Why fertility preservation rates of transgender men are much lower than those of transgender women.

RESEARCH QUESTION: What are the fertility preservation rates of transgender women and transgender men, and what are the factors that affect their decision-making? DESIGN: This prospective study included 97 transgender women and 91 transgender men referred to the Gender Clinic of the study medical centre's Endocrinology Institute and to the Gan Meir Community Health Care Centre. The responders completed a 28-item questionnaire during 2018. RESULTS: Most of the transgender women and transgender men wished to parent a child (67.4% and 61.9%, respectively, P = 0.447), but only 40.4% of the transgender women and 5.8% of the transgender men used fertility preservation (P < 0.001). The main reasons for not pursuing fertility preservation were unwillingness to postpone gender-affirming treatment (58.8% and 74.0%, respectively, P = 0.076), preference to adopt a child (58.8% and 60.9%, respectively, P = 0.818) and cost (44.9% and 60.9%, respectively, P = 0.086). Factors related to the fertility preservation process itself were specifically chosen by transgender men compared with transgender women as the reason for not pursuing this treatment, including distress caused by the fertility preservation technique (60.3% versus 29.3%, respectively, P = 0.006), fear of gender dysphoria caused by hormonal treatment (63.5% versus 28.3%, P = 0.002) and concern over the attitude of medical staff (44% versus 19%, P = 0.027). CONCLUSIONS: Fertility preservation rates were considerably lower among transgender men than transgender women, strongly related to the fertility preservation process itself. Finding ways to overcome the obstacles confronted by transgender individuals, especially transgender men, will enhance their future biological parenting.

Low-Dose Cyproterone Acetate Treatment for Transgender Women.

BACKGROUND: Transgender women with intact gonads receive lifelong hormonal treatment to suppress physiologic androgen production, the optimal efficacious and safe cyproterone acetate (CPA) dose has not been established. AIM: To assess the effectiveness and safety of low-dose (10-20 mg/day) compared with high-dose (50-100 mg/day) CPA treatment. METHODS: We conducted a historical cohort study of transgender women treated at a tertiary center for transgender health. OUTCOME MEASURES: Serum levels of testosterone, estradiol, prolactin, gonadotrophins, liver enzymes, and lipids. RESULTS: There were 38 transgender women in the low-dose group and 26 in the high-dose group. Age (median 24.9 years, interquartile range [IQR] 21-30 vs 25 years, IQR 19-35) and follow-up time (median 12 months, IQR 6-23 vs 15 months, IQR 12-36) were similar in the low- and high-dose groups, respectively. Serum gonadotropins and testosterone were suppressed to a similar level at all time points in both groups. Prolactin levels increased significantly in both groups, however, with a more substantial increase in the high- vs the low-dose group (804 ± 121 vs 398 ± 69 mIU/ml at 12 months, respectively, P = .004). Total cholesterol, high-density lipoprotein, low-density lipoprotein, and triglyceride levels were not significantly affected by the dose. CLINICAL IMPLICATIONS: We suggest an adjustment of current clinical practice guidelines to recommend lower doses of CPA for the treatment of transgender women. STRENGTHS & LIMITATIONS: This is the first demonstration that low-dose CPA treatment of transgender women is effective. Limitations include a relatively small sample and retrospective study design. CONCLUSION: Low-dose CPA treatment of transgender women is as effective as high-dose treatment and possibly safer. Zohar NE, Sofer Y, Yaish I, et al. Low-Dose Cyproterone Acetate Treatment for Transgender Women. J Sex Med 2021;18:1292-1298.

Good pain, bad pain: illness perception and physician attitudes towards rheumatoid arthritis and fibromyalgia patients.

