Q-122 as a novel, non-hormonal, oral treatment for vasomotor symptoms in women taking tamoxifen or an aromatase inhibitor after breast cancer: a phase 2, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Vasomotor symptoms (hot flushes and night sweats) are experienced by more than two-thirds of women with breast cancer taking oral adjuvant endocrine therapy. Safe and effective treatments are lacking. Q-122 is a novel, non-hormonal compound that has shown promise for reducing vasomotor symptoms by modulation of oestrogen-responsive neurons in the hypothalamus. We aimed to assess the efficacy and safety of Q-122 in women with breast cancer taking oral adjuvant endocrine therapy and experiencing vasomotor symptoms. METHODS: We conducted a multicentre, randomised, double-blind, placebo-controlled, proof-of-concept, phase 2 trial at 18 sites in Australia, New Zealand, and the USA. Eligible participants were women, aged 18-70 years, taking a stable dose of tamoxifen or an aromatase inhibitor following breast cancer and experiencing at least 50 self-reported moderate to severe vasomotor symptoms per week. Participants were randomly assigned (1:1) using an interactive web response system to oral Q-122 100 mg or identical placebo, twice daily for 28 days. Randomisation was stratified by BMI (≤30 kg/m2 or >30 kg/m2) and use of any of a selective serotonin reuptake inhibitor, selective norepinephrine reuptake inhibitor, gabapentin, or pregabalin. Q-122 and placebo capsules were identical in appearance and containers identically labelled. During the double-blind treatment and analysis phases, the participants, investigators, clinical research organisation staff, and sponsor were masked to treatment allocation. The primary outcome was the difference in the mean percentage change from baseline in the Vasomotor Symptom Severity Score of moderate and severe hot flushes and night sweats (msVMS-SS) between Q-122 and placebo after 28 days of treatment. Primary analysis was by modified intention-to-treat and safety was assessed in all participants receiving at least one dose of study drug. This study is registered at ClinicalTrials.gov, NCT03518138. FINDINGS: Between Oct 24, 2018, and Sept 9, 2020, 243 patients were screened, 131 of whom were randomly assigned and received treatment (Q-122 n=65 and placebo n=66). Q-122 resulted in a significantly greater mean percentage change in msVMS-SS from baseline over 28 days of treatment compared with placebo (least squares mean: Q-122 -39% [95% CI -46 to -31] vs placebo -26% [-33 to -18]; p=0·018). Treatment-emergent adverse events were generally mild to moderate and similar between the two groups (treatment-related treatment-emergent adverse events in 11 [17%] of 65 patients in the Q-122 group vs nine [14%] of 66 in the placebo group); zero patients in the Q-122 group and two (3%) patients in the placebo group had serious adverse events. INTERPRETATION: Q-122 is an effective and well tolerated non-hormonal oral treatment for vasomotor symptoms in women taking oral adjuvant endocrine therapy after breast cancer. Our results support the conduct of larger and longer studies of Q-122, with potential use extending to postmenopausal women who require an alternative to menopausal hormone therapy. FUNDING: QUE Oncology.

Pregnancy outcomes in women with endometriosis and/or ART use: a population-based cohort study.

