Medical treatment in gender dysphoric adolescents endorsed by SIAMS-SIE-SIEDP-ONIG.

PURPOSE: Despite international guidelines being available, not all gender clinics are able to face gender dysphoric (GD) youth population needs specifically. This is particularly true in Italy. Centers offering specialized support are relatively few and a commonly accepted Italian approach to GD youth has still not been defined. The aim of the present Position Statement is to develop and adhere to Italian guidelines for treatment of GD adolescents, in line with the "Dutch Approach", the Endocrine Society (ES), and the World Professional Association for Transgender Health (WPATH) guidelines. METHODS: An in-depth brainstorming on the application of International guidelines in the Italian context was performed by several dedicated professionals. RESULTS: A staged approach, combining psychological support as well as medical intervention is suggested. In the first phase, individuals requesting medical help will undergo a psycho-diagnostic procedure to assess GD; for eligible adolescents, pubertal suppression should be made available (extended diagnostic phase). Finally, from the age of 16 years, cross-sex hormonal therapy can be added, and from the age of 18 years, surgical sex reassignment can eventually be performed. CONCLUSIONS: The current inadequacy of Italian services offering specialized support for GD youth may lead to negative consequences. Omitting or delaying treatment is not a neutral option. In fact, some GD adolescents may develop psychiatric problems, suicidality, and social marginalization. With access to specialized GD services, emotional problems, as well as self-harming behavior, may decrease and general functioning may significantly improve. In particular, puberty suppression seems to be beneficial for GD adolescents by relieving their acute suffering and distress and thus improving their quality of life.

Investigation on psychological symptoms improves ANDROTEST accuracy in predicting hypogonadism in subjects with sexual dysfunction.

The role of psychological symptoms in recognizing late-onset hypogonadism (LOH) is still controversial. The aim of the study is to evaluate the association between LOH and specific psychological symptoms, and to verify whether investigating intra-psychic domain improves the accuracy of a validated case-history tool (ANDROTEST) in detecting LOH. A consecutive series of 1009 subjects (mean age 49.23±13.34) consulting for sexual dysfunction was studied. Intra-psychic symptoms were investigated by Middlesex Hospital Questionnaire (MHQ), a self-reported questionnaire for screening of mental disorders. A minimum set of two MHQ items was identified through iterative receiver-operating characteristic analysis, with assessment of sensitivity and specificity for hypogonadism (calculated free testosterone <0.225 nmol l(-1)) in an exploratory sample of 462 patients. Sensitivity and specificity were verified in a validation sample of 547 subjects, in which the final two-item version showed an accuracy of 58.4±3.2% in detecting hypogonadism. The combination of the two-item score with ANDROTEST increased the accuracy in predicting hypogonadism (0.741±0.029; P<0.0001) when compared with ANDROTEST (0.696±0.018; P<0.0001) and the two-item score (P<0.05) alone. Hence, combining these two psychological symptoms with a physical scoring system improves its ability in detecting hypogonadism. The combination of the scores should be tested in other studies.

Stable extramarital affairs are breaking the heart.

The relationship between extramarital affairs and cardiovascular risk is still not completely clarified. The aim of this study was to investigate whether extramarital affairs have a protective effect on cardiovascular risk or, conversely, a deleterious one. Among patients studied, 91.8% of the whole sample reported no or occasional extramarital affairs, while 8.2% declared a stable secondary relationship. During a median follow-up of 4 [0-8] years, 95 major adverse cardiovascular events (MACE), eight of which were fatal, were observed. Cox analysis, after adjustment for confounding factors, showed that presence of stable extramarital affair was associated with a higher incidence of MACE (HR = 2.13 [1.12; 4.07], p = 0.023). The introduction in the Cox model of patient perceived partner's hypoactive sexual desire (PPPHSD) attenuates the association (HR 1.86 [0.93; 3.70], p = 0.078). The sample was therefore divided according to PPPHSD. We observed that unadjusted incidence of MACE was significantly associated with presence of extramarital affairs only in men reporting a primal partner without PPPHSD. This association was also confirmed in a Cox regression model, after adjusting for confounders (HR = 2.87 [1.81; 6.98], p = 0.020). We can conclude that to be unfaithful represents an independent risk factor for MACE. Therefore, infidelity induces not only heart trouble in the betrayed partners, but seems to be also able to increase the betrayer's heart-related events.

