Obstetrics and Gynaecology - Research Publications

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    Surviving and thriving after breast cancer treatment
    Saunders, CM ; Stafford, L ; Hickey, M (WILEY, 2022-09-05)
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    The long-term association between bilateral oophorectomy and depression: a prospective cohort study
    Brauner, EV ; Wilson, LF ; Koch, T ; Christensen, J ; Dehlendorff, C ; Duun-Henriksen, AK ; Priskorn, L ; Abildgaard, J ; Simonsen, MK ; Jorgensen, JT ; Lim, Y-H ; Andersen, ZJ ; Juul, A ; Hickey, M (LIPPINCOTT WILLIAMS & WILKINS, 2022-03)
    OBJECTIVE: Depression is a leading cause of disability globally and affects more women than men. Ovarian sex steroids are thought to modify depression risk in women and interventions such as bilateral oophorectomy that permanently change the sex steroid milieu may increase the risk of depression. This study aimed to investigate the associations between unilateral and bilateral oophorectomy and depression over a 25-year period (1993-2018) and whether this varied by age at oophorectomy or use of menopausal hormone therapy. METHODS: Twenty-five thousand one hundred eighty-eight nurses aged ≥45 years from the Danish Nurse Cohort were included. Nurses with depression prior to baseline were excluded. Poisson regression models, with log-transformed person-years as offset, were used to assess the associations between oophorectomy and incident depression. Nurses who retained their ovaries were the reference group. RESULTS: Compared with nurses with retained ovaries, bilateral oophorectomy was associated with a slightly higher rate of depression (rate ratio [RR], 1.08; 95% confidence interval [CI], 0.95-1.23), but without statistical significance. However, when stratified by age at oophorectomy, compared with nurses with retained ovaries, bilateral oophorectomy at age ≥51 years was associated with higher rates of depression (RR 1.16; 95% CI, 1.00-1.34), but not bilateral oophorectomy at age <51 years (RR 0.86; 95% CI, 0.69-1.07); P value for difference in estimates = 0.02. No association between unilateral oophorectomy and depression was observed. CONCLUSIONS: In this cohort of Danish female nurses, bilateral oophorectomy at age ≥51 years, but not at younger ages, was associated with a slightly higher rate of depression compared with those who retained their ovaries.
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    Oophorectomy and rate of dementia: a prospective cohort study
    Uldbjerg, CS ; Wilson, LF ; Koch, T ; Christensen, J ; Dehlendorff, C ; Priskorn, L ; Abildgaard, J ; Simonsen, MK ; Lim, Y-H ; Jorgensen, JT ; Andersen, ZJ ; Juul, A ; Hickey, M ; Brauner, E (LIPPINCOTT WILLIAMS & WILKINS, 2022-05-01)
    Objective: Globally, dementia disproportionally affects women, which is not fully explained by higher female longevity. Oophorectomy at any age leads to the permanent loss of ovarian sex steroids, potentially increasing the risk of dementia. We aimed to investigate the association between oophorectomy and dementia and whether this was conditional on age at oophorectomy, hysterectomy or use of hormone therapy (HT). Methods: A prospective study of 24,851 female nurses from the Danish Nurse Cohort. Nurses were followed from age 60 years or entry into the cohort, whichever came last, until date of dementia, death, emigration or end of follow-up (December 31, 2018), whichever came first. Poisson regression models with log-transformed person-years as offset were used to estimate the associations. Results: During 334,420 person-years of follow-up, 1,238 (5.0%) nurses developed dementia and 1,969 (7.9%)/ 1,016 (4.1%) contributed person-time after bilateral-/unilateral oophorectomy. In adjusted analyses, an 18% higher rate of dementia was observed following bilateral oophorectomy (aRR 1.18: 95% CI, 0.89-1.56) and 13% lower rate (aRR 0.87: 95% CI, 0.59-1.23) following unilateral oophorectomy compared to nurses who retained their ovaries. Similar effects were detected after stratification according to age at oophorectomy. No statistically significant modifying effects of hysterectomy or HT were detected (Pinteraction≥0.60). Conclusions: Bilateral, but not unilateral, oophorectomy was associated with an increased rate of incident dementia. We were unable to establish whether this association was conditional on hysterectomy or HT use. Although an increase in dementia after bilateral oophorectomy is biologically plausible, limited statistical power hampers the precision of the estimates.