STUDY QUESTION: What is the association between endometriosis and adverse pregnancy outcomes with ART use and non-use? SUMMARY ANSWER: Endometriosis and ART use are both associated with increased risk of preterm birth, antepartum haemorrhage, placenta praevia and planned birth (caesarean delivery or induction of labour). WHAT IS KNOWN ALREADY: There are contradictory findings on the association between endometriosis and adverse pregnancy outcomes, and many large studies have not considered the effect of ART use. STUDY DESIGN, SIZE, DURATION: Population-based cohort study of 578 221 eligible pregnancies during 2006-2015, comparing pregnancy outcomes across four groups (No endo/no ART, No endo/ART, Endo/no ART and Endo/ART). PARTICIPANTS/MATERIALS, SETTING, METHODS: All female residents of New South Wales, Australia aged 15-45 years and their index singleton pregnancy of at least 20 weeks gestation or 400 g birthweight. Linked hospital, pregnancy/birth and mortality data were used. Modified Poisson regression with robust error variances was used to estimate adjusted risk ratios (aRRs) and 99% CIs, adjusting for sociodemographic and pregnancy factors. MAIN RESULTS AND THE ROLE OF CHANCE: Compared to women without endometriosis who had pregnancies without ART use, there was increased risk of preterm birth (<37 weeks) in all groups [No endo/ART (aRR 1.85, 99% CI 1.46-2.34), Endo/no ART (aRR 1.24, 99% CI 1.06-1.44), Endo/ART (aRR 1.93, 99% CI 1.11-3.35)] and antepartum haemorrhage [No endo/ART (aRR 1.99, 99% CI 1.39-2.85), Endo/no ART (aRR 1.31, 99% CI 1.03-1.67), Endo/ART (aRR 2.69, 99% CI 1.30-5.56)] among pregnancies affected by endometriosis or ART use, separately and together. There was increased risk of placenta praevia [No endo/ART (aRR 2.26, 99% CI 1.42-3.60), Endo/no ART (aRR 1.66, 99% CI 1.18-2.33)] and planned birth [No endo/ART (aRR 1.08, 99% CI 1.03-1.14), Endo/no ART (aRR 1.11, 99% CI 1.07-1.14)] among pregnancies with endometriosis or ART use, separately. There was increased risk of placental abruption [No endo/ART (aRR 2.36, 99% CI 1.12-4.98)], maternal morbidity [No endo/ART (aRR 1.67, 99% CI 1.07-2.62)] and low birthweight (<2500 g) [No endo/ART (aRR 1.45, 99% CI 1.09-1.93)] among pregnancies with ART use without endometriosis. There was decreased risk of having a large-for-gestational age infant [Endo/no ART (aRR 0.83, 99% CI 0.73-0.94)] among pregnancies with endometriosis without ART use. LIMITATIONS, REASONS FOR CAUTION: Endometriosis is often under-diagnosed and women with a history of hospital diagnosis of endometriosis may represent those with more symptomatic or severe disease. If the effects of endometriosis on pregnancy are greater for those with more severe disease, our results may over-estimate the effect of endometriosis on adverse pregnancy outcomes at a population level. We were unable to assess the effect of endometriosis stage or typology on the study outcomes. WIDER IMPLICATIONS OF THE FINDINGS: These results suggest that women with endometriosis including those who used ART to achieve pregnancy are a higher-risk obstetric group requiring appropriate surveillance and management during their pregnancy. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the Prevention Research Support Program, funded by the New South Wales Ministry of Health. The funder had no role in the design, data collection and analysis, interpretation of results, manuscript preparation or the decision to submit the manuscript for publication. The authors have no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

A study of pregnancy after endometrial ablation using linked population data.

INTRODUCTION: Endometrial ablation encapsulates a range of procedures undertaken to destroy the endometrial lining of the uterus as a treatment for heavy menstrual bleeding in women who no longer wish to bear children. Pregnancy following ablation, while unlikely, can occur and may carry higher rates of complications. The aim of this study was to identify factors associated with post-endometrial ablation pregnancy and to describe pregnancy and birth outcomes for post-endometrial ablation pregnancies. MATERIAL AND METHODS: This population-based data linkage study included all female residents of New South Wales, Australia, aged 15-50 years with a hospital admission between July 2001 to June 2014 who birthed between July 2001 and June 2015. Cox proportional hazard regression was used to estimate associations between women's characteristics and post-endometrial ablation pregnancy of at least 20 weeks' gestation. Descriptive statistics were used to characterize pregnancy and birth outcomes. RESULTS: Of 18 559 women with an endometrial ablation, 575 (3.1%) had a post-ablation pregnancy of at least 20 weeks' gestation. Nulliparity (adjusted hazard ratio [aHR] 12.2, 95% confidence interval [CI] 9.1-16.2), older age (35-39 years: aHR 0.39, 95% CI 0.29-0.51; 40-44 years: aHR 0.06, 95% CI 0.04-0.11), marital status (single: aHR 0.67, 95% CI 0.55-0.83; widowed/divorced/separated: aHR 0.58, 95% CI 0.36-0.94) and a diagnosis of heavy menstrual bleeding (aHR 0.09, 95% CI 0.07-0.13) were associated with post-ablation pregnancy. There were high rates of cesarean delivery (43%), preterm birth (13%), twin or higher order pregnancies (9%) and stillbirth (13.3/1000 births) among these post-ablation pregnancies. CONCLUSIONS: Nulliparity at the time of endometrial ablation is associated with increased risk of post-ablation pregnancy, highlighting the importance of careful discussion and consideration of treatment options for heavy menstrual bleeding.

