|
Minnesota
Medicine
Published monthly by the Minnesota
Medical Association
July 2003/Volume 86
Transgender Health
by Jamie Feldman M.D., Ph.D., and Walter
Bockting, Ph.D.
Abstract
Transgender persons represent an underserved
community in need of sensitive, comprehensive health care. This
article presents a literature-based review of the health needs of
the transgender patient. Physicians, whether or not they choose to
provide hormone therapy, will likely encounter patients with gender
identity issues at some point in their practice. A transgender
health assessment should involve recognition of possible gender
identity disorder, history-taking with respect to prior and current
use of hormones or surgical interventions, as well as general
physical, mental, and sexual health histories. Physical exam and
screening tests need to be based on the organ systems present rather
than the perceived gender of the patient. Physicians should be aware
of common hormone regimens and their associated risks. Finally,
patients best explore transgender issues in a setting of respect and
trust, in which confidentiality concerns are addressed, and clinic
staff are educated about transgender issues.
Individuals who assume the social and/or physical characteristics
of the other gender have been designated by a variety of terms, such
as “transvestite” or “transsexual.” Recently, the term “transgender”
has been used to broadly describe people who transcend the
conventional boundaries of gender, irrespective of their physical
status or sexual orientation. Transgender persons range from those
who cross-dress to those who have undergone sex reassignment surgery
(see
Table 1). While definitive data on the number of transgender
persons are lacking, particularly in the United States,
international estimates are 1 male-to-female transsexual per 11,900
persons, and 1 per 30,400 persons for female-to-male transsexuals.
People with other transgender identities, such as bigender persons,
and drag kings and queens, appear to collectively outnumber
transsexuals.1 Although the number of transgender persons in
Minnesota is unknown, the prevalence may be greater than average
because of the availability of transgender-appropriate health care
in the Twin Cities. Transgender persons can be found in small
communities as well as major urban centers, but those in small towns
or rural areas may keep their identities secret because of fear of
being stigmatized.
The social stigmatization of transgender identity and behavior
leads many transgender individuals to maintain a traditional gender
role while keeping their transgender identity closeted. Individuals
may be uncomfortable with their bodies and lack access to sensitive
and knowledgeable providers; this can result in their avoiding
medical care.2,3 Many do not have a primary care physician nor
access to preventive health services. An estimated 30% to 40% of
transgender persons in the United States do not have a regular
physician and often rely on urgent care and emergency room
physicians for their immediate health care needs.4,5 A Minnesota
study of transgender health seminar participants found that 15%
lacked health insurance and 45% had not informed their primary care
doctor of their transgender identity.6 Transgender patients are a
medically underserved population, presenting both challenges and
rewards for the physicians who care for them.
Transgender-Specific Health Issues
Transgender health care involves addressing both general medical
conditions and concerns related to cross-gender hormone therapy.
Because transgender persons often do not have a primary care
physician, many may present with poorly controlled conditions, such
as hypertension and diabetes. In addition, because of fear of
revealing transgender status and a perception that they are not at
risk, they may not be receiving regular screening for certain
cancers, including breast or prostate cancer. The use of feminizing
or masculinizing hormones means that physicians need to pay
particular attention to cardiovascular and other risks factors and
coordinate care with the hormone provider; the details and risks of
these hormones are described in a separate section. Mental health
care is also an important component of treating the transgender
patient.
Presentation
The transgender patient may present in a variety of ways. The
“closeted” transgender patient may reveal cross-dressing behavior or
avoidance of elements of the physical exam, such as pelvic or
testicular exams. A diagnosis of gender identity disorder (GID) may
be appropriate in patients who exhibit distress regarding their
bodies, particularly about primary or secondary sex characteristics.
