Search

STUDY OBJECTIVE: To explore the role of progestins as potential contributing factors for the development of hepatocellular adenoma (HA) METHODS: We describe 3 cases of adolescents and young adults who developed HA while on norethindrone (NET), as well as their management. In addition, we provide a comprehensive literature review on the association between progestins and HA. RESULTS: Since 1983, 16 cases of HA in patients on progestins have been reported. Ten patients were on NET and 5 on a prodrug of NET (4 on norethindrone acetate [NETA] and 1 on lynestrenol). One individual had a norgestrel implant. Eight subsequently ceased all hormones: 4 experienced a size reduction, and 3 had complete resolution of their HA. Among our patients, 1 ceased NET and instead had a levonorgestrel intrauterine device inserted, and another swapped from NET to oral medroxyprogesterone acetate. Both experienced complete resolution of their HA. The third ceased NET and underwent a hysterectomy, with size reduction of her HA. CONCLUSION: These cases and the literature review suggest an association between progestin exposure, in particular NET and its prodrugs, and the development of HA. The pathophysiology is unknown but may include peripheral conversion of NET and NETA to ethinyl estradiol or a specific action of 19-nortestosterone derivatives on hepatocytes, especially those with higher systemic doses compared with the levonorgestrel intrauterine device. There are no case reports relating to other forms of progestins, such as 17-hydroxyprogesterone, which may be important when considering alternative therapeutic options in females requiring effective menstrual management who have comorbidities.

STUDY OBJECTIVE: Few studies have explored what specific outcome measures contained in assessment tools for period and pelvic pain are most relevant to adolescents. Co-design is a valuable method of ensuring input from those with lived experience. The Longitudinal Study of Teenagers with Endometriosis Periods and Pelvic Pain in Australia (LongSTEPPP) Co-Design Periods Survey comprised an anonymous online survey of adolescents' experience of menstruation to inform patient-reported outcome measures for the larger 5-year project. METHODS: Adolescents aged 12-18 years whose periods had commenced at least 3 months previously and with demonstrated capacity to consent were invited to participate in an online survey. Recruitment was primarily via social media channels. RESULTS: Of the 1811 adolescents who participated, 85% reported that periods had a "moderate" or greater impact on their life. Pain (90.7%), heavy flow (56.2%), and worry about leakage (49%) were common reasons for missed activities. Menstrual symptoms were wide-ranging and included cramping, nausea, poor energy, and impacts on mood. When asked where adolescents sought assistance with their periods, 39.8% had seen their general practitioner, 21.3% their school nurse, and almost 1 in 10 had consulted a mental health practitioner (9.3%). To manage menstrual symptoms, heat packs (66.0%), over-the-counter medications (55.8%), and prescription medications (28.6%) were used. CONCLUSION: We found a lack of menstrual health awareness in adolescents. Periods had a significant effect on their lives, and adolescents commonly missed activities. In managing menstruation, a wide range of practitioners were consulted. Nearly a third were prescribed medication to manage their periods. These findings have directed the longitudinal study as to how best to capture outcome measures that reflect the impact of periods on adolescents.

STUDY OBJECTIVES: Mayer-Rokitansky-Küster-Hauser Syndrome (MRKH) is characterized by the congenital absence of the uterus and vagina, sometimes with associated extragenital anomalies. Currently there is limited literature on pelvic pain and co-morbid pain syndromes in people with MRKH. The aims of this scoping review were to summarize existing literature on pelvic and generalized persistent pain syndromes associated with MRKH and to identify knowledge gaps for further research into this field. METHODS: This scoping review followed the Joanna Briggs Institute framework. The population of interest was patients with a diagnosis of MRKH. MEDLINE, CINAHL, Scopus, Cochrane, Embase and Emcare databases were searched. Excluded were articles that did not meet the inclusion criteria or critical appraisal standards. The resultant articles were reviewed by 2 independent researchers while a third was used in cases of disagreement. A descriptive analytical method was used for data analysis. RESULTS: We screened 3348 articles for eligibility, 39 articles met criteria, which described 1353 cases of MRKH. 4 studies described baseline pelvic pain in MRKH, 19 described acute presentations and 13 described post-intervention pain levels. CONCLUSION: Despite the paucity of research, this review found that cyclical pelvic pain was mostly present in women with uterine remnants, whilst pelvic pain in those without remnants was poorly understood. There were no studies exploring generalized persistent pain syndromes in MRKH. Further cross-sectional studies are needed to elucidate prevalence and levels of pain syndromes in MRKH.

