Chiara Manieri

Cross‐Sex Hormonal Treatment and Body Uneasiness in Individuals with Gender Dysphoria

INTRODUCTION Cross-sex hormonal treatment (CHT) used for gender dysphoria (GD) could by itself affect well-being without the use of genital surgery; however, to date, there is a paucity of studies investigating the effects of CHT alone. AIMS This study aimed to assess differences in body uneasiness and psychiatric symptoms between GD clients taking CHT and those not taking hormones (no CHT). A second aim was to assess whether length of CHT treatment and daily dose provided an explanation for levels of body uneasiness and psychiatric symptoms. METHODS A consecutive series of 125 subjects meeting the criteria for GD who not had genital reassignment surgery were considered. MAIN OUTCOME MEASURES Subjects were asked to complete the Body Uneasiness Test (BUT) to explore different areas of body-related psychopathology and the Symptom Checklist-90 Revised (SCL-90-R) to measure psychological state. In addition, data on daily hormone dose and length of hormonal treatment (androgens, estrogens, and/or antiandrogens) were collected through an analysis of medical records. RESULTS Among the male-to-female (MtF) individuals, those using CHT reported less body uneasiness compared with individuals in the no-CHT group. No significant differences were observed between CHT and no-CHT groups in the female-to-male (FtM) sample. Also, no significant differences in SCL score were observed with regard to gender (MtF vs. FtM), hormone treatment (CHT vs. no-CHT), or the interaction of these two variables. Moreover, a two-step hierarchical regression showed that cumulative dose of estradiol (daily dose of estradiol times days of treatment) and cumulative dose of androgen blockers (daily dose of androgen blockers times days of treatment) predicted BUT score even after controlling for age, gender role, cosmetic surgery, and BMI. CONCLUSIONS The differences observed between MtF and FtM individuals suggest that body-related uneasiness associated with GD may be effectively diminished with the administration of CHT even without the use of genital surgery for MtF clients. A discussion is provided on the importance of controlling both length and daily dose of treatment for the most effective impact on body uneasiness.

Metabolic and cardiovascular outcomes in a group of adult patients with Turner's syndrome under hormonal replacement therapy

OBJECTIVE Turners syndrome (TS) is a rare genetic disorder caused by complete or partial X chromosome monosomy in a phenotypic female, and it is associated with increased morbidity and mortality for cardiovascular diseases, impaired glucose tolerance, and dyslipidemia. SUBJECTS AND METHODS In 30 adult TS patients under chronic hormonal replacement therapy (HRT), 17β-estradiol (E(2)), body mass index (BMI), waist circumference, fasting glucose and insulin, homeostatic model assessment (HOMA) index, serum lipids, oral glucose tolerance test (OGTT), 24 h ambulatory blood pressure monitoring (ABPM), and intima-media thickness (IMT) were evaluated and compared with those in 30 age- and sex-matched controls (CS). RESULTS No difference was found between TS and CS in E(2) and BMI, whereas waist circumference was higher (P<0.05) in TS (77.7±2.5 cm) than in CS (69.8±1.0 cm). Fasting glucose in TS and in CS was similar, whereas fasting insulin, HOMA index, and 2 h glucose after OGTT were higher (P<0.0005) in TS (13.2±0.8 mUI/l, 2.5±0.2, and 108.9±5.5 mg/dl respectively) than in CS (9.1±0.5 mUI/l, 1.8±0.1, and 94.5 ± 3.8 mg/dl respectively). Total cholesterol was higher (P<0.05) in TS (199.4 ± 6.6 mg/dl) than in CS (173.9±4.6 mg/dl), whereas no significant differences in high-density lipoprotein, low-density lipoprotein, and triglycerides were found between the two groups. In 13% of TS, ABPM showed arterial hypertension, whereas IMT was <0.9 mm in all TS and CS. A negative correlation between insulin levels, HOMA index, or 2 h glucose after OGTT and E(2) was present in TS. CONCLUSIONS Our results indicate that adult patients with TS under HRT are connoted by higher frequency of central obesity, insulin resistance, hypercholesterolemia, and hypertension.