GID is characterized by a strong and persistent cross-gender
identification, accompanied by persistent discomfort with their sex
or sense of inappropriateness in the gender role of that
sex.7
Although GID may manifest in childhood, male-to-female
transgender patients tend to seek psychological or medical
intervention in their mid-thirties to fifties,8 while female-to-male
patients present in their late teens to early thirties. As the
transgender population is becoming more visible, however, younger
patients, including children and adolescents, are presenting with
transgender concerns.
Most transgender patients are open about their identity, although
at clinic visits they may appear in clothes, cosmetics, and
hairstyles that conform to their birth sex. Transgender patients who
are making the transition to living in the desired gender role may
present with some elements of each gender. Patients may also vary
their presentation from visit to visit. Patients often use 2 names:
a birth name and a chosen name that they use when they are
presenting in the desired gender role. Although multiple names can
pose a problem for clinic records, they represent a vital part of a
transgender patient’s identity and should be accommodated whenever
possible.
Patients best explore transgender issues in a setting of respect
and trust. This requires using the appropriate names and pronouns,
reassuring the patient about confidentiality, educating clinic staff
and colleagues regarding transgender issues, and respecting the
patient’s wishes, whenever possible, regarding potentially sensitive
physical exams and tests (such as pelvic ultrasounds or mammograms).
With most patients, open and caring communication is all that is
required.
Health History
Transsexuals and other transgender persons often utilize hormonal
or surgical interventions to bring their bodies into greater
congruence with their gender identity.9,10 Thus, a thorough history
of transgender-specific interventions is essential. (For many
nontranssexual transgender patients, hormones and surgery are less
of a concern, and the portions of the history related to hormone use
will be brief.) Elements of a transgender-specific history should
include the following questions:
1. Have you undergone sex reassignment surgery or other
feminizing/masculinizing procedures? If not, do you plan to pursue
surgery in the future?
2. Are you currently on cross-gender
hormones? Which ones and for how long? Have you had any
complications or concerns? Have you used hormones in the past? If
not, do you plan to pursue hormone therapy in the
future?
3. Are you seeing a therapist? Does she or he
specialize in gender and/or sexual health issues?
Medically unsupervised use of hormones is common among
transgender patients who have limited access to care.11,12 Patients
may borrow hormones from friends or buy them on the black market.
Needle sharing is not uncommon and should be asked about.
Increasingly, transgender persons are purchasing hormones over the
Internet, usually from foreign suppliers and with little or no
physician involvement. Physicians should also inquire about “herbal
hormones”—phytoestrogens or androgen-like compounds sold as dietary
supplements.
General Health Maintenance
Health maintenance for transgender patients should be based on
age, family and personal health risk factors, and the organ systems
present. Physical exams should be structured based on the organs
present rather than the perceived gender of the patient. Transgender
persons who have undergone sex reassignment surgery are often
unaware of residual breast or prostate tissue, and this can lead to
diagnostic delay.13,14 Because prostate tissue remains after sex
reassignment surgery, prostate exams should be performed in
postoperative male-to-female patients; a few cases of prostate
cancer have been reported in such patients.15,16 If there is any
significant breast tissue, the patient needs routine breast exams.
This includes female-to-male patients who have residual tissue
postmastectomy. If the uterus and cervix are present, pelvic exams
and Pap smears need to be done on a regular basis. In female-to-male
patients who have not had penetrative vaginal intercourse, these may
be deferred. If they are on testosterone therapy, the vaginal mucosa
may become atrophic, resulting in painful pelvic examinations. Using
the smallest speculum with generous lubricant is helpful, along with
a 1-finger bimanual technique, if needed. If the patient is at
otherwise low risk for cervical cancer, Pap smears can be done every
3 years. Physicians should be alert for the signs and symptoms of
polycystic ovarian syndrome, as an increased incidence has been
noted among female-to-male transgender patients.17
Certain health maintenance measures take on added importance in
the transgender patient. Smoking cessation minimizes many risks
associated with both masculinizing and feminizing hormone therapy
and should be aggressively pursued. Hepatitis B vaccination should
be offered to all sexually active patients. All patients, especially
those on hormone therapy, benefit from a program of aerobic and
weight-bearing exercise to minimize weight gain and maximize bone
density. Calcium supplementation may also be helpful for patients
transitioning between genders. For patients at increased
cardiovascular risk, the primary care provider needs to work with
the hormone provider in order to minimize hormone doses where
possible and implement aggressive lipid-lowering therapies when
indicated, including a low-fat, low-cholesterol diet. Careful
monitoring of blood pressure and use of appropriate antihypertensive
agents can also minimize risk of stroke and coronary artery disease.
