Gender Dysphoria 

Updated: Apr 24, 2019
Author: Mohammed A Memon, MD; Chief Editor: Glen L Xiong, MD 

Overview

Practice Essentials

Gender dysphoria is a diagnosis that refers to people whose gender at birth is contrary to the one they identify with. It is a product of highly complex genetic, neurodevelopmental, and psychological factors.

Glossary of terms

Transgender (adj.): an umbrella term for a person whose gender identity, gender expression or behavior does not conform to that typically associated with the sex to which they were assigned at birth. Many transgender people receive hormonal treatment and some undergo surgery to bring their bodies into alignment with their gender identity. Transgender people may have sexual orientation as straight, gay or bisexual.

Sexual orientation: refers to enduring physical, romantic and/or emotional attraction to another person.

Gender identity: a person's internal deeply held sense of their gender and refers to an individual's identification as male, female, some of both or occasionally neither male nor female. 

Transsexual: an individual who seeks, or has undergone, a social transition from male to female or female to male. This transition may or may not involve hormonal treatment and surgery. Many transgender people do not identify as transsexual and prefer to be called transgender. It is best to ask which term and pronouns (he or she, him or her) a person prefers. The term transgender should be used as an adjective, not as a noun, so it is preferable to use terms such as transgender people, or transgender men and transgender women. It is also worthy of note that transgender identity is not dependent upon physical appearance or medical procedures.

Gender non-conforming: when a person's gender identity, role or expression differs from the cultural norms prescribed for the people of a particular sex. 

Genderqueer: refers to a person who typically expresses a fluidity of gender and sometimes sexual orientation. They may express themselves as male or female and occasionally define their gender as neither male nor female. Some may not identify themselves as transgender.

Cross-dresser (formerly called transvestite): generally refers to a man who occasionally wears clothes of opposite sex, wears makeup and uses accessories associated with women. They typically identify themselves as heterosexual. Their expression of gender in this particular way is not done for entertainment purposes. The term "drag queens" generally refers to men who dress as women and "drag kings" refers to women who dress as men for the purpose of entertainment for media, bars, clubs, etc.

Diagnosis

According to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5),[1] for a person to be diagnosed with gender dysphoria, there must be a marked difference between the individual’s expressed/experienced gender and his or her assigned (natal) gender, and it must continue for at least 6 months. In children, the desire to be of the other gender must be present and verbalized. The condition must cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.

Not all transgender people experience dysphoria, and some controversy exists among the medical community regarding the necessity of the psychiatric diagnosis of gender dysphoria. Many transgender advocates believe that inclusion of this diagnosis increases awareness and helps advocate for health insurance that covers the medically necessary treatment recommended for transgender people. Being transgender is no longer classified as a mental illness by the World Health Organization. In the agency's 11th International Classification of Diseases (ICD) catalog,  "gender incongruence"—the organization's term for people whose gender identity is different from the gender they were assigned at birth—has been moved out of the mental disorders chapter and into the organization's sexual health chapter.[2]

Treatment

The World Professional Association for Transgender Health's (WPATH-SOC)[3]  standards of care are intended to be flexible in order to meet the diverse health care needs of transsexual, transgender, and gender non-conforming people. WPATH-SOC suggested general clinical guidelines for hormone therapy and surgical treatments for gender dysphoria that allow individual health professionals and programs to modify them according to the individual needs of persons with gender dysphoria.

Therapeutic approaches include:

  1. Changes in gender expression and role by living part time or full time in desired gender role
  2. Hormone therapy
  3. Sex change surgery
  4. Psychotherapy that includes individual, couple, family and group therapy

Psychological intervention may be beneficial. Individual treatment focuses on understanding and dealing with gender issues. The form of treatment that helps one person may not help other alleviating the symptoms of gender dysphoria. Group, marital, and family therapy can provide a helpful and supportive environment.

Hormone therapy may also be necessary. Agents that may be considered include luteinizing hormone–releasing hormone (LHRH) agonists, progestational compounds, spironolactone, flutamide, cyproterone acetate, ethinyl estradiol, conjugated estrogen, and testosterone cypionate.

Sexual reassignment surgery (SRS) may be appropriate for selected patients.

