Sociodemographic profile, health-related behaviours and experiences of healthcare access in Italian transgender and gender diverse adult population.

PURPOSE: Information on the general health of transgender and gender diverse (TGD) individuals continues to be lacking. To bridge this gap, the National Institute of Health in Italy together with the National Office against Racial Discriminations, clinical centres, and TGD organizations carried out a cross-sectional study to define the sociodemographic profile, health-related behaviours, and experiences of healthcare access in Italian TGD adult population. METHODS: A national survey was conducted by Computer-Assisted Web Interviewing (CAWI) technique. Collected data were compared within the TGD subgroups and between TGD people and the Italian general population (IGP). RESULTS: TGD respondents were 959: 65% assigned female at birth (AFAB) and 35% assigned male at birth (AMAB). 91.8% and 8.2% were binary and non-binary TGD respondents, respectively. More than 20% of the TGD population reported to be unemployed with the highest rate detectable in AMAB and non-binary people. Cigarette smoking and binge drinking were higher in the TGD population compared with IGP (p < 0.05), affecting TGD subgroups differently. A significant lower percentage of AFAB TGD people reported having had screening for cervical and breast cancer in comparison with AFAB IGP (p < 0.0001, in both cases). Over 40% was the percentage of AFAB and non-binary TGD people accessing healthcare who felt discriminated against because of their gender identity. CONCLUSIONS: Our results are a first step towards a better understanding of the health needs of TGD people in Italy in order to plan the best policy choices for a more inclusive public health.

Transition from pediatric to adult care in patients with Turner syndrome in Italy: a consensus statement by the TRAMITI project.

PURPOSE: Transition from pediatric to adult care is associated with significant challenges in patients with Turner syndrome (TS). The objective of the TRansition Age Management In Turner syndrome in Italy (TRAMITI) project was to improve the care provided to patients with TS by harnessing the knowledge and expertise of various Italian centers through a Delphi-like consensus process. METHODS: A panel of 15 physicians and 1 psychologist discussed 4 key domains: transition and referral, sexual and bone health and oncological risks, social and psychological aspects and systemic and metabolic disorders. RESULTS: A total of 41 consensus statements were drafted. The transition from pediatric to adult care is a critical period for patients with TS, necessitating tailored approaches and early disclosure of the diagnosis to promote self-reliance and healthcare autonomy. Fertility preservation and bone health strategies are recommended to mitigate long-term complications, and psychiatric evaluations are recommended to address the increased prevalence of anxiety and depression. The consensus also addresses the heightened risk of metabolic, cardiovascular and autoimmune disorders in patients with TS; regular screenings and interventions are advised to manage these conditions effectively. In addition, cardiac abnormalities, including aortic dissections, require regular monitoring and early surgical intervention if certain criteria are met. CONCLUSIONS: The TRAMITI consensus statement provides valuable insights and evidence-based recommendations to guide healthcare practitioners in delivering comprehensive and patient-centered care for patients with TS. By addressing the complex medical and psychosocial aspects of the condition, this consensus aims to enhance TS management and improve the overall well-being and long-term outcomes of these individuals.

The TRansition Age Management in Turner syndrome in Italy (TRAMITI) project aims to improve care for individuals with Turner Syndrome (TS) during their transition from pediatric to adult care. A team of 15 physicians and 1 psychologist collaborated to create a comprehensive set of 41 consensus statements, covering four key areas: transition and referral, sexual and bone health and oncological risks, social and psychological aspects and systemic and metabolic disorders. The consensus statements highlight the importance of patient-centered care, early intervention and long-term monitoring. They emphasize a multidisciplinary approach to address the complex medical and psychosocial aspects of TS. During the critical transition period, tailored approaches and early disclosure of the diagnosis are recommended to promote self-reliance and healthcare autonomy. To mitigate long-term complications, the consensus addresses fertility preservation and bone health strategies. It also recommends psychological or psychiatric evaluations to tackle the increased prevalence of anxiety and depression in patients with TS. In addition, strategies for addressing the heightened risk of metabolic, cardiovascular and autoimmune disorders in patients with TS are proposed. Regular screenings and interventions are advised to effectively manage these conditions. Furthermore, cardiac abnormalities, including aortic dissections, require close monitoring and early surgical intervention if specific criteria are met. Overall, the TRAMITI consensus statement provides valuable insights and evidence-based recommendations. It offers guidance for healthcare practitioners in delivering comprehensive and patient-centered care for individuals with TS. By addressing both medical and psychosocial aspects, the consensus aims to enhance TS management and improve the well-being and long-term outcomes of those affected by this genetic disorder.

