality and total life expectancy. Epidemiology. 2005;16:556–62. [PubMed] [Google Scholar]
96. Chlebowski RT, Hendrix SL, Langer RD, et al. for the WHI Investigators. Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women: the Women's Health Initiative randomized trial. JAMA. 2003;289:3243–53. [PubMed] [Google Scholar]
97. Wassertheil-Smoller S, Hendrix SL, Limacher M, et al. for the WHI Investigators. Effect of estrogen plus progestin on stroke in postmenopausal women: the Women's Health Initiative: a randomized trial. JAMA. 2003;289:2673–84. [PubMed] [Google Scholar]
98. Women's Health Initiative Steering Committee. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial. JAMA. 2004;291:1701–12. [PubMed] [Google Scholar]
99. Reisner SL, Deutsch MB, Bhasin S, et al. Advancing methods for US transgender health research. Curr Opin Endocrinol Diabetes Obes. 2016;23:198–207. [PMC free article] [PubMed] [Google Scholar]
Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5366074/
0 Response to "Shoud I Continue to Take Antiandrogens After Srs"
Post a Comment