Purpose: This descriptive study aimed to assess the characteristics of pelvic pain and explore predictive factors for pelvic pain in transgender (trans) individuals using testosterone therapy. Methods: An online cross-sectional survey was open between August 28, 2020, and December 31, 2020, to trans people presumed female at birth, using testosterone for gender affirmation, living in Australia, and >16 years of age. The survey explored characteristics of pelvic pain following initiation of testosterone therapy, type and length of testosterone therapy, menstruation history, and relevant sexual, gynecological, and mental health experiences. Logistic regression was applied to estimate the effect size of possible factors contributing to pain after starting testosterone. Results: Among 486 participants (median age = 27 years), 351 (72.2%)* reported experiencing pelvic pain following initiation of testosterone therapy, described most commonly as in the suprapubic region and as "cramping." Median duration of testosterone therapy was 32 months. Persistent menstruation, current or previous history of post-traumatic stress disorder, and experiences of pain with orgasm were associated with higher odds of pelvic pain after testosterone therapy. No association was observed with genital dryness, intrauterine device use, previous pregnancy, penetrative sexual activities, touching external genitalia, or known diagnoses of endometriosis, vulvodynia, vaginismus, depression, anxiety, or obesity. Conclusions: Pelvic pain is frequently reported in trans people following initiation of testosterone therapy. Given the association with persistent menstruation and orgasm, as well as the known androgen sensitivity of the pelvic floor musculature, further research into pelvic floor muscle dysfunction as a contributor is warranted.

BACKGROUND: An incidental finding of a thickened endometrium on ultrasound in the postmenopausal patient without bleeding is a common presentation to gynaecological services; however there is limited evidence to guide clinical practice as to when hysteroscopic evaluation and endometrial sampling is required. AIMS: To determine the endometrial thickness at which endometrial sampling is indicated in asymptomatic postmenopausal women referred with thickened endometrium on ultrasound. MATERIALS AND METHODS: A single-centre retrospective case series of postmenopausal women without bleeding undergoing hysteroscopy was conducted. Logistic regression was used to examine the association between a range of variables and pre-malignant or malignant pathology and endometrial thickness. The optimal endometrial thickness threshold was identified to maximise model sensitivity. RESULTS: A total of 404 postmenopausal women were included in this study, having undergone a hysteroscopy at the study site between 1 July 2008 and 30 June 2018. The mean (SD) age of patients at presentation was 65 (9.09) years and the mean body mass index was 29.86 kg/m2 (6.52). Of these women, nine (2.2%) were diagnosed with endometrial carcinoma and seven (1.7%) had endometrial hyperplasia with atypia. The most common histopathological finding was of a benign endometrial polyp (153: 37.9%). When including hyperplasia with or without atypia in histopathology of interest, a cut-off of ≥9 mm provides the greatest sensitivity (83.3%) and specificity (63.8%) for a diagnosis of pre-malignant or malignant pathology (classification accuracy of 64.8%; area under the receiver operating characteristic: 0.7358, 95% CI: 0.6439, 0.8278) in this cohort. CONCLUSIONS: Using an endometrial thickness of ≥9 mm can be used as a cut-off for endometrial sampling in postmenopausal women without bleeding.

Girls and adolescents, aged 0-19 years make up almost 30% of the world's female population yet their specific healthcare needs often slip between the gaps of pediatrics and adult women's health. Pediatric and adolescent gynecology is the clinical field that endeavors to address the reproductive health needs of this age group. The environment and psychosocial well-being, social determinants of health, have direct bearing on reproductive health, affecting menstrual cycles, menstrual hygiene, and risks for unintended pregnancy and sexually transmitted infections. This narrative review will highlight common gynecologic conditions of adolescents, especially where diagnosis and management are distinct from adult women. It will also present preventive health strategies to improve reproductive health through vaccination, improved access to hygiene supplies and contraception.

Adolescents with differences of sex development (DSD) often have complex medical, surgical, and psychological care needs and require age-appropriate resources. This cross-sectional study describes the past and current experiences of adolescents and young adults with DSD and their need for information and support. Participants aged 14−30 years with DSD diagnoses were identified, either from departmental records at the Royal Children’s Hospital (RCH), Melbourne, Australia, or from the private practice of a gynecologist linked to RCH. Anonymized data were collected from a specifically designed online survey. Of the 314 successfully traced patients, 91 (28.9%) completed the survey. Amongst respondents, older age was strongly correlated with higher levels of distress at the time of disclosure (b = 0.67, p < 0.001). People who reported greater understanding of their condition (b = −0.45, p = 0.010) and higher levels of support (b = −0.40, p = 0.003) identified lower levels of current distress. Respondents preferred to receive information from a specialist doctor, GP, or websites and reported information needs being highest during adolescence. Only one in four respondents recalled ever being offered psychological support. A number of perceived barriers to accessing support were identified. Our findings indicate that young people’s information and support needs may be best met by improving online resources, as well as increasing introductions to knowledgeable and appropriate primary care physicians, psychological services, and peer support groups. Further work to promote and increase engagement with psychological and peer support for those with DSD will be important.