SIGIS-SIAMS-SIE position statement of gender affirming hormonal treatment in transgender and non-binary people.

PURPOSE: Gender Incongruence (GI) is a marked and persistent incongruence between an individual's experienced and the assigned gender at birth. In the recent years, there has been a considerable evolution and change in attitude as regards to gender nonconforming people. METHODS: According to the Italian Society of Gender, Identity and Health (SIGIS), the Italian Society of Andrology and Sexual Medicine (SIAMS) and the Italian Society of Endocrinology (SIE) rules, a team of experts on the topic has been nominated by a SIGIS-SIAMS-SIE Guideline Board on the basis of their recognized clinical and research expertise in the field, and coordinated by a senior author, has prepared this Position statement. Later on, the present manuscript has been submitted to the Journal of Endocrinological Investigation for the normal process of international peer reviewing after a first internal revision process made by the SIGIS-SIAMS-SIE Guideline Board. RESULTS: In the present document by the SIGIS-SIAMS-SIE group, we propose experts opinions concerning the psychological functioning, gender affirming hormonal treatment, safety concerns, emerging issues in transgender healthcare (sexual health, fertility issues, elderly trans people), and an Italian law overview aimed to improve gender non-conforming people care. CONCLUSION: In this Position statement, we propose experts opinions concerning the psychological functioning of transgender people, the gender-affirming hormonal treatment (full/partial masculinization in assigned female at birth trans people, full/partial feminization and de-masculinization in assigned male at birth trans people), the emerging issues in transgender health care aimed to improve patient care. We have also included an overview of Italian law about gender affirming surgery and registry rectification.

Venous thrombo-embolism as a complication of cross-sex hormone treatment of male-to-female transsexual subjects: a review.

Administration of cross-sex hormones to male-to-female transsexual subjects, usually oestrogens + often anti-androgens, such as cyproterone acetate, carries a risk of venous thromboembolism (VTE). VTE usually occurs in the first year of oestrogen administration. Ethinyl oestradiol, due to its chemical structure, was in 2003 identified as a major factor in the occurrence of VTE. Most clinics do not prescribe ethinyl oestradiol any longer, but people who take hormones without medical supervision use often oral contraceptives containing ethinyl oestradiol, many times in overdose. Cessation of use of ethinyl oestradiol and peri-operative thrombosis prophylaxis for surgery have reduced prevalence rate of VTE. Other oral oestrogens should not be overdosed, and transdermal oestrogen is to be preferred. Thrombosis prophylaxis for surgery is mandatory. It seems advisable to stop hormone use at least 2 weeks before major surgery, to be resumed only after 3 weeks following full mobilisation.

Effects of long-term high dose testosterone administration on vaginal epithelium structure and estrogen receptor-α and -ß expression of young women.

To date, the effects of long-term testosterone (T) administration on the human vagina are not completely understood. Thus, the aim of this study was to investigate the effects of long-term T treatment on vaginal tissue histology, estrogen receptor alpha (ERα) and beta (ERß) expression and proliferation in female to male transsexual subjects (FtM). We compared vaginal samples from FtM subjects with those of premenopausal women (PrM) and postmenopausal women (M) not receiving any hormonal treatment for at least 2 years. Vaginal tissue samples from 16 FtM subjects treated with T (intramuscular injections of 100 mg Testoviron Depot/7-10 days for at least 1 year), undergoing sex reassignment surgery, and 16 PrM and 16 M subjects undergoing a vaginal hysterectomy for prolapse, were collected. For each sample, morphology, glycogen content, proliferation (ki-67), ERα and ERß expression were evaluated. Vaginal samples from FtM showed a loss of normal architecture of the epithelium, intermediate and superficial layers were completely lost, and glycogen content was depleted. T administration resulted in a strong proliferation reduction when compared with both M and PrM subjects. Stromal and epithelial ERα as well as ERß were significantly decreased in FtM when compared with PrM subjects. In conclusion, our data suggests that systemic T administration at supraphysiological dosage, determines profound changes in histomorphology and reduces ERs expression and proliferation of vaginal epithelium.

