Joint developmental trajectories of internalizing and externalizing problems from mid-childhood to late adolescence and childhood risk factors: Findings from a prospective pre-birth cohort.

There is limited evidence on heterogenous co-developmental trajectories of internalizing (INT) and externalizing (EXT) problems from childhood to adolescence and predictors of these joint trajectories. We utilized longitudinal data from Raine Study participants (n = 2393) to identify these joint trajectories from 5 to 17 years using parallel-process latent class growth analysis and analyze childhood individual and family risk factors predicting these joint trajectories using multinomial logistic regression. Five trajectory classes were identified: Low-problems (Low-INT/Low-EXT, 29%), Moderate Externalizing (Moderate-EXT/Low-INT, 26.5%), Primary Internalizing (Moderate High-INT/Low-EXT, 17.5%), Co-occurring (High-INT/High-EXT, 17%), High Co-occurring (Very High-EXT/High-INT, 10%). Children classified in Co-occurring and High Co-occurring trajectories (27% of the sample) exhibited clinically meaningful co-occurring problem behaviors and experienced more adverse childhood risk-factors than other three trajectories. Compared with Low-problems: parental marital problems, low family income, and absent father predicted Co-occurring and High Co-occurring trajectories; maternal mental health problems commonly predicted Primary Internalizing, Co-occurring, and High Co-occurring trajectories; male sex and parental tobacco-smoking uniquely predicted High Co-occurring membership; other substance smoking uniquely predicted Co-occurring membership; speech difficulty uniquely predicted Primary Internalizing membership; child's temper-tantrums predicted all four trajectories, with increased odds ratios for High Co-occurring (OR = 8.95) and Co-occurring (OR = 6.07). Finding two co-occurring trajectories emphasizes the importance of early childhood interventions addressing comorbidity.

Experiences of Oncofertility Decision-Making and Care in a National Sample of Adolescent and Young Adult Cancer Patients and Parents.

Purpose: Cancer and its treatments are known to compromise fertility in adolescents and young adults (AYAs). The emotional burden of possible infertility is reduced in those who receive supportive oncofertility care. In legal minors, provision of health care must consider the legal context and desire that AYAs have for autonomous decision-making, together with their competence to make health decisions. This has important implications for how oncofertility discussions may, or may not, involve parents. The aim of this study was to explore oncofertility decision-making and care experiences in a national Australian sample of AYA cancer patients and their parents. Methods: AYAs aged 15-25 years and parents were recruited from 17 cancer care sites and CanTeen Australia as part of a national AYA cancer care study. The cross-sectional survey included open-ended questions regarding oncofertility care experiences. We used reflexive thematic analysis to identify themes. Results: Data were available for 99 AYAs and 111 parents. Four themes were identified: emotional care needs; parent-AYA dynamics including AYA autonomy and agency; decision-making considerations including values and practicalities; and reflections on oncofertility care and follow-up. Both AYAs and parents placed importance on AYA autonomy in fertility decision-making, but many AYAs appreciated the role of parents in providing support and guidance throughout the process. Conclusion: Health care professionals are encouraged to autonomously engage AYAs around fertility decision-making, while concurrently offering opportunities that promote parental support. Better psychological support and follow-up oncofertility care are also needed.

Experiences of Family and Partner Support in Fertility Decision-Making Among Adolescents and Young Adults with Cancer: A National Australian Study.

Purpose: To understand how adolescents and young adults (AYAs) with cancer experience family and partner involvement in fertility preservation (FP) decision-making. Methods: As part of a nationally representative Australian cross-sectional study of 15-25-year olds with cancer, 196 participants (mean age 19.9 [standard deviation 3.2] years at diagnosis; 51% male) were surveyed regarding FP decision-making. Results: One hundred sixty-one (83%) participants reported discussion of potential effects of cancer and its treatment on fertility, of whom 57 (35%) did not undertake FP (51% of females; 19% of males). Parental involvement (mothers 62%, fathers 45%) in decision-making was considered helpful, including for 73% of 20-25-year olds with partners. Sisters and brothers were involved less often, yet rated helpful in 48% and 41% of cases, respectively. Older participants were more likely than younger ones to have involved partners (47% vs. 22%, p = 0.001) and less likely to have involved mothers (56% vs. 71%, p = 0.04) or fathers (39% vs. 55%, p = 0.04). Conclusion: This is the first quantitative study to explore family and partner involvement in AYA FP decision-making in both females and males in a nationally representative sample. Parents are important resources who commonly assist AYAs with these complex decisions. Although many AYAs will be the main decision-makers when it comes to FP, particularly as AYAs mature, these data suggest that resources and support should be available for and inclusive of parents, partners, and siblings.

