Endogenous testosterone concentrations and muscle mass, strength and performance in women, a systematic review of observational studies.

OBJECTIVE: To explore the associations between endogenous testosterone blood concentrations and muscle mass, strength and performance in community dwelling women. DESIGN, PATIENTS AND MEASUREMENTS: Online databases, including Ovid MEDLINE, EMBASE and Web of Science, were searched for observational studies, with at least 100 female participants, reporting associations between endogenous testosterone blood concentrations and muscle mass, strength and performance. The findings were synthesized in a narrative review. Heterogeneity in study design and analysis precluded a meta-analysis. RESULTS: Of the 36 articles retrieved for full-text review, 10 met the inclusion criteria. Eight studies were cross-sectional, 1 longitudinal and 1 provided both cross-sectional and longitudinal data. Testosterone was measured by liquid chromatography-tandem mass spectrometry in two studies and by immunoassay in 8. An association between total testosterone and muscle mass, strength or performance in women was not found. The studies of calculated free or bioavailable testosterone and lean muscle mass reported a positive association, but no association was reported for muscle strength or performance. Each included study was limited by a high risk of bias in at least one assessed domain. CONCLUSIONS: This review does not support an association between testosterone and muscle mass, strength or performance in women. This, together with the reported associations between free or bioavailable testosterone and muscle mass should be interpreted cautiously due to the predominant use of immunoassay and the inaccuracy of calculated variables. Additionally, biological significance of nonprotein bound testosterone has not been established. Further studies examining the relationship between precisely measured testosterone and muscle mass and function in women are required.

The association between sex hormones and the change in brain-predicted age difference in older women.

OBJECTIVE: The role of circulating sex hormones on structural brain ageing is yet to be established. This study explored whether concentrations of circulating sex hormones in older women are associated with the baseline and longitudinal changes in structural brain ageing, defined by the brain-predicted age difference (brain-PAD). DESIGN: Prospective cohort study using data from NEURO and Sex Hormones in Older Women; substudies of the ASPirin in Reducing Events in the Elderly clinical trial. PATIENTS: Community-dwelling older women (aged 70+ years). MEASUREMENTS: Oestrone, testosterone, dehydroepiandrosterone (DHEA), and sex-hormone binding globulin (SHBG) were quantified from plasma samples collected at baseline. T1-weighted magnetic resonance imaging was performed at baseline, 1 and 3 years. Brain age was derived from whole brain volume using a validated algorithm. RESULTS: The sample comprised of 207 women not taking medications known to influence sex hormone concentrations. A statistically higher baseline brain-PAD (older brain age relative to chronological age) was seen for women in the highest DHEA tertile compared with the lowest in the unadjusted analysis (p = .04). This was not significant when adjusted for chronological age, and potential confounding health and behavioural factors. Oestrone, testosterone and SHBG were not associated with brain-PAD cross-sectionally, nor were any of the examined sex hormones or SHBG associated with brain-PAD longitudinally. CONCLUSION: No strong evidence of an association between circulating sex hormones and brain-PAD. Given there is prior evidence to suggests sex hormones may be important for brain ageing, further studies of circulating sex hormones and brain health in postmenopausal women are warranted.

Performance of artificial intelligence in 7533 consecutive prevalent screening mammograms from the BreastScreen Australia program.