OBJECTIVES: Rheumatoid arthritis (RA) and fibromyalgia syndrome (FM) are common diagnoses encountered in rheumatology practice, but do not enjoy the same status. We aimed to examine physician's illness perceptions regarding these two rheumatologic disorders and to evaluate how they correlate with their relationship with these patients. METHODS: Forty-five rheumatologists were enrolled in the study. Demographic data were registered. Measures collected included the Brief Illness Perception Questionnaire (BIPQ) and the Difficult Doctor- Patient Relation Questionnaire (DDPRQ-10). Both were recorded twice, related to FM and RA. Empathy and burnout were also assessed. RESULTS: Of 45 physicians included in the study, only 53% were willing to accept FM patients. FM was considered a more severe disease than RA (FM-BIPQ mean score 54, SD 5.5 versus RA-BIPQ mean 45.6 SD 6.5, p<0.00) in terms of treatment control, understanding and emotional response generated by the disease. Doctor-patient relationship was perceived more difficult with FM patients compared to RA patients (FM-DDPRQ mean score 35.1, SD 9.2 versus RA-DDPRQ mean 19.6, SD 7.1, p<0.00), and was significantly correlated to the patient's concern about the illness (p<0.034) and patient's emotional response (p<0.036). Resistance to accept FM patients was largely influenced by difficult doctor-patient relationship. Higher levels of empathy were found in physicians experiencing less difficulty with FM patients. CONCLUSIONS: FM patients were perceived as more difficult than RA patients, with a high level of concern and emotional response. A high proportion of physicians were reluctant to accept them because they feel emotional/psychological difficulties meeting and coping with these patients.

Pain and transition: evaluating fibromyalgia in transgender individuals.

OBJECTIVES: As members of a gender minority, transgender individuals face many challenges. Many experience distress, depression, anxiety and suicidal ideation related to gender non-conformity and transphobia. Stress and trauma may contribute to the development of fibromyalgia (FM) syndrome, characterised by widespread pain and fatigue. The prevalence of FM among transgenders is not known. METHODS: Transgender participants were recruited at a specialised clinic. Questionnaires included the Widespread Pain Index (WPI), the Symptom Severity Score (SSS) and the SF-36. Data concerning hormonal treatment protocols was retrieved from charts. The current prevalence of FM was determined, as well as the prevalence before and after testosterone treatment among TM. Pearson correlations were calculated between all measures. RESULTS: 115 participants were recruited, 62.6% transgender men (TM), 37.4% transgender women (TW). 17 individuals (14.8%) fulfilled the 2011 modified ACR FM criteria, for a rate of 19.4% among TM and 6.98% among TW. Among TM, FM was associated with younger age, smoking and SF-36 sub-scales related to physical functioning, role limitation due to physical pain, fatigue, pain and general health. Among TW, FM was associated with social status, employment, depression, existing medical treatment and substance abuse, as well as SF-36 subscales related to role limitations affected due to pain. CONCLUSIONS: Fibromyalgia symptoms are highly prevalent among Israeli transgender individuals and may be related to psychological distress and gender dysphoria. Healthcare professionals treating transgenders should remain vigilant for the occurrence of chronic pain, fatigue and other FM-related symptoms and be prepared to treat and/or refer such patients accordingly.

Long-term all-cause mortality and its association with cardiovascular risk factors in thyroid cancer survivors: an Israeli population-based study.

BACKGROUND: The global incidence of thyroid cancer (TC) has risen considerably during the last three decades, while prognosis is generally favorable. We assessed the long-term all-cause mortality in TC survivors compared to the general population, and its association with cardiovascular risk factors. METHODS: Individuals diagnosed with TC during 2001-2014 (TC group) and age- and sex-matched individuals from the same Israeli healthcare system without thyroid disease or a cancer history (non-TC group) were compared. Cox regression hazard ratios (HRs) and 95% confidence intervals (95%CIs) for all-cause mortality were calculated by exposure status. RESULTS: During a 15-year follow-up (median 8 years), 577 TC survivors out of 5677 (10.2%) TC patients and 1235 individuals out of 23,962 (5.2%) non-TC patients died. The TC survivors had an increased risk of all-cause mortality (HR = 1.89, 95%CI 1.71-2.10), after adjusting for cardiovascular risk factors already present at follow-up initiation. This increased risk was most pronounced in the 55- to 64-year-old age group (HR = 1.49, 95%CI 1.33-1.67). The TC survivors who died by study closure had more hypertension (14.6% vs. 10.3%, P = 0.002), more dyslipidemia (11.4% vs. 7.2%, P <  0.001), and more cardiovascular disease (33.6% vs. 22.3%, P = 0.05) compared to those who died in the non-TC group. CONCLUSIONS: This large cohort study showed higher all-cause mortality with a higher prevalence of hypertension, dyslipidemia, and cardiovascular disease among TC survivors compared to matched non-TC individuals. Primary and secondary prevention of cardiovascular risk factors in TC survivors is mandatory.

Fertility preservation rates among transgender women compared with transgender men receiving comprehensive fertility counselling.