BACKGROUND: Endometriosis affects one in nine Australian women of reproductive age, and is often associated with pain and infertility. However, many women may be asymptomatic, or present with alternative symptoms. AIM: To identify reasons for initial specialist referral among patients with endometriosis. MATERIAL AND METHODS: Patients were identified as having endometriosis intraoperatively based on International Classification of Diseases coding. Operation reports were reviewed and graded for severity of disease. This cohort was then retrospectively audited to identify reasons for initial referral to the general gynaecology, endosurgery, gynae-oncology, reproductive medicine outpatient departments (OPD) at the Mercy Hospital for Women in Melbourne between 1 February 2015 and 31 December 2016. RESULTS: Three hundred patients were identified as having endometriosis at laparoscopy, including 90 women with Stage IV disease. Patients were a mean (SD) age of 33.1 (7.6) years. While pain remained a common reason for referral (61.7% of referrals), 36.7% of women with Grade IV disease did not have pain included in their referral letter. Severe disease was associated with increased age (regression coefficient 0.05; 95% CI: 0.03-0.07, P < 0.01), but not with pain symptoms. Women referred with ovarian cysts or masses were more likely to be diagnosed with severe disease (regression coefficient 0.69; 95% CI: 0.37-1.01, P < 0.01). CONCLUSION: Although pelvic pain is not a good predictor for a diagnosis of endometriosis, it remains a common symptom among women with the disease. However, more than one in three patients with Grade IV endometriosis presented without mention of pain symptoms, encouraging clinicians to adopt a broader approach to the presenting symptoms of endometriosis.

The high incidence and burden of pelvic pain are increasingly recognised in both the healthcare sector and by the general public. Current approaches to management assume that the diagnosis and remediation of identified lesions will ease this burden. The evidence base and successes in other areas of medicine would suggest that this assumption requires reconsideration.

BACKGROUND: Persistent pelvic pain affects between 10-20% of women with a significant impact on their physical and mental health, sexual relationships, families and society. Estimates of the cost to women and the community is over $9 billion/annum. Although endometriosis is considered a leading cause of pelvic pain, no symptoms reliably allow the identification of those with and without endometriosis. Furthermore, the significance of mild endometriosis is now debated. The optimal clinical approach for pelvic pain and endometriosis remains unclear, with increasing evidence of other contributing factors such as central sensitisation. Studies to date have significant limitations due to their sample size, relatively short follow-up, and inclusion of only women with laparoscopically identified endometriosis. AIMS: To undertake a real-world study of women referred with pain to gynaecology outpatients of a women's hospital and explore factors influencing three-year outcomes. MATERIALS AND METHODS: Five hundred women will be randomised to one of two gynaecology units. The units will provide routine clinical care but their approaches to management of women with pelvic pain and endometriosis differ: one with skilled endoscopic gynaecologists has greater emphasis on surgery, the other, gynaecologists have more medical expertise in managing pain and menstrual problems. Participants will complete six-monthly questionnaires regarding pain and quality of life for three years. This information will not be available to clinicians. Their medical care will be followed from their medical records. The cost of outpatient care and admissions will be calculated. Data will be analysed using STATA software with appropriate post hoc tests. Australian and New Zealand Clinical Trials Registry (ANZCTR:ACTRN12616000150448).

AIM: To describe the characteristics, management and outcomes of a cohort of young people with dysmenorrhea presenting to a tertiary adolescent gynecology service, managed primarily with medical interventions. METHODS: A retrospective cohort study was conducted at the Royal Children's Hospital in Melbourne, Australia. Data were collected from medical records of patients presenting with dysmenorrhea and/or pelvic pain. RESULTS: Of 154 patients, mean age of presentation was 15.7 years (SD = 2.2) and mean duration of pain was 14.9 months (SD = 10.8). Regular cycles were reported by 64.5%, and heavy menstrual bleeding (HMB) in 67.8%. Patients self-reporting HMB reported less pain on the day prior to menses than those not reporting HMB (P < 0.005). At follow-up, therapeutic interventions included nonsteroidal anti-inflammatory drugs, tranexamic acid and cyclic or continuous combined oral contraceptive pills. Laparoscopies were undertaken in 12 (8.1%) patients, with normal findings in 8 (66.7%). Secondary dysmenorrhea was identified in 10 patients: of these, endometriosis was identified in one patient and unilateral obstructive Müllerian anomalies in six. Overall, 92.2% of patients had improvement in symptoms after treatment. CONCLUSION: Laparoscopy and endometriosis rates in patients presenting to a tertiary center were lower than previously reported, with most patients achieving symptom improvement without laparoscopy.