OBJECTIVES: To assess the performance of an artificial intelligence (AI) algorithm in the Australian mammography screening program which routinely uses two independent readers with arbitration of discordant results. METHODS: A total of 7533 prevalent round mammograms from 2017 were available for analysis. The AI program classified mammograms into deciles on the basis of breast cancer (BC) risk. BC diagnoses, including invasive BC (IBC) and ductal carcinoma in situ (DCIS), included those from the prevalent round, interval cancers, and cancers identified in the subsequent screening round two years later. Performance was assessed by sensitivity, specificity, positive and negative predictive values, and the proportion of women recalled by the radiologists and identified as higher risk by AI. RESULTS: Radiologists identified 54 women with IBC and 13 with DCIS with a recall rate of 9.7%. In contrast, 51 of 54 of the IBCs and 12/13 cases of DCIS were within the higher AI score group (score 10), a recall equivalent of 10.6% (a difference of 0.9% (CI -0.03 to 1.89%, p = 0.06). When IBCs were identified in the 2017 round, interval cancers classified as false negatives or with minimal signs in 2017, and cancers from the 2019 round were combined, the radiologists identified 54/67 and 59/67 were in the highest risk AI category (sensitivity 80.6% and 88.06 % respectively, a difference that was not different statistically). CONCLUSIONS: As the performance of AI was comparable to that of expert radiologists, future AI roles in screening could include replacing one reader and supporting arbitration, reducing workload and false positive results. CLINICAL RELEVANCE STATEMENT: AI analysis of consecutive prevalent screening mammograms from the Australian BreastScreen program demonstrated the algorithm's ability to match the cancer detection of experienced radiologists, additionally identifying five interval cancers (false negatives), and the majority of the false positive recalls. KEY POINTS: • The AI program was almost as sensitive as the radiologists in terms of identifying prevalent lesions (51/54 for invasive breast cancer, 63/67 when including ductal carcinoma in situ). • If selected interval cancers and cancers identified in the subsequent screening round were included, the AI program identified more cancers than the radiologists (59/67 compared with 54/67, sensitivity 88.06 % and 80.6% respectively p = 0.24). • The high negative predictive value of a score of 1-9 would indicate a role for AI as a triage tool to reduce the recall rate (specifically false positives).

A brief intervention for improving alcohol literacy and reducing harmful alcohol use by women attending a breast screening service: a randomised controlled trial.

OBJECTIVES: To assess the effectiveness of a brief alcohol intervention for improving awareness of alcohol as a breast cancer risk factor, improving alcohol literacy, and reducing alcohol consumption by women attending routine breast screening. DESIGN: Single-site, double-blinded randomised controlled trial. SETTING: Maroondah BreastScreen (Eastern Health, Melbourne), part of the national breast cancer screening program. PARTICIPANTS: Women aged 40 years or more, with or without a history of breast cancer and reporting any alcohol consumption, who attended the clinic for routine mammography during 5 February - 27 August 2021. INTERVENTION: Active arm: animation including brief alcohol intervention (four minutes) and lifestyle health promotion (three minutes). CONTROL ARM: lifestyle health promotion only. MAJOR OUTCOME MEASURE: Change in proportion of women who identified alcohol use as a clear risk factor for breast cancer (scaled response measure). RESULTS: The mean age of the 557 participants was 60.3 years (standard deviation, 7.7 years; range, 40-87 years); 455 had recently consumed alcohol (82%). The proportions of participants aware that alcohol use increased the risk of breast cancer were larger at four weeks than at baseline for both the active intervention (65% v 20%; odds ratio [OR], 41; 95% confidence interval [CI], 18-97) and control arms of the study (38% v 20%; OR, 4.9; 95% CI, 2.8-8.8), but the change over time was greater for the active intervention arm (arm × time: P < 0.001). Alcohol literacy also increased to a greater extent in the active than the control arm, but alcohol consumption did not significantly change in either arm. CONCLUSION: A tailored brief alcohol intervention for women attending breast screening was effective for improving awareness of the increased breast cancer risk associated with alcohol use and alcohol literacy more broadly. Such interventions are particularly important given the rising prevalence of risky drinking among middle-aged and older women and evidence that even very light alcohol consumption increases breast cancer risk. REGISTRATION: ClinicalTrials.gov, NCT04715516 (prospective; 20 January 2021).

Widespread movement of meltwater onto and across Antarctic ice shelves.

Surface meltwater drains across ice sheets, forming melt ponds that can trigger ice-shelf collapse, acceleration of grounded ice flow and increased sea-level rise. Numerical models of the Antarctic Ice Sheet that incorporate meltwater's impact on ice shelves, but ignore the movement of water across the ice surface, predict a metre of global sea-level rise this century in response to atmospheric warming. To understand the impact of water moving across the ice surface a broad quantification of surface meltwater and its drainage is needed. Yet, despite extensive research in Greenland and observations of individual drainage systems in Antarctica, we have little understanding of Antarctic-wide surface hydrology or how it will evolve. Here we show widespread drainage of meltwater across the surface of the ice sheet through surface streams and ponds (hereafter 'surface drainage') as far south as 85° S and as high as 1,300 metres above sea level. Our findings are based on satellite imagery from 1973 onwards and aerial photography from 1947 onwards. Surface drainage has persisted for decades, transporting water up to 120 kilometres from grounded ice onto and across ice shelves, feeding vast melt ponds up to 80 kilometres long. Large-scale surface drainage could deliver water to areas of ice shelves vulnerable to collapse, as melt rates increase this century. While Antarctic surface melt ponds are relatively well documented on some ice shelves, we have discovered that ponds often form part of widespread, large-scale surface drainage systems. In a warming climate, enhanced surface drainage could accelerate future ice-mass loss from Antarctic, potentially via positive feedbacks between the extent of exposed rock, melting and thinning of the ice sheet.