RESEARCH QUESTION: What is the fertility preservation rate among transgender women who have received professional fertility counselling compared with transgender men? DESIGN: This retrospective cohort study included 56 transgender women and 56 transgender men referred for comprehensive fertility counselling at the Gender Clinic of the Tel Aviv Sourasky Medical Center's Fertility Institute between January 2017 and April 2019. Statistical analyses were performed to compare transgender men with transgender women who preserved fertility and transgender people who preserved fertility and those that did not. RESULTS: The fertility preservation rate of transgender women was significantly higher than that of transgender men (85.7% versus 35.7%, respectively, P < 0.001). The fertility preservation rate among transgender women was associated with being older and not having undergone gender-affirming hormone (GAH) treatment. The fertility preservation rate was higher among adolescent transgender boys compared with adolescent transgender girls (35% versus 6.25%, respectively, P = 0.005). The duration of GAH treatment among the transgender men who preserved fertility was 70 months compared with 18.6 months for transgender women (P = 0.05). All transgender boys opted for oocyte cryopreservation, while half of the transgender men who had not started GAH opted for oocyte cryopreservation, and half of those who had already started on GAH opted for embryo cryopreservation. CONCLUSIONS: High fertility preservation rates among transgender individuals were found after comprehensive fertility counselling. Fertility preservation rates among adults were higher among transgender women compared with transgender men, while the opposite was found in transgender adolescents.

Differential Endocrine and Metabolic Effects of Testosterone Suppressive Agents in Transgender Women.

OBJECTIVE: Suppression of testosterone secretion and/or action in transgender women using cyproterone acetate (CPA), spironolactone, or gonadotropin-releasing hormone analogues (GA) is achieved through various mechanisms. Our objective was to characterize possible differential effects of these compounds on metabolic and endocrine variables. METHODS: We conducted a historic cohort study of transgender patients treated in a tertiary referral center. A longitudinal analysis of treatment naïve patients and a cross-sectional analysis of the whole cohort at the last visit was carried out. RESULTS: Among 126 transgender women (75 treatment-naïve), CPA was the predominant androgen suppressive therapy (70%), followed by spironolactone (17.6%), and GA (10.2%). Among those who were treatment-naïve, the increase in serum prolactin levels over baseline was greater at 3 months following CPA initiation (mean change 397 ± 335 mIU/L) than following spironolactone (20.1 ± 87 mIU/L) or GA initiation (64.6 ± 268 mIU/L; P = .0002). Prolactin levels remained higher in the CPA-treated group throughout follow-up, irrespective of estradiol levels, which were similar between the groups. A worse metabolic profile was associated with treatment with CPA than with spironolactone or GA. In the CPA compared to the spironolactone and GA groups, high-density lipoprotein-cholesterol levels were lower (47.1 ± 10.4, 54.4 ± 12.2, and 60.3 ± 13, respectively; P = .0076), while body mass index levels (24.3 ± 5, 21.7 ± 2.3, and 20.7±3.1 kg/m2; P = .03), and systolic (117 ± 12.1, 109 ± 12.2, and 105 ± 13.3mm Hg; P = .01) and diastolic (74 ± 9, 65.6 ± 5.5, and 65.4 ± 11 mm Hg; P = .0008) blood pressure levels were higher at the last visit. CONCLUSION: Treatment of transgender women with CPA was associated with hyperprolactinemia and a worse cardiovascular risk profile than treatment with spironolactone or GA. ABBREVIATIONS: BMI = body mass index; CPA = cyproterone acetate; E2 = estradiol; FSH = follicle-stimulating hormone; GA = gonadotropin-releasing hormone analogues; LH = luteinizing hormone.

Ovarian stimulation outcomes among transgender men compared with fertile cisgender women.

PURPOSE: To compare assisted reproductive technology (ART) outcomes among transgender men with those of fertile cisgender women. METHODS: This retrospective cohort study included 12 transgender men, six with no testosterone exposure and six after testosterone treatment, and 12 cisgender women (oocyte donors) who underwent ART in our institution between June 2017 and December 2019. Statistical analyses compared ART data and outcomes between three groups: cisgender women, transgender men without testosterone exposure, and transgender men after testosterone exposure. Comparisons were also made between transgender men with and without testosterone exposure. RESULTS: The transgender men with no testosterone exposure (23.3 ± 4 years) were significantly younger than the transgender men who had undergone testosterone treatment (30.3 ± 3.8 years; P = 0.012) and the cisgender women (29.1 ± 3.1 years; P = 0.004). The amount of FSH used for ovulation induction (1999 ± 683 mIU/mL) was significantly lower among transgender men without prior testosterone exposure compared with that among cisgender women (3150 ± 487 mIU/mL; P = 0.007). There were no differences in the peak estradiol levels, the number of oocytes retrieved, the number of MII oocytes, and the oocyte maturity rates between the three groups. Five out of six testosterone-treated transgender men underwent embryo cryopreservation, and they all achieved good-quality embryos. CONCLUSIONS: Transgender men have an excellent response to ovulation stimulation even after long-term exposure to testosterone. Oocyte/embryo cryopreservation is, therefore, a feasible and effective way for them to preserve their fertility for future biological parenting.