BACKGROUND: Chronic pelvic pain (CPP) is a common condition which significantly impacts the quality of life and wellbeing of many women. Laparoscopy with histopathology is recommended for investigation of pelvic pain and identification of endometriosis with concurrent removal. Never-the-less, the association between endometriosis and pelvic pain is challenging, with endometriosis identified in only 30-50% of women with pain. AIMS: To explore the predictors for undergoing surgery, for identifying endometriosis and endometriosis severity in a cohort of women with CPP. MATERIALS AND METHODS: This study forms part of the Persistent Pelvic Pain project, a prospective observational cohort study (ANZCTR:ACTRN12616000150448). Women referred to a public gynaecology clinic with pain were randomised to one of two gynaecology units for routine care and followed for 36 months with 6-monthly surveys assessing demographics, medical history, quality of life, and pain symptoms measured on a Likert scale. Operative notes were reviewed and endometriosis staged. RESULTS: Of 471 women recruited, 102 women underwent laparoscopy or laparotomy, of whom 52 had endometriosis (n = 37 stage I-II; n = 15 Stage III-IV). Gynaecology unit, pelvic pain intensity and lower parity were all predictors of surgery (odds ratio (OR) 0.342; 95% CI 0.209-0.561; OR 1.303; 95% CI: 1.079-1.573; OR 0.767; 95% CI: 0.620-0.949, respectively). There were no predictors identified for endometriosis diagnosis and the only predictor of severity was increasing age (OR 1.155; 95% CI: 1.047-1.310). CONCLUSIONS: Gynaecology unit and pain intensity were key predictors of undergoing laparoscopy; however, pain severity did not predict endometriosis diagnosis or staging. These findings indicate the need to review current frameworks guiding practice toward surgery for pelvic pain.

AIM: Management of children with differences/disorders of sex development (DSD) is complex with limited evidence to guide clinical decisions. Regular multidisciplinary team meetings were set up in Sydney and Melbourne paediatric hospitals to enable systematic peer review of complex decision-making. We aim to describe the workload and role of these meetings. METHODS: The multidisciplinary team forum includes invited representatives from endocrinology, urology, gynaecology, genetics, psychology, social work, clinical ethics, laboratory and hospital executive and meetings occur 1-3 times monthly. Descriptive data were collected from de-identified meeting referrals and minutes between August 2012 to August 2018 (Sydney) and January 2014 to August 2018 (Melbourne). RESULTS: A total of 192 referrals (142 new and 50 follow-ups) aged 1 week to 17 years were discussed across the two sites. 46, XY DSD (n = 81) was the most common sub-classification. Consideration of surgical options and optimal management of gonads with malignant potential were amongst the common reasons for referral to the multidisciplinary team meetings. Surgical interventions were considered but not recommended after review for 38 of 154 (24.7%) procedures. Gonad retention to allow potential functional benefit was recommended in 15/46 (32.6%) referrals. Evidence of premalignant or malignant changes was found in 20/57 (35%) gonads removed, with dysgenetic features and atrophy/streak features in 6 (10.5%) and 27 (47.4%) gonads respectively. CONCLUSION: Formal DSD multidisciplinary team meetings provide a framework and opportunity for multi and interdisciplinary discussions amongst representatives from several specialities to help make complex decision-making.

BACKGROUND: GATA-binding protein 4 (GATA4) and Friend of GATA 2 protein (FOG2, also known as ZFPM2) form a heterodimer complex that has been shown to influence transcription of genes in a number of developmental systems. Recent evidence has also shown these genes play a role in gonadal sexual differentiation in humans. Previously we identified four variants in GATA4 and an unexpectedly large number of variants in ZFPM2 in a cohort of individuals with 46,XY Differences/Disorders of Sex Development (DSD) (Eggers et al, Genome Biology, 2016; 17: 243). METHOD: Here, we review variant curation and test the functional activity of GATA4 and ZFPM2 variants. We assess variant transcriptional activity on gonadal specific promoters (Sox9 and AMH) and variant protein-protein interactions. RESULTS: Our findings support that the majority of GATA4 and ZFPM2 variants we identified are benign in their contribution to 46,XY DSD. Indeed, only one variant, in the conserved N-terminal zinc finger of GATA4, was considered pathogenic, with functional analysis confirming differences in its ability to regulate Sox9 and AMH and in protein interaction with ZFPM2. CONCLUSIONS: Our study helps define the genetic factors contributing to 46,XY DSD and suggests that the majority of variants we identified in GATA4 and ZFPM2/FOG2 are not causative.