Global Consensus Position Statement on the Use of Testosterone Therapy for Women.

This Statement is being simultaneously published in the journals Climacteric, Maturitas, Journal of Sexual Medicine, and Journal of Clinical Endocrinology and Metabolism on behalf of the International Menopause Society, The European Menopause and Andropause Society, The International Society for Sexual Medicine, and The Endocrine Society, respectively. This Position Statement has been endorsed by the International Menopause Society, The Endocrine Society, The European Menopause and Andropause Society, The International Society for Sexual Medicine, The International Society for the Study of Women's Sexual Health, The North American Menopause Society, The Federacion Latinoamericana de Sociedades de Climaterio y Menopausia, The Royal College of Obstetricians and Gynaecologists, The International Society of Endocrinology, The Endocrine Society of Australia, and The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

Androgen-based therapies in women.

Androgens play a key biological role in libido and sexual arousal in women, and knowledge about their complex role in other systems remains ambiguous and incomplete. This narrative review examines the role of endogenous androgens in women's health throughout the life span before focusing on evidence surrounding the use of androgen-based therapies to treat postmenopausal women. The role of testosterone as a therapeutic agent in women continues to attract controversy as approved preparations are rare, and use of off-label and compounded formulations is widespread. Despite this androgen therapy has been used for decades in oral, injectable, and transdermal formulations. Responses to androgen therapy have been demonstrated to improve aspects of female sexual dysfunction, notably hypoactive sexual desire disorder, in a dose related manner. Substantial research has also been conducted into the role of androgens in treating aspects of the genitourinary syndrome of menopause (GSM). Evidence for benefits beyond these is mixed and more research is required regarding long-term safety. However, It remains biologically plausible that androgens will be effective in treating hypoestrogenic symptoms related to menopause, either through direct physiological effects or following aromatization to estradiol throughout the body.

The need for biopsychosocial menopause care: a narrative review.

IMPORTANCE AND OBJECTIVE: Menopause is a reproductive transition affecting half the world's population. Stigma and limited availability of evidence-based treatments that support biopsychosocial well-being mean that this life stage is often associated with challenging symptoms and reduced quality of life (QoL). The aim of this review was to examine the extent literature on psychological and mind-body interventions to manage perimenopausal and postmenopausal symptoms, and apply an interdisciplinary clinical, research, and cultural knowledge framework to guide recommendations for improving QoL and healthy aging in this population. We also aimed to understand the ideal delivery mode for such interventions. METHODS: Using Scopus, Medline, and PubMed, a review of systematic reviews, guidelines, and randomized controlled trials was undertaken to examine the use of psychological and mind-body interventions to improve menopause-related QoL and symptoms, including hot flushes, depression, anxiety, fatigue, pain, and sleep; conclusions were based on an analysis of this available evidence and linked to clinical and cultural considerations. DISCUSSION AND CONCLUSION: Empirical support exists for a number of psychological and mind-body approaches to support QoL and symptoms during the menopause transition. The literature also identifies the need for menopause care that is culturally responsive.An online multimodal model of menopause care is thus recommended, incorporating evidence-based treatments (eg, cognitive behavioral therapy, yoga, hypnosis) and treatment techniques (eg, mindfulness, and education including nutrition support), as well as First Nations wisdom. We also recommend financial well-being approaches to support people undergoing menopause. Integrated, multimodal approaches should be available online to remove time, location, and healthcare access barriers, and be designed with diverse consumers to ensure equity for those underserved due to region, LGBTIQ+ assigned female at birth status, and for multicultural and First Nations people.