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    Cardiovascular mortality after bilateral oophorectomy: a prospective cohort study
    Olesen, CS ; Koch, T ; Uldbjerg, CS ; Gregersen, LS ; Christensen, J ; Dehlendorff, C ; Priskorn, L ; Wilson, LF ; Lim, Y-H ; Jorgensen, JT ; Andersen, ZJ ; Juul, A ; Abildgaard, J ; Hickey, M ; Braeuner, EV (LIPPINCOTT WILLIAMS & WILKINS, 2022-01)
    OBJECTIVES: Bilateral oophorectomy permanently reduces endogenous estrogen exposure and may increase cardiovascular mortality in women. This study aimed to investigate the association between bilateral oophorectomy and cardiovascular mortality and whether this association was conditional on hysterectomy or on the use of hormone therapy at the time of study entry. METHODS: A prospective cohort study of 25,338 female nurses aged ≥ 45 years within the Danish Nurse Cohort. Nurses were enrolled in 1993 or 1999 and followed until death, emigration, or end of follow-up on December 31, 2018, whichever came first. Exposure was bilateral oophorectomy. Outcome was cardiovascular mortality. Associations were estimated using Poisson regression models with log person-years as the offset. RESULTS: A total of 2,040 (8.1%) participants underwent bilateral oophorectomy. During a mean follow-up of 21.2 (SD: 5.6) years, 772 (3.0%) nurses died from cardiovascular disease. In adjusted analyses, a 31% higher rate of cardiovascular mortality was observed after bilateral oophorectomy (aMRR 1.31; 95% CI, 0.88-1.96) compared with women who retained their ovaries. No evidence of effect modification by use of hormone therapy at baseline or by hysterectomy on the association between bilateral oophorectomy and cardiovascular mortality was observed. CONCLUSION: Bilateral oophorectomy may be associated with cardiovascular mortality in women, but the estimate was not statistically significant. Additionally, we were unable to make firm conclusions regarding the possible modifying role of hormone therapy and hysterectomy on this potential association. Additional studies are needed to replicate this work.
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    What happens after menopause? (WHAM): A prospective controlled study of symptom profiles up to 12 months after pre-menopausal risk-reducing salpingo-oophorectomy
    Moss, KM ; Mishra, GD ; Krejany, EO ; Hickey, M (ACADEMIC PRESS INC ELSEVIER SCIENCE, 2022-10)
    Objective. Understanding how symptoms cluster after premenopausal risk-reducing salpingo-oophorectomy (RRSO) can inform patient expectations but information is lacking. We aimed to identify symptom profiles after RRSO, changes over time, and the effect of hormone therapy (HT). Method. Participants were premenopausal women from a longitudinal controlled study (What Happens After Menopause? (WHAM)). Menopausal symptoms were prospectively measured in three groups: pre-menopausal comparisons who retained their ovaries (n = 99), RRSO HT users (n = 57) and RRSO non-HT users (n = 38). Symptoms (hot flashes, night sweats, low desire, vaginal dryness, poor sleep, anxiety/depression) were measured at baseline (pre-surgery) and at 3, 6 and 12 months using standardised questionnaires. Latent transition analysis was used to identify symptom profiles post-RRSO, and the probability of changing profiles over time. Results. Three symptom profiles were identified: Most Symptoms (81–87% non-HT; 36–41% HT; 7–9% comparisons), Few Symptoms (7–13% non-HT; 36–42% HT; 77–80% comparisons), and Sexual Symptoms (0–10% non-HT; 17–27% HT; 14–15% comparisons). Most of the non-HT group reported Most Symptoms at 3 months with only a 2% chance of improvement by 12 months. The HT group were split between profiles at 3 months with a 5–13% chance of improvement by 6 months (14% chance of worsening), and a 12–32% chance of improvement by 12 months (4–25% chance of worsening). Conclusions. Symptoms cluster into distinct profiles after premenopausal RRSO. Most non-HT users are highly symptomatic with little chance of improvement by 12 months. In contrast, two-thirds of HT users have fewer symptoms and a much higher chance of improvement. These findings can inform patient decision-making and expectations.