BACKGROUND: This study investigates the health-related quality of life (HRQOL) of female patients with congenital adrenal hyperplasia (CAH) in Malaysia. The objectives were to attain socio-demographic and medical data on these Malaysian females with CAH and establish their health-related quality of life (HRQOL) in comparison to age matched diabetic controls. METHODS: A cross-sectional study was conducted over 6 months in the two main tertiary centres for CAH patients in Malaysia. Participants including 59 female-raised CAH patients (mean age ± SD = 16.3 ± 4.2 years, range 10-28 years) compared to 57 age-matched female diabetic patients (mean age ± SD = 16.5 ± 3.4 years, range 10-26 years). Socio-demographic and medical profiles was obtained through semi-structured interviews. HRQOL of participants were evaluated utilising validated, Malay translated questionnaires which were age appropriate: Pediatric Quality of Life Inventory (PedsQL v4.0) scales for Child (8-12) and Adolescent (13-18) and Medical Outcome Survey 36-item Short Form version. These were then compared to the diabetic controls. RESULTS: The CAH participants consisted of children (ages 10-12 years, n = 12), adolescents (ages 13-17 years, n = 29) and adults (≥ 18 years, n = 18). The majority were Malays (64.4%) and had salt-wasting CAH (67.8%). There were no significant differences between the total mean score of the HRQOL of the combined children and adolescents CAH group (total mean score ± SD = 81.6 ± 17.9, 95% CI = 75.6-87.6) when compared to age-matched diabetic patients (total mean score ± SD = 80.8 ± 11.0, 95% CI = 77.0-84.5, P = 0.81, effect size = 0.05); no significant difference between the adult CAH and diabetic controls in the physical [median score (IQR) CAH vs diabetics; 49.3 (11.4) vs. 50.2 (6.1), P = 0.60, effect size = 0.09] and the mental composite scores [median score (IQR) CAH vs. diabetics; 47.8 (14.1) vs. 50.0 (10.8), P = 0.93, effect size = 0.01]. CONCLUSIONS: The HRQOL of the Malay

AIM: To review presentations, diagnostic processes and time to diagnosis of presentations of imperforate hymen at one tertiary paediatric hospital over a 10-year period. The aim was to improve knowledge, enable targeted education and reduce unnecessary tests and diagnostic delay for this congenital obstructive disorder of the female reproductive tract. METHODS: A pragmatic, retrospective, observational study was conducted of all female patients, aged younger than or equal to 18 years of age, presenting to the Royal Children's Hospital, Melbourne, over an 18-year period. Presenting symptom(s), time to diagnosis, investigations ordered and number of health-care professionals consulted prior to diagnosis were recorded. RESULTS: A total of 27 patients met eligibility criteria, and 85% presented with pain (23/27). Pain was frequently associated with other symptoms (15/23). Over three quarters of patients consulted more than one health-care professional prior to diagnosis (22/27). Of the 27 patients, 19 had imaging undertaken prior to diagnosis. CONCLUSIONS: Paediatric and adolescent females managed at our tertiary paediatric hospital are experiencing diagnostic uncertainty and the unnecessary ordering of imaging prior to a diagnosis of imperforate hymen. Targeted education is recommended to health professionals managing female paediatric and adolescent patients.

BACKGROUND: Clinician and patient factors impact on the management of chronic pelvic pain (CPP) with medical, surgical or combined approaches possible, although none have proven superior. AIMS: To understand the characteristics of women offered laparoscopic pelvic surgery for CPP. MATERIALS AND METHODS: We performed an observational study of women referred with CPP. They were asked to complete a study questionnaire regarding their symptoms, medical history, quality of life and pain catastrophisation. Examination and ultrasound findings were collected from patient records. Gynaecologists who recommended a laparoscopy completed a survey detailing their reasoning at the time of booking. The outcomes were investigated using a Cox proportional hazards ratio (HR) model. RESULTS: Of 211 participants, 59 (28%) were booked for laparoscopic surgery during the study timeframe. Factors increasing the rate of laparoscopy included severe dysmenorrhoea (Cox HR = 1.94; P = 0.017), unsuccessful trial of hormonal therapy (Cox HR = 1.81; P = 0.044), prior abdominal surgery (Cox HR = 1.79; P = 0.030), prior pelvic laparoscopy (Cox HR = 2.00; P = 0.007) and past diagnosis of endometriosis (Cox HR = 5.44; P = 0.010). Abnormal vaginal examination (Cox HR = 2.86; P = 0.019) and ultrasound probe tenderness (Cox HR = 2.52; P < 0.001) also increased the likelihood of surgery. Surgical and non-surgical patients did not differ in family history, quality of life or pain catastrophisation. Of gynaecologists' questionnaires, 75% were returned. Results indicated they were most influenced by the severity or duration of pain and least by examination or ultrasound findings. CONCLUSIONS: The characteristics of women booked for surgery were in keeping with the features evidence suggests increases the risk of pathology. There were some discrepancies between patient characteristics elicited in the questionnaires and those indicated by gynaecologists to influence their decision.

