Obstetrics and Gynaecology - Research Publications
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ItemAdverse metabolic phenotype of adolescent girls with non-alcoholic fatty liver disease plus polycystic ovary syndrome compared with other girls and boys(WILEY-BLACKWELL, 2016-05)BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) and polycystic ovary syndrome (PCOS) share risk associations of adiposity and insulin resistance. We examined the impact of a PCOS diagnosis on the metabolic phenotype of adolescent girls with NAFLD and compared this to girls without PCOS or NAFLD and to age-matched boys. METHODS: Community-based adolescents from the Raine Cohort participated in assessments for NAFLD (572 girls and 592 boys) and PCOS (244 girls). One hundred and ninety-nine girls attended both assessments. RESULTS: Amongst the 199 girls, PCOS was diagnosed in 16.1% and NAFLD in 18.6%. NAFLD was diagnosed in 10.1% of the boys. NAFLD was more prevalent in girls with PCOS than girls without PCOS (37.5% vs 15.1%, P = 0.003). Girls with NAFLD plus PCOS had greater adiposity (waist circumference, body mass index, suprailiac skinfold thickness [SST], serum androgens, high-sensitivity C-reactive protein, ferritin, homeostasis model assessment for insulin resistance (HOMA-IR), and lower serum sex hormone binding globulin levels than girls with NAFLD without a PCOS diagnosis (all P < 0.05). Girls with NAFLD plus PCOS had similar adiposity, HOMA-IR, and adiponectin levels to boys with NAFLD, but more adiposity, serum leptin and HOMA-IR than both girls and boys without NAFLD. PCOS (odds ratios 2.99, 95% confidence intervals 1.01-8.82, P = 0.048) and SST (odds ratios 1.14, 95% confidence intervals 1.08-1.20, P < 0.001) independently predicted NAFLD in adolescent girls, however, serum androgens and HOMA-IR levels did not. CONCLUSIONS: Adolescent girls with NAFLD plus PCOS have a similar metabolic phenotype to boys with NAFLD. Increasing SST and pre-existing PCOS independently predict NAFLD in adolescent girls.
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ItemMechanisms of HIV Transmission in Depo-Provera Users: The Likely Role of Hypoestrogenism(LIPPINCOTT WILLIAMS & WILKINS, 2016-01-01)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.
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ItemNo Preview AvailableHow does adjuvant chemotherapy affect menopausal symptoms, sexual function, and quality of life after breast cancer?(LIPPINCOTT WILLIAMS & WILKINS, 2016-09)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.
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ItemTeenage mothers(ROYAL AUSTRALIAN COLLEGE GENERAL PRACTITIONERS, 2016-10)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.
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ItemA randomized, double-blind, crossover trial comparing a silicone-versus water-based lubricant for sexual discomfort after breast cancer(SPRINGER, 2016-07)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.
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ItemNo Preview AvailableIdentification of genes differentially expressed in menstrual breakdown and repair(OXFORD UNIV PRESS, 2016-12-01)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.
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ItemAnti-Mullerian hormone serum concentrations of women with germline BRCA1 or BRCA2 mutations(OXFORD UNIV PRESS, 2016-05)STUDY QUESTION: Do women with ITALIC! BRCA1 or ITALIC! BRCA2 mutations have reduced ovarian reserve, as measured by circulating anti-Müllerian hormone (AMH) concentration? SUMMARY ANSWER: Women with a germline mutation in ITALIC! BRCA1 have reduced ovarian reserve as measured by AMH. WHAT IS KNOWN ALREADY: The DNA repair enzymes encoded by ITALIC! BRCA1 and ITALIC! BRCA2 are implicated in reproductive aging. Circulating AMH is a biomarker of ovarian reserve and hence reproductive lifespan. STUDY DESIGN, SIZE, DURATION: This was a cross-sectional study of AMH concentrations of 693 women at the time of enrolment into the Kathleen Cuningham Foundation Consortium for research in the Familial Breast Cancer (kConFab) cohort study (recruitment from 19 August 1997 until 18 September 2012). AMH was measured on stored plasma samples between November 2014 and January 2015 using an electrochemiluminescence immunoassay platform. PARTICIPANTS/MATERIALS, SETTING, METHODS: Eligible women were from families segregating ITALIC! BRCA1 or ITALIC! BRCA2 mutations and had known mutation status. Participants were aged 25-45 years, had no personal history of cancer, retained both ovaries and were not pregnant or breastfeeding at the time of plasma storage. Circulating AMH was measured for 172 carriers and 216 non-carriers from families carrying ITALIC! BRCA1 mutations, and 147 carriers and 158 non-carriers from families carrying ITALIC! BRCA2 mutations. Associations between plasma AMH concentration and carrier status were tested by linear regression, adjusted for age at plasma storage, oral contraceptive use, body mass index and cigarette smoking. MAIN RESULTS AND THE ROLE OF CHANCE: Mean AMH concentration was negatively associated with age ( ITALIC! P < 0.001). Mutation carriers were younger at blood draw than non-carriers ( ITALIC! P ≤ 0.031). ITALIC! BRCA1 mutation carriers had, on average, 25% (95% CI: 5%-41%, ITALIC! P = 0.02) lower AMH concentrations than non-carriers and were more likely to have AMH concentrations in the lowest quartile for age (OR 1.84, 95% CI: 1.11-303, ITALIC! P = 0.02). There was no evidence of an association between AMH concentration and ITALIC! BRCA2 mutation status ( ITALIC! P = 0.94). LIMITATIONS, REASONS FOR CAUTION: AMH does not directly measure the primordial follicle pool. The clinical implications of the lower AMH concentrations seen in ITALIC! BRCA1 mutation carriers cannot be assessed by this study design. WIDER IMPLICATIONS OF THE FINDINGS: Women with a germline mutation in ITALIC! BRCA1 may have reduced ovarian reserve. This is consistent with other smaller studies in the literature and has potential implications for fertility and reproductive lifespan. STUDY FUNDING/COMPETING INTERESTS: kConFab is supported by a grant from the Australian National Breast Cancer Foundation, and previously by the National Health and Medical Research Council (NHMRC), the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. K.A.P. is an Australian National Breast Cancer Foundation Practitioner Fellow. J.L.H. is a NHMRC Senior Principal Research Fellow. M.H. is a NHMRC Practitioner Fellow. R.A.A. reports personal fees from Roche Diagnostics & Beckman Coulter outside the submitted work and C.S. reports other earnings from Melbourne IVF outside the submitted work. The remaining authors have nothing to declare and no conflicts of interest.