Q: How does one define transgender?

A: Transgender definition is - of, relating to, or being a person whose gender identity differs from the sex the person had or was identified as having at birth; especially: of, relating to, or being a person whose gender identity is opposite the sex the person had or was identified as having at birth.

Q: How does one define gender fluidity?

A: Definition of gender-fluid: of, relating to, or being a person whose gender identity is not fixed.  There are also people who identify as “gender fluid,” a mix of both genders, and may feel more male on some days and more female on others.

Q: Does transgender (TGD) imply sexual orientation?

A: No, transgender does not imply sexual orientation.[1]

Q: Do we know how many TGD individuals there are with MS?

A: The total number of transgender MS patients is not known. In the United States, studies estimate that 0.3% of adults identify as transgender, which is approximately 1 million people.[6] The incidence of pediatric transgender patients is not known. The military health system identified transgender youths in their health records in .003% of military personnel therefore there may also be a significant number of transgender pediatric MS patients, approximately 15,000 youths nationally.[7]

Q: Can TGD hormone therapy increase the risk of MS?

A: There is an English hospital retrospective cohort study examining associations of transgenderism or “gender identity disorders” and risk of MS in 1157 male to female transgender patients and 2390 female to male. This study found an association with transgenderism and subsequent diagnosis of MS in the TGD males suggesting a role for low testosterone or feminizing hormones as a risk for MS. [8]

Q: What is known about testosterone and MS?

A: There is a known association between gonadal hormones and MS, seen in higher risk of MS in females and in female animal models of MS as well as less disease activity in female animal models treated with testosterone suggesting anti- inflammatory and or neuroprotective action of testosterone.[8]  Studies have seen high prevalence of hypogonadism in male MS patients and improved cognition, immune outcome and slowed brain atrophy in small studies of male MS patients treated with testosterone yet no effect on gad enhancing brain lesions.[9]   Low testosterone levels were associated with increase in EDSS and worsening cognitive decline as seen in the Single Digit Modalities Test.[10]  Larger studies of testosterone , in other conditions, demonstrate concern in term of; prostate cancer, cardiovascular risks and erythrocytosis leading to thrombotic events which needs to be monitored for, therefore additional studies are needed to determine the use of testosterone in MS patients.[11]

Q: What is known about estrogens and MS?

A: The majority of MS patients are female, this likely relates to sex hormones. Sex hormones likely modulate the immune system through lowering proinflammation and enhance anti-inflammatory responses as well through TH2 activity [12].  The level of MS disease activity is related to hormonal secretions such as decrease in relapse rate with pregnancy.[13] Estradiol has been evaluated as a possible therapy for MS in small studies due to the decrease in MS activity during pregnancy, showing preserved gray matter with resultant cognitive preservation.[14] Female sex hormones play a role in disease activity in MS.

Q: Does the TGD MS patient face unique medical challenges?

A: The pediatric and adult patient with Multiple Sclerosis (MS) face substantial challenges when coping with a chronic illness. The transgender MS patient may experience additional challenges as well as difficulties and barriers to care within a MS Center. Care issues in a TGD MS patient may include: risk of hormonal therapies , surgical planning, socioeconomic challenges, family planning and inclusive care.[15]

How can a MS Center remain inclusive to all patients?

  1. Inclusive welcoming culture- staff, EMR with ability for inclusive history taking; preferred patient identified name and pronoun, gender neutral terminology options and identity, physical clinical site (bathrooms).
  2. Focus on the patient experience through open communication with the patient.
  3. Provide access to comprehensive care through multidisciplinary teams.
  4. Educate staff on TGD related care, provide educational resources, review nondiscrimination polices of institution.

Q: What does Cleveland Clinic offer the transgender patient? Care?

A: Cleveland Clinic has Transgender surgical center for comprehensive medical and surgical care.

We also have the Pride Clinic: 216.444.3672.

For Pediatric and adolescents, there is a GUIDE Clinic, to support youth gender questioning.

Cleveland Clinic follows the Human Rights Campaign Healthcare quality index guidelines: patient non-discrimination equal visitation, employment practices and training in LGBTQ centered care.

Cleveland Clinic has a health essentials on transgender care: Transgender Care: 3 Things You Should Understand.

Q: Do TGD people face difficulties in general medical care and what is being done about any medical inequities?