Interventions to improve oncofertility knowledge and decision-making in patients with low health literacy: A systematic review.

OBJECTIVE: To conduct a systematic review of interventions that improve knowledge, health and decision-related outcomes in cancer, fertility or the intersection of both among low health literacy (LHL) patients. METHODS: Articles published from 2000 to March 2022 in English were identified through searching MEDLINE, PsycInfo, and Embase databases on 29/03/2022. Studies were independently screened against eligibility criteria and appraised for quality. A narrative synthesis of data was presented. RESULTS: Of 235 citations, 11 studies (2585 participants) investigating three categories were included: decision-support tools (n = 8), mobile health applications (n = 2) and communication tools (n = 1). No eligible study was identified for fertility or oncofertility. All interventions integrated multimedia or interactivity to supplement plain-language text. Decision aids and mobile health applications improved knowledge, reduced decisional conflict and increased clarity around cancer-related choices. Overall, findings favoured the use of online interventions tailored for LHL patients. CONCLUSION: There is a lack of data on LHL interventions in fertility and oncofertility. In cancer, LHL interventions improved knowledge and decision-making outcomes. The ideal intervention remains inconclusive. PRACTICE IMPLICATIONS: Lack of engagement with LHL needs in oncofertility and fertility settings have implications for informed treatment decision-making. In cancer, further research is required to ascertain most effective intervention format.

Exploring the experiences and priorities of women with a diagnosis of ovarian cancer.

PURPOSE: Ovarian cancer is the third most common gynaecological cancer among women, yet remains under-researched. Past studies suggest that women who present with ovarian cancer have more supportive care needs compared to women experiencing other gynaecological cancers. This study explores the experiences and priorities of women with a diagnosis of ovarian cancer and whether age may influence these needs and experiences. METHODS: Participants were recruited by a community organization, Ovarian Cancer Australia (OCA), via a social media campaign promoted on Facebook. Participants were asked to rank priorities around living with ovarian cancer, and to endorse which supports and resources they had used to address those priorities. Distributions of priority rankings and resource use were compared by age (19-49 vs. 50+ years). RESULTS: Two hundred and eighty-eight people completed the consumer survey and most respondents were 60-69 years (33.7%). Priorities did not vary by age. Fear of cancer recurrence was identified by 51% respondents as the most challenging aspect of having ovarian cancer. Compared with older respondents, a higher proportion of young participants were more inclined to use a mobile app version of the OCA resilience kit (25.8% vs 45.1%, p=0.002) and expressed interest in using a fertility preservation decision aid (2.4% vs 25%, p<0.001). CONCLUSION: Fear of recurrence was participants' primary concern, presenting an opportunity to develop interventions. Information delivery needs to consider age-specific preferences to better reach the target audience. Fertility is more important to younger women and a fertility preservation decision aid may address this need.

Priorities for alleviating menopausal symptoms after cancer.