Corrigendum: Widespread movement of meltwater onto and across Antarctic ice shelves.

This corrects the article DOI: 10.1038/nature22049.

Antarctic ice shelf potentially stabilized by export of meltwater in surface river.

Meltwater stored in ponds and crevasses can weaken and fracture ice shelves, triggering their rapid disintegration. This ice-shelf collapse results in an increased flux of ice from adjacent glaciers and ice streams, thereby raising sea level globally. However, surface rivers forming on ice shelves could potentially export stored meltwater and prevent its destructive effects. Here we present evidence for persistent active drainage networks-interconnected streams, ponds and rivers-on the Nansen Ice Shelf in Antarctica that export a large fraction of the ice shelf's meltwater into the ocean. We find that active drainage has exported water off the ice surface through waterfalls and dolines for more than a century. The surface river terminates in a 130-metre-wide waterfall that can export the entire annual surface melt over the course of seven days. During warmer melt seasons, these drainage networks adapt to changing environmental conditions by remaining active for longer and exporting more water. Similar networks are present on the ice shelf in front of Petermann Glacier, Greenland, but other systems, such as on the Larsen C and Amery Ice Shelves, retain surface water at present. The underlying reasons for export versus retention remain unclear. Nonetheless our results suggest that, in a future warming climate, surface rivers could export melt off the large ice shelves surrounding Antarctica-contrary to present Antarctic ice-sheet models, which assume that meltwater is stored on the ice surface where it triggers ice-shelf disintegration.

The impact of endometriosis on work ability in young Australian women.

BACKGROUND: Whereas symptomatic endometriosis may affect work performance, the impact of endometriosis in the general community is not known. AIMS: The associations between endometriosis and each of sick leave and work ability, were investigated in a large sample of non-healthcare seeking women. MATERIALS AND METHODS: This community-based, cross-sectional study recruited 6986 women, aged 18-39 years, from three eastern states of Australia between 11 November 2016 and 21 July 2017. Women were identified as having endometriosis if they had undergone a pelvic ultrasound and reported a diagnosis of endometriosis. Working women completed the Work Ability Index. RESULTS: Participants were predominantly of European ancestry (73.1%) and 46.8% were overweight or had obesity. The prevalence of endometriosis was 5.4% (95%CI 4.9-6.0%) with the highest prevalence of 7.7% (95%CI 6.5 to 9.1%) for women aged 35-39 years. Among the 4618 working women, those with endometriosis had significantly more sick days from work (33.6% reported ≥10 days vs 13.5%, overall χ2 P < 0.001). Endometriosis was associated with a greater likelihood of poor to moderate work ability, after adjusting for age, body mass index, ethnicity, relationship status, student status, insecure housing, being a carer for another person, parity, ever use of assisted reproductive technologies, and depressed mood (odds ratio 1.90, 95%CI 1.40-2.58, P < 0.001). CONCLUSIONS: This study provides new evidence that the negative impact of endometriosis on work attendance and work ability is not limited to women with prevalent symptoms and severe disease, but appears to encompass women across a broader spectrum of this condition in the community.

Testosterone and androstenedione are positively associated with anti-Müllerian hormone in premenopausal women.