Background: Girls born with congenital adrenal hyperplasia have virilized external genitalia. There is considerable debate regarding both the outcomes of feminizing genitoplasty and timing of the surgery in this population. Objective: To investigate outcomes of females 46,XX individuals with CAH in Malaysia, the surgical outcomes of feminizing genitoplasty (FG) and their attitudes toward surgery. Study Design: This is a cross-sectional study involving the two main tertiary centers in Malaysia. All 46,XX patients with CAH and raised female, who had undergone FG were identified and invited to participate. Data on socio-demographic, medical profiles, and attitudes toward surgery were collected. A standardized evaluation of the external genitalia was undertaken including the anatomic and cosmetic evaluation by independent gynecologists. Results: Of 61 individuals identified, 59 participated-consisting of children (n = 12), adolescents (n = 29) and adults (n = 18). All but one had classical CAH (98.3%) and had undergone FG (n = 55, 93.2%) with surgery mostly undertaken by pediatric surgeons trained in DSD work (n = 44, 74.6%). Complications overall were low (20.3%), with repeat surgery rate of 9.1%. External genital examination was performed in 38 participants. Overall 36.8% had absent clitoral glands and 39.5% had a persistent urogenital sinus and in 10.5%, no vaginal orifices were seen. Poor cosmetic outcomes were present in 42.1% with 55.3% recommended for further assessment under general anesthetic. Almost half participants did not venture an opinion on FG, those who did varied from having a positive attitude toward it (18 participants) to 3 opining that it should not be done, or avoided or delayed. From the participants, 35.5% preferred FG to be done early in life compared to 44.0% of the parents. Conclusions: The reoperation rates of the feminizing genitoplasty surgeries were low however due to the anatomic and cosmetic outcomes, reassessment of the external genita

Premature ovarian insufficiency involves amenorrhea and elevated follicle-stimulating hormone before age 40, and its genetic basis is poorly understood. Here, we study 13 premature ovarian insufficiency (POI) patients using whole-exome sequencing. We identify PREPL and TP63 causative variants, and variants in other potentially novel POI genes. PREPL deficiency is a known cause of syndromic POI, matching the patients' phenotype. A role for TP63 in ovarian biology has previously been proposed but variants have been described in multiorgan syndromes, and not isolated POI. One patient with isolated POI harbored a de novo nonsense TP63 variant in the terminal exon and an unrelated patient had a different nonsense variant in the same exon. These variants interfere with the repression domain while leaving the activation domain intact. We expand the phenotypic spectrum of TP63-related disorders, provide a new genotype:phenotype correlation for TP63 and identify a new genetic cause of isolated POI.

AIM: To audit the clinical features and outcomes for all patients referred to our centre with concerns regarding labial appearance. METHODS: Young females referred to a paediatric/adolescent gynaecology tertiary centre between 2000 and 2012 with concerns regarding their labial appearance were retrospectively identified. Adolescents presenting with anomalies were excluded. Retrospective chart review was undertaken to identify reasons for referral, patient characteristics, outcome of referral and concurrent health problems. RESULTS: In total, 46 females presenting with concerns about labial appearance were identified. Five were excluded. Median age of the study population was 14.5 years (range 5-21 years). Only four (9.8%) underwent surgery after a minimum of five consultations each, with mental health review in three of four cases prior to surgery. None of the 41 patients had documented abnormal labia; however, 6 patients had asymmetry, and 3 had a labial width of >5 cm. Of mothers, 24% (n = 10) raised the initial concern regarding labial appearance to a physician, of whom, 50% of patients had a comorbid condition. In total, 70.7% initially reported interference with daily activities, and 87.8% were reassured following discussion. CONCLUSIONS: With appropriate education and counselling, the majority of girls with concerns regarding labial appearance can be managed without surgery. Overall, our data support current international policy that female cosmetic genital surgery not be performed in mature minors unless there are specific indications. More research about characteristics of patients referred with labial concerns, definition of labial size and long-term satisfaction of conservative versus surgical methods is necessary to determine the best approach.