OBJECTIVE: To determine treatment priorities in women cancer patients attending a dedicated Menopausal Symptoms After Cancer service. METHODS: Cancer type and stage were abstracted from medical records. Women ranked up to three symptoms as treatment priorities from the list "hot flushes/night sweats," "mood changes," "vaginal dryness or soreness," "sleep disturbances," "feeling tired or worn out (fatigue)," "sexual problems and/or pain with intercourse," "joint pain," and "something else" with free-text response. For each prioritized symptom, patients completed standardized patient-reported outcome measures to determine symptom severity and impact. RESULTS: Of 189 patients, most had breast cancer (48.7%, n = 92), followed by hematological (25.8%, n = 49), gynecological (18.0%, n = 34), or colorectal (2.6%, n = 5). The highest (first-ranked) treatment priority was vasomotor symptoms (33.9%, n = 64), followed by fatigue (18.0%, n = 34), vaginal dryness/soreness (9.5%, n = 18), and sexual problems/pain with intercourse (9.5%, n = 18). Symptoms most often selected in the top three ("prioritized") were fatigue (57.7%, n = 109), vasomotor symptoms (57.1%, n = 108), and sleep disturbance (49.2%, n = 93). In patients who prioritized vasomotor symptoms, medians on the "problem," "distress," and "interference" dimensions of the Hot Flash Related Daily Interference Scale were, respectively, 6.0 (interquartile range [IQR], 5.0-8.0), 5.5 (IQR, 3.0-8.0), and 5.0 (IQR, 3.-7.0), indicating moderate severity. In patients who prioritized fatigue, the median Fatigue Scale score was 28 (IQR, 19-36), 37% worse than general population. CONCLUSIONS: Vasomotor symptoms, fatigue, sexual problems, and vaginal dryness/soreness were the leading priorities for treatment. Understanding symptom severity and patient priorities will inform better care for this growing population.

Efficacy of interventions to manage sexual dysfunction in women with cancer: a systematic review.

IMPORTANCE: Cancer and its treatment negatively affect female sexual health and function. The prevalence of female sexual dysfunction after cancer is between 33% and 43%. Numerous studies have addressed treatment options for sexual dysfunction in women with cancer, but it still remains a challenge to select the most efficacious option for patients. OBJECTIVE: To compile and appraise recent evidence of any interventions for managing sexual dysfunction in female cancer survivors. EVIDENCE REVIEW: A literature search of the electronic databases MEDLINE, EMBASE, PsycINFO, and Cochrane Central Register of Controlled Trials (January 2011 to February 2021) was conducted using general search terms of "women", "cancer", "intervention", "sexual dysfunction". We included randomized controlled trials (RCTs) and uncontrolled before-after studies that evaluated the efficacy of intervention for female sexual dysfunction in women with history of cancer. Methodological quality of studies was assessed using Risk of Bias (RoB) 2.0 for RCTs and National Institutes of Health (NIH) assessment tools for uncontrolled before-after studies. FINDINGS: Thirty-six studies were included for qualitative synthesis (14 RCTs (n = 1284), 17 uncontrolled trials (n = 589), and 5 cohort studies (n = 497). Only four studies were at low risk of bias. Topical interventions (vaginal gels or creams) were able to alleviate vaginal dryness and dyspareunia, with intravaginal dehydroepiandrosterone (DHEA) (6.5 mg) gel showing evidence of improved sexual function. Evidence for estriol-lactobacilli vaginal tablets was unreliable due to a small-scale study. Psychoeducational therapy (internet-based cognitive behavioral therapy [CBT]) studies typically were at high risk of bias, but all displayed significant improvements of sexual function. Both laser therapy (fractional CO2 and erbium) and multimodal approach studies were at concerning risk of bias, although suggesting beneficial effects on sexual function. CONCLUSIONS AND RELEVANCE: The most reliable evidence for improvement was from a study of DHEA vaginal gel, but in general, gels or creams were useful in reducing dyspareunia. Pharmacological, psychoeducational, laser therapy, and multimodal approaches demonstrated potential in managing cancer-related sexual issues, but most were small in size (10-70 participants), with moderate to high risk of bias. Therefore, large-scale, double-blind, RCTs with long-period follow-up, and at low risk of bias are needed to show efficacy for these interventions.

Video Summary : http://links.lww.com/MENO/A912 .

Night Shift Among Women: Is It Associated With Difficulty Conceiving a First Birth?