Vernix Caseosa Peritonitis Causing Acute Abdomen After Cesarean Section: A Case Series.

BACKGROUND Vernix caseosa peritonitis (VCP) is a rare complication that typically presents following an otherwise uneventful cesarean section. Leakage of vernix caseosa into the peritoneum is thought to elicit a granulomatous foreign body reaction. Symptoms can be similar to other acute abdominal conditions, and diagnosis is confirmed by intraoperative findings and histological examination. Peritoneal lavage with supportive measures is the mainstay of treatment and recovery. CASE REPORT Case 1 was a 30-year-old woman who developed right iliac fossa pain, fever, tachycardia, and tachypnea less than a week after her lower segment cesarean section (LSCS). She underwent a laparoscopy for a peritonitic abdomen and concern for intra-abdominal sepsis. A peritoneal biopsy demonstrated histological changes consistent with VCP. Case 2 was a 39-year-old woman who underwent a LSCS. After discharge, she re-presented with generalized abdominal pain. With computed tomography (CT) scan findings suggestive of appendicitis, an appendectomy was performed, and vernix caseosa was detected in all quadrants. Case 3 was a 33-year-old woman who presented with fever, vomiting, diarrhea, and iliac fossa pain 9 days following an LSCS. She was given analgesia and antibiotics for a pelvic fluid collection noted on CT scan. She re-presented with tense swelling and pain above her cesarean section incision. Laparoscopy revealed adhesions over the lower abdomen and pelvis and white plaques suggestive of vernix caseosa along the peritoneal side walls. CONCLUSIONS The rising incidence of cesarean births worldwide creates the potential for increased numbers of VCP cases. Greater recognition of VCP is warranted to prevent unnecessary procedures.

Treating menopause - MHT and beyond.

Every woman who lives past midlife will experience menopause, which, by definition, is complete cessation of ovarian function. This process might occur spontaneously (natural menopause) or be iatrogenic (secondary menopause), and can be further classified as 'early' if it occurs before the age of 45 years and 'premature' if it occurs before the age of 40 years. Globally, the mean age of natural menopause is 48.8 years, with remarkably little geographic variation. A woman's age at menopause influences health outcomes in later life. Early menopause is associated with a reduced risk of breast cancer, but increased risks of premature osteoporosis, cardiovascular disease and premature death. The cardinal symptoms of menopause, and adverse health sequelae, are due to loss of ovarian oestrogen production. Consequently, menopausal hormone therapy (MHT) that includes oestrogen or an oestrogenic compound ameliorates menopausal symptoms, while preventing menopause-associated bone loss and cardiometabolic changes. Importantly, comprehensive care of postmenopausal women involves lifestyle optimization (attention to nutrition and physical activity, reducing alcohol consumption and not smoking) and treating other established chronic disease risk factors. This Review offers a commentary specifically on the contemporary use of MHT and novel pharmaceutical alternatives to manage menopausal symptoms.

Global Consensus Position Statement on the Use of Testosterone Therapy for Women.

This Position Statement has been endorsed by the International Menopause Society, The Endocrine Society, The European Menopause and Andropause Society, The International Society for Sexual Medicine, The International Society for the Study of Women's Sexual Health, The North American Menopause Society, The Federacion Latinoamericana de Sociedades de Climaterio y Menopausia, The Royal College of Obstetricians and Gynecologists, The International Society of Endocrinology, The Endocrine Society of Australia, and The Royal Australian and New Zealand College of Obstetricians and Gynecologists.

The Management of Menopausal Symptoms in Women Following Breast Cancer: An Overview.

The improved detection and successful treatment of breast cancer, resulting in better survival rates, has led to an increasing number of women living with the effects of treatment modalities and their long-term consequences. Menopausal symptoms following breast cancer can occur at an earlier age, be more severe and significantly influence a woman's overall wellbeing, in particular, sexual function, quality of life and adherence to treatment. There is a dearth of good quality evidence on the safest and most effective treatment options available for these women, and this article aims to summarize the current available treatments. Pertinent to these women is general advice, such as avoidance of triggers, and lifestyle modifications. Following which, non-pharmacological interventions, including cognitive behavior therapy (CBT), hypnosis, acupuncture, stellate ganglion nerve block and complementary agents, are discussed. Pharmacological therapies and their safety profile in these high-risk women are then examined; namely, menopausal hormone therapy, progestogens, antidepressants (selective serotonin reuptake inhibitors and selective noradrenaline reuptake inhibitors), gabapentin, clonidine and intra-vaginal dehydroepiandrosterone (DHEA). Finally, neurokinin 3 receptor antagonists, promising new agents for the treatment of troublesome menopausal vasomotor symptoms, are discussed.