OBJECTIVE: To document associations between anti-Müllerian hormone (AMH) and circulating androgens in nonhealthcare-seeking premenopausal women. DESIGN: Community-based, cross-sectional study. SETTING: Eastern states of Australia. PARTICIPANTS: Women aged 18-39 years not using systemic hormones, not pregnant or breastfeeding within 3 months, and not postmenopausal. MEASUREMENTS: AMH, measured by the Beckman Access 2, 2 site immunometric assay from fresh samples, and testosterone, androstenedione, dehydroepiandrosterone (DHEA) and 11-oxygenated C19 steroids, measured by liquid chromatography-tandem mass spectrometry. RESULTS: Data were available for 794 women, median age of 33 years (range: 18-39). 76.1% were of European ancestry and 48.2% were parous. Serum AMH was positively associated with testosterone (rho = .29, p < .001) androstenedione (rho = .39, p < .001) and DHEA (rho = .10, p = .005) but not 11-ketoandrostenedione or 11-ketotestosterone. When adjusted for age, body mass index and smoking, using quantile regression, independent positive associations remained between AMH and testosterone (ß coefficient: 20.90, 95% confidence interval [CI]: 13.79-28.03; p < .001) and androstenedione (ß coefficient: 5.90, 95% CI: 3.76-8.03; p < .001). The serum concentration of testosterone was greater at the top AMH quintile than other quintiles (0.56 nmol/L [range: 0.21-1.90] vs. 0.36 nmol/L [range: 0.13-0.87]; p = .001) in women with self-reported polycystic ovary syndrome. CONCLUSIONS: The positive associations between serum testosterone and androstenedione and AMH in premenopausal women is consistent with androgens directly or indirectly influencing AMH production during follicular development. As the highest AMH concentrations are most likely to be seen in women with multifollicular ovaries, it would be expected that women with multifollicular ovaries would have higher serum testosterone. Therefore, whether hyperandrogenemia and multifollicular ovaries should be considered independent characteristics of polycystic ovary syndrome warrants review.

Differing performance of two assays for the measurement of anti-Mullerian hormone in premenopausal women: A cross-sectional study.

OBJECTIVE: To compare the performance of two anti-Mullerian (AMH) assays over a range of concentrations, in samples collected from young women. DESIGN: A cross-sectional method-comparison study of 168 non-healthcare-seeking women. PARTICIPANTS: Included women were aged 18-39 years, not recently pregnant, breast feeding or using systemic hormones. MEASUREMENTS: Serum AMH levels were analysed with the Beckman Coulter Access 2 assay from fresh samples and the Ansh picoAMH assay using samples stored at -80°C, in a parallel setting. Comparisons between the two assays were examined using Bland-Altman plots. RESULTS: Participants had a mean ± SD age of 32.6 ± 5.4 years and body mass index of 28.1 ± 7.9 kg/m2 , and 60.1% were parous. Although the assay results were highly correlated (Spearman correlation .982, P < .001), the relationship between the assays was nonlinear. Serum AMH values below 4 pmol/L were lower with the picoAMH assay compared with the Access AMH assay (mean difference in this range was -0.49 pmol/L), but for samples with a mean value above 10 pmol/L, the picoAMH assay consistently measured higher than the Access AMH assay (mean difference in this range was +8.2 pmol/L). As AMH concentrations increased the absolute discrepancy between the assays also increased. CONCLUSIONS: This study demonstrates that despite the high correlation between two commercially available AMH assays, the assays performed in a discordant manner at high and low concentrations. Hence, the results of these assays are not interchangeable, highlighting the need to establish specific reference limits for individual assays to guide clinical decision-making and the challenge of establishing future universal cut-offs for the application of AMH levels in clinical practice.

Longitudinal changes over three years in sex steroid hormone levels in women aged 70 years and over.

OBJECTIVE: Sex steroid levels in women vary with increasing age from the age of 70 years (70+). Whether this reflects change within individuals with age or a survival advantage is not known. This study aimed to determine the stability of circulating sex steroids and SHBG over time in individual women aged 70+. DESIGN: A prospective cohort study. PARTICIPANTS: 400 women, aged 70+ not using any sex steroid, anti-androgen/oestrogen or glucocorticoid therapy. MAIN OUTCOME MEASUREMENTS: Sex steroid concentrations, measured by liquid chromatography-tandem mass spectrometry and sex hormone-binding globulin (SHBG) by immunoassay, in paired blood samples drawn 3 years apart and analysed together. RESULTS: 400 women, median (IQR) age 78.0 (8.6) years, were included in the analysis. Mean testosterone concentrations were statistically significantly higher in follow-up samples compared with baseline. The change was modest (mean change 31 pmol/L, 95% confidence interval (CI) 2.4-59.8; p = .034), and an increase was not observed in all women. There was a statistically significant decline in mean body mass index (mean change -0.4 kg/m2 , 95% CI 0.6 to -0.3; p < .001) and a significant increase in the mean serum SHBG concentration (mean change 4.0 nmol/L, 95% CI 2.7-5.4; p < .001). The change observed in testosterone was not explained by the observed change in SHBG. There was no significant change in the mean oestrone or dehydroepiandrosterone concentration. CONCLUSIONS: Testosterone concentrations in women aged 70+ were more likely to increase than decrease. Whether increasing testosterone concentrations in older women confer a survival advantage needs investigation.