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.

Three-dimensional transvaginal sonography in local staging of cervical carcinoma: description of a novel technique and preliminary results.

OBJECTIVE: To evaluate the feasibility of three-dimensional multiplanar sonography in the local staging of cervical carcinoma. METHODS: Between January 2005 and May 2006, 14 patients with invasive cervical carcinoma underwent transvaginal volume ultrasound examination prior to primary surgery. Parametrial invasion was evaluated in the coronal plane, while both bladder and rectal invasion were evaluated in the sagittal plane. Ultrasound findings were compared with surgical and histological results. RESULTS: In 12 of the 14 cases, three-dimensional ultrasound findings were compatible with pathology results. In the remaining two cases, either infiltration of right parametrium or rectal invasion were suspected at ultrasound but not confirmed at pathology. CONCLUSIONS: Despite the small number of patients evaluated, three-dimensional multiplanar sonography appears to be a promising technique in the local staging of cervical carcinoma.

Short-term modification of sex hormones is associated with changes in ghrelin circulating levels in healthy normal-weight men.

The aim of this study was to evaluate the effect of selective and short-term sex hormone modifications on ghrelin levels in normal-weight eugonadal men undergoing hormonal contraceptive treatments. Seven men received an oral progestin [cyproterone acetate (CPA) or dienogest (DNG)] 10 mg/day for 3 weeks (CPA-DNG group), 7 CPA orally 5 mg/day in association with testosterone enanthate (TE) im 200 mg/week for 8 weeks (CPA-TE group), and 7 placebo (PLAC) for 8 weeks (PLAC group). Anthropometry and blood levels of LH, FSH, testosterone, estradiol, glucose, insulin and total ghrelin were evaluated. At baseline, no parameters differed among the three groups. After treatment, LH and FSH decreased in both CPA-DNG and CPA-TE groups, whereas they did not change in the PLAC group. Testosterone and estradiol decreased in the CPA-DNG group to the hypogonadal range, increased in the CPA-TE group to supraphysiological concentrations and, as expected, remained unchanged in the PLAC group. Total ghrelin levels increased in the CPA-DNG, decreased in the CPA-TE and did not change in the PLAC group. Ns modifications in the other parameters were observed in any group, demonstrating that the short-term changes of circulating sex hormones are able to modify ghrelin levels. These data, therefore, suggest that sex steroids are important regulators of ghrelin in normal-weight healthy men too.

Follistatin decreases activin-stimulated FSH secretion with no effect on GnRH-stimulated FSH secretion in prepubertal male monkeys.

Follistatin is an activin-binding glycoprotein that decreases FSH secretion in vitro and in vivo in rats. The mechanism by which follistatin acts is unclear, but it has been suggested that it may bind endogenous activin and neutralize its effects. In this study, we wished to test the ability of follistatin to suppress FSH secretion in vivo in primates whose FSH secretion has been stimulated by activin or by GnRH. Six prepubertal male monkeys were injected intravenously with human recombinant follistatin at the dose of 90 micrograms/kg or 180 micrograms/kg plus activin (90 micrograms/kg) or GnRH (10 micrograms/kg). Frequent blood samples were drawn for 12 hours following each injection. Bio FSH and LH levels were measured in those samples. GnRH and activin each stimulated FSH bioactivity. Both doses of follistatin significantly inhibited the activin-induced increase in FSH (p < 0.05). The GnRH-induced increase in FSH was not affected by follistatin. LH levels were not affected by follistatin in any of the studies. These data suggest that follistatin can suppress the activin-induced increase in FSH in primates and is consistent with the hypothesis that follistatin can block the physiological effects of endogenous activin in primates. This effect is likely to be due to the binding of follistatin to activin either in the peripheral circulation or at the pituitary level.