A daily aspirin is indicated in those patients at increased
cardiovascular risk and patients older than 40 or smokers on
estrogen therapy.
The patient’s hormonal status determines which screening or
monitoring tests are needed. If the patient is not on hormones, then
screening is equivalent to that for nontransgender patients of the
same age and natal sex. If the patient is on hormonal therapy,
especially the higher doses used prior to reassignment surgery, the
suggested labs noted in Table
2 should be performed. If another physician is prescribing the
hormones, that physician should monitor the lab work. Occasionally,
however, insurance will not cover lab work done outside the primary
care clinic, and the primary care physician should work closely with
the hormone provider to determine appropriate tests and
schedule.
Mental Health
Mental health maintenance for the transgender patient is
particularly important and should include periodic depression
screening and helping the patient connect with transgender support
services. Although rigorous studies are limited, one retrospective
study suggests that transgender patients do not appear to have
higher rates of mental illness overall compared with the general
population.18 However, depression is not uncommon among transgender
patients. Of the respondents in a San Francisco study, 30% to 40%
reported taking medication for a mental health condition, and 32%
reported prior suicide attempts.5 Sixty-two percent of respondents
in a Minnesota survey reported having seen a mental health counselor
in the previous 3 months.7 Rates of chemical dependency among
transgender persons are not well studied but may be higher than that
of the general population, due to self-medication for depression as
well as high rates of exposure to discrimination and abuse.
Physicians need to screen for these conditions routinely and refer
to transgender-sensitive treatment providers as needed.
Sexual Health
Sexual orientation is distinct from gender identity, and
transgender patients may be heterosexual, bisexual, gay, or lesbian
in their orientation. HIV and STDs, including hepatitis B and C,
disproportionately affect the transgender community.3,11,19
High-risk sexual behaviors, such as having multiple partners,
engaging in sex work, and not using condoms regularly, account for
much of the increased prevalence.20 Sharing needles used to inject
hormones is a contributing factor.
Transgender Hormone Therapy
Transgender hormone therapy is a medical intervention strongly
desired by many transgender persons. In addition to the physical
changes hormone therapy induces, the act of using the hormones is
itself an affirmation of gender identity.2,9,10 Studies of
presurgical transsexuals indicate improved psychological adjustment
and quality of life with hormone therapy.21,22 Transgender patients
desiring hormone therapy may ask their primary care physician to
provide this treatment. Currently, no standardized training in
transgender hormone therapy is available for physicians; both
primary care and specialist physicians choose to provide this care.
Regardless of specialty, it is strongly recommended that the hormone
provider and patient work with a therapist trained in treating
gender identity issues because the process of making the transition
to a desired gender involves profound mental, social, emotional,
economic, and legal changes in a patient’s life. Hormone therapy can
be both an enriching and complicating element in this transition.
Thus, the advantages of working with a specialized gender team or in
close consultation with a mental health specialist cannot be
overemphasized. These professionals can provide a wide variety of
resources to assist the transgender patient (and hormone provider)
in this complex process. One important resource is the Program in
Human Sexuality at the University of Minnesota, which provides
comprehensive, interdisciplinary care and consultation in the area
of gender identity and transgender health.