Background

Gender dysphoria is a diagnosis that refers to people whose gender at birth is contrary to the one they identify with. It constitutes a new diagnostic class in the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), replacing the DSM-IV diagnosis of gender identity disorder.[1]

The DSM-5 diagnostic criteria for gender dysphoria include strong and persistent cross-gender identification that extends beyond a desire for a perceived cultural advantage. Adolescents and adults may have a preoccupation with getting rid of primary and secondary sex characteristics, and they may believe that they were born as the wrong sex. People with gender dysphoria do not have a concurrent physical intersex condition. Patients report significant distress or impairment in social, occupational, or other important areas of functioning.

Diagnostic criteria (DSM-5)

Adolescents and adults

According to DSM-5, the first requirement for the diagnosis of gender dysphoria in adolescents and adults is a marked incongruence between the patient’s experienced or expressed gender and his or her assigned gender.[1] This incongruence must have lasted for at least 6 months and must include at least 2 of the following 6 criteria:

  • Marked incongruence between the patient’s experienced or expressed gender and his or her primary or secondary sex characteristics

  • Strong desire to be rid of his or her primary or secondary sex characteristics (or, in young adolescents, to prevent the development of the anticipated secondary characteristics)

  • Strong desire for the primary or secondary sex characteristics of the other gender

  • Strong desire to be of the other (or some alternative) gender

  • Strong desire to be treated as the other (or some alternative) gender

  • Strong conviction of having the typical feelings and reactions of the other (or some alternative) gender

The second requirement is that the condition be associated with clinically significant distress or impairment of social, occupational, or other important areas of functioning.

In addition, the clinician should specify whether the condition is occurring in conjunction with a disorder of sex development and, if so, should code that disorder as well.

The clinician may also specify whether the individual has made the transition to living in the desired gender on a full-time basis.

Children

The first requirement for the diagnosis of gender dysphoria in children is, again, a marked incongruence between the patient’s experienced or expressed gender and his or her assigned gender.[1] This incongruence must have lasted for at least 6 months and must include at least 6 of the following 8 criteria (with the first criterion being mandatory):

  • Strong desire to be of the other (or some alternative) gender or insistence that one already is

  • Strong preference for cross-dressing or simulating female attire (boys); strong preference for typical masculine clothing and resistance to typical feminine clothing (girls)

  • Strong preference for cross-gender roles in make-believe or fantasy play

  • Strong preference for the stereotypical toys, games, or pastimes of the other gender

  • Strong preference for playmates of the other gender

  • Strong rejection of typically masculine toys, games, and activities, with strong avoidance of rough play (boys); strong rejection of typically feminine toys, games, and activities (girls)

  • Strong dislike of one’s sexual anatomy

  • Strong desire for the primary or secondary sex characteristics that match one’s experienced gender

The second requirement is that the condition be associated with clinically significant distress or impairment of social, school, or other important areas of functioning.

In addition, the clinician should specify whether the condition is occurring in conjunction with a disorder of sex development and, if so, should code that disorder as well.

Etiology

Psychological factors

In a 1968 publication, rooted in psychoanalytic theory, Stoller described a typical background from which a male transsexual might emerge.[4]

In this scenario, a woman whose mother did not encourage her daughter’s femininity marries a passive man, for a relationship that is unsatisfactory for both but is often lasting.[4] This depressed woman has a male child. A blissful symbiosis is established between mother and son. The father does not try to break the symbiosis and tends to stay away from home. Excessive physical and emotional closeness to the mother for too long a time leads to feminine identification and behaviors that secretly please the mother, who reinforces them.

Stroller viewed this nonconflictual learning process as similar to imprinting. In contrast, he viewed homosexuality and transvestism as end results of defense against the trauma of dangerous and painful interpersonal relationships.

In a 1974 publication, Person and Ovesey postulated a different, yet still psychosocial, etiology that was based on a study of 10 primary transsexuals (individuals with gender dysphoria).[5]

Although all 10 subjects in the study envied girls and engaged in cross-dressing behavior, starting at age 3-10 years, none believed he was a girl, and 9 gave no history of feminine behavior.[5] They were loners, with few age mates of either sex, and they had feelings of anxiety, depression, and loneliness. They were asexual and loathed their male characteristics. Their wish to be female was based on a fantasy of symbiotic fusion with the mother as a way of dealing with extreme separation anxiety.