Role of gonadotrophin releasing hormone secretory dynamics in the control of the human menstrual cycle.

The pattern of episodic gonadotrophin releasing hormone (GnRH)-driven luteinizing hormone (LH) secretion changes dynamically across the human menstrual cycle. Adherence to a specific regimen of pulse amplitude and frequency is critical for normal ovulation, menstrual cyclicity and reproductive function. Derangements of episodic LH secretion are associated with anovulation. We have shown that in the human slowing of GnRH-induced LH pulses results in lower ovulatory rates and dysfunctions of the mid-cycle LH surge. This information is relevant for the understanding of the endocrine dynamics of the menstrual cycle both in normal and anovulatory subjects.

Endocrine response determines the clinical outcome of pulsatile gonadotropin-releasing hormone ovulation induction in different ovulatory disorders.

To accrue systematic information in different ovulatory disorders on the precise relationship among endocrine response, clinical outcome, and the occurrence of complications, we treated 114 patients with pulsatile GnRH (2.5-5.0 micrograms, iv, every 60 min) for 187 cycles and compared them to 20 normal menstrual cycles. Thirty of these patients had primary hypogonadotropic amenorrhea (PHA; 40 cycles), 33 had other forms of hypogonadotropic hypogonadism (HH; 55 cycles), and 51 had polycystic ovary syndrome (PCOS; 92 cycles). Daily blood samples were drawn for hormone determinations. In PCOS, 50 cycles were preceded by GnRH analog suppression. PHA treatment cycles were characterized by the reestablishment of a normal endocrine pattern, almost no dose-related endocrine differences, elevated ovulatory (93%) and conception rates (23%), and no multiple pregnancies. In the HH subjects the ovulatory (91%) and pregnancy rates (31%) were high; however, while the lower GnRH dose elicited a normal endocrine pattern, the 5-micrograms dose induced excessive folliculogenesis and high estradiol levels and was associated with most of the multiple pregnancies of this study (three of four). GnRH analog suppression was successfully used to avoid recurrence of ovarian over-stimulation in two HH subjects. Finally, GnRH analog suppression in PCOS permitted normalization of the follicular phase endocrine pattern, achievement of good ovulatory (76%) and pregnancy (28%) rates, and avoidance of multiple pregnancies; however, luteal phase steroid secretion was abnormal, and the abortion rate remained elevated (43%). Obesity was associated with a reduced ovulatory rate in PCOS, but not in hypogonadotropic, subjects. Thus, we can conclude that in pulsatile GnRH ovulation induction: 1) a profound hypogonadotropic condition, whether spontaneous as in PHA or induced with GnRH analogs as in other ovulatory disorders, is associated with optimal menstrual cycle restoration, high ovulatory and conception rates, and virtually absent risks of multiple pregnancy; 2) residual hypothalamic activity in HH may be responsible for supraphysiological pituitary-ovarian stimulation and result in multiple pregnancy unless a low GnRH dose (2.5 micrograms/bolus) or GnRH analog pretreatment is employed; 3) obesity does not affect treatment outcome in hypogonadotropic patients; and 4) the high spontaneous abortion rate in PCOS may be related to corpus luteum dysfunction.

Polycystic ovary syndrome: abnormalities and management with pulsatile gonadotropin-releasing hormone and gonadotropin-releasing hormone analogs.

Ovulation induction with pulsatile gonadotropin-releasing hormone achieves high ovulatory and pregnancy rates in hypogonadotropic hypogonadism while limiting the occurrence of ovarian hyperstimulation and multiple pregnancy. However, this form of therapy is apparently less effective in polycystic ovary syndrome. The administration of a gonadotropin-releasing hormone analog for 4 to 8 weeks before the initiation of pulsatile gonadotropin-releasing hormone ovulation induction can temporarily correct endocrine abnormalities of polycystic ovary syndrome, such as excessive luteinizing hormone and androgen secretion, and improve ovulatory and pregnancy rates in these patients. For optimal results, this pretreatment should probably be repeated before each pulsatile gonadotropin-releasing hormone ovulation induction cycle. Obesity is associated with a lower success rate, and spontaneous abortion remains a prominent complication in polycystic ovary syndrome even after gonadotropin-releasing hormone analog suppression. With this regimen the risks of ovarian hyperstimulation and multiple pregnancy are virtually abolished. Thus, pulsatile gonadotropin-releasing hormone appears to be highly effective and safe for ovulation induction in patients with polycystic ovary syndrome also, provided that this treatment is preceded by pituitary-ovarian suppression with a gonadotropin-releasing hormone analog.