Any physician interested in providing transgender hormone therapy
should be familiar with the standards of care developed by the Harry
Benjamin International Gender Dysphoria Association. The standards,
which are available at www.hbigda.org/soc.html, outline
recommendations for treating gender identity disorder, including
hormonal and surgical interventions.23 They recommend that, before
receiving hormone therapy, the patient be at least 18 years old,
understands what hormones medically can and cannot do, understands
the social benefits and risks, and undergoes at least 3 months of
therapy and/or at least 3 months of a “real-life experience.” This
experience involves living full time and continually in the desired
gender role, including dressing and interacting socially at home and
work as the desired gender. A letter of support from a mental health
specialist in gender identity is also required before initiating
hormone therapy.
Masculinizing and feminizing medications have the potential for
numerous drug interactions (see below), and the physician needs to
be cognizant of these before prescribing other medications. Although
a primary care provider need not be conversant with the details of
masculinizing and feminizing hormone therapy, some familiarity with
the medications, usual dosages, and side effects is helpful.
Feminizing regimens generally include some form of estrogen plus a
testosterone-blocking agent, usually spironolactone and/or
finasteride. Some regimens may include a progestin as well. Estrogen
may be given in oral, patch, or injectable form, and examples of
common dosages and major side effects are presented in Table
3. Masculinization regimens usually involve testosterone, which
comes in injectable, patch, and topical gel forms. Examples of
common dosages and major side effects are listed in Table
4.
Medical Conditions Associated with Transgender Hormone
Therapy
Transgender patients on hormones are at higher risk for a number
of acute and chronic diseases, including diabetes, cardiovascular
disease, thromboembolic events, and liver abnormalities. Patients
who have these conditions prior to hormone therapy, or who have
other risk factors for these conditions will need closer follow-up
once they begin hormones. Studies of the long-term effects of
transgender hormone therapy are limited; however, research on the
effects of hormones in other settings can be informative. However,
applying research involving oral contraceptives and postmenopausal
hormone replacement to a transgender population may be limited by
differences in drug dosages, age of the population, and the levels
of endogenous hormones.
Type 2 Diabetes Mellitus
Estrogen is known to impair glucose tolerance, and there have
been case reports of new-onset type 2 diabetes among male-to-female
transgender patients on estrogen.24 Studies of women on oral
contraceptives and hormone replacement therapy have shown decreased
glucose tolerance but no increased incidence of diabetes.25-27
However, these data may not apply to biologically male transgender
patients who have other risk factors for type 2 diabetes. A study of
glucose tolerance among hyperandrogenic women on oral contraceptives
demonstrated a significant reduction in glucose tolerance and the
development of diabetes in 2 of the 16 women,28 suggesting that the
presence of endogenous androgens plays a role in glucose metabolism.
In addition, patients on feminizing hormones often gain weight and
body fat, which may contribute to glucose intolerance.
Cardiovascular Disease
The effects of feminizing hormones on cardiovascular disease are
not well characterized. There are several case reports of myocardial
infarction and ischemic stroke among male-to-female transgender
persons on hormone therapy.29-31 This would be consistent with the
increased risk noted among women on oral contraceptives. However, a
retrospective study of 816 male-to-female patients in the
Netherlands found no increase compared with rates in the general
population.32 Studies in both women and male-to-female transgender
patients on estrogen therapy demonstrate increased HDL and decreased
LDL cholesterol.33,34 Prospective studies of hormone replacement
among postmenopausal women, however, have indicated no benefit and a
probable increased risk for cardiovascular events with combined
estrogen and progesterone therapy.35,36 Oral estrogen therapy, both
in postmenopausal women and male-to-female transgender patients, is
known to increase triglycerides and has precipitated pancreatitis in
several cases.36 Exogenous estrogen can increase blood pressure, and
transgender patients at risk may develop overt
hypertension.
Patients on masculinizing regimens experience increases in LDL
and decreases in HDL cholesterol that put them at increased risk of
atherosclerotic disease.38,39 Once more, the incidence of
cardiovascular events among female-to-male transgender persons on
testosterone therapy has not been well characterized; however, no
extra morbidity was seen in the Netherlands study.32 Transgender
patients on testosterone may be at higher risk of hypertension as
well. Strong family history of cardiovascular disease, smoking,
obesity, and hypertension increase the risks ordinarily associated
with cross-gender hormone therapy.