Stoller described the psychoanalytic etiology of female transsexualism as unclear but listed some preliminary findings, as follows:

  • Neither the mother nor the father of the girl has a gender disorder

  • The mother is unable to function in the first months or year of the daughter’s life, because of deep depression (or, in a minority of cases, paranoia or physical illness)

  • The child knows that the mother is present but beyond emotional reach

  • The father does not minister to his wife; rather, he has the daughter minister to her

  • The daughter is described as vigorous, ungraceful, and unattractive in infancy

  • The father engages the daughter in activities that interest him, thus promoting masculine behavior

  • By the age of 4-5 years, the daughter already yearns to have the anatomic insignias of maleness, a yearning born out of pain and conflict from premature maternal separation

It should be kept in mind that these ideas are preliminary postulates rather than established facts; confirming data are unavailable.

Retrospective studies in adult transsexuals have shown differences in recalled child-rearing patterns between transsexuals and normative groups. Male-to-female transsexuals characterized their fathers as less emotionally available, less warm, more rejecting, and overly controlling. Female-to-male transsexuals characterized both parents as more rejecting and less emotionally warm, but they characterized only their mothers, not their fathers, as overprotective.

It has been argued that the development of transsexualism is the “result of a non-conflictual process, where gender identity is precociously fixed [and] ... considered to be an entirely particular phenomenon, so that its aetiology must be clearly distinguished from both perversions and atypical sex change requests.”[6] Essentially, the boy has had a happy symbiosis with the mother and develops from early infancy an identity with the female gender, which the family adapts to and supports.[7, 8]

Biologic factors

Biomedical research into transsexualism has investigated several areas. Girls with congenital adrenal hyperplasia (CAH), a condition causing prenatal exposure to a relatively high level of androgens, have been examined to determine whether male gender identity develops even if XX-chromosome individuals are raised as females. A few such cases have been reported. In most cases, however, girls assigned and reared consistently as girls do not become transsexuals.

Transsexualism has not been observed in males or females exposed to progestogens in utero, which might have antiandrogenic or androgenic qualities, nor has it been found upon exposure to estrogenic drugs, such as diethylstilbestrol (DES). Nevertheless, some atypical aspects of gender role behavior have been observed.

In 1983, Dörner et al found that male-to-female transsexuals, like females, showed a rise in luteinizing hormone (LH) levels after estrogen stimulation as a consequence of prenatal exposure to imbalanced sex steroid levels[9] ; the opposite occurred in female-to-male transsexuals. However, other studies that used more rigorous endocrine methodologies were unable to replicate this study’s findings.

Several hypothalamic nuclei in humans have been reported to be sexually dimorphic with respect to size or shape, including the following:

  • A sexually dimorphic nucleus (SDN) of the preoptic area of the hypothalamus (SDN-POA61)

  • Two cell groups in the anterior hypothalamus (isonicotinic acid hydrazide [INAH]-262-64 and INAH-362)

  • The darkly staining posteromedial component of the bed nucleus of the stria terminalis (BNST-dspm)

  • The suprachiasmatic nucleus (SCN) and the central subdivision of the bed nucleus of the stria terminalis (BSTc)

These sex differences in the hypothalamus are believed to underlie sex differences in gender identity, reproduction, and sexual orientation. Clearly, more solid well-designed research into the biology of these disorders is needed.

Some studies suggest that male gender identity may be partly mediated through the androgen receptor.[10] The relative contribution of sex hormones and other nonhormonal factors may be an area where further research is needed.[11]

Epidemiology

According to DSM-5, the prevalence of gender dysphoria is 0.005–0.014% for adult natal males and 0.002-0.003% for adult natal females.[1] In Europe, 1 per 30,000 adult males and 1 per 100,000 adult females seek sexual reassignment surgery (SRS).