Safety and effectiveness of a novel home-use therapeutic ultrasound device for the treatment of vaginal dryness in postmenopausal women: a pilot study.

To evaluate safety and effectiveness of therapeutic ultrasound for treatment of postmenopausal vaginal dryness. In a pilot study, postmenopausal women with self-reported vaginal dryness were randomized (1:1) to double-blind ultrasound treatment (n = 21) or sham (n = 21) for 12 weeks. Primary effectiveness endpoint was change from baseline to week 12 in Vaginal Assessment Scale symptoms (dryness, soreness, irritation, dyspareunia). Secondary effectiveness endpoint was scoring of clinician-reported Vaginal Health Index (elasticity, fluid, pH, mucosa, moisture). After 12 weeks, participants received open-label ultrasound treatment to 1 year. Safety endpoint was treatment-emergent adverse events. In the modified intent-to-treat population, women showed (mean ± standard error) reduction in Vaginal Assessment Scale with ultrasound treatment versus sham (n = 15, −0.5 ± 0.2 vs n = 15, −0.4 ± 0.3; P = 0.9) and improved Vaginal Health Index (n = 9, 2.7 ± 0.9 vs n = 9, 0.6 ± 1.4; P = 0.3). In the per-protocol analysis population, ultrasound treatment (n = 9) versus sham (n = 8) significantly reduced symptoms score (−0.6 ± 0.3 vs −0.0 ± 0.4; P = 0.05) and significantly improved Vaginal Health Index (2.7 ± 0.9 vs −0.4 ± 1.2; P = 0.03). Improvement in effectiveness endpoints were seen at 1 year compared with baseline. There were no differences in treatment-emergent adverse events between ultrasound treatment versus sham and no serious adverse events. Home-use ultrasound was safe and effective for treating vaginal dryness after 12 weeks. Effectiveness was maintained to 1 year. Therapeutic ultrasound could offer a new, nonhormonal treatment option for postmenopausal women with vulvovaginal atrophy.

Complementary and hormonal therapy for vasomotor symptom relief: a conservative clinical approach.

Vasomotor symptoms are the most common menopausal symptom experienced by women and the leading reason menopausal women seek health care advice. The recent shift towards a more conservative use of hormone therapy (HT) during menopause has prompted the need for treatment regimens to be individualized according to symptom severity. Our objective was to develop a new algorithm that enables practitioners to customize treatment regimens according to symptom severity. In order to develop a comprehensive treatment algorithm, we conducted a literature review and considered the findings from recently published treatment guidelines from around the world. We also evaluated the results of systematic reviews investigating the efficacy and safety of complementary and alternative medicines. We found a growing trend away from prescription HT in women with mild to moderate symptoms and an increasing trend toward lifestyle modification and the use of complementary and alternative medicines. On the basis of these findings, we have developed an algorithm that accounts for symptom severity. The algorithm presented here provides treatment options based on symptom severity and a comprehensive approach for integrating lifestyle modifications and complementary therapies with prescription treatment regimens.

Therapy for menopausal symptoms during and after treatment for breast cancer : safety considerations.