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    Randomized control trial of a decision aid for women considering elective egg freezing: The Eggsurance study protocol
    Peate, M ; Sandhu, S ; Braat, S ; Hart, R ; Norman, R ; Parle, A ; Lew, R ; Hickey, M ; Eggsurance, CG (SAGE PUBLICATIONS LTD, 2022)
    BACKGROUND: Uptake of elective egg freezing has increased globally. The decision to freeze eggs is complex, and detailed, unbiased information is needed. To address this, we developed an online Decision Aid for women considering elective egg freezing. Decision Aids are the standard of care to support complex health decisions. OBJECTIVES: This study will measure the impact of the Decision Aid on decision-making (e.g. decisional conflict, engagement in decision-making, distress, and decision delay) and decision quality (e.g. knowledge, level of informed choice, and regret). METHODS AND ANALYSIS: A single-blinded two-arm parallel-group randomized controlled trial. Women considering elective egg freezing will be recruited using social media, newsletters, and fertility clinics. Data will be collected at baseline (recruitment), 6-month, and 12-month post-randomization. The primary hypothesis is that the intervention (Decision Aid plus Victorian Assisted Reproductive Technology Authority website) will reduce decisional conflict (measured using the Decisional Conflict Scale) at 12 months more than control (Victorian Assisted Reproductive Technology Authority website only). Secondary outcomes include engagement in decision-making (Perceived Involvement in Care Scale), distress (Depression, Anxiety, and Stress Scale), decision delay, knowledge, informed choice (Multi-dimensional Measure of Informed Choice), and decisional regret (Decisional Regret Scale). ETHICS: The study was approved by the University of Melbourne Human Research Ethics Committee (Ethics ID: 2056457). Informed consent will be obtained from all participants prior to enrolment. DISCUSSION: This is the first international randomized controlled trial that aims to investigate the effect of an elective egg freezing Decision Aid on decision-related outcomes (e.g. decisional conflict, informed choice, and regret). It is anticipated that participants who receive the Decision Aid will have better decision and health outcomes. REGISTRATION DETAILS: ACTRN12620001032943: Comparing different information resources on the process and quality of decision-making in women considering elective egg freezing.
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    A longitudinal examination of perinatal testosterone, estradiol and vitamin D as predicators of handedness outcomes in childhood and adolescence
    Richards, G ; Tan, DW ; Whitehouse, AJO ; McManus, IC ; Beaton, AA ; Hickey, M ; Maybery, MT ; Licari, MK ; Lawson, L (ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD, 2022-11-02)
    The developmental origins of handedness remain elusive, though very early emergence suggests individual differences manifesting in utero could play an important role. Prenatal testosterone and Vitamin D exposure are considered, yet findings and interpretations remain equivocal. We examined n = 767 offspring from a population-based pregnancy cohort (The Raine Study) for whom early biological data and childhood/adolescent handedness data were available. We tested whether 18-week maternal circulatory Vitamin D (25[OH]D), and testosterone and estradiol from umbilical cord blood sampled at birth predicted variance in direction of hand preference (right/left), along with right- and left-hand speed, and the strength and direction of relative hand skill as measured by a finger-tapping task completed at 10 (Y10) and/or 16 (Y16) years. Although higher concentrations of Vitamin D predicted more leftward and less lateralized (regardless of direction) relative hand skill profiles, taken as a whole, statistically significant findings typically did not replicate across time-point (Y10/Y16) or sex (male/female) and were rarely detected across different (bivariate/multivariate) levels of analysis. Considering the number of statistical tests and generally inconsistent findings, our results suggest that perinatal testosterone and estradiol contribute minimally, if at all, to subsequent variance in handedness. Vitamin D, however, may be of interest in future studies.