Venous Thromboembolic Diease
Patients on feminizing hormones are at a significantly increased
risk of thromboembolic events, including pulmonary embolism. A 1989
retrospective study demonstrated a 45-fold increase in
thromboembolic events.40 The risk appears to be higher among
patients older than 40 (12% compared with 2% incidence), patients on
oral estrogen, and smokers—which is consistent with findings in
women on oral contraceptives. This risk appears to be lowered with
the use of transdermal estrogen.32 It is vital to screen transgender
patients who are on hormones for a personal or family history of
clotting disorders as well as educate them regarding the signs and
symptoms of deep venous thrombosis and pulmonary embolus. Smoking
cessation and daily aspirin therapy may reduce this risk.
Liver Abnormalities
Mild elevation of liver enzymes is not unusual with feminizing
hormones but rarely results in clinical hepatitis or hepatic
adenoma.41,42 In the United States, testosterone is administered in
transdermal or intramuscular routes primarily, with minimal effect
on the liver. Cholelithiasis, however, is more common among patients
on estrogen, consistent with findings in nontransgender women on
oral contraceptives or hormone replacement therapy.32,42
Hyperprolactinemia
Exogenous estrogen is known to increase serum prolactin levels,
and modest levels of hyperprolactinemia are common among transgender
patients on feminizing therapy. Higher elevations are associated
with higher estrogen dose and advanced age.43 Most cases remit when
the estrogen dose is lowered. Although there are reports of
pituitary enlargement and prolactinomas among male-to-female
patients,44 these are relatively rare. Except for galactorrhea, few
patients experience any symptoms related to high prolactin
levels.
Osteoporosis
The effect of cross-gender hormones on bone density is
controversial. Both estrogen and testosterone maintain bone density;
however, the transition to a testosterone-based system may not be
sufficient in female-to-male patients.45 Loss of density is likely
in those patients who are not fully adherent to hormone therapy,
those who have undergone reassignment surgery and discontinued
maintenance hormones, and female-to-male patients.46 Calcium
supplementation and weight-bearing exercise are indicated for all
transgender patients on hormones. Densitometry screening may be
indicated for patients at increased risk of osteoporosis.
Cancer
The cancer risks associated with cross-gender hormone therapy are
not well understood. Among female-to-males, the effects of
testosterone on breast cancer risk prior to mastectomy are unknown.
Even with mastectomy, some patients elect to leave a small amount of
breast tissue to improve the chest contour. These patients may
continue to need mammograms, although the interval of screening is
entirely unknown.14 Preoperative female-to-male patients may also be
at increased risk of ovarian cancer.47 Although there is no
recognized screening test for ovarian cancer, physicians should have
a low threshold for further evaluation of adnexal masses.
Androgen therapy causes significant atrophy in the cervical
epithelium, mimicking dysplasia on the Pap smear.48 However, these
changes are not well characterized in the literature, and colposcopy
may be indicated in patients at increased risk. For patients
otherwise at low risk of cervical cancer, ASCUS and low-grade SIL
Pap smears are unlikely to represent precancerous lesions. If the
patient has had little or no penetrative intercourse, the patient is
at low risk of developing cervical dysplasia, and frequent Pap
smears can be traumatic.
Although there does not appear to be an increased risk of
endometrial carcinoma among patients on masculinizing therapy,
dysfunctional uterine bleeding is not uncommon and should be
evaluated with pelvic ultrasound or endometrial biopsy in patients
older than 35. The risk of other carcinomas in female-to-male
patients on testosterone therapy appears to be equivalent to that in
the nontransgendered population.
