Ir Med J. 2006 May;99(5):146-8



Abstract
(GID) is a relatively rare condition of atypical gender development in which there is a psychological perception of self as masculine or feminine which is incongruent with ones phenotype. GID replaced the term Transsexualism in DSM-IV in 1994. The demographics of GID in Ireland have not been established. Since 2000 we have received 52 referrals of individuals with confirmed GID to our endocrine service for consideration for hormonal treatment (HT). Of the 52 patients 45 have male to female (MTF) GID (mean age 38.9 years) and 7 have female to male (FTM) GID (mean age 30.7 years). The age at presentation in this group is approximately 9 years older than in international series for both MTF (39 years v 30yrs) and FTM (31yrs v 22yrs). The karyotype where analysed has been normal for their phenotypic sex. Twenty-three of the patients had received HT prior to attending our clinic that in only one case had been prescribed by a specialist. A number of patients had obtained HT via the internet or from overseas sources without medical review. Eighteen of the patients have been or are married and 14 of the group have children. The scale of referrals confirms that GID exists in the Irish population to a significant degree. Thus an appropriate care pathway for people with the condition needs to be established. This will facilitate optimum medical management of the patient group and a coherent approach to the many difficult social issues faced individuals with this disorder.




Introduction
(GID) is a relatively rare condition of atypical gender development in which there is a psychological perception of self as masculine or feminine which is incongruent with ones phenotype. It is described in ICD-10 and DSM-IV-TR and affected patients may need medical treatments/interventions to facilitate a transition to live in accordance with the identified gender rather than with the phenotype. Whilst the ICD-10 (WHO,1992) and DSM-IV-TR (APA,1994) descriptions vary slightly, each provides a reliably sound and valid template for diagnosis ^1,2. The term GID replaced transsexualism in 1980 and has a reported incidence worldwide of up to one in thirty thousand for male to female (MTF) and up to one in one hundred and twenty thousand for female to male (FTM) ^3,4. There is increasing evidence that the areas in the brain that are implicated in the determination of gender (in particular the bed nucleus of the striae terminalis and the sexual dimorphic nucleus along the third ventricle of the hypothalamus) may be responsible in a causal way for the condition ^5,6.

GID is a condition in which there are many social, medical and psychological issues that need to be addressed simultaneously. There are significant medical risks associated with the treatment of this group of patients and internationally the preferred approach to the management of GID involves a multidisciplinary team with three main specialists - the mental health professional (MHP), the endocrinologist and the surgeon working together.

Since 2000 the Department of Diabetes and Endocrinology in St Columcille’s Hospital and St Vincent’s University Hospital has provided an endocrine service for this patient population. Formal links have been established with some of the referring mental health professionals and with St Patrick’s Hospital. Here we present a review of the first 52 patients with gender identity disorder referred for endocrine assessment. The scale of the referrals gives some indication of the true prevalence of the condition in Ireland for the first time and highlights the need for developing clear pathways of care involving the relevant disciplines.

Methods
The patient population described consists of all new referrals to the Endocrine Service from 2000 to December 2004 with an established diagnosis of GID. This diagnosis was confirmed in writing by the referring MHP including a statement that the patient was ready to start the hormonal stage of their treatment. At the first visit, each patient had their history documented and underwent physical examination. Relevant past medical diagnoses documented at baseline included: diabetes mellitus (DM); hypercholesterolemia; clotting disorders; coronary artery disease; peptic ulcer disease; cigarette smoking; alcohol intake; psychiatricIrish Medical Journal May 2006 Volume 100 number disease. Routine investigations performed on each patient included a full blood count, renal and liver function, bone profile, random lipid profile and glucose and a pituitary-gonadal hormone profile (including FSH;LH;T4;TS H;testosterone;oestradiol;prolactin). Where the patients were agreeable a chromosomal analysis was performed.