A: Disparities in health care for transgender persons have been well established in the literature. Additionally, recent nationwide surveys have highlighted significant disparities in healthcare for transgender persons, who are currently considered a “priority population.” The gaps in quality healthcare are often attributed to many interrelated factors including; internalized stigma of providers and lack of training in the past addressing transgender-specific health care needs in medical school/residency programs which is now changing.[2] It has been reported that medical biases toward transgender patients include; denial of health care, verbal harassment, and discrimination have provided significant barriers to transgender persons seeking health care. These medical biases can lead to patient frustrations and possibly missing or delaying care.[3] [4] [5] To rectify discrimination, multiple groups have proposed standards of medical care and the Human Rights Campaign Healthcare Equality Index has focused on a core criteria of lesbian gay bisexual transgender queer (LGBTQ) patient centered care: patient non-discrimination, equal visitation, employment practices and training in LGBTQ centered care. (Human Rights Campaign)[1]

Q: Are there unique medical issues in TGD MS patients?

A: Treatment of transgenderism in accordance with the World Professional Association for Transgender Health recommends hormonal therapy, psychotherapy, changes in gender expression and potential surgical sex reassignment.

Common transgender treatments include cross sex hormone therapy, genital reassignment surgery, nongenital surgical procedures of the face, breast or body, speech and voice therapy, and facial hair removal.[16]


Male to female:

The most studied treatment regimen for MtF individuals involves the use of feminizing hormones (e.g. estrogen) and anti-androgens (e.g. gonadotropin-releasing hormone analogues) which reduce testosterone secretion or neutralize testosterone activity.

Female to Male:

There are reports of increased risk of metabolic conditions due to hormone therapies, both estrogen and testosterone, higher risk of substance abuse, smoking, domestic violence and mental health disorders, these should all be screened for in routine medical care.[17]

Vitamin D binding may change due to hormone therapy and annual levels are recommended due to the possible effect of Vitamin D with MS activity.[18]

Feminizing hormone therapy can be associated with increased risk of ischemic strokes and thromboembolism, these risk factors need to be considered in TGD MS patients on these therapies with new onset symptoms.[19]

Both testosterone and estrogens have been reported to be neuroprotective in EAE, their effect in TGD MS patient is not known.[20] Cross sex treatment of TGD persons is typically uneventful but a caregiver needs to remain vigilant of the natal organs, i.e.- prostate/ breasts and the potential effect of hormone therapy on various tissues and seek care in a comprehensive center familiar with short and long term medical needs of TGD patients. For example, testosterone can metabolize to estrogens and effect remaining endometrium, and needs to be considered when considering hormone therapy and long term risks.[21] Male to female transsexual people receives treatment with anti- androgens and estrogens, the effect on MS is not known. They may have vaginoplasty or neovaginas, early data does not show an increase in colon cancers yet these surgeries can affect bladder functions in MS patients. Female to male transsexual people receive testosterone to virilize them, the administered testosterone can be partially aromatized to estradiol, and this may increase the risk of breast and other cancers. Estradiol has been investigated as a therapy for MS yet the overall effect on TGD MS patients is not known.[11] Estradiol has been shown to induce changes in the immune system, the use of estradiol in TGD MS patients and its effects on MS activity in this population are not known.[22]

Q: Are there unique psychological issues in TGD MS patients?

A: A recent survey showed transgender individuals reported higher rates of psychological distress including; “depression, anxiety, and suicidality at 39% compared with 5% for the general U.S. population; 40% had attempted suicide at some time in their life compared with 4.6% in the general population.”[23] Additionally, depression and anxiety are a common comorbidity in patients with multiple sclerosis (MS) which is often associated with poorer quality of life. The lifetime prevalence rate of developing depression in MS is as high as 50%.[24] Although there are well-established barriers to transgender individuals seeking health care, a recent study found that transgender individuals who reported a transgender-inclusive provider were less likely to report symptoms of depression, anxiety and suicidality as compared to transgender individuals who did not report a transgender-inclusive provider.

Q: What does Mellen Center Behavioral Medicine recommend for the TGD MS patient?

A: Screen Regularly for Mood Symptoms, Such as Depression and Anxiety. Refer to Behavioral Medicine if Necessary.

Q: What disease modifying therapy can a TGD MS patients use?

A: There is no evidenced based research to guide disease modifying therapy use in the TGD MS patient.

Q: How can the EMR help in the care of TGD MS patients?

A: Mellen Center uses Epic EMR, this has a capability to routinely document preferred pronoun and name, gender, gender neutral terminology and take a detailed sex and gender including transgender history, surgical history and hormone use.

For more information please see: New EHR Tools Enable Providers to Better Serve LGBT Patients.



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