Sociodemographic and Clinical Features of Gender Identity Disorder: An Italian Multicentric Evaluation

INTRODUCTION Male to female (MtFs) and female to male (FtMs) subjects with gender identity disorder (GID) seem to differ with regard to some sociodemographic and clinical features. Currently, no descriptive studies focusing on MtFs and FtMs attending an Italian clinic are available. AIM To describe the sociodemographic characteristics of a GID population seeking assistance for gender transition and to assess possible differences in those features between MtFs and FtMs. METHODS A consecutive series of 198 patients was evaluated for gender dysphoria from July 2008 to May 2011 in four dedicated centers. A total of 140 subjects (mean age 32.6 ± 9.0 years old) meeting the criteria for GID, with their informed consent and without genital reassignment surgery having already been performed, were considered (92 MtFs and 48 FtMs). Diagnosis was based on formal psychiatric classification criteria. MAIN OUTCOME MEASURES Medical history and sociodemographic characteristics were investigated. Subjects were asked to complete the Body Uneasiness Test (a self-rating scale exploring different areas of body-related psychopathology), Symptom Checklist-90 Revised (a self-rating scale to measure psychological state), and the Bem Sex Role Inventory (a self-rating scale to evaluate gender role). The presence of psychiatric comorbidities was evaluated using the Structured Clinical Interviews for Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) (SCID I and SCID II). RESULTS Several significant differences were found between MtFs and FtMs regarding lifestyle and sociodemographic factors and in psychometric test scores. No differences were found in terms of psychiatric comorbidity. CONCLUSIONS This is the first large study reporting the sociodemographic characteristics of a GID sample referring to Italian clinics, and it provides different profiles for MtFs and FtMs. In particular, FtMs display significantly better social functioning.

Antiandrogenic properties of spironolactone. Clinical trial in the management of female hirsutism

The effect of spironolactone on female hirsutism was studied in 18 patients. The drug was administered at the dose of 400 mg for the first ten days and 300–200 mg later on in a first group of women (Group A); a second group (Group B) was given 200 mg spironolactone for the whole length of therapy. A significant decrease of the index of Ferriman and Gallwey (p = 0.01) was noted from the 100th day of treatment; acne and seborrhoea improved concomitantly. Plasma total testosterone values fell from 0.64 + 0.24 ng/ml to 0.32 ± 0.12 ng/ml (p = 0.002) during the first 5 days only in the patients of Group A; in the other patients no significant changes were observed. PRL did not significantly change from prefreatment values; FSH and LH values at the 5th, 10th, and 15th day of therapy did not show a uniform course in both groups. On the basis of these results spironolactone administration appears promising in the therapy of female hirsutism.

Radiological treatment of male varicocele: technical, clinical, seminal and dosimetric aspects