In children, gender dysphoria is 2–4.5 times more common among natal boys than among natal girls. In adolescents, the male-to-female ratio is closer to parity. In adults, the male-to-female ratio is generally weighted toward natal males, ranging from 1:1 to 6.1:1; however, it tends toward natal females in both Japan (1:2.2) and Poland (1:3.4).

Prognosis

Transgender adults may be more likely to have unhealthy habits and medical issues than cisgender individuals. A study of 3075 transgender adults and 719,567 cisgender adults found that transgender individuals were more likely to smoke, to be sedentary, and to not have health insurance.Transgender individuals were also 30% more likely to report their health as "fair" or "poor" and 66% more likely to experience severe mental distress.[12]

Existing case reports do not indicate that psychotherapy produces complete and long-term reversal of cross-gender identity. Transsexuals are not a homogeneous group. Some transsexuals do not show severe psychopathology. Diagnosing and treating this disorder early can reduce the chances of depression, emotional distress, and suicide. Gender dysphoria is not the same as homosexuality. How the gender conflict occurs is different in each person. For example, some people may cross-dress, while others want sex change surgery. Some people of one gender privately identify more with the other gender.[13]

People who are born with ambiguous genitalia, which can raise questions about their gender, may qualify for the diagnosis of gender dysphoria.[13]

SRS may be a viable treatment solution for some. Satisfactory results are reported in 87% of male-to-female and 97% of female-to-male SRS patients. Factors associated with relatively poor post-SRS functioning include the following:

  • Transvestic disorder

  • Effeminate homosexuality

  • SRS performed late in life

  • Bad surgical results

  • Suicidal intentions

  • Inadequate social functioning

  • Loss of work and family

  • Uncooperative attitude toward clinicians

  • Enduring resistance towards being transsexual

Outcome studies suggest that transsexuals without severe psychopathology are better off when treated promptly after diagnosis. Transsexuals who have severe psychopathology, are not homosexual, or have a late-onset gender identity disorder should not necessarily be excluded from SRS; however, they require more care and extensive evaluation and therapeutic support before SRS is deemed viable.

Patient Education

Patients should be educated about the differences between true transsexualism and other gender issues, such as transvestic fetishism, nonconformity to stereotypical sex role behaviors, gender dysphoria, and homosexuality. Both patients and their families need to understand the complexities of gender dysphoria, its enduring nature, and the challenges that it typically presents.

Treatment options should be discussed. When SRS is being considered, it should be explained that the procedure does not produce a trouble-free life. Additionally, work and social adjustment issues must be discussed, and plans for addressing these concerns must be developed. The importance of continuing family support and understanding should also be addressed. Finally, the need for long-term therapy and social support should be discussed and encouraged when appropriate.

Patient and family education remains an important aspect of treatment. An extensive summary of standards of care for transsexual, transgender, and gender-nonconforming people is available from the World Professional Association for Transgender Health (WPATH).[3]

 

Presentation

History

Criteria required for the diagnosis of gender dysphoria are outline in the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5).[1] Making the diagnosis can be complicated because the results of psychological testing are not conclusive. Some individuals distort information in order to gain access to sexual reassignment surgery (SRS). Accordingly, the diagnostic process must be extensive and thus is necessarily time-consuming.

The Standards of Care for the Health of Transsexual, Transgender, and Gender Nonconforming People by the World Professional Association for Transgender Health (WPATH-SOC),[3] formerly known as the Benjamin Standards of Care, outline a 2-phase diagnostic process for patients seeking SRS:

  • Phase I - A formal diagnosis is made on the basis of DSM-5 or International Classification of Diseases (ICD) criteria; risk factors are estimated in an effort to ensure that the individual can tolerate the life changes that SRS will bring

  • Phase II - The individual’s ability to live in the desired sex role is tested because he or she will have to live permanently in that role; the family is informed, and the patient’s name is changed; assessment of whether to administer hormone therapy is made; psychotherapy is required

The diagnostic process for adolescents seeking SRS includes all of the above, as well as the following:

  • The patient must show a lifelong cross-gender identity that increased at puberty

  • Serious psychopathology must be absent

  • The person must be able to function socially without significant problems

Preliminary follow-up observations include the following:

  • Heterosexual transsexuals appear to have poorer outcomes than homosexual transsexuals do

  • Gender-confused individuals (patients who do not meet the full criteria for transsexualism), transvestites, effeminate homosexuals, older individuals, and those resisting transsexualism generally have poorer post-SRS functioning

  • Patients who have undergone female-to-male SRS tend to do better than those who have undergone male-to-female SRS

 

DDx

Diagnostic Considerations

The differential diagnosis should include nonconformity to stereotypical sex role behaviors, transvestic fetishism, gender dysphoria not otherwise specified (with a concurrent congenital intersex condition), and schizophrenia.