Background: Asynchrony in circadian processes alters many physiological systems, including female reproduction. Thus, there are possible reproductive consequences of night shift work for women including menstrual irregularity, endometriosis, and prolonged time to conception. This study examined whether women who worked night shift were more likely than those who did not to require fertility treatment to conceive a first birth, whether they had specific infertility diagnoses, and if such relationships were age-specific. Methods: In a retrospective data linkage study of 128,852 primiparous women, fertility treatment data were linked to the state perinatal registry for South Australia (1986-2002). Potential exposure to night shift work was assessed using a job-exposure matrix. First, the association between night shift work and fertility treatment was assessed among (1) all women, then (2) women in paid employment, using logistic regression. Interactions between age and shift work status were also examined. Secondly, among women who conceived with fertility treatment, we assessed associations between night shift work and type of infertility diagnosis. Potential confounders were considered in all analyses. Results: Among women ≤35 years, night shift workers were more likely to require fertility treatment (all: OR = 1.40, 95% CI 1.19-1.64; in paid employment: OR = 1.27, 95% CI 1.08-1.50). There were no associations among women >35 years. Ethnicity, socioeconomic status and smoking did not affect these results. Among women who underwent fertility treatment, night shift workers were more likely than day workers to have menstrual irregularity (OR = 1.42, 95% CI 1.05-1.91) or endometriosis (OR = 1.34, 95% CI 1.00-1.80). Conclusions: Night shift work may contribute to increased need for fertility treatment in younger women. This increased risk may reflect young women's vulnerability in terms of poor tolerance of night shift work, and/or lack of control and choice about shift schedule.

Exploring factors that impact uptake of risk-reducing bilateral salpingo-oophorectomy (RRBSO) in high-risk women.

OBJECTIVE: Only risk-reducing bilateral salpingo-oophorectomy (RRBSO) has been shown to reduce ovarian cancer deaths in high-risk women. Uptake of RRBSO is, however, suboptimal and reasons are not well defined. More information is needed about the barriers to RRBSO and patient needs for information and care. METHODS: Cross-sectional study including the Perception of Cancer Risk Scale, factors affecting decision-making about RRBSO, and unmet information needs were measured using a purpose-designed questionnaire. RESULTS: Of the 193 high-risk women aged 30 to 50 approached, 60 (31%) agreed to participate. Respondents were either considering or had recently undergone premenopausal RRBSO. Most (49/60) had no personal history of cancer; 11/60 had previous breast cancer. Overall, responses did not differ between pre- and post-RRBSO participants. The main barriers to RRBSO were surgical menopause and loss of fertility. Other concerns included the impact on sexual function and bone health. Reduction in ovarian cancer risk and prolonged life expectancy were the main drivers for RRBSO. Participants understood that RRBSO reduced cancer risk, although most substantially overestimated their personal ovarian cancer risk. High-risk women wanted more information about how to manage the short- and long-term consequences of surgical menopause. CONCLUSIONS: Concerns about surgical menopause and loss of fertility are barriers to RRBSO for high-risk women despite understanding the benefits of reduced cancer risk. There is an unmet need for more information about effectively managing the noncancer consequences of RRBSO in premenopausal women. : Video Summary:http://links.lww.com/MENO/A478.

What information do healthcare professionals need to inform premenopausal women about risk-reducing salpingo-oophorectomy?

OBJECTIVE: The aim of this study was to identify the unmet information needs of healthcare professionals managing risk-reducing bilateral salpingo-oophorectomy (RRBSO) in premenopausal women. METHODS: A cross-sectional survey of healthcare professionals managing high-risk women in Victoria, Australia. Questions included roles and responsibilities around RRBSO, perceived barriers to uptake of RRBSO, and unmet information needs. RESULTS: One hundred eighteen healthcare professionals across 10 different disciplines and specialties were approached to participate, of whom 47 completed the survey. Most respondents were genetic counselors (47%) or nurses (19%) and all worked in the public health system. Almost all (81%) provided information about RRBSO, but there was considerable uncertainty about who was responsible for making decisions with high-risk women about RRBSO. Most (85%) were "quite a bit" or "extremely" confident about informing high-risk women about ovarian cancer risk reduction from RRBSO and the surgical procedure (47%), but only one-third were "quite a bit" or "extremely" confident about discussing (36%) or managing (31%) surgical menopause. Furthermore, surgical menopause was considered the main barrier (88%, "quite a bit" or "extremely") to RRBSO. Most healthcare professionals (78%) wanted more information and resources about surgical menopause for high-risk women. CONCLUSIONS: There is uncertainty around the roles and responsibilities of healthcare professionals managing high-risk women around RRBSO. Surgical menopause is perceived as a major barrier to RRBSO and healthcare professionals lack confidence in managing this outcome. : Video Summary:http://links.lww.com/MENO/A477.