Breast cancer is the most common newly diagnosed cancer in women. Life-time risk in the US is 1 in 8 (13.2%), in the UK it is 1 in 9 and in Australia it affects 1 in 11 women, of whom approximately 27% will be premenopausal at the time of their diagnosis. Many of these women will experience a sudden menopause as a result of chemotherapy, endocrine therapy or surgical interventions. For these women, the onset of menopausal symptoms is often sudden and severe. The management of such symptoms remains controversial. Women experiencing menopausal symptoms after breast cancer should be encouraged to avoid identifiable triggers for their symptoms and to consider lifestyle modification as a means of controlling those symptoms. When such measures fail, non-hormonal treatments may also be considered. These include clonidine, gabapentin and some antidepressants. Randomised trials have shown a significant difference in the symptom relief associated with various selective serotonin reuptake inhibitors and selective serotonin and noradrenaline (norepinephrine) reuptake inhibitors compared with placebo. Many women elect to use non-prescription complementary therapies to alleviate their menopausal symptoms. Systematic reviews of phytoestrogens have, however, failed to demonstrate significant relief of menopausal symptoms. More than 20 clinical trials have been conducted examining the relationship between postmenopausal hormone replacement therapy and breast cancer recurrence. The majority of these have been observational and have shown no increased risk of recurrence. However, the largest randomised trial that has thus far been conducted was recently halted because of a reported increase in the risk of recurrence amongst users of hormone replacement therapy. Tibolone, a selective tissue estrogen activity regulator, is a compound that exerts clinical effects both by receptor-mediated actions and tissue selective enzyme inhibition, and has been shown in preclinical studies to have different effects to estrogen on the breast. Although tibolone may prove safer than estrogen for long-term use in breast cancer survivors, the results of a large randomised trial are awaited to confirm this.The decision on how best to manage menopausal symptoms must thus be made on an individual basis and after thorough discussion and evaluation of the risks and benefits of each potential intervention.

Ethical implications of digital images for teaching and learning purposes: an integrative review.

BACKGROUND: Digital photography has simplified the process of capturing and utilizing medical images. The process of taking high-quality digital photographs has been recognized as efficient, timely, and cost-effective. In particular, the evolution of smartphone and comparable technologies has become a vital component in teaching and learning of health care professionals. However, ethical standards in relation to digital photography for teaching and learning have not always been of the highest standard. The inappropriate utilization of digital images within the health care setting has the capacity to compromise patient confidentiality and increase the risk of litigation. Therefore, the aim of this review was to investigate the literature concerning the ethical implications for health professionals utilizing digital photography for teaching and learning. METHODS: A literature search was conducted utilizing five electronic databases, PubMed, Embase (Excerpta Medica Database), Cumulative Index to Nursing and Allied Health Literature, Educational Resources Information Center, and Scopus, limited to English language. Studies that endeavored to evaluate the ethical implications of digital photography for teaching and learning purposes in the health care setting were included. RESULTS: The search strategy identified 514 papers of which nine were retrieved for full review. Four papers were excluded based on the inclusion criteria, leaving five papers for final analysis. Three key themes were developed: knowledge deficit, consent and beyond, and standards driving scope of practice. CONCLUSION: The assimilation of evidence in this review suggests that there is value for health professionals utilizing digital photography for teaching purposes in health education. However, there is limited understanding of the process of obtaining and storage and use of such mediums for teaching purposes. Disparity was also highlighted related to policy and guideline identification and development in clinical practice. Therefore, the implementation of policy to guide practice requires further research.

Ongoing ethical issues concerning authorship in biomedical journals: an integrative review.

Health professionals publishing within the field of health sciences continue to experience issues concerning appropriate authorship, which have clinical, ethical, and academic implications. This integrative review sought to explore the key issues concerning authorship from a bioethical standpoint, aiming to explore the key features of the authorship debate. Studies were identified through an electronic search, using the PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Scopus databases of peer-reviewed research, published between 2009 and 2014, limited to English language research, with search terms developed to reflect the current issues of authorship. From among the 279 papers identified, 20 research papers met the inclusion criteria. Findings were compiled and then arranged to identify themes and relationships. The review incorporated a wide range of authorship issues encompassing equal-credited authors, honorary (guest/gift) and ghost authorship, perception/experiences of authorship, and guidelines/policies. This review suggests that the International Committee of Medical Journal Editors' (ICMJE) recommended guidelines for authorship are not reflected in current authorship practices within the domain of health sciences in both low-and high-impact-factor journals. This devaluing of the true importance of authorship has the potential to affect the validity of authorship, diminish the real contributions of the true authors, and negatively affect patient care.