Male-to-female patients appear to be at low risk for breast
cancer despite long-term estrogen exposure, although there have been
several case reports in the literature.49-51 Recent evidence
suggests an increased risk among postmeno-pausal women on hormone
replacement therapy.36,52-54 I presently recommend yearly breast
exams and mammograms starting at age 40 for patients on hormones who
have even modest breast development. Mammograms and self-breast exam
also serve to support the transsexual patient’s female gender
identity. Cases of cancer in the neovagina of postoperative patients
have been reported, and persons at risk of HPV infection may benefit
from Pap smear screening.55 As noted earlier, prostate cancer has
been reported in both preoperative and postoperative transsexual
patients. Prostate cancer screening, including PSA testing, should
be discussed with all male-to-female patients age 50 and older.
Conclusion
Transgender persons represent an underserved community in need of
sensitive, comprehensive health care. Physicians, whether or not
they choose to provide hormone therapy, will likely encounter
patients with gender identity issues at some point in their
practice. A transgender health assessment should involve recognition
of possible gender identity disorder, prior and current use of
hormones or surgical interventions, as well as general physical,
mental, and sexual health histories. Physical exam and screening
tests need to be based on the organ systems present rather than the
perceived gender of the patient. Physicians should be aware of
common hormone regimens and their associated risks. Finally,
patients best explore transgender issues in a setting of respect and
trust, which requires using appropriate names and pronouns,
addressing confidentiality concerns, and educating clinic staff and
colleagues regarding transgender issues. A variety of resources are
available to assist physicians, patients, and their families in
addressing transgender issues (see resource list on p. 28). MM
Jamie Feldman is an assistant professor in the Department of
Family Practice and Community Health at the University of Minnesota
and is on the faculty of the Program in Human Sexuality. Walter
Bockting is an assistant professor in the Department of Family
Practice and Community Health at the University of Minnesota and
coordinates transgender services in the Program in Human
Sexuality.
Selected Transgender Resources for
Family Physicians
This list is not exhaustive; a comprehensive list is
available from the Harry Benjamin International Gender Dysphoria
Association.
Harry Benjamin International Gender Dysphoria
Association
Web site: www.hbigda.org
Bean Robinson,
Ph.D., executive director
1300 South Second Street, Suite
180
Minneapolis, MN 55454
612/625-1500
International Foundation for Gender
Education
Web site: www.ifge.org
P.O. Box
540229
Waltham, MA 02454-0229
781/894-8340
International Journal of Transgenderism
Web
site: www.symposion.com/ijt/
Gender Education and Advocacy
Web site:
www.gender.org
P.O. Box 33724
Decatur, GA
30033-0724
770/939-0244
Program in Human Sexuality/Center for Sexual
Health
University of Minnesota
Web site:
www.med.umn.edu/fp/phs/phsindex.htm
1300 South Second
Street
Minneapolis, MN 55454
612/625-1500
References
1. Bakker A, van Kesteren PJ, Gooren LJ, Bezemer PD. The
prevalence of transsexualism in The Netherlands. Acta Psychiatr
Scand. 1993;87:237-8.
2. Kammerer N, Mason T, Connors M. Transgender health and social
service needs in the context of HIV risk. Int J Transgenderism.
1999;3(1+2). Available at:
http://www.symposion.com/ijt/hiv_risk/kammerer.htm. Accessed June 5,
2003.
3. Clements K, Wilkinson W, Kitano K, Marx R. HIV prevention and
health service needs of the transgender community in San Francisco.
Int J Transgenderism. 1999;3:1-17. Available at:
http://www.symposion.com/ijt/hiv_risk/clements.htm. Accessed June 5,
2003.
4. Clements K, Katz M, Marx R. Transgender Community Health
Project: Descriptive Results. San Francisco, CA: San Francisco
Department of Public Health; 1999.
5. Xavier J. The Washington, D.C. transgender needs assessment
survey: final report for phase two. Washington, D.C.: Gender
Education and Advocacy; 2000.
6. Bockting WO. All Gender Health: HIV/STD prevention in the
context of transgender-specific, comprehensive sexuality education.