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    Creativity in lockdown: Understanding how music and the arts supported mental health during the COVID-19 pandemic by age group
    Chmiel, A ; Kiernan, F ; Garrido, S ; Lensen, S ; Hickey, M ; Davidson, JW (FRONTIERS MEDIA SA, 2022-10-06)
    Recent research has indicated that many people around the world turned to artistic creative activities (ACAs) to support their mental health during COVID-19 lockdowns. However, studies have also shown that the negative psychosocial impacts of the pandemic have disproportionately affected young people, suggesting that the use of ACAs to support mental health in lockdown may have varied across age groups. This study investigated how Australians in four different age groups (18-24, 25-34, 35-54, and 55+) engaged in ACAs to support their mental health during the 2020 pandemic lockdowns. Participants (N = 653) recruited from the general public completed an online survey between May and October 2020, in which they reported which ACAs they had undertaken during the pandemic using an established list. Participants subsequently ranked undertaken ACAs in terms of effectiveness at making them "feel better," and those who had engaged in musical ACAs also completed the Musical Engagement Questionnaire (MusEQ). Additionally, ratings of anxiety (GAD7) and depression (PHQ9) symptoms were obtained and examined for potential variations across four diverse variables: age, exercise, gender and state/territory of residence. ACA rankings showed that younger participants overwhelmingly rated musical activities as most effective, while, with the exception of singing, those aged 55+ rated non-musical activities as being most effective. These differences were further supported by ratings for all six MusEQ subscales, with responses strongly indicating that the youngest participants (aged 18-24) used music in significantly different ways during the pandemic than participants in all other age groups. Specifically, these youngest participants were more likely to integrate music into daily life, use music for emotion regulation, respond to music in embodied ways, and use music to perform a social identity. In line with prior research, further analyses indicated that symptoms of anxiety and depression were lessened for older participants, as well for those who reported exercising more during the lockdowns. These findings provide insight into how ACAs can support mental health during a pandemic crisis for specific age groups, which may inform future policy directions, and suggestions for how this can be done are provided.
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    AYA 'Can-Sleep' programme: protocol for a stepped-care, cognitive behavioural therapy-based approach to the management of sleep difficulties in adolescents and young adults with cancer
    Vaughan, E ; Ftanou, M ; Lewin, J ; Murnane, A ; Berger, I ; Wiley, JF ; Hickey, M ; Bullen, D ; Jefford, M ; Goldin, J ; Stonehouse, J ; Thompson, K (BMC, 2022-07-28)
    BACKGROUND: Sleep problems are reported in up to 50% of adolescents and young adults (AYA) with cancer. Cognitive behavioural therapy for insomnia (CBTi) is considered the gold-standard treatment. In the AYA population, CBTi is associated with improvements in insomnia, daytime sleepiness, fatigue and quality of life. In adults, stepped-care interventions can improve accessibility to CBTi. This study aims to evaluate the acceptability and feasibility of a stepped-care CBTi programme in AYA with cancer. METHODS AND ANALYSIS: AYA (target N = 80) aged 16-25 with a diagnosis of cancer will be screened using the Insomnia Severity Index (ISI) and Epworth Sleepiness Scale (ESS). When sleep difficulties are identified by the ISI and/or ESS, they will be screened for obstructive sleep apnoea and restless leg syndrome and referred to a sleep service if indicated. The remainder with sleep difficulties will be offered a stepped-care sleep programme including CBT self-management and coaching (first step). Participants will then be rescreened at 5 weeks, and those with ongoing sleep difficulties will be offered individualised CBT (second step). Recruitment and retention rates, adherence to intervention and time taken to deliver screening and intervention will be collected to assess the feasibility of the programme. AYA and clinicians will complete evaluation surveys to assess the acceptability of the AYA Can-Sleep programme. DISCUSSION: We seek to contribute to the evidence base regarding screening and treatment of sleep difficulties in the AYA population by implementing the AYA Can-Sleep programme and determining its feasibility and acceptability as an approach to care in an Adolescent & Young Adult Cancer Service.