Clinical considerations and key issues in the management of patients with Erdheim-Chester Disease: a seven case series.

BACKGROUND: Erdheim-Chester Disease (ECD), a non Langerhans' cell histiocytosis of orphan nature and propensity for multi-systemic presentations, comprises an intricate medical challenge in terms of diagnosis, treatment and complication management. OBJECTIVES: The objectives are to report the clinical, radiological and pathological characteristics, as well as cardinal therapeutic approaches to ECD patients and to provide clinical analyses of the medical chronicles of these complex patients. METHODS: Patients with biopsy proven ECD were audited by a multi-disciplinary team of specialists who formed a coherent timeline of all the substantial clinical events in the evolution of their patients' illness. RESULTS: Seven patients (five men, two women) were recruited to the study. The median age at presentation was 53 years (range: 39 to 62 years). The median follow-up time was 36 months (range: 1 to 72 months). Notable ECD involvement sites included the skeleton (seven), pituitary gland (seven), retroperitoneum (five), central nervous system (four), skin (four), lungs and pleura (four), orbits (three), heart and great vessels (three) and retinae (one). Prominent signs and symptoms were fever (seven), polyuria and polydipsia (six), ataxia and dysarthria (four), bone pain (four), exophthalmos (three), renovascular hypertension (one) and dyspnea (one). The V600E BRAF mutation was verified in three of six patients tested. Interferon-α treatment was beneficial in three of six patients treated. Vemurafenib yielded dramatic neurological improvement in a BRAF mutated patient. Infliximab facilitated pericardial effusion volume reduction. Cladribine improved cerebral blood flow originally compromised by perivenous lesions. CONCLUSIONS: ECD is a complex, multi-systemic, clonal entity coalescing both neoplastic and inflammatory elements and strongly dependent on impaired RAS/RAF/MEK/ERK signaling.

Sperm parameters in Israeli transgender women before and after cryopreservation.

BACKGROUND: The application of fertility preservation, initially intended for oncological patients prior to gonadotoxic treatment, has extended in recent years to transgender and gender-non-conforming individuals undergoing therapy for gender compatibility. OBJECTIVES: To examine semen quality and survival in transgender women pursuing semen cryopreservation in the presence or absence of gender-affirming hormonal medication. MATERIALS AND METHODS: In this retrospective cohort study, we reviewed data of 74 consecutive transgender women presenting for semen cryopreservation at a single center between 2000 and 2019. Semen parameters before and after cryopreservation were compared to a control group composed of 100 consecutive sperm bank donor candidates. A subgroup analysis of subjects who had used gender-affirming hormonal treatment was also performed. RESULTS: Compared to the control group, transgender women had lower total sperm count (144.0 vs. 54.5 million, respectively, p < 0.001), lower sperm motility percentage (65.0% vs. 51.0%, respectively, p < 0.001), and lower total motile sperm count (94.0 vs. 27.0 million, respectively, p < 0.001). Values were further decreased in transgender women who had received hormonal treatment before sperm cryopreservation. Post-thawing motility rate remained lower in the transgender group compared to the control group (20.0% vs. 45.0%, respectively, p < 0.001), and the total motile count remained lower as well (2.7 vs. 9.0 million, respectively, p < 0.001). Following sperm cryopreservation, the post-thaw decreases in total motile sperm count were higher in the transgender group compared with the control group (91.5% vs. 90.0%). Further subdivision in the transgender group showed that the decrease in total motile sperm count was lower for transgender women who did not use gender-affirming hormonal treatment compared to those who did (-89.7% vs. -92.6%, respectively, p < 0.01). DISCUSSION AND CONCLUSION: Sperm parameters in transgender women are poor compared to candidates for sperm donation representing the general population. Specimens collected after discontinuation of gender-affirming hormone treatments were further impaired. Moreover, post-thawing sperm total motile count, motility, and overall sperm survival were reduced in transgender women.

