Maria Cristina Meriggiola

Diagnostic accuracy of 18F-FDG PET/CT in characterizing ovarian lesions and staging ovarian cancer: correlation with transvaginal ultrasonography, computed tomography, and histology.

AimsTo (a) assess the accuracy of 18F-FDG PET/CT in distinguishing malignant from benign pelvic lesions, compared to transvaginal ultrasonography (TVUS) and (b) to establish the role of whole-body 18F-FDG PET/CT, compared to contrast enhanced computed tomography (CT), in staging patients with ovarian cancer. PatientsFifty consecutive patients with a pelvic lesion, already scheduled for surgery on the basis of physical examination, TVUS, and serum Ca125 levels, were enrolled in the study. Patients age ranged between 23 and 89 years (mean 64). All patients underwent TVUS including a colour Doppler study followed by a thorax and abdominal CT scan, and whole-body 18F-FDG PET/CT within 2 weeks prior to surgery. Histological findings obtained at surgery were taken as the ‘gold standard’ to compare 18F-FDG PET/CT and TVUS, and 18F-FDG PET/CT vs. CT. When tissue analysis showed ovarian cancer, the accuracy of 18F-FDG PET/CT and CT were compared for the purpose of obtaining a precise staging. ResultsAt surgery, the ovarian lesions were malignant in 32/50 patients (64%) and benign in the remaining 18/50 patients (36%). The sensitivity, specificity, NPV, PPV and accuracy of 18F-FDG PET/CT were 87%, 100%, 81%, 100% and 92%, respectively, compared with 90%, 61%, 78%, 80% and 80%, respectively, for TVUS. In staging ovarian cancer, 18F-FDG PET/CT results were concordant with final pathological staging in 22/32 (69%) patients while CT results were concordant in 17/32 (53%) patients. CT incorrectly down-staged four out of six stage IV patients by missing distant metastasis in the liver, pleura, mediastinum, and in left supraclavicular lymph nodes, which were correctly detected by 18F-FDG PET/CT. ConclusionPET/CT with 18F-FDG provides additional value to TVUS for the differential diagnosis of benign from malignant pelvic lesions, and to CT for the staging of ovarian cancer patients.

Male Hormonal Contraception: A Double-Blind, Placebo-Controlled Study

BACKGROUNDnThis study was performed to assess spermatogenesis suppression and safety of a new combination of an etonogestrel (ENG) implant combined with testosterone undecanoate (TU) injections for male contraception. This is the first large placebo-controlled study for male hormonal contraception.nnnDESIGN AND STUDY SUBJECTSnIn this double-blind, multicenter study, we randomly assigned 354 healthy men to receive either a low- or high-release ENG implant sc combined with im TU injections (750 mg every 10 or 12 wk or 1000 mg every 12 wk) or placebo implant and injections. Treatment duration was 42 or 44 wk and posttreatment follow-up at least 24 wk.nnnRESULTSnOverall, spermatogenesis was suppressed to 1 million/ml or less at wk 16 in 89% of men, with approximately 94% in two high-release ENG groups. Suppression was maintained up to the end of the treatment period in 91% of men. For all men who completed the treatment period, 3% never achieved 1 million/ml or less. Median recovery time to a sperm concentration above 20 million/ml was 15 wk (mean 17 wk, 95% confidence interval 16-18 wk). Treatment was well tolerated. As compared with the placebo group, more men in the active treatment groups reported adverse events such as weight gain, mood changes, acne, sweating, or libido change. For both spermatogenesis suppression and safety, differences were small between the active treatment groups.nnnCONCLUSIONSnThe combination of an ENG implant with TU injections is a well-tolerated male hormonal method, providing effective and reversible suppression of spermatogenesis. Although the results are good, there is still room for improvement, possibly by adjusting the dose regimen or changing the mode of application.

Cross-sex hormone administration changes pain in transsexual women and men.

Abstract Chronic pain is gender‐related, since there is a clear predominance of one sex with respect to the other in most pain syndromes. Gonadal hormones are known to affect the occurrence and incidence of pain. Transsexuals receive cross‐sex hormones to develop and maintain somatic characteristics of the opposite sex: male to female transsexuals (MtF) are administered estrogens and anti‐androgens, while female to male transsexuals (FtM) are administered androgens. Hence, these subjects represent a model to study the relationship between sex hormones and pain. Questionnaires dealing with sociodemographic data and pain (occurrence, frequency, duration, intensity, location and associated symptoms) were administered to both MtF and FtM transsexuals under hormone treatment for sex reassignment for at least 1 year. Forty‐seven MtF and 26 FtM completed the questionnaires. Fourteen of the 47 MtF (29.8%) reported painful conditions, which in 11 subjects were not present before the beginning of hormone treatment. Pain consisted mainly of headaches and breast and musculoskeletal pain. Five subjects suffered from more than one pain condition. Sixteen of the 26 FtM (61.5%) reported pain. In 11 subjects, the pain was present before the beginning of hormone intake, and in 6 of them it improved after testosterone administration. These data suggest that marked changes in sex hormones affect the occurrence of pain in a high percentage of humans but not in all of them. Whether these effects are due to peripheral or central actions of sex steroids is unknown.