Patients with a significant family history of coronary artery disease or complaining of symptoms of coronary disease had a resting ECG and exercise stress test performed. Patients found to have hypertension on initial presentation underwent 24hr ambulatory blood pressure monitoring plus echocardiography. Patients who smoked were told that they would not be eligible for hormone therapy (HT) if they continued smoking due to the increased risk of thrombo-embolic disease.

The effects of and risks of HT were discussed with each patient at their first visit to enable them to make an informed decision at their second visit regarding HT. Where possible, and assuming there were no contraindications to therapy, an attempt was made to commence treatment at the second visit. All baseline investigations were reviewed with each patient at their second clinic visit. All of our patients have been referred for baseline bone densitometry studies.

Results

Baseline Medical Investigations:
Forty-six of the patients (MTF=40/ FTM=6) have had their baseline hormone profile checked; these have all been in keeping with the biologic sex of the patient. However, 10 patients’ profiles revealed evidence of suppression of gonadotrophins secretion (MTF=8/FTM=2). Twenty-three patients had accessed HT prior to attending this service and the sources of this are summarized in Table 3.

Twenty-three patients were found to have an abnormal random lipid profile on presentation (MTF=22/FTM=1). However, only three of these, all MTF, required lipid-lowering therapy following further investigations. None of the patients had diabetes. Two of our patients, both MTF, were newly diagnosed with essential hypertension and have been commenced on anti-hypertensive therapy. The five patients who have had their Karyotype assessed have results in keeping with their anatomical sex.

Treatments to Date
43 of our group (MTF=36/FTM=7) are currently receiving HT. The reasons for the other 9 patients not being on therapy currently are presented in Table 2. There have been two significant adverse events with one patient having a thrombotic stroke and one patient an episode of severe mood disturbance necessitating withdrawal of therapy. In the latter case HT was successfully re-commenced. HT has been otherwise welltolerated in those attending. Twenty-six of the patients (MTF=24/FTM=2) are currently on aspirin to minimize the risk of thrombo-embolic events. 16 of the patients (MTF=10/FTM=6) have undergone surgery to date. The majority of the operations have involved either breast surgery (mastectomy or augmentation) or removal of the endogenous source of hormone
production (oophorectomy or orchidectomy). Three of the MTF patients have completed sex reassignment.

Discussion
This paper reports for the first time a large group of patients in Ireland with GID. Given that we are reporting from one center and are aware that we are not reviewing all patients with a diagnosis of GID, the report indicates that the prevalence of GID in this country is likely to be in line with the internationally reported literature of one in thirty thousand for men and one in one hundred and twenty thousand in women ³. There is an obvious need for clear pathways of care for GID within the medical profession in this country. This has also been highlighted in the recent report of the equality authority ⁹. The only previous report of GID in Ireland referred to its occurrence in a male with Klinefelters syndrome ¹².

GID is a psychiatric diagnosis that can only be made by a mental health professional (MHP) in the absence of another untreated mental illness that may be contributing to feelings of gender identity. The work that demonstrates neuronal cell numbers in key areas within the brain involved in the control of gender are female in their distribution in MTF patients indicates that there may be a central ie hypothalamic cause for the condition. In these studies they controlled for the possible effects of hormone treatment by looking at hypogonadal males and males treated for prostate cancer with estrogen therapy. The areas of focus within the brain have in particular been the bed nucleus of the striae terminalis and the sexual dimorphic nucleus along the third ventricle of the hypothalamus, areas that are known to be involved in determination of gender ^5,6.

Our patients were referred from two major sources a MHP or a general practitioner (GP). Those referred by an MHP were considered to have a definitive diagnosis and no unresolved mental health issues making them unsuitable for HT. In line with international criteria, we require that this be clearly indicated in the referral letter by the MHP before initiating HT. Those referred to us directly by their GPs were referred from our clinic for psychiatric assessment to confirm the diagnosis of GID and were reviewed by us subsequently with a view to assessing their suitability for HT.