Substituting serum anti-Müllerian hormone for polycystic ovary morphology increases the number of women diagnosed with polycystic ovary syndrome: a community-based cross-sectional study.

STUDY QUESTION: Can serum anti-Müllerian hormone (AMH) replace polycystic ovary morphology (PCOM) determined by ultrasound as a diagnostic component of polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: Despite good correlations between serum AMH and PCOM, the use of a high serum AMH as a proxy for PCOM resulted in the reclassification of PCOS in 5% of study participants, with the main effect being more women identified, although some women previously classified as having PCOS were no longer classified as such. WHAT IS KNOWN ALREADY: AMH has been proposed as an alternative to PCOM as a diagnostic component of PCOS. Previous studies are limited by poorly defining PCOS, use of infertile women as comparators, measurement of hormones by immunoassay that lack precision in the female range, low-resolution ovarian ultrasound and inconsistent handling and storage of serum samples. STUDY DESIGN, SIZE, DURATION: This is an Australian cross-sectional study of 163 non-healthcare-seeking women. PARTICIPANTS/MATERIALS, SETTING, METHODS: Serum AMH was measured by both the Ansh picoAMH assay and the Beckman Coulter Access 2 (BA2) assay, in parallel with androgens measured by liquid chromatography-tandem mass spectrometry, in blood samples of women, not pregnant, breast feeding or using systemic steroids, who also underwent high-resolution ovarian ultrasound. PCOS was determined by the Rotterdam criteria with PCOM defined by the Androgen Excess-PCOS Taskforce recommendation of ≥25 follicles in at least one ovary. Cut-off serum concentrations that best identified women as having PCOM were identified by receiver operator characteristic (ROC) curves. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 163 women, mean (SD) age 32.5 (5.5) years, who provided a blood sample and had both ovaries visualized on ultrasound were included in the analysis. Women with isolated PCOM had higher median (range) Ansh AMH and BA2 AMH concentrations than those with no PCOS characteristics [56.9 pmol/l (34.6, 104.2) versus 18.7 (3.2, 50.9), P = 0.002 and 38.5 pmol/l (22.2, 100.2) versus 16.7 (3.5, 38.9), P = 0.002, respectively]. An AMH ≥ 44.0 pmol/l, suggested by the ROC curve, identified 80.6% of women with PCOM, falsely identified 15.2% of women without PCOM as having PCOS and had a positive predictive value of 55.6%. The negative predictive value was 94.9%. An AMH BA2 assay cut-off of ≥33.2 pmol/l provided a sensitivity of 80.6%, a specificity of 79.5% and a positive predictive value for PCOM of 48.1%. The negative predictive value was 94.6% for PCOM. When serum AMH was used in the place of PCOM as a diagnostic criterion for PCOS, the Ansh assay resulted in an additional seven women classified as having PCOS and no longer classified one woman as having PCOS. For the BA2 assay, eight additional and two fewer women were classified as having PCOS. Overall, both assays resulted in six more women being classified as having PCOS. LIMITATIONS, REASONS FOR CAUTION: Women with functional hypogonadotrophic hypogonadism were not excluded and may have been misclassified as having an oligo-amenorrhoea-PCOM phenotype. As study participants were predominantly Caucasian/White, our findings cannot be generalized to women of other ethnicities. WIDER IMPLICATIONS OF THE FINDINGS: Although serum AMH reflects the number of developing ovarian follicles, the absolute values vary between assays and specific reference ranges for individual assays are required. Irrespective of the assay used, replacing PCOM with serum AMH to diagnose PCOS in a community-based sample altered the number of women classified as having or not having PCOS. Consequently, although overall the risk of women being identified as having PCOS would be increased, some women would no longer be classified as having this condition. STUDY FUNDING/COMPETING INTEREST(S): The study was supported by the Norman Beischer Research Foundation and the Grollo-Ruzzene Foundation. S.R.D. is an NHMRC Senior Principal Research Fellow (Grant No. 1135843). S.R.D. reports unrelated support that includes grants from the NHMRC Australia, personal fees for educational activities from Besins Healthcare, Abbott Chile, BioFemme and Pfizer Australia, personal Advisory Board/consultancy fees from Theramex, Abbott Laboratories, Astellas, Mayne Pharmaceuticals, Roche Diagnostics, Lawley Pharmaceuticals and Que Oncology and has received institutional grant funding from Que Oncology and Ovoca research. The other authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Use of community-based reference ranges to estimate the prevalence of polycystic ovary syndrome by the recognised diagnostic criteria, a cross-sectional study.