Relationship between umbilical cord sex hormone binding globulin, sex steroids, and age at menarche: a prospective cohort study.

OBJECTIVE: To study the role of the prenatal environment in regulating reproductive development by measuring the prospective association between umbilical cord concentrations of sex hormone binding globulin (SHBG; principal regulator of sex steroid activity), bioavailable sex steroids, and age at menarche. DESIGN: Prospective population-based cohort. SETTING: Not applicable. PATIENT(S): In 286 female members of the Western Australian Pregnancy (Raine) cohort, concentrations of SHBG and steroids (estrogens: estrone, estradiol, estriol and estetrol [E4]; androgens: total testosterone, Δ4-androstenedione, androstenedione and dehydroepiandrosterone) were measured by liquid chromatography-tandem mass spectrometry from archived umbilical cord blood samples collected at birth. Bioavailable concentrations of testosterone and estradiol were calculated along with total composite measures of androgen and estrogen bioactivity. SHBG was measured by ELISA. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Age of menarche was calculated from date of menarche, collected prospectively by questionnaire sent home with participants at the year 10 follow-up. RESULT(S): Higher maternal education, higher body mass index, and the presence of antepartum hemorrhage were all significantly associated with earlier age at menarche. The bioavailable sex steroid measures accounted for 8.3% of the variance in age at menarche. Further, both SHBG and E4 concentrations accounted for a significant proportion of unique variance in age at menarche. CONCLUSION(S): Lower SHBG and higher E4 concentrations in umbilical cord blood were associated with earlier age at menarche. These results suggest that the prenatal sex steroid environment contributes toward pubertal development and age at menarche.

Managing menopausal symptoms after cancer: an evidence-based approach for primary care.

Impaired ovarian function and menopausal symptoms are common after cancer treatment. Menopausal symptoms often occur at an earlier age in women with cancer, and may be more severe than in natural menopause; they may be the most persistent and troubling sequelae of cancer. A third of female patients with cancer report dissatisfaction with the quality and length of physician-patient discussions about reproductive health, including menopause. Systemic menopausal hormone therapy is the most effective treatment for menopausal symptoms, but it is not suitable for all patients after cancer - where it is unsuitable, alternative effective non-hormonal treatments are available. Effective pharmacological agents available to treat vasomotor symptoms include selective serotonin reuptake inhibitors, serotonin-noradrenaline reuptake inhibitors, clonidine and gabapentin. There is increasing evidence supporting cognitive behavioural therapy for the treatment of vasomotor symptoms, in self-help or group settings. Vaginal atrophy can be treated with vaginal (topical) oestrogen with minimal systemic absorption; topical vaginal lubricants may help with vaginal dryness and dyspareunia, with some evidence suggesting that silicone-based products may be more effective than water-based ones. Bone health may be impaired in post-menopausal women with cancer or in cancer survivors, particularly in women with treatment-related menopause or in women receiving anti-oestrogen therapies; this should be managed in addition to menopausal symptoms. Primary care physicians should be aware of the troublesome and ongoing nature of menopausal symptoms after cancer, should discuss them with all patients after cancer treatment, and should consider treatment or referral to a specialist for appropriate management.

Managing menopausal symptoms after breast cancer - A multidisciplinary approach.

More than 6 million women worldwide are living with a past diagnosis of breast cancer. Most survive their illness, and management of the long-term consequences of treatment has become a priority in cancer care. Menopausal symptoms affect most breast cancer survivors and may significantly impair quality of life. We describe a multidisciplinary model to evaluate and manage these women using a patient-focused approach. The 'Multidisciplinary Menopause After Cancer Clinic' includes gynecologists, endocrinologists, GPs, a psychologist and a clinical nurse specialist. Benefits of this model include improved coordination of patient care, education, communication and evidence-based decision making.

Sexual inactivity in partnered female cancer survivors.