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.

The age-related decline of testosterone is associated with different specific symptoms and signs in patients with sexual dysfunction.

In males, testosterone (T) levels decline with ageing. Several symptoms characteristic of the ageing process are similar to those related to hypogonadism. The aim of the present study was to evaluate the specific association among hypogonadism-related symptoms and signs and the ageing process. A consecutive series of 1647 (mean age 52.4 +/- 13.1 years) male patients with sexual dysfunction were investigated. Several hormonal and biochemical, instrumental and psychological parameters were studied. The parameters significantly associated with total levels in the entire cohort, after adjustment for confounders, were studied as a function of age and T quartiles. In all age quartiles, low T was associated with higher waist circumference and triglyceride levels and with an increased prevalence of metabolic syndrome. The prevalence of hypoactive sexual desire decreased as a function of T only in the youngest (17- to 42-year old) age quartile as well as the reported reduction in nocturnal erections. In the oldest age quartile, we found an inverse relationship between T levels and the prevalence of severe erectile dysfunction and a positive relationship with intercourse frequency. Accordingly, in the oldest age quartile, subjects with higher T levels showed better penile flow at penile colour doppler ultrasound as well as a better lipid profile. Finally, an inverse association between somatized anxiety and T levels was observed only in the oldest age quartile. In conclusion, our study shows for the first time that in subjects with sexual dysfunction, some hypogonadism-related symptoms can be age-specific. In particular, low T is associated with sexual dysfunction more often in the oldest subjects.

Cardiovascular risk engines can help in selecting patients to be evaluated by dynamic penile color doppler ultrasound.

General dynamic penile color doppler ultrasound (D-PCDU) screening in patients with erectile dysfunction (ED) has been questioned due to an inadequate cost-benefit ratio. The aim of the present study is to evaluate the validity of different risk scores in the identification of patients being screened for arteriogenic ED (AED) at D-PCDU. A consecutive series of 738 patients with ED was studied. AED was defined when peak systolic velocity (PSV) was lower than 25 cm/sec. The assessment of cardiovascular risk was evaluated using different risk engines, derived from the Framingham, the PROCAM and the Progetto Cuore studies. An iterative receiver operator characteristic (ROC) curve analysis was used to determine the most proper threshold for different scales for the screening of AED. Among the patients studied, 52 (7%) had PSV<25 cm/sec. The area under the ROC curves for pathological PSV in relation to cardiovascular risk estimated with different engines was 0.762+/-0.03, 0.716+/-0.03, and 0.667+/-0.03 for Progetto Cuore, Framingham, and PROCAM engines, respectively. Sensitivity and specificity of Progetto Cuore estimated risk were 67%, 71% when a threshold of 15% was chosen. Corresponding figures for Framingham and PROCAM engine were 74%, 57% and 69%, 55%, respectively. If D-PCDU is performed only on patients with cardiovascular risk >15%, who represent about 1/4 of all patients (26.8%), as estimated by Progetto Cuore, about 70% of cases of arteriogenic ED can be identified. Estimated cardiovascular risk, assessed through risk engines, could be used to identify patients who should undergo D-PCDU evaluation for the diagnosis of AED.

A trans-stereoselective synthesis of 3-Halo-4-alkyl(aryl)-NH-azetidin-2-ones

[formula: see text] Conrotatory ring closure of 1-halo-3-aza-4-alkyl-1,3-dienes in refluxing toluene gives rise to 3-halo-4-aryl-2-azetidinones in satisfactory yields. Dehalogenation of the resulting beta-lactams by tris(trimethylsilyl)silane furnished 3-unsubstituted azetidinones, valuable intermediates in the synthesis of biologically active compounds.

[The pathogenetic bases of hemicrania]. / Basi patogenetiche dell'emicrania.