Presented at the Fifth International Congress on Crossdressing, Sex,
and Gender Issues. Philadelphia, PA, Oct. 1, 2000.
7. American Psychiatric Association. Diagnostic and statistical
manual of mental disorders. 4th ed. Washington, D.C.: American
Psychiatric Association; 1994.
8. Blanchard R. A structural equation model for age at clinical
presentation in nonhomosexual male gender dysphorics. Arch Sex
Behav. 1994;23:311-20.
9. Gay and Lesbian Medical Association and LGBT health experts.
Healthy People 2010 Companion Document for Lesbian, Gay, Bisexual
and Transgender (LGBT) Health. San Francisco, CA: Gay and Lesbian
Medical Association; 2001.
10. Bockting WO, Robinson BE, Rosser BR. Transgender HIV
prevention: a qualitative needs assessment. AIDS Care.
1998;10:505-25.
11. Hope-Mason T, Conners MM, Kammerer CA. Transgenders and HIV
Risks: Needs Assessment. Boston, MA: Department of Public Health
HIV/AIDS Bureau; 1995.
12. Dean L, Meyer I, Robinson K, et al. Lesbian, Gay, Bisexual,
and Transgender Health: Findings and Concerns. J Gay Lesbian Med
Assoc. 2000;4:102-51.
13.Green J. Utilization of health care among FTMs in the United
States. XVII Harry Benjamin International Gender Dysphoria
Association Symposium, Galveston, TX, Oct 31, 2001. Abstract
available at: http://www.symposion.com/ijt/hbigda/2001/07_green.htm.
Accessed June 5, 2003.
14. Eyler AE. FTM breast cancer: community awareness and
illustrative cases. XVIII Harry Benjamin International Gender
Dysphoria Association Sympo-sium, Galveston, TX, Oct 31, 2001.
Abstract available at:
http://www.symposion.com/ijt/hbigda/2001/41_eyler.htm. Accessed June
5, 2003.
15. Gooren LJ, Asscheman H, Newling D. Prostate cancer in the
male to female transsexual. Int J Transgenderism. 1997;1.
16. van Haarst EP, Newling DW, Gooren LJ, Asscheman H, Prenger
DM. Metastatic prostatic carcinoma in a male-to-female transsexual.
Br J Urol. 1998;81:776.
17. Bosinski HA, Peter M, Bonatz G, Arndt R, Heidenreich M,
Sippell WG, Wille R. A higher rate of hyperandrogenic disorders in
female-to-male transsexuals. Psychoneuroendocrinology.
1997;22:361-80.
18. Cole CM, O’Boyle M, Emory LE, Meyer WJ, 3rd. Comorbidity of
gender dysphoria and other major psychiatric diagnoses. Arch Sex
Behav. 1997;26:13-26.
19. Elifson KW, Boles J, Posey E, Sweat M, Darrow W, Elsea W.
Male transvestite prostitutes and HIV risk. Am J Public Health.
1993;83:260-2.
20. Sykes D. Transgendered people: An “invisible” population.
California HIV/AIDS Update. 1999;12:1-6.
21. Leavitt F, Berger JC, Hoeppner JA, Northrop G. Presurgical
adjustment in male transsexuals with and without hormonal treatment.
J Nerv Ment Dis. 1980;168:693-7.
22. Kuiper B, Cohen-Kettenis P. Sex reassignment surgery: a study
of 141 Dutch transsexuals. Arch Sex Behav. 1988;17:439-57.
23. Harry Benjamin International Gender Dysphoria Association
Sym-posium. The Standards of Care for Gender Identity Disorders. 6th
version. Dusseldorf, 2001. Available at
http://www.symposion.com/ijt/soc_2001/index.htm. Accessed June 17,
2003.
24. Feldman J. New onset of Type 2 Diabetes Mellitus with
feminizing hormone therapy: Case Series. Int J Transgenderism.