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    Menopause, hysterectomy, menopausal hormone therapy and cause-specific mortality: cohort study of UK Biobank participants
    Xu, Z ; Chung, H-F ; Dobson, AJ ; Wilson, LF ; Hickey, M ; Mishra, GD (OXFORD UNIV PRESS, 2022-08-25)
    STUDY QUESTION: What is the association between menopausal hormone therapy (MHT) and cause-specific mortality? SUMMARY ANSWER: Self-reported MHT use following early natural menopause, surgical menopause or premenopausal hysterectomy is associated with a lower risk of breast cancer mortality and is not consistently associated with the risk of mortality from cardiovascular disease or other causes. WHAT IS KNOWN ALREADY: Evidence from the Women's Health Initiative randomized controlled trials showed that the use of estrogen alone is not associated with the risk of cardiovascular mortality and is associated with a lower risk of breast cancer mortality, but evidence from the Million Women Study showed that use of estrogen alone is associated with a higher risk of breast cancer mortality. STUDY DESIGN, SIZE, DURATION: Cohort study (the UK Biobank), 178 379 women, recruited in 2006-2010. PARTICIPANTS/MATERIALS, SETTING, METHODS: Postmenopausal women who had reported age at menopause (natural or surgical) or hysterectomy, and information on MHT and cause-specific mortality. Age at natural menopause, age at surgical menopause, age at hysterectomy and MHT were exposures of interest. Natural menopause was defined as spontaneous cessation of menstruation for 12 months with no previous hysterectomy or oophorectomy. Surgical menopause was defined as the removal of both ovaries prior to natural menopause. Hysterectomy was defined as removal of the uterus before natural menopause without bilateral oophorectomy. The study outcome was cause-specific mortality. MAIN RESULTS AND THE ROLE OF CHANCE: Among the 178 379 women included, 136 790 had natural menopause, 17 569 had surgical menopause and 24 020 had hysterectomy alone. Compared with women with natural menopause at the age of 50-52 years, women with natural menopause before 40 years (hazard ratio (HR): 2.38, 95% CI: 1.64, 3.45) or hysterectomy before 40 years (HR: 1.60, 95% CI: 1.23, 2.07) had a higher risk of cardiovascular mortality but not cancer mortality. MHT use was associated with a lower risk of breast cancer mortality following surgical menopause before 45 years (HR: 0.17, 95% CI: 0.08, 0.36), at 45-49 years (HR: 0.15, 95% CI: 0.07, 0.35) or at ≥50 years (HR: 0.28, 95% CI: 0.13, 0.63), and the association between MHT use and the risk of breast cancer mortality did not differ by MHT use duration (<6 or 6-20 years). MHT use was also associated with a lower risk of breast cancer mortality following natural menopause before 45 years (HR: 0.59, 95% CI: 0.36, 0.95) or hysterectomy before 45 years (HR: 0.49, 95% CI: 0.32, 0.74). LIMITATIONS, REASONS FOR CAUTION: Self-reported data on age at natural menopause, age at surgical menopause, age at hysterectomy and MHT. WIDER IMPLICATIONS OF THE FINDINGS: The current international guidelines recommend women with early menopause to use MHT until the average age at menopause. Our findings support this recommendation. STUDY FUNDING/COMPETING INTEREST(S): This project is funded by the Australian National Health and Medical Research Council (NHMRC) (grant numbers APP1027196 and APP1153420). G.D.M. is supported by NHMRC Principal Research Fellowship (APP1121844), and M.H. is supported by an NHMRC Investigator Grant (APP1193838). There are no competing interests. TRIAL REGISTRATION NUMBER: N/A.