Studies of regional cerebral blood flow in migraine with aura have shown that the aura phase is associated with hypoperfusion in the cortical area which relates topographically to the clinical symptoms. Thus, the previously hypoperfused area becomes hyperperfused. However, there is no strict association between hyperperfusion and headache. The mode of hypoperfusion propagation recalls the circulatory manifestations of experimental cortical spreading depression. In addition, there are no focal cerebral blood flow abnormalities in migraine without aura. During the headache phase of migraine, dilation of both the large extra- and intracranial arteries takes place. A bulk of biochemical evidence has suggested that the pain in migraine is caused by blood vessels which are dilated and sensitized by circulating pain-producing substances e.g. bradykinin, serotonin and histamine (sterile inflammation). Recently, perivascular trigeminal fibres (trigeminovascular system) which, when stimulated, release sensory peptides (substance P and the calcitonin gene-related peptide) capable of provoking marked vasodilation and plasma extravasation (neurogenic inflammation) have been identified. Thus, the activation of the trigeminovascular system is probably involved in the vasodilatative and nociceptive phenomena of the migraine attack. The finding of a reduced endorphinergic brain tonus in migraine patients supports the hypothesis of a central nociceptive derangement in migraine. Nonetheless, the exact relationship between vasodilation and headache remains to be defined. However, the potent antimigraine effectiveness of sumatriptan--an agonist of the serotonin receptors which selectively constricts dilated arteries during the migraine attack--once again stresses the fact that serotonin is probably the crucial factor in the link between vasodilation and headache.

Action of nimodipine on sympathomimetic mydriatics in humans.

In 12 healthy volunteers, the effects of a single oral dose of nimodipine (40 mg) on pupil size and on the mydriasis induced by conjunctival instillation of tyramine and phenylephrine were studied by using a TV monocular infrared pupillometer. Nimodipine alone was unable to modify the pupil area. When compared with placebo, the Ca2+ entry blocker reduced the pupil dilation caused by tyramine, whereas it did not affect the phenylephrine-induced mydriasis. Since tyramine provokes mydriasis by releasing neuronal norepinephrine, a full adrenoceptor agonist, whereas phenylephrine acts only on alpha 1-adrenoceptors insensitive of extracellular Ca2+, the hypothesis may be advanced that a heterogeneous population of alpha-adrenoceptors, located in the human iris dilator muscle and differently sensitive to Ca2+ entry blockade, is responsible for the reduction of the tyramine-induced mydriasis. Apart from this putative mechanism, the results suggest that nimodipine reduces the pupillary response to adrenergic activation in the human eye.

Long-term ergotamine abuse: effect on adrenergically induced mydriasis.

The mydriatic action of sympathomimetic eyedrops after a therapeutic dose of ergotamine was measured in migraine patients with and without histories of long-term ergotamine abuse. Mydriasis induced by the postsynaptic alpha 1-agonist phenylephrine was similar in both groups of patients tested, whereas pupillary dilation caused by the release of noradrenaline tyramine was markedly greater in patients with histories of ergotamine abuse. The enhanced response to tyramine disappeared after drug withdrawal. These findings indicate that continuous ergotamine medication causes a reversible alterations in iris sympathetic transmission. This manifestation may reflect a central inhibition of pupillary sympathetic activity.

The treatment of congenital constricting bands by Ombredanne's two stage operation. Review of 13 cases.

The authors report their experience in the treatment of congenital constricting bands by Ombrédanne's two stage operation. Fourteen bands completely encircled the limb and 2 were incomplete. The patients were followed up from 6 months to 15 years (average 3 years) and in all cases the results were excellent. The literature on the pathogenesis is reviewed.

Surgical treatment of metatarsus varus during the growth period.

The writers describe their experience in the treatment of congenital metatarsus varus. They describe an original technique for anterior transfer or shortening of peroneus brevis which they consider to be indicated when the varus deformity is less than 15 degrees and is correctable manually. They also describe Heyman's technique and give their results in twenty-five cases. They consider that this operation is indicated only for varus deformity of the forefoot exceeding 15 degrees which is correctable manually. In both these techniques it is essential that the hindfoot should be in the correct midline axis. Where manual correction of the hindfoot is not possible they advise Dillwyn Evans' operation. In varus deformity of the 1st metatarsal exceeding 15 degrees, and not correctable manually, they suggest osteotomy of the base of this bone, displacing it the correct degree and fixing it with a wedge of homoplastic bone inserted into the gap.