Purpose.The purpose of this study was to present our experience with percutaneous treatment of male varicocele considering technical, clinical, seminal and dosimetric aspects.Materials and methods.At baseline and at 6 months’ follow–up, 290 male patients aged between 18 and 37 (average age 27.3 years) with left (266 cases) or bilateral (24 cases) varicocele underwent clinical assessment, Doppler ultrasonography (US), laboratory testing of free and total serum testosterone, leutenising hormone (LH) and follicle stimulating hormone (FSH) gonadotropins, inhibin B and spermiogram. In 223 cases, selective catheterisation of the spermatic vein was performed with a right transfemoral approach. Two hundred and six out of 223 underwent radiological treatment of varicocele; in 194, hydroxy–poliethoxydocanol (Aetoxysclerol) was used only whereas in 12 cases (5.8%), 5 ml of absolute alcohol and a Gianturco coil (0.038–in. Cook coil, 10 mmx50 mm) were also used. In 17/223 patients (7.6%), sclerotherapy was contraindicated or not technically feasible. Sixty–seven patients refused radiological treatment and were used as a control group. In 20 patients, the following parameters were measured: dose area product, entrance surface dose, effective dose and gonad dose.Results.Technical success was achieved in 206/223 cases; two phlebographic examinations (immediately following administration of the sclerosing agent and after 15–20 min) showed prethrombotic endoluminal alterations of the internal spermatic vein. At 6 months’ follow–up, 172/206 patients (83.49%) showed complete resolution of the varicocele whereas 34/206 (16.5%) had only partial disengorgement of the pampiniform plexus. In these 206 patients, the spermogram showed a significant increase in sperm concentration (52.1±4.1 vs. 44.2±3.6 million/ml, p=0.002) and motility (40.5±2.2 vs. 33.3±2.0%, p=0.0001), with negligible morphological changes. In the control group and in the other 17 untreated patients, no variations in seminal parameters were observed. The following minor procedural complications were recorded: two cases of acute abdominal pain, three of vagal crisis during administration of sclerosing agent that resolved spontaneously and two of spermatic cord inflammation that resolved within days after medical therapy. We recorded no statistically significant differences with regard to testicular volume or serum hormone levels between the treated and untreated groups. Maximum effective dose and maximum gonad dose equivalent were 6.9 mSv and 0.69 mSv, respectively.Discussion and conclusions.Percutaneous radiological treatment of varicocele is a minimally invasive technique, which is well tolerated by patients and able to significantly improve seminal parameters. The principal technical limitation to percutaneous treatment is related to difficult selective catheterisation of the spermatic vein due to anatomic alterations, spasms and intimal dissection of the vein. Moreover, when the cremasteric vein is incontinent, inguinal surgical ligation provides better results. In the majority of cases, administration of at least 3 ml sclerosing agent at 3% ensures occlusion of the gonadic vein above the abdominal collaterals, which are responsible for long–term recurrence if not treated. In the remaining cases, absolute alcohol and metallic coils can be used to complete the treatment. The positive results in seminal parameters do not, however, allow for reliable assessment of patients’ fertility. Finally, we believe that radiological procedures are not indicated or justified when prolonged catheterisation with elevated gonadic irradiation is needed.

Dimensional Profiles of Male to Female Gender Identity Disorder: An Exploratory Research

INTRODUCTION Male-to-Female Gender Identity Disorder (MtF GID) is a complex phenomenon that could be better evaluated by using a dimensional approach. AIM To explore the aggregation of clinical manifestations of MtF GID in order to identify meaningful variables describing the heterogeneity of the disorder. METHODS A consecutive series of 80 MtF GID subjects (mean age 37 +/- 10.3 years), referred to the Interdepartmental Center for Assistance Gender Identity Disorder of Florence and to other Italian centers from July 2008 to June 2009, was studied. Diagnosis was based on formal psychiatric classification criteria. Factor analysis was performed. MAIN OUTCOME MEASURES Several socio-demographic and clinical parameters were investigated. Patients were asked to complete the Bem Sex Role Inventory (BSRI, a self-rating scale to evaluate gender role) and Symptom Checklist-90 Revised (SCL-90-R, a self-rating scale to measure psychological state). RESULTS Factor analysis identified two dimensional factors: Factor 1 was associated with sexual orientation, and Factor 2 related to behavioral and psychological correlates of early GID development. No correlation was observed between the two factors. A positive correlation between Factor 2 and feminine BSRI score was found, along with a negative correlation between Factor 2 and undifferentiated BSRI score. Moreover, a significant association between SCL-90-R Phobic subscale score and Factor 2 was observed. A variety of other socio-demographic parameters and clinical features were associated with both factors. CONCLUSIONS Behavioral and psychological correlates of Factor 1 (sexual orientation) and Factor 2 (gender identity) do not constitute the framework of two separate clinical entities, but instead represent two dimensions of the complex MtF GID structure, which can be variably intertwined in the same subject. By using factor analysis, we offer a new approach capable of delineating a psychopathological and clinical profile of MtF GID patients.

Endocrine treatment of transsexual persons: An Endocrine Society clinical practice guideline - commentary from a European perspective

The treatment of transsexual subjects is a challenging task for the endocrinologist who, in collaboration with the mental health professional and the surgeon, is called upon to confirm the diagnosis and adjust hormonal treatment aimed at suppressing endogenous sex hormones and to develop hormone characteristics of the desired gender. These guidelines are structured to provide evidence-based suggestions or, where evidence is lacking, expert recommendations on diagnostic procedures and hormonal treatment in adolescent and adult transsexuals, including long-term care and eligibility for surgery. The multidisciplinary approach to treatment, the additional diagnostic role of hormone administration and the need to maintain hormone levels within the physiological range are key suggestions stressed in the guidelines which are particularly important for an endocrinologist unfamiliar with this field. The need for psychological assessment before surgery is not common in many countries and should be stressed further in the guidelines. Some important issues such as time and method of hormone withdrawal before surgery together with when and which hormones should be administered after sex reassignment surgery has been completed also remain unclear. These guidelines represent a pivotal document for endocrinologists setting a standard for the care of transsexuals and providing directions for future research.