AIMS: This study sought to observe the rate and timing of spontaneous resolution of labial adhesions that had been diagnosed in pre-pubertal girls. The secondary aim was to evaluate the conservative approach to management of labial adhesions that has been advocated by the Gynaecology Department, by assessing the rates of concurrent uro-gynaecological symptoms in this population, as well as parent satisfaction with their child's management. METHODS: A retrospective chart review was performed of all patients diagnosed with labial adhesions in the Department of Paediatric and Adolescent Gynaecology between 2000 and 2017. Patients and their parents (depending on the age of the patient at the time of this study) were then invited to participate in follow-up surveys and questionnaires and clinical examination. RESULTS: Of 148 girls identified, the median age of the follow-up participants (n = 45) was 6.1 years (2.6-27.2 years), compared with that of the entire cohort of 7.4 years (1-27 years). After a median follow-up period of 2.6 years (0.4-20.7 years), 40% (18/45) of girls reported and/or had findings that supported resolution of labial adhesions without treatment. Two parents (4%) sought treatment elsewhere after their appointment. A history of UTI was reported in 30% (14/45) of patients, and 16% (7/45) had a known history of vulvovaginitis. CONCLUSIONS: Our findings support the natural history of spontaneous resolution of labial adhesions. Concurrent uro-gynaecological conditions that developed were successfully treated according to standard treatments. A conservative approach to the management of labial adhesions is associated with very low rates of parental concern and intervention.

STUDY OBJECTIVE: No studies have specifically considered paternal understanding of menstruation. This study aimed to establish the degree of understanding of fathers of adolescent girls with menstrual symptoms relative to mothers. DESIGN AND SETTING: This was a cross-sectional survey-based study. Adolescent patients attending an outpatient gynecology clinic for dysmenorrhea and/or heavy menstrual bleeding and their parents were invited to complete surveys. PARTICIPANTS: Sixty surveys were completed (24 of 40 daughters, 20 of 40 mothers, 16 of 40 fathers). INTERVENTIONS AND MAIN OUTCOME MEASURES: Surveys aimed to test parents' understanding of menstrual symptoms and potential medications, as well as fathers' concerns with their daughters' health. RESULTS: The fathers' knowledge of menstrual symptoms was poorer than mothers, although most knew heavy menstrual bleeding (15/16, 94%) and mood swings (14/16, 87%). Many parents answered "don't know" or did not answer questions about potential consequences of medications, although parents were clearly concerned about side effects. Most fathers (13/16, 81%) were open to discussing menstrual concerns with daughters; however, only 54% (13/24) of daughters were open to such discussions. Of fathers, 81% (13/16) were sympathetic/concerned, 56% (9/16) felt helpless, and 13% (2/16) were frustrated when daughters were in pain. When asked about effects, 88% (14/16) of fathers (79% [15/20] of mothers) were worried about their daughter's welfare and 63% (10/16) (55% [11/20] of mothers) about schooling. CONCLUSION: We present, to our knowledge, the first insight into fathers' knowledge of their daughters' menstrual health. Overall, parents have an incomplete picture of menstrual symptoms. Even in this cohort, which could be expected to be well informed because of their daughters' attendance at a tertiary hospital, it is clear that further knowledge would assist them caring for their daughters.

BACKGROUND: We examined the association between unwanted sexual experiences and cervical cancer, cervical intraepithelial neoplasia 3, adenocarcinoma in situ, diagnosed ≤25 years of age. METHODS: A case-control study of women ≤55 years who attended gynecological hospitals in Australia between 1983 and 2007. Cases were ≤25 years when diagnosed with disease, control group 1 were "older women" >25 years at diagnosis; control group 2 were "well women" ≤25 years attending preventive health clinics. A self-administered postal survey was utilized. The main outcome measures were prevalence of childhood sexual abuse (<16 years) and unwanted adolescent sexual experiences (between 16 and 18 years) in cases compared to controls. RESULTS: Of 400 contactable subjects, 251 participated (62.8%). Prevalence of childhood sexual abuse in cases (26.6% [25/94]) was similar to other groups. Prevalence of childhood genital contact abuse in cases with cervical cancer was 45.5% [5/11], compared to older women (20% [10/50], p = 0.08) and well women (13.8% [8/58], p = 0.01), and was marginally more common compared to well women when adjusted for other lifestyle factors (odds ratio [OR]: 4.7 [1.0-22.6], p = 0.05). Prevalence of unwanted adolescent sexual experiences in cases was 28.9% [33/114]. Prevalence of adolescent penile-genital contact experiences in cervical cancer cases was 46.7% [7/15], compared to older women (9.4%, [6/64], p < 0.001) and well women (13.7%, [10/73], p = 0.003), and was more common compared to well women when adjusted for lifestyle (OR: 5.9 [1.4-24.9], p = 0.02) and sexual health risk factors (OR: 5.6 [1.4-22.1] p = 0.01). CONCLUSIONS: Unwanted sexual experiences with genital contact were a risk factor for invasive cervical cancer ≤25 years, likely due to a complex interplay of biological and environmental factors.