Sublingual Estradiol Offers No Apparent Advantage Over Combined Oral Estradiol and Cyproterone Acetate for Gender-Affirming Hormone Therapy of Treatment-Naive Trans Women: Results of a Prospective Pilot Study.

Purpose: Chronic gender-affirming hormone therapy (GAHT) with sublingual estradiol (SLE) has not been studied. We aimed to compare GAHT with SLE only, to combined oral (CO) estradiol and cyproterone acetate, in treatment-naive trans women. Methods: Twenty-two trans women enrolled into either the CO arm or the SLE-only arm (0.5 mg four times daily) in this 6-month prospective study. Anthropometric and laboratory variables were collected at baseline and 3 and 6 months. At the study beginning and end, body composition was measured by dual-energy X-ray absorptiometry and bioelectrical impedance, and gender dysphoria, sexual desire, and function were assessed by validated questionnaires. Results: Subjects in the SLE were older, 26.3±5.8 years versus 20.1±2.3 years, p=0.006. All anthropometric, body composition, and laboratory variables were identical at baseline. Although dysphoria appeared greater, and sexual function lower at baseline in the CO group, this canceled out after age adjustment. Both treatments induced similar biochemical and hormonal changes. Creatinine, hemoglobin and cholesterol decreased significantly, while testosterone was suppressed to the same level in both groups: 3.22 [1.47-5.0] nmol/L in the SLE group and 2.41 [0.55-8.5] nmol/L in the CO, p=0.65. Significant changes in body composition toward a more feminine body were noted in both groups. Dysphoria did not significantly improve in either group, while sexual desire and function decreased at six months in both, p<0.001. Conclusions: Both treatments achieved similar clinical changes. At this stage, SLE, which repeatedly induces alarming excursions of serum estradiol throughout the day, appears to offer no advantage over the CO approach.

Transgender men's preferences when choosing obstetricians and gynecologists.

BACKGROUND: Transgender men are a marginalized population with unique health care needs. However, their usage of health services is low because of considerable discrimination. A major factor in their avoidance is patient-provider interactions. METHODS: This cross-sectional study included 102 transgender men who anonymously completed a 55-item questionnaire in clinic, between 10/2017 and 01/2019. In addition, 92 transgender women filled out the part about family physician's preferences. We examined which characteristics transgender men prefer in their obstetricians/gynecologists in order to promote their usage of healthcare services. RESULTS: A small majority of the transgender men (54.1%) had no gender preference for their obstetrician/gynecologist, while 42.9% preferred a female obstetrician/gynecologist and 3.1% preferred a male obstetrician/gynecologist. Most transgender men with a same-gender preference preferred female obstetricians/gynecologists for both invasive procedures (e.g., pelvic examination, 97.4%) and non-invasive procedures (e.g., cesarean section, 60%). The reasons for preferences regarding invasive procedures were feeling comfortable, embarrassment and feeling that female obstetricians/gynecologists are gentler. Transgender men who preferred female obstetricians/gynecologists ranked ability (90.5%), sexual tolerance (92.9%) and gender identity tolerance (90.5%) as the top three desirable qualities of obstetricians/gynecologists, while the responders who did not prefer female ranked ability (94.6%), experience (92.9%) and knowledge (92.9%) as the top three qualities. Transgender men with female preferences considered female obstetricians/gynecologists to be more accepting of gender identity compared to the responders that did not prefer females (47.5% vs. 9.1%, P < .001).. CONCLUSION: A small majority of the transgender men exhibited no gender preference when choosing an obstetrician/gynecologist, although 42.9% preferred females. The latter choice was associated with the assumption that female obstetricians/gynecologists are more tolerant towards their transgender men patients. Educating the medical staff about their special needs and establishing dedicated SGM centers staffed with high percentages of female healthcare providers are highly recommended.

Adoption of the transoral endoscopic vestibular approach by head and neck surgeons without prior laparoscopic/robotic experience.