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

INTRODUCTIONnCross-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.nnnAIMSnThis 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.nnnMETHODSnA consecutive series of 125 subjects meeting the criteria for GD who not had genital reassignment surgery were considered.nnnMAIN OUTCOME MEASURESnSubjects 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.nnnRESULTSnAmong 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.nnnCONCLUSIONSnThe 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.

Effects of Three Different Testosterone Formulations in Female-to-Male Transsexual Persons

INTRODUCTIONnGender dysphoria is characterized by a strong discomfort with the gender assigned at birth and the urge to live as a member of the opposite gender. The acquisition of phenotypic features of the desired gender requires the use of cross-sex hormones. Female-to-male (FtM) transsexual persons are treated with testosterone to induce virilization.nnnAIMnThe aim of the study was to assess the effects of three different testosterone formulations on body weight and composition and metabolic and bone parameters.nnnMETHODSnForty-five FtM transsexuals were randomly assigned to receive testoviron depot (i.m.: 100u2009mg/10 days; nu2009=u200915), testosterone gel (50u2009mg/die; nu2009=u200915), and testosterone undecanoate (i.m.: 1,000u2009mg every 6 weeks for the first 6 weeks and then every 12 weeks, nu2009=u200915). FtM individuals were studied before, at week 30, and at week 54 of testosterone treatment.nnnMAIN OUTCOME MEASURESnAnthropometric, metabolic, bone, hematological, and biochemical parameters were evaluated at baseline and after 12 months of treatment.nnnRESULTSnLean body mass significantly increased and fat mass decreased in all groups. No modifications were reported in fasting insulin and insulin sensitivity index. High-density plasma lipoprotein levels declined significantly and low-density lipoprotein concentrations increased significantly in the three groups. The activated partial thromboplastin time and factor I did not change while prothrombin time significantly increased in all groups. At week 54, all subjects were amenorrheic and time to amenorrhea did not differ between the three groups. Current general life satisfaction was increased in all subjects after 1 year of treatment.nnnCONCLUSIONSnOne-year testosterone administration in FtM transsexuals appears to be very safe with no differences among the testosterone formulations used. Our study is preliminary, and the detection of subtle or long-term differences in the effects of the three formulations may require further larger and longer term studies in this and other populations.

Long-term influence of combined oral contraceptive use on the clinical course of relapsing–remitting multiple sclerosis

OBJECTIVEnTo assess the long-term effects of combined oral contraceptives (COCs) on the clinical course of relapsing-remitting multiple sclerosis (RRMS), focusing on disability progression and evolution to secondary-progressive multiple sclerosis (SPMS).nnnDESIGNnRetrospective and exploratory study.nnnSETTINGnAcademic medical center.nnnPATIENT(S)nA total of 174 women with clinically confirmed MS; of these, 33 had evolved to SPMS at the time of enrollment in the study, whereas 141 still had a relapsing-remitting form of disease.nnnINTERVENTION(S)nWomen were interviewed to obtain gynecologic and obstetric history.nnnMAIN OUTCOME MEASURE(S)nExpanded Disability Status Scale (EDSS); Multiple Sclerosis Severity Score (MSSS); annualized relapse rate; evolution to SPMS.nnnRESULT(S)nMean±SD duration of disease was 14.3±9.8 years. Compared with non-users of COCs, COC users had lower EDSS scores and MSSS only in the subset of the population with prior or current immunomodulatory treatment. Nonuse of COCs was a predictor of disease evolution in SPMS, whether treated or not with immunomodulatory drugs. The annualized relapse rate was not influenced by COC use. No differences in EDSS scores and evolution to SPMS depending on COC formulation were detected.nnnCONCLUSION(S)nOur results suggest that COC use is associated with a less severe disease and less severe evolution. Whether different doses or types of progestin may have different effects remains to be defined.