2002;6. Available at:
http://www.symposion.com/ijt/ijtvo06no02_01.htm. Accessed June 5,
2003.
25. Russell-Briefel R, Ezzati TM, Perlman JA, Murphy RS. Impaired
glucose tolerance in women using oral contraceptives: United States,
1976-1980. J Chronic Dis. 1987;40:3-11.
26 Rimm EB, Manson JE, Stampfer MJ, et al. Oral contraceptive use
and the risk of type 2 (non-insulin-dependent) diabetes mellitus in
a large prospective study of women. Diabetologia.
1992;35:967-72.
27. Manson JE, Rimm EB, Colditz GA, et al. A prospective study of
postmeno-pausal estrogen therapy and subsequent incidence of
non-insulin-dependent diabetes mellitus. Ann Epidemiol.
1992;2:665-73.
28. Nader S, Riad-Gabriel MG, Saad MF. The effect of a
desogestrel-containing oral contraceptive on glucose tolerance and
leptin concentrations in hyperandrogenic women. J Clin Endocrinol
Metab. 1997;82:3074-7.
29. Biller J, Saver JL. Ischemic cerebrovascular disease and
hormone therapy for infertility and transsexualism. Neurology.
1995;45:1611-3.
30. Fortin CJ, Klein T, Messmore HL, O’Connell JB. Myocardial
infarction and severe thromboembolic complications. As seen in an
estrogen-dependent transsexual. Arch Int Med. 1984;144:1082-3.
31. deMarinis M, Arnett EN. Cerebro-vascular occlusion in a
transsexual man taking mestranol. Arch Intern Med.
1978;138:1732-3.
32. van Kesteren PJ, Asscheman H, Megens JA, Gooren LJ. Mortality
and morbidity in transsexual subjects treated with cross-sex
hormones. Clin Endo-crinol. 1997;47:337-42.
33. Damewood MD, Bellantoni JJ, Bachorik PS, Kimball AW, Jr.,
Rock JA. Exogenous estrogen effect on lipid/lipoprotein cholesterol
in transsexual males. J Endocrinol Invest. 1989;12:449-54.
34. The Writing Group for the PEPI Trial. 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.
35. Grady D, Herrington D, Bittner V, et al. Cardiovascular
disease outcomes during 6.8 years of hormone therapy: Heart and
Estrogen/progestin Replacement Study follow-up (HERS II). JAMA.
2002;288:49-57.
36. Rossouw JE, Anderson GL, Prentice RL, et al. Risks and
benefits of estrogen plus progestin in healthy postmenopausal women:
principal results From the Women’s Health Initiative randomized
controlled trial. JAMA. 2002;288:321-33.
37. Glueck CJ, Lang J, Hamer T, Tracy T. Severe
hypertriglyceridemia and pancreatitis when estrogen replacement
therapy is given to hypertriglyceridemic women. J Lab Clin Med.
1994; 123:59-64.
38. Goh HH, Loke DF, Ratnam SS. The impact of long-term
testosterone replacement therapy on lipid and lipoprotein profiles
in women. Maturitas. 1995;21:65-70.
39. McCredie RJ, McCrohon JA, Turner L, Griffiths KA, Handelsman
DJ, Celermajer DS. Vascular reactivity is impaired in genetic
females taking high-dose androgens. J Am Coll Cardiol.
1998;32:1331-5.
40. Asscheman H, Gooren LJ, Eklund PL. Mortality and morbidity in
transsexual patients with cross-gender hormone treatment.
Metabolism. 1989;38:869-73.
41. Kirk S. Feminizing Hormonal Therapy for the Transgendered.
Pitts-burgh, PA: Together Lifeworks, 1999.
42. Futterweit W. Endocrine therapy of transsexualism and
potential complications of long-term treatment. Arch Sex Behav.
1998;27:209-26.
43. Asscheman H, Gooren LJ, Assies J, Smits JP, de S. Prolactin
levels and pituitary enlargement | 