BACKGROUND: Transoral endoscopic vestibular approach (TOEVA) for thyroidectomy (TOETVA) and parathyroidectomy (TOEPVA) is gaining popularity, yet knowledge is based on a limited number of studies, mostly performed by surgeons experienced in laparoscopic\robotic surgery. METHODS: All patients who underwent TOEVA at our institution between February 2018 and October 2019 were followed prospectively. Main outcomes were ability to accomplish surgery endoscopically (failure defined as conversion to open approach) and complications. RESULTS: Seventy-one patients (52 TOETVA and 19 TOEPVA) were included. 98% (51/52) and 100% (19/19) of TOETVA and TOEPVA surgeries were accomplished endoscopically, respectively. Transient vocal cord and mental nerve injuries rates were 8.4% (6/71) and 2.8% (2/71), respectively. Thyroid carcinoma was diagnosed in 27 patients (51.9%), all completely excised with clean margins. CONCLUSIONS: Adoption of the TOEVA suggested framework by head and neck surgeons without prior experience in laparoscopic/robotic techniques is feasible resulting in nearly 100% of surgeries accomplished endoscopically.

The Effect of the PCSK9 Inhibitor Evolocumab on Aldosterone Secretion among High Cardiovascular Risk Patients: A Pilot Study.

Elevated low-density lipoprotein (LDL) cholesterol is one of the leading causes of cardiovascular disease. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors reduce LDL cholesterol levels with subsequent reductions in cardiovascular morbidity. Elevated aldosterone levels are also associated with a greater risk of cardiovascular morbidity. There are currently no published data on the impact of PCSK9 inhibitor monotherapy on the secretion of aldosterone. The aim of this study was to examine the effect of monotherapy with the PSCK9 inhibitor evolocumab on the lipid profile and aldosterone secretion level in high-risk cardiovascular patients. Lipid profile, sodium, potassium, aldosterone, cortisol, plasma renin activity, and adrenocorticotropic hormone (ACTH) levels were analyzed at baseline and after 3 months of evolocumab therapy. Each participant underwent a 250 mcg ACTH stimulation test upon study entry. Eight women and seven men were included in the study. Their median total cholesterol, LDL cholesterol, lipoprotein (a), apolipoprotein B100, and baseline and stimulated aldosterone levels were significantly lower after 3 months of evolocumab therapy. These heretofore unreported findings indicate that reductions in unstimulated and stimulated aldosterone secretion under evolocumab therapy could be associated with reductions in cardiovascular events, a possibility that warrants further investigation.

Scarless Neck Feminization: Transoral Transvestibular Approach Chondrolaryngoplasty.

Importance: Chondrolaryngoplasty or reduction of laryngeal prominence is a gender affirmation surgery for transgender women, or for male patients desiring an aesthetic surgery. Several variations of the procedure were suggested, yet to date, all described chondrolaryngoplasty procedures involved a visible neck scar. Objective: To describe a novel technique for scarless chondrolaryngoplasty, transoral endoscopic vestibular approach (TOEVA)-chondrolaryngoplasty, and to report the results of first ever performed cases. Design, Setting, and Participants: This was a prospective cohort at an academic referral center. Adult transgender women, interested in chondrolaryngoplasty who never had previous surgery of their neck or vocal folds, were offered both transcervical chondrolaryngoplasty and scarless TOEVA-chondrolaryngoplasty. Four patients aged 21 to 33 years, who preferred TOEVA-chondrolaryngoplasty, were consented and recruited. Interventions: The surgical technique was successfully examined on two cadavers. Subsequently, all surgical procedures were conducted according to the described study protocol and technique, between April and June 2019. Main Outcomes: Vocal assessment was recorded preoperatively and repeated 4 to 6 weeks after surgery for comparison. Surgical documentations as well as adverse surgical events and complications were recorded. To measure outcome, 1-2 months postoperatively, all patients filled an outcome instrument for aesthetic chondrolaryngoplasty (seven questions on a 5-point Likert scale) based on previously designed questionnaires for chondrolaryngoplasty and facial plastic surgery. Results: Duration of operative time ranged from 90 to 150 min. No adverse events or complications were recorded during surgery. All patients were discharged 1 day postoperatively. A single patient had a mild temporary mental hypoesthesia that resolved 2 months after surgery, no other complications were encountered. Vocal folds' function remained unchanged in all four patients. All operated patients were highly satisfied with the surgical results as measured by the outcome instrument; three out of the four patients responded with perfect scores, and the fourth patient responded with 90% of the perfect score. Conclusions: This report is the first description of scarless chondrolaryngoplasty through TOEVA. On a series of four patients, TOEVA-chondrolaryngoplasty appeared to be safe, with no adverse events or major complication, and with extremely high patient satisfaction. Further clinical evidence is required to establish a widespread use of this surgical technique.