Comorbidity

Lifetime psychiatric comorbidity in this disorder is high, and this should be taken into account in the assessment and treatment planning of gender dysphoria. Twenty-nine percent of the patients had no concurrent or lifetime-associated disorders; 39% percent fulfilled the criteria for current and 71% for current and/or lifetime-associated disorders. Forty-two percent of the patients were diagnosed with one or more personality disorders.[14]

Differential Diagnoses

  • Body Dysmorphic Disorder

  • Paraphilic Disorder

  • Schizophrenia

 

Treatment

Approach Considerations

Modalities that may be considered in the treatment of gender dysphoria include pharmacologic therapy, psychological and other nonpharmacologic therapies, and sexual reassignment surgery (SRS). Negative attitudes toward SRS appear to be changing among professionals, and scientific interest is increasing. Nevertheless, it must be kept in mind that SRS does not promote a trouble-free life. Post-SRS psychotherapy may substantially improve overall outcome.

Pharmacological treatments in children and adolescents are even more complex. This highly vulnerable population with gender dysphoria suffers through intense psychopathological burden. Puberty suppression by gonadotropin-releasing hormone analog (GnRHa) is prescribed to relieve the distress associated with pubertal development in adolescents with gender dysphoria. According to data published on long-term outcome of puberty suppression with GnRHas and subsequent hormonal and surgical treatment reflects possibility of improved psychological outcomes. Brain imaging study results did not show negative effects of the treatment on brain development.[15] Psychological support and puberty suppression both are found to be associated with an improved global psychological functioning in gender dysphoric adolescents.[16]

Psychological and Speech Therapy

Psychological intervention may be beneficial. Individual treatment focuses on understanding and dealing with gender issues. Group, marital, and family therapy can provide a helpful and supportive environment.

Speech therapy may help male-to-female individuals use their voice in a more feminine manner.

Pharmacologic Therapy

Hormone therapy may also be necessary. Consequently, the endocrinologist should be involved in multiple phases of the treatment process.[6]

In male-to-female individuals, original sex characteristics can be suppressed with luteinizing hormone–releasing hormone (LHRH) agonists, progestational compounds (eg, medroxyprogesterone), spironolactone, flutamide, and cyproterone acetate. Breasts, increased body fat, and a more feminine body shape can be promoted with ethinyl estradiol (0.1-0.5 mg/day) and conjugated estrogen (7.5-10 mg/day). In female-to-male individuals, facial and body hair growth may be promoted with testosterone cypionate (200 mg IM every 2 weeks).

Pharmacotherapy may also be required for comorbid psychiatric diagnoses. Patients commonly experience symptoms of depression, anxiety, or psychosis. Medications may include antidepressants, anxiolytics, and antipsychotics. Clinically referred children and adolescents with gender dysphoria appear to have a higher incidence of autism spectrum disorder than is found in the general population[1] ; this may be true of adults as well.[17]

Sexual Reassignment Surgery

Controversy exists regarding whether adolescents should be allowed to pursue SRS. Many countries deny SRS to adolescents; however, early treatment may be beneficial in adolescents whose secondary sex characteristics (eg, facial hair, lowered voice, and breast development) have not yet developed fully. In such cases, parental involvement and approval are essential.

Complications

Complications may occur after SRS. In persons who undergo male-to-female SRS, the vagina can scar and become shorter and narrower, necessitating additional surgical intervention. Bouts of recurring cystitis are common. In persons who undergo female-to-male SRS, considerable scarring may occur as a consequence of breast tissue removal. Additionally, surgical complications from phalloplasty (construction of a scrotum with plastic testicles and a penislike appendage) are not uncommon.