Endocrine care of transpeople part I. A review of cross‐sex hormonal treatments, outcomes and adverse effects in transmen

Gender dysphoria (GD) is characterized by discomfort with the assigned or birth gender and the urge to live as a member of the desired sex. The goal of medical and surgical treatment is to improve the well‐being and quality of life of transpeople. The acquisition of phenotypic features of the desired gender requires the use of cross‐sex hormonal therapy (CHT). Adult transmen are treated with testosterone to induce virilization. In adolescents with severe and persistent GD, consideration can be given to arresting puberty at Tanner Stage II and if dysphoria persists, CHT is generally started after 16 years of age. Currently available short‐ and long‐term safety studies suggest that CHT is reasonably safe in transmen. Monitoring of transmen should be more frequent during the first year of cross‐sex hormone administration reducing to once or twice per year thereafter. Long‐term monitoring after sex reassignment surgery (SRS) includes annual check‐ups as are carried out for natal hypogonadal men. In elderly transmen, special attention should be paid to haematocrit in particular. Screening for breast and cervical cancer should be continued in transmen not undergoing SRS.

Sexuality and Psychopathological Aspects in Premenopausal Women with Metabolic Syndrome

INTRODUCTIONnMetabolic syndrome (MetS) is a cluster of cardiovascular risk factors that have been suggested to impact female sexual function.nnnAIMSnThis study aims to assess the prevalence of female sexual dysfunction (FSD) in premenopausal women with MetS compared with healthy controls (HC). Psychopathological aspects and the relationship to FSD were also evaluated in both groups.nnnMETHODSnTwo hundred four premenopausal women, of whom 98 had diagnosis of MetS, were asked to complete the Female Sexual Function Index (FSFI), the Female Sexual Distress Scale (FSDS), and the Middlesex Hospital Questionnaire (MHQ). Routine laboratory tests and anthropometric measurements were routinely performed.nnnMAIN OUTCOME MEASURESnFSFI and FSDS questionnaires, prevalence of FSD, and MHQ scores.nnnRESULTSnIn the MetS group compared with the HC group, we found: a lower global FSFI score (P=0.005), higher prevalence of pathological scores compared with HC group, and lower scores in the desire, arousal, lubrication, and orgasm domains. An inverse correlation between the FSFI score and the number of risk factors for MetS was detected. MetS women reported significantly higher total scores in the somatization and depression domains when compared with the HC group. The logistic regression showed that high triglycerides (odds ratio [OR] 3.097; 95% confidence interval [CI] 1.272-7.542; P=0.026) and somatization (OR 7.068; CI 95% 2.291-21.812; P=0.001) are independently associated with FSD in premenopausal women.nnnCONCLUSIONSnOur results indicate a higher prevalence of sexual dysfunction in MetS women. A number of risk factors for MetS are positively associated with FSD and higher triglycerides seem to be the strongest predictors of sexual dysfunction. Psychopathological dimensions such as somatization are strongly associated with sexual dysfunction.

Changes in Vaginal Physiology of Menopausal Women with Type 2 Diabetes

INTRODUCTIONnMetabolic disorders, such as type 2 diabetes, have been associated with an increased risk of development of female sexual dysfunction (FSD). In experimental studies, vascular, neuronal, and hormonal responsiveness alteration at vaginal level were proposed as contributors to the onset of FSD in women with diabetes; however, conclusive data on humans are still lacking.nnnAIMSnThe study aimed to assess changes in vascularization, sex steroid receptors, nitric oxide synthase, and aquaporin-2 (AQP2) expression occurring at vaginal level in women with diabetes.nnnMETHODSnVaginal biopsies were obtained from 21 postmenopausal women, 10 of whom were diagnosed as having type 2 diabetes mellitus. CD31, estrogen receptor-α (ERα) and androgen receptor (AR) expression and localization were analyzed by immunostaining. Expression of endothelial (eNOS) and neuronal (nNOS) nitric oxide synthase isoforms and AQP2 were also assessed in vaginal samples.nnnMAIN OUTCOMES MEASURESnChanges in vaginal vascularization, sex steroids receptor, eNOS, nNOS and AQP2 expression.nnnRESULTSnVaginal samples from women with diabetes showed an increased microvessel density in the lamina propria, which were morphologically disrupted suggesting an angiogenic compensatory mechanism. While no differences were seen in ERα, AR expression was significantly reduced in the vaginal epithelium and lamina propria of women with diabetes. Similarly, the gene and protein expressions of both nNOS and eNOS were significantly reduced in patients with diabetes, while AQP2 mRNAs level did not significantly differ between the two groups.nnnCONCLUSIONnDiabetes greatly impacts vaginal physiology, being associated with alterations of the vaginal lamina propria vascular network, nitrergic signaling, and AR expression. These alterations may contribute to the increased risk of FSD development in women with diabetes.

Cyproterone acetate vs leuprolide acetate in combination with transdermal oestradiol in transwomen: a comparison of safety and effectiveness.

To retrospectively compare the effectiveness and safety of 1‐year administration of transdermal oestradiol (TE) with cyproterone acetate (CPA) or leuprolide acetate (Leu) in transwomen.