Evidence for a specific role of GnRH pulse frequency in the control of the human menstrual cycle.

An adequate frequency of gonadotropin-releasing hormone (GnRH) pulses appears to be important for physiological gonadotropin secretion. However, limited information exists on the exact role of this parameter in the regulation of the human menstrual cycle. Thus we studied gonadotropin and gonadal steroid secretion in 32 women with primary hypogonadotropic amenorrhea who received pulsatile GnRH (60 to 120 micrograms/day) at 60- or 120-min intervals for a total of 64 ovulation induction cycles. Ovulation was achieved in 94% of 60-min and in 70% of 120-min cycles P less than 0.05). In the follicular phase of ovulatory cycles, estradiol (E2) levels did not differ among the four groups; however, mean luteinizing hormone (LH) levels were lower (P less than 0.005), and the midcycle LH surge was severely blunted in cycles of subjects receiving 120 micrograms/day (5 micrograms/bolus) GnRH every 120 min compared with subjects receiving the same dose of GnRH per day or per bolus every 60 min. Luteal progesterone (only in 60 micrograms/day GnRH cycles) and E2 levels were lower in 120-min than in 60-min cycles (P less than 0.05). The use of the higher daily GnRH dose (120 micrograms/day) reduced or abolished the frequency-associated hormone level differences. We conclude that a low frequency of pulsatile GnRH in women 1) decreases mean LH levels and blunts the midcycle gonadotropin surge, 2) does not increase follicle-stimulating hormone concentrations, and 3) is associated with a reduced rate of ovulation.

The abnormal response of polycystic ovarian disease patients to exogenous pulsatile gonadotropin-releasing hormone: characterization and management.

Pulsatile GnRH administration for induction of ovulation is often ineffective in polycystic ovarian disease (PCOD) patients. To clarify and correct the endocrine mechanisms underlying this deranged response we gave pulsatile GnRH (5 micrograms, iv, every 60 min) to idiopathic hypogonadotropic hypogonadism (IHH) patients with primary amenorrhea for 19 cycles and to PCOD patients for 24 cycles before (pre-A) and for 25 cycles after (post-A) GnRH analog suppression. Compared to IHH, pre-A cycles were characterized by elevated LH, estradiol, and testosterone; reduced luteal phase progesterone; and low ovulatory (38%) and pregnancy rates (8%). Conversely, LH, estradiol, and follicular phase testosterone levels were lower in post-A than in pre-A cycles, while luteal phase progesterone was higher; the endocrine pattern of post-A cycles closely resembled the one of IHH cycles. The ovulatory and pregnancy rates of PCOD patients improved remarkably in post-A cycles (90% and 38%, respectively). Excessive body weight was associated with a lower incidence of ovulation in both pre-A (15%) and post-A cycles (75%). A worse endocrine pattern and a lower ovulatory rate (50%) were obtained when a second consecutive post-A cycle occurred without repeating GnRH analog suppression. No signs of even mild ovarian hyperstimulation and no multiple pregnancies were recorded in the post-A cycles. We conclude that in PCOD 1) deranged pituitary sensitivity, excessive ovarian androgen secretion, and obesity critically affect folliculogenesis and ovulation; 2) pituitary-gonadal suppression with a GnRH analog markedly improves the endocrine and clinical responses to pulsatile GnRH ovulation induction; 3) optimal results can be achieved only when each pulsatile GnRH cycle is preceded by GnRH analog suppression; and 4) pulsatile GnRH is highly effective and safe for ovulation induction, provided that PCOD subjects are pretreated with a GnRH analog.