 

Guidelines

Guidelines Summary

Royal College of Psychiatrists

In October 2013, the Royal College of Psychiatrists in the United Kingdom issued new guidelines for the assessment and treatment of gender dysphoria, which include the following:[18, 19]

  • Gender treatment should involve a multidisciplinary team

  • People with gender dysphoria should have access to high-quality care without unnecessarily long waits

  • People with gender dysphoria have a right to psychotherapy and counseling as part of their treatment

  • Treatment should recognize the preferences, needs, and circumstances of the particular patient

  • Treatments that have been initiated for adolescents should continue into adulthood without interruption

  • More research should be encouraged, including research on patient outcome and satisfaction with interventions and transition

American Psychological Association

In 2015, the American Psychological Association adopted Guidelines for Psychological Practice with Transgender and Gender Nonconforming Clients in order to describe affirmative psychological practice with transgender and gender nonconforming (TGNC) clients. There are 16 guidelines in this document that guide TGNC-affirmative psychological practice across the lifespan, from TGNC children to older adults. The guidelines are organized into five clusters: (a) foundational knowledge and awareness; (b) stigma, discrimination, and barriers to care; (c) lifespan development; (d) assessment, therapy, and intervention; and (e) research, education, and training.[20, 21]

World Professional Association for Transgender Health

The World Professional Association for Transgender Health (WPATH) currently publishes the Standards of Care (SOC), to provide clinical guidelines for health care of transsexual, transgender and gender non-conforming persons in order to maximize health and well-being by revealing gender dysphoria.[22] The latest version of the SOC is available here.

Endocrine Society

In 2017, the Endocrine Society updated its Endocrine Treatment of Transsexual Persons: An Endocrine Society Clinical Practice Guideline.[23]

The new guideline states that only trained mental health professionals (MHPs) should diagnose gender dysphoria (GD)/gender incongruence in adults. These MHPs should be well-versed in the Diagnostic and Statistical Manual of Mental Disorders (DSM) and/or the International Statistical Classification of Diseases and Related Health Problems (ICD) and trained in diagnosing psychiatric disorders and distinguishing between GD/gender incongruence and conditions that have similar features. MHPs working with children and adolescents should also possess training in child and adolescent developmental psychology and psychopathology.

The Society recommends against puberty blocking and gender-affirming hormone treatment in prepubertal children with GD/gender incongruence. However, it may be offered to adolescents, and GnRH analogues can be used if indicated. Sex hormone treatment should be initiated using a gradually increasing dose schedule. Treatment should include periodic monitoring of hormone levels and metabolic parameters, as well as assessments of bone density and the impact upon prostate, gonads, and uterus.

It is advised that clinicians approve genital genderaffirming surgery only after completion of at least 1 year of consistent and compliant hormone treatment. Clinicians should inform pubertal children, adolescents, and adults seeking genderconfirming treatment of their options for fertility preservation. This surgery should be delayed in cases involving gonadectomy and/or hysterectomy until the patient is at least 18 years old.

 

 

Medication

Medication Summary

The goal of pharmacotherapy is to inhibit or promote the expression of secondary sex characteristics in males and females.

According to the largest study to date of transgender people in the United States, transgender women are at increased risk for venous thromboembolism (VTE) and ischemic stroke, particularly if they initiate some form of estrogen therapy. Researchers identified 2842 transfemales (assigned male at birth but transitioning to female) and 2118 transmales (assigned female at birth) from electronic health records and followed them for an average of 3.5 to 4 years from the first evidence of their transgender status. They then matched these two groups to a large cohort of cisgender men and women. Results show transwomen had a 1.9-fold higher risk of VTE over the full follow-up interval compared with cisgender men and about a 2-fold higher risk relative to cisgender women. The risk of ischemic stroke for transwomen was about 1.2-fold higher than for cisgender men and 1.9-fold higher than for cisgender women.[24, 25]

Progestins

Class Summary

These agents may be used to inhibit the secretion of pituitary gonadotropins.