Seventeen of the 52 patients have self-reported feeling depressed, and some of these have been prescribed antidpressant medication by GPs. However, relatively few have a diagnosis of depression from a psychiatrist. Preliminary studies in this population indicate a relief of symptoms of psychometrically measured depression when post-tested following intervention and commencement of treatment for GID (Kelly, Pittman and Caska, unpublished data). This would support the authors’ subjective assessment of intervention in this patient group.

The age at presentation in this group is approximately 9 years older than in international series for both MTF (39 years v 30yrs) and FTM (31yrs v 22yrs). This is likely to reflect the cultural barriers to personal acceptance of the diagnosis in Ireland also the absence of a pathway of care for this patient group in Ireland leading to later interaction with the health service. Over half of the patients had experienced significant difficulties accessing any health services related to the condition. It is also of note that a significant number of patients (n=9) accessed hormonal therapy either from internet sources or overseas clinics. In these patients treatment was commenced without explanation of risk or assessment of medical or psychological suitability for treatment. This clearly places the patient at increased risk of medical and psychological side effects without access to appropriate follow up. GID is a condition that is associated with a 4 fold increase in mortality over the general population due to a combination of psychiatric and medical consequences of the condition ¹¹. Late presentation, combined with unsupervised HT and accessing of surgery without appropriate referral, as occurred in 2 of our patients, will all combine to worsen the outcome in this patient group.

The fact that a significant number of this cohort have either been married (n=18) or have children (n=14) seems initially surprising. This probably reflects the efforts these individuals make to deny or repress the effects of the condition. It also underlines the importance of early assessment,evaluation, diagnosis and treatment intervention. In a UK population Whitehead and Holland reported even higher figures - 67% married and 47% having been parents. The familial status greatly complicates treatment modalities from a psychological perspective, and there are no simple resolutions to this complex issue. Accurate and early diagnosis however of GID may well avoid the situation of spouse and children being so prevalent.

The basis behind the endocrine treatment of GID is straightforward. Male patients are given oestrogen and female patients are given testosterone. For both the groups of patients, some centers are currently advocating the use of gonadotrophin releasing hormone analogues to switch off at a hypothalamic level – through non-competitive means – endogenous sex hormone production. This approach operates on the principle that by turning off endogenous sex hormone production first, one can then potentially decrease the overall dose of exogenous sex hormone therapy required to achieve the same end result yet at the same time decreasing
the risk of adverse effects from high hormone concentrations. We are now advocating this as our first line approach in the endocrine management of GID. We are changing our patients to this more uniform approach– effectively a chemical gonadectomy combined with physiological hormone replacement.

There is also a possible role for anti-androgen treatment in MTF patients but it does carry its own risk of adverse effects. We tend to reserve it for patients having particularly difficult issues with facial hair. All of the MTF patients are routinely started on aspirin therapy to minimize their risk of thrombotic events. A recent study shows that FTM patients actually have a lower risk of thrombosis and do not require aspirin therapy ⁷. Most patients with GID are eager for some degree of surgical intervention so their anatomical appearance is more in keeping with their underlying gender preference. However, not all patients plan to go on to full gender reassignment and within the international guidelines for management of GID it is not essential to have plans for the nature or extent of surgery at the time of starting HT ⁸. The timing and extent of surgery needs to be tailored to the individual patient. Some of our patients have travelled independently overseas to obtain surgeries, at significant financial cost, that they felt were unavailable to them here. There is a need for consistency in the adapting of the international guidelines on this area of the patients care to the Irish Healthcare system so that patients are aware of the pathway and timeframe they are likely to follow.

This review of the first five years of referrals to the endocrine service of patients with GID highlights the need for clear service development in this country for this patient group. Services need to be delivered within the existing structures of mental health and endocrinology. Where possible local delivery of the service is to be favoured – and certainly would be by the patients.

The developing field of research into this condition is focussing on hypothalamic alterations in GID and is a growing area of interest. The Irish College of Psychiatry and the Royal College of Physicians of Ireland should work together to ensure a safe, accurate and efficient management pathway for patients with GID in this country is established.

References

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