OBJECTIVE: To measure sexual activity in a clinic population of partnered female cancer survivors, and to better understand reasons for sexual inactivity in this population. MATERIALS AND METHODS: Partnered peri- or post-menopausal cancer survivors seen at a specialty clinic for menopause symptoms after cancer completed Fallowfield's Sexual Activity Questionnaire, quality of life measures (the Functional Assessment of Cancer Therapy General, Breast Cancer, and Endocrine Symptom Scales), and the Greene Climacteric Scale. Responses were compared between those who were sexually active and those who were not. RESULTS: Of 316 partnered women who reported sexual activity status, most were breast cancer survivors (n=268, 85%) and were sexually active (n=227, 72%). Women who were not sexually active (n=89, 28%) were slightly older than those who were active (53.1v 51.0 years, p=0.049) but did not differ in menopausal status, time since cancer diagnosis, or treatment with chemotherapy, anti-estrogenic endocrine therapy or menopausal hormone therapy. Loss of interest in sex (78%) and being too tired (44%) were the most common reasons for sexual inactivity. Those who were not sexually active were more likely to be dissatisfied with their sex lives (adjusted odds ratio (aOR) 3.52, 95% CI 1.66-7.48) and to have lost interest in sex (aOR 2.12, 95% CI 1.22-3.67). Compared with sexually active women, sexually inactive women were significantly less likely to feel sexually attractive or "able to feel like a woman" (respectively, aOR 2.51, 95% CI 1.01-6.24; aOR 2.21, 95% CI 1.32-3.71) and more likely to feel bothered by a weight change and self-conscious about the way they dressed, and to be bothered by hair loss (respectively, aOR 1.84, 95% CI 1.10-3.05; aOR 2.75, 95% CI 1.63-4.64; aOR 1.85, 95% CI 1.04-3.29). Those who were not sexually active had significantly lower average scores on breast-cancer-related quality of life than sexually active women but did not differ in physical, social or functional well-being or menopause-related quality of life. Pain with intercourse and vaginal dryness were equally common in both groups (respectively, sexually inactive 45.5% v. active 38.3%, aOR 1.28, 95%CI 0.75-2.18; 48.8% v. 49.5%, aOR 0.94, 95% CI 0.57-1.56). CONCLUSIONS: Over one-quarter of partnered cancer survivors in this clinic-based sample were not sexually active. Sexually inactive women were more dissatisfied with their sex lives, felt less attractive and more self-conscious about their appearance. The reasons for sexual inactivity in cancer survivors are multifaceted and complex and rates of vaginal dryness and dyspareunia did not differ between sexually active and inactive women, suggesting that interventions to improve sexual function which are limited to treating vaginal dryness are unlikely to be effective.

Differential Gene Expression in Menstrual Endometrium From Women With Self-Reported Heavy Menstrual Bleeding.

Heavy menstrual bleeding (HMB) is a significant social and public health issue for menstruating women. Development of targeted treatments has been limited by poor understanding of local mechanisms underlying HMB. We aimed to determine how gene expression differs in menstrual phase endometrium from women with HMB. Menstrual phase endometrial biopsies were collected from women with (n = 7) and without (n = 10) HMB (regular menstrual cycles, no known pelvic pathology), as well as women with uterine fibroids (n = 7, n = 4 had HMB). Biopsies were analyzed using Illumina Sentrix Human HT12 arrays and data analyzed using "Remove Unwanted Variation-inverse". Ingenuity Pathway Analysis and the Database for Annotation, Visualization and Integrated Discovery v6.7 were used to identify gene pathways, functional gene clusters, and upstream regulators specific to the clinical groupings. Individual genes of interest were examined using quantitative polymerase chain reaction. In total, 829 genes were differentially expressed in one or more comparisons. Significant canonical pathways and gene clusters enriched in controls relative to both HMB and fibroid groups suggest the mechanisms responsible for HMB include modifications of the endometrial inflammatory or infection response. In contrast, differentially expressed genes in women with fibroids suggest modifications of hemoglobin, antigen processing, and the major histocompatibility complex (class II, beta chain) activity. In conclusion, HMB associated with fibroids may be regulated by different endometrial mechanisms from HMB in women without fibroids and from normal menstrual bleeding. These novel data provide numerous testable hypotheses that will advance our understanding of the mechanisms responsible for HMB.

Teenage mothers.