Medroxyprogesterone (Depo-Provera, Provera)

Medroxyprogesterone may reduce the secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the pituitary by decreasing the amount of gonadotropin-releasing hormone (GnRH) secreted by the hypothalamus. This suppression, in turn, suppresses sex characteristics in males.

Gonadotropin-Releasing Hormone Agonists

Class Summary

Gonadotropin-releasing hormone (GnRH) analogs produce a hypogonadotrophic-hypogonadal state by down-regulation of the pituitary gland.

Leuprolide (Eligard, Lupron Depot, Lupron Depot-Ped)

Leuprolide suppresses ovarian and testicular steroidogenesis by decreasing luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels. With long-term administration, this agent suppresses gonadotropic responsiveness to endogenous gonadotropin-releasing hormone (GnRH), thereby reducing secretion of LH and FSH, which, in turn, reduces ovarian and testicular steroid production.

Goserelin (Zoladex)

Goserelin suppresses ovarian and testicular steroidogenesis by decreasing luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels. With long-term administration, this agent suppresses gonadotropic responsiveness to endogenous gonadotropin-releasing hormone (GnRH), thereby reducing secretion of LH and FSH, which, in turn, reduces ovarian and testicular steroid production.

Nafarelin (Synarel)

Nafarelin is an analog of gonadotropin-releasing hormone (GnRH) that is approximately 200 times more potent than natural endogenous GnRH. With long-term administration, this agent suppresses gonadotropic responsiveness to endogenous GnRH, thereby reducing secretion of LH and FSH, which, in turn, reduces ovarian and testicular steroid production.

Aldosterone Antagonists, Selective

Class Summary

Aldosterone antagonists may block androgen receptors.

Spironolactone (Aldactone)

Spironolactone is an aldosterone antagonist that competes with testosterone and dihydrotestosterone receptor sites. It also reduces free testosterone levels as more is bound by the increased quantity of sex hormone–binding globulin (SHBG). It is used most effectively in combination with an oral contraceptive.

Antineoplastics, Antiandrogens

Class Summary

Antiandrogens are another group of agents used as a first-line therapy for hirsutism. However, the teratogenic potential of these drugs means that they should be used in conjunction with adequate contraception in women of reproductive age.

Flutamide

Flutamide is a nonsteroidal antiandrogen that inhibits androgen uptake or binding of androgen to target tissues.

Oral Contraceptives

Class Summary

Oral contraceptives inhibit ovarian androgen production and are probably the first choice for young women with hirsutism who do not want to become pregnant. Oral contraceptives are inexpensive, and they promote regular uterine bleeding. Oral contraceptives can be used in combination with antiandrogens or other agents.

Ethinyl Estradiol, drospirenone, and levomefolate (Beyaz)

This combination of estrogen and progestin suppresses ovarian production of androgens.

Ethinyl estradiol and norethindrone (Estrostep Fe)

This combination of estrogen and progestin suppresses ovarian production of androgens.

Ethinyl estradiol and norgestimate (Ortho Tri-Cyclen)

This combination of estrogen and progestin suppresses ovarian production of androgens.

Ethinyl Estradiol and Drospirenone (Yaz)

This combination of estrogen and progestin suppresses ovarian production of androgens.

Norethindrone acetate and ethinyl estradiol (Ortho-Novum, Nortrel, Cyclofem)

This combination of estrogen and progestin suppresses ovarian production of androgens.

Estrogen Derivatives

Class Summary

These hormones are used for replacement therapy in hypogonadism associated with a deficiency or absence of endogenous testosterone or estrogen.

Estrogens, conjugated (Premarin)

Estrogen is important in the development and maintenance of the female reproductive system and secondary sex characteristics, promoting the growth and development of the vagina, uterus, fallopian tubes, and breasts. It affects the release of pituitary gonadotropins; causes capillary dilatation, fluid retention, and protein anabolism; increases the water content of cervical mucus; and inhibits ovulation.

Androgens

Class Summary

Androgens are used for replacement therapy in hypogonadism associated with a deficiency or absence of endogenous testosterone.

Testosterone (Testim, Androderm, Depo-Testosterone, Androderm, AndroGel)

Testosterone is an anabolic steroid that promotes and maintains secondary sex characteristics in androgen-deficient males.