STUDY QUESTION: Does the application of reference ranges for sex steroids and the modified Ferriman-Gallwey (mFG) scale established in the community from which the study sample was drawn, combined with the most conservative polycystic ovary morphology (PCOM) criteria to the recognised diagnostic criteria for polycystic ovary syndrome (PCOS) improve the certainty of diagnosis of PCOS in non-healthcare-seeking women? SUMMARY ANSWER: Despite application of the stringent definitions of the elements used to diagnose PCOS in a non-healthcare seeking community-based sample, the risk of diagnostic uncertainty remains. WHAT IS KNOWN ALREADY: There is heterogeneity in prevalence estimates for PCOS due, in part, to lack of standardisation of the elements comprising the recognised National Institutes of Health (NIH), Rotterdam and Androgen Excess Society (AE-PCOS) diagnostic criteria. The AE-PCOS Society proposed refinements to the definitions of biochemical androgen excess and PCOM that can now be incorporated into these sets of diagnostic criteria to estimate PCOS prevalence. STUDY DESIGN, SIZE, DURATION: An Australian cross-sectional study of 168 non-healthcare-seeking women. PARTICIPANTS/MATERIALS, SETTING, METHODS: The 168 included women were aged 18-39 years, euthyroid and normoprolactinemic, not recently pregnant, breast feeding or using systemic hormones. Each provided menstrual history and assessment of the mFG, had measurement of sex steroids by liquid chromatography, tandem mass spectrometry, and a pelvic ultrasound. The presence of PCOS was determined using modified (m) NIH, Rotterdam, and AE-PCOS criteria according to AE-PCOS Society recommendations. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, 10.1% of the included participants met the mNIH PCOS criteria, which requires the presence of menstrual dysfunction, while 18.5% met the mRotterdam and 17.5% the AE-PCOS criteria, with the latter requiring hyperandrogenism. Eight of the 27 participants with menstrual dysfunction, 10 of 31 women with PCOM, and 39 of 68 women with hyperandrogenism had no other feature of PCOS. Of the 19 participants with hyperandrogenaemia, 10 met the mNIH criteria (52.5%) and 14 met both the mRotterdam and AE-PCOS criteria (78.9%). Women who had the combination of hyperandrogenism and PCOM explained the greatest discrepancy between the mNIH and the other criteria. LIMITATIONS, REASONS FOR CAUTION: Clinical androgenisation relied on participant self-assessment, which has been shown to be valid when compared with clinician assessment. The sample size was a function of both the strict inclusion criteria and the requirements of non-healthcare-seeking women having a blood draw and pelvic ultrasound which may have introduced a selection bias. WIDER IMPLICATIONS OF THE FINDINGS: Despite applying stringent cut-offs for serum androgens, the mFG scale and the ovarian follicle count, these criteria remain arbitrary. Accordingly, healthy women may be captured by these criteria, and misidentified as having PCOS, while women with the condition may be missed. Consequently, PCOS remains a diagnosis to be made with care. STUDY FUNDING/COMPETING INTEREST(S): The study was supported by the Grollo-Ruzzene Foundation. Dr S.R.D. is an NHMRC Senior Principal Research Fellow (Grant no. 1135843). S.R.D. has been paid for developing and delivering educational presentations for Besins Healthcare, BioFemme and Pfizer Australia, has been on Advisory Boards for Theramex, Abbott Laboratories, Mayne Pharmaceuticals and Roche and a consultant to Lawley Pharmaceuticals and Que Oncology and has received has received institutional grant funding for Que Oncology research; there are no other relationships or activities that could appear to have influenced the submitted work. TRIAL REGISTRATION NUMBER: N/A.

Recharge of a subglacial lake by surface meltwater in northeast Greenland.