STUDY OBJECTIVES: Benign müllerian papillomas of the genital tract are rare and, hence, can be mistaken for vaginal rhabdomyosarcoma on initial clinical review. This review of the literature will consolidate the previous cases of müllerian papilloma reported and looks for clues to differentiate the 2 entities. DESIGN AND SETTING: We provide a case report and literature review, with patients from a pediatric adolescent gynecology clinic in a tertiary center. METHODS: We conducted a search of English-language publications from 1951 (the first case report) until January 2014 by using the search words "Müllerian papilloma" and "prepubertal bleeding." References from previous published reports were also obtained for completeness. MAIN OUTCOME: Literature review of benign müllerian papilloma. RESULTS: Since 1951, 56 cases of müllerian papilloma were reported, including 4 cases at our institution. Comorbid conditions were found in 31.5% of cases (with 3 cases associated with mesenchymal tumors). The average length of time from onset of symptoms (primarily vaginal bleeding) to diagnosis was 6.7 months (range, 1 day to 3 years), with only 1 case diagnosed incidentally. Median age of presentation was 5 years (range, 1 day to 52 years). Most cases were localized and resected with ease. Histology reveals complex papillary lesions without cytologic atypia. CONCLUSION: Benign müllerian papilloma is distinguished from the more significant diagnosis of vaginal rhabdomyosarcoma by initial length of vaginal bleeding at presentation, lack of vaginal wall extension, ease of resection, and histopathology. This is compared with vaginal rhabdomyosarcoma which commonly exhibits both localized and distant spread.

BACKGROUND: Disorders of sex development (DSD) are congenital conditions in which chromosomal, gonadal, or phenotypic sex is atypical. Clinical management of DSD is often difficult and currently only 13% of patients receive an accurate clinical genetic diagnosis. To address this we have developed a massively parallel sequencing targeted DSD gene panel which allows us to sequence all 64 known diagnostic DSD genes and candidate genes simultaneously. RESULTS: We analyzed DNA from the largest reported international cohort of patients with DSD (278 patients with 46,XY DSD and 48 with 46,XX DSD). Our targeted gene panel compares favorably with other sequencing platforms. We found a total of 28 diagnostic genes that are implicated in DSD, highlighting the genetic spectrum of this disorder. Sequencing revealed 93 previously unreported DSD gene variants. Overall, we identified a likely genetic diagnosis in 43% of patients with 46,XY DSD. In patients with 46,XY disorders of androgen synthesis and action the genetic diagnosis rate reached 60%. Surprisingly, little difference in diagnostic rate was observed between singletons and trios. In many cases our findings are informative as to the likely cause of the DSD, which will facilitate clinical management. CONCLUSIONS: Our massively parallel sequencing targeted DSD gene panel represents an economical means of improving the genetic diagnostic capability for patients affected by DSD. Implementation of this panel in a large cohort of patients has expanded our understanding of the underlying genetic etiology of DSD. The inclusion of research candidate genes also provides an invaluable resource for future identification of novel genes.

INTRODUCTION: The management of vaginal agenesis is currently determined by geographical location and surgeon preference. The optimal treatment is unknown and the majority of articles on technique and outcome focus on personal case series with little standardisation of reporting and follow-up. METHODS: Six thousand six hundred and ninety-one articles concerning the management of vaginal agenesis were systematically reviewed, with 162 fitting the inclusion criteria. RESULTS: Only one randomised control trial was included with the remaining articles made up of case series or case reports. The bowel vaginoplasty method was most commonly reported historically with 945 patients and 45 articles included. The Vecchietti procedure had the shortest operative time, but the highest number of urological injuries (2.1 %). The split thickness procedure had the highest infection rate (4.2 %) and re-operation rate (7.84 %). CONCLUSION: Overall, the conservative method using dilation had the fewest complications, with an average vaginal length of 6.65 cm (± 1.39 cm). However, with an operative procedure full consent is imperative, as is an understanding of the need for postoperative dilation with the majority of techniques.

Anorexia nervosa (AN) initiates an adaptive response at the level of the hypothalamus, which results in a complex interplay involving most elements of the neuroendocrine axis. Consequences of onset of disease in adolescence include amenorrhoea, pubertal arrest with potential loss of target height, and osteoporosis with reduced capacity for future attainment of peak bone mass. With recovery, delay in restoration of menses is common. Hormonal therapies for restoration of bone mineral density (BMD) in adolescents have shown limited efficacy. This review will discuss the reproductive endocrine effects of AN in adolescence, and discuss new investigative tools for monitoring restoration of reproductive function and BMD in this population.