BACKGROUND: Australia's teenage birth rate has fallen to historic lows, but teenage motherhood still occurs and can be challenging for mother and baby. OBJECTIVE: The aim of this article is to review current evidence on the epidemiology and clinical care of teenage pregnancy and parenting, and provide recommendations around management of these young people in Australia. DISCUSSION: Teenage mothers may have experienced family, sexual, and partner violence, family disruption, and socioeconomic disadvantage. Outcomes on a range of peripartum measures are worse for teenage mothers and their babies. Longer term risks for the mother include depression and rapid repeat pregnancy; for the child, intergenerational teenage parenthood; and for both, socioeconomic disadvantage. Teenage motherhood occurs more often within communities where poverty, Aboriginal and Torres Strait Islander status and rural/remote location intersect. General practitioners play a critical role in identification of at-risk teens, preventing unintended teenage pregnancy, clinical care of pregnant teens, and promoting the health and wellbeing of teenage mothers and their children.

Identification of genes differentially expressed in menstrual breakdown and repair.

STUDY QUESTION: Does the changing molecular profile of the endometrium during menstruation correlate with the histological profile of menstruation. SUMMARY ANSWER: We identified several genes not previously associated with menstruation; on Day 2 of menstruation (early-menstruation), processes related to inflammation are predominantly up-regulated and on Day 4 (late-menstruation), the endometrium is predominantly repairing and regenerating. WHAT IS KNOWN ALREADY: Menstruation is induced by progesterone withdrawal at the end of the menstrual cycle and involves endometrial tissue breakdown, regeneration and repair. Perturbations in the regulation of menstruation may result in menstrual disorders including abnormal uterine bleeding. STUDY DESIGN, SIZE DURATION: Endometrial samples were collected by Pipelle biopsy on Days 2 (n = 9), 3 (n = 9) or 4 (n = 6) of menstruation. PARTICIPANTS/MATERIALS, SETTING, METHODS: RNA was extracted from endometrial biopsies and analysed by genome wide expression Illumina Sentrix Human HT12 arrays. Data were analysed using 'Remove Unwanted Variation-inverse (RUV-inv)'. Ingenuity pathway analysis (IPA) and the Database for Annotation, Visualization and Integrated Discovery (DAVID) v6.7 were used to identify canonical pathways, upstream regulators and functional gene clusters enriched between Days 2, 3 and 4 of menstruation. Selected individual genes were validated by quantitative PCR. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, 1753 genes were differentially expressed in one or more comparisons. Significant canonical pathways, gene clusters and upstream regulators enriched during menstrual bleeding included those associated with immune cell trafficking, inflammation, cell cycle regulation, extracellular remodelling and the complement and coagulation cascade. We provide the first evidence for a role for glutathione-mediated detoxification (glutathione-S-transferase mu 1 and 2; GSTM1 and GSTM2) during menstruation. The largest number of differentially expressed genes was between Days 2 and 4 of menstruation (n = 1176). We identified several genes not previously associated with menstruation including lipopolysaccharide binding protein, serpin peptidase inhibitor, clade B (ovalbumin), member 3 (SERPINB3) and -4 (SERPINB4), interleukin-17C (IL17C), V-set domain containing T-cell activation inhibitor 1 (VTCN1), proliferating cell nuclear antigen factor (KIAA0101/PAF), trefoil factor 3 (TFF3), laminin alpha 2 (LAMA2) and serine peptidase inhibitor, Kazal type 1 (SPINK1). Genes related to inflammatory processes were up-regulated on Day 2 (early-menstruation), and those associated with endometrial repair and regeneration were up-regulated on Day 4 (late-menstruation). LIMITATIONS, REASONS FOR CAUTION: Participants presented with a variety of endometrial pathologies related to bleeding status and other menstrual characteristics. These variations may also have influenced the menstrual process. WIDER IMPLICATIONS OF THE FINDINGS: The temporal molecular profile of menstruation presented in this study identifies a number of genes not previously associated with the menstrual process. Our findings provide valuable insight into the menstrual process and may present novel targets for therapeutic intervention in cases of endometrial dysfunction. LARGE SCALE DATA: All microarray data have been deposited in the public data repository Gene Expression Omnibus (GSE86003). STUDY FUNDING AND COMPETING INTERESTS: Funding for this work was provided by a National Health and Medical Research Council of Australia (NHMRC) Project Grant APP1008553 to M.H., P.R. and J.G. M.H. is supported by an NHMRC Practitioner Fellowship. P.P. is supported by a NHMRC Early Career Fellowship. The authors have no conflict of interest to declare.