Indeterminate nodules by the Bethesda system for reporting thyroid cytopathology in Israel: Frequency, and risk of malignancy after reclassification of follicular thyroid neoplasm with papillary-like features.

OBJECTIVE: We aimed to determine the frequency and risk of malignancy (ROM) for indeterminate thyroid nodules, categories III (B3) and IV (B4) of the Bethesda System for Reporting Thyroid Cytopathology (BSRTC), at a large institution in Israel. Additionally, we investigated the impact of redefining follicular neoplasm with papillary-like nuclear features (NIFTP) as non-malignant on malignancy rates. METHODS: In this retrospective study of all thyroid fine needle aspirations (FNAs) performed at Tel Aviv-Sourasky Medical Center between January 2013 and December 2015, we assessed ROM for B3 and B4 nodules. Potential risk factors thought to affect a-priori ROM were assessed. Suspected NIFTP lesions were re-examined, and if proven, reclassified as benign. RESULTS: 3701 nodules were sampled in 2919 FNAs performed on 2674 patients. B3 reports comprised 7.7% of all nodules (n = 284); B4 represented 3.6% (n = 132). In multivariate logistic regression, male gender, being of former Soviet Union origin, and smoking increased ROM for B3 nodules by a factor of 7.97 (P = 0.002; CI: 2.2-23.4), 9.15 (P = 0.021; CI:1.4-60.0), and 11.0 (P = 0.001; CI 2.8-44.8), respectively. Reclassifying NIFTP decreased ROM from 14% to 12.5% for B3, and from 26.7% to 25% for B4 nodules. NIFTP comprised 9.5% of previously diagnosed resected malignant tumors. CONCLUSIONS: The relative frequencies of B3 and B4 nodules and their associated malignancy rates were consistent with previous series. Risk factors identified for malignancy may help characterize patients most likely to benefit from surgery. Reclassifying NIFTP had a substantial impact on the ROM in the resected tumors previously diagnosed as malignant.

A Single Radioactive Iodine Treatment Has a Deleterious Effect on Ovarian Reserve in Women with Thyroid Cancer: Results of a Prospective Pilot Study.

BACKGROUND: Women of reproductive age with differentiated thyroid cancer (DTC) often need radioactive iodine (RAI) treatment after surgery. In contrast to the well-documented effect of RAI on testicular function, the potential negative effects of this treatment on ovarian reserve have been largely dismissed. The objective of this pilot study was to examine the possibility that RAI treatment is deleterious to the ovarian reserve by prospectively measuring the concentration of anti-Müllerian hormone (AMH) after RAI treatment. METHODS: Thirty premenopausal women (Mage = 34 years; range 20-45 years) with a new diagnosis of DTC scheduled to undergo RAI ablation were recruited for this study. All of them had TNM stage 1 disease (T1-3, N0, or N1, M0), and were scheduled to receive RAI activities ranging from 30 to 150 mCi. AMH was measured at baseline and at 3, 6, 9, and 12 months after the administration of RAI. RESULTS: Of the 30 women, only 24 returned after the baseline assessment. RAI treatment resulted in a significant decrease in AMH concentrations at three months, from 3.25 ± 2.75 to 1.9 ± 1.74 ng/mL (p < 0.0001). Only partial recovery was subsequently documented. Eighty-two percent of subjects had final values below baseline levels, such that at one year, serum AMH was still 32% lower than prior to treatment (2.36 ± 1.88 ng/mL; p < 0.005). The only two continuous variables that correlated with the extent of AMH reduction at three months were the woman's age (r = 0.51; p = 0.02) and the age at menarche (r = 0.48; p = 0.03). Importantly, the RAI dose was not associated with the extent of AMH reduction and neither were smoking or the use of birth control pills. Older subjects (≥35 years) were significantly more likely to experience a marked AMH reduction at three months (63.7 ± 18.5% vs. 33.1 ± 29.2%; p = 0.01). The only predictor of recovery after one year was the extent of AMH decrease at three months: the lower the decline, the higher the chances for recovery. CONCLUSIONS: RAI in DTC has a rapid and profound effect on ovarian reserve, with only a partial recovery potential. In an era of declining human fertility, it is of relevance to recognize the potentially adverse effect of RAI in women of reproductive age. AMH measurement may be useful as a tool in this decision-making process.