Postmenopausal virilization in a woman with gonadotropin dependent ovarian hyperthecosis

We report a case of a 66-yr-old woman with progressive hair balding, hirsutism and virilization. Gonadotropins and estradiol levels were in the postmenopausal range; total testosterone (TT), free testosterone (FT) and 17-hydroxyprogesterone (17-OHP) were elevated with dehydroepiandrosterone sulphate, androstendione and Cortisol serum levels in the normal range, as 24-hr free urinary Cortisol. TT, FT and 17-OHP were normalized, and FSH and LH fell to premenopausal levels on 18th day after a single im injection of the GnRH analogue (GnRHa), triptorelin. Then, a diagnosis of hyperandrogenism of ovarian origin was made and bilateral ovariectomy was performed. Histological study of gonadal tissue revealed diffuse stromal hyperplasia of both ovaries with occasional nests of luteinized cells. With immunoperoxidase techniques these cells stained positively for testosterone and progesterone. One month after surgery, androgen levels were normalized together with regression of most of the clinical signs of virilization. In conclusion, our patient showed a severe virilization developed after menopause; hormonal investigations suggested a gonadotropin dependent ovarian hyperandrogenism, confirmed by histological examination; the presence of luteinized cells in the ovarian stroma was responsible for hyperandrogenism, as confirmed by the immunoperoxidase technique.

Childhood maltreatment in subjects with male-to-female gender identity disorder.

Childhood maltreatment (CM) is quite common and constitutes a nonspecific risk factor for a range of different psychiatric symptoms during lifespan. It has been demonstrated that sexual minorities are at higher risk of maltreatment and abuse, and a high proportion of transsexual subjects report CM. The aim of this study is to evaluate the prevalence of reported CM in a clinical sample of patients with male-to-female Gender Identity Disorder (MtF GID), and to explore the relationship between these early life events, body image and different psychopathological and clinical variables. A consecutive series of 162 patients with male genotype was evaluated from July 2008 to May 2010. A total of 109 subjects (mean age 36±10 years) meeting the criteria for MtF GID and giving their informed consent were considered. The occurrence of CM experiences was evaluated through a face-to-face clinical interview. Patients were asked to complete the Body Uneasiness Test and Symptom Checklist-90 Revised. More than one-fourth of patients reported CM. Maltreated subjects reported a higher body dissatisfaction and display a worse lifetime mental health. The presence of reported CM in these patients has relevant psychopathological implications, and therefore should be carefully investigated.

Prolonged treatment with N-acetylcysteine and L-arginine restores gonadal function in patients with polycistic ovary syndrome

Nitric oxide (NO) plays a wide spectrum of biological actions including a positive role in oocyte maturation and ovulation. Free radicals levels have been shown elevated in polycistic ovary syndrome (PCOS) and therefore would be responsible for quenching NO that, in turn, would play a role in determining oligo- or amenorrhea connoting PCOS. Eight patients with PCOS displaying oligo-amenorrhea from at least 1 yr underwent a combined treatment with N-acetylcysteine (NAC) (1200 mg/die) plus L-arginine (ARG) (1600 mg/die) for 6 months. Menstrual function, glucose and insulin levels, and, in turn, homeostasis model assessment (HOMA) index were monitored. Menstrual function was at some extent restored as indicated by the number of uterine bleedings under treatment (3.00, 0.18–5.83 vs 0.00, 0.00–0.83; p<0.02). Also, a well-defined biphasic pattern in the basal body temperature suggested ovulatory cycles. The HOMA index decreased under treatment (2.12, 1.46–4.42 vs 3.48, 1.62–5.95; p<0.05). In conclusion, this preliminary, open study suggests that prolonged treatment with NAC+ARG might restore gonadal function in PCOS. This effect seems associated to an improvement in insulin sensitivity.