A randomized, double-blind, crossover trial comparing a silicone- versus water-based lubricant for sexual discomfort after breast cancer.

Discomfort during sexual activity is common after breast cancer. Vaginal estrogens are effective but commonly avoided due to systemic absorption. Despite the large commercial market for vaginal lubricants, no randomized studies have compared products. We aimed to compare efficacy and acceptability of two major types of lubricant for discomfort during sexual activity in postmenopausal breast cancer patients. In a single-center, randomized, double-blind, AB/BA crossover design, sexually active postmenopausal breast cancer patients used each lubricant for 4 weeks. The primary patient-reported efficacy outcome was total discomfort related to sexual activity (Fallowfield Sexual Activity Questionnaire Discomfort subscale SAQ-D). Acceptability was measured by patient preference and reported intention to continue using the products. Of 38 women analyzed, over 90 % experienced clinically significant sexually related distress at baseline. Water- and silicone-based lubricants did not differ statistically in efficacy based on total sexual discomfort (difference 0.7, 95 % confidence interval (CI) 0-1.4, p = 0.06). In a post hoc analysis, pain/discomfort during penetration improved more during silicone-based lubricant use than during water-based lubricant use (odds ratio 5.4, 95 % CI 1.3-22.1, p = 0.02). All aspects of sexual discomfort measured with diaries were reported more commonly with water- than silicone-based lubricant. Almost twice as many women preferred silicone-based to water-based lubricant than the converse (n = 20, 65 %, vs. n = 11, 35 %). 88 % continued to experience clinically significant sexually related distress despite use of either lubricant. Total sexual discomfort was lower after use of silicone-based lubricant than water-based, but many women continue to experience sexually related distress.

How does adjuvant chemotherapy affect menopausal symptoms, sexual function, and quality of life after breast cancer?

OBJECTIVE: The aim of the study was to determine the association between adjuvant chemotherapy for breast cancer and menopausal symptoms, sexual function, and quality of life. METHODS: Participants attended a menopause clinic with a dedicated service for cancer survivors at a large tertiary women's hospital. Information about breast cancer treatments including adjuvant chemotherapy was collected from medical records. Menopausal symptoms were recorded with the Greene Climacteric Scale and Functional Assessment of Cancer Therapy, Breast Cancer, and Endocrine Symptom Subscales. Sexual symptoms were recorded using Fallowfield's Sexual Activity Questionnaire. Quality of life was measured with Functional Assessment of Cancer Therapy scales. RESULTS: The severity of vasomotor, psychological, or sexual symptoms (apart from pain) did not differ between those who had received adjuvant chemotherapy (n = 339) and other breast cancer survivors (n = 465). After adjustment for current age, time since menopause, and current use of antiestrogen endocrine therapy, the risk of "severe pain" with sexual intercourse was twice as common after chemotherapy (31.6% vs 20.0%, odds ratio [OR] 2.18, 95% CI 1.25-3.79). Those treated with chemotherapy were more likely to report "severe problems" with physical well-being (OR 1.92, 95% CI 1.12-3.28) and lower breast cancer-specific quality of life (OR 1.89 95% CI 1.13-3.18), but did not differ in other quality of life measures. CONCLUSIONS: In this large study of breast cancer patients presenting to a specialty menopause clinic, previous chemotherapy was not associated with current vasomotor or psychological symptoms. Severe pain with intercourse was significantly more common in those treated with adjuvant chemotherapy.

Critical Review: Mechanisms of HIV Transmission in Depo-Provera Users: The Likely Role of Hypoestrogenism.

Almost half of new HIV infections worldwide occur in women, and vaginal intercourse is the most common mode of transmission. Accumulating evidence suggests that depot medroxyprogesterone acetate may increase HIV transmission, but little is known about the underlying mechanisms. We propose that hypoestrogenism in depot medroxyprogesterone acetate may contribute to increased HIV transmission. We present supportive evidence and propose potential interventions to prevent or treat vaginal hypoestrogenism using vaginal estrogens.