In a warming climate, surface meltwater production on large ice sheets is expected to increase. If this water is delivered to the ice sheet base it may have important consequences for ice dynamics. For example, basal water distributed in a diffuse network can decrease basal friction and accelerate ice flow, whereas channelized basal water can move quickly to the ice margin, where it can alter fjord circulation and submarine melt rates. Less certain is whether surface meltwater can be trapped and stored in subglacial lakes beneath large ice sheets. Here we show that a subglacial lake in Greenland drained quickly, as seen in the collapse of the ice surface, and then refilled from surface meltwater input. We use digital elevation models from stereo satellite imagery and airborne measurements to resolve elevation changes during the evolution of the surface and basal hydrologic systems at the Flade Isblink ice cap in northeast Greenland. During the autumn of 2011, a collapse basin about 70 metres deep and about 0.4 cubic kilometres in volume formed near the southern summit of the ice cap as a subglacial lake drained into a nearby fjord. Over the next two years, rapid uplift of the floor of the basin (which is approximately 8.4 square kilometres in area) occurred as surface meltwater flowed into crevasses around the basin margin and refilled the subglacial lake. Our observations show that surface meltwater can be trapped and stored at the bed of an ice sheet. Sensible and latent heat released by this trapped meltwater could soften nearby colder basal ice and alter downstream ice dynamics. Heat transport associated with meltwater trapped in subglacial lakes should be considered when predicting how ice sheet behaviour will change in a warming climate.

Prevalence of Low Sexual Desire With Associated Distress Across the Adult Life Span: An Australian Cross-Sectional Study.

BACKGROUND: Although hypoactive sexual desire dysfunction (HSDD; low sexual desire with personal distress) negatively impacts well-being, contemporary life-course prevalence data for HSDD are lacking. AIM: To document, in an epidemiologic study, the prevalence of low sexual desire with associated distress (epidemiological HSDD [eHSDD]), and associated psychosocial factors in Australian women. METHODS: A cross-sectional study of 10,554 women, aged 18-79 years, recruited from the community was performed. MAIN OUTCOME MEASURES: Low desire was determined by corresponding questions in the Profile of Female Sexual Function and Female Sexual Function Index. HSDD was defined as having a low desire and Female Sexual Distress Scale-Revised score of ≥11. CLINICAL TRANSLATION: Clinicians need to be aware that young women often experience sexually related distress whereas low desire with associated distress is most common in women at midlife. RESULTS: The majority of the participants were partnered (66.5%) and 38.9% were recently sexually inactive. Low desire prevalence increased from age 18-24 years to 75-79 years (27.4%, 95% CI 25.5-29.3 vs 91.6%, 95% CI 88.3-94.1, P < .001). Just over half of all participants aged 25-39 years had sexually related personal distress, after which the prevalence declined with age (P < .001). 10,259 participants provided sufficient information for eHSDD classification. eHSDD increased from age 18-24 years (12.2%, 95% CI 10.8-13.7) to 40-44 years (33.4%, 95% CI 28.5-38.8), remained constant until 60-64 years (33.1%, 95% CI 28.3-38.4), and progressively declined to 7.3% (95% CI 4.8-10.9) by 75-79 years. HSDD was significantly, positively associated with being partnered (P < .001), sexually inactive (P < .001), more educated (P = .001), and psychotropic medication use (P < .001), and negatively with Asian ethnicity (P < .001). STRENGTHS & LIMITATIONS: This study involved the assessment of desire using a single question derived from the Profile of Female Sexual Function or the Female Sexual Function Index. CONCLUSION: eHSDD is most prevalent at midlife. Furthermore, the likelihood of eHSDD is greater for women who are partnered, sexually inactive, more educated, or taking psychotropic medications. Taken together these findings should aid health professionals in identifying women most at risk of eHSDD. Zheng J, Islam RM, Bell RJ, et al. Prevalence of Low Sexual Desire With Associated Distress Across the Adult Life Span: An Australian Cross-Sectional Study. J Sex Med 2020;17:1885-1895.

Endogenous doesn't always mean innocuous: a scoping review of iron toxicity by inhalation.

Ambient air pollution is a leading risk factor for the global burden of disease. One possible pathway of particulate matter (PM)-induced toxicity is through iron (Fe), the most abundant metal in the atmosphere. The aim of the review was to consider the complexity of Fe-mediated toxicity following inhalation exposure focusing on the chemical and surface reactivity of Fe as a transition metal and possible pathways of toxicity via reactive oxygen species (ROS) generation as well as considerations of size, morphology, and source of PM. A broad term search of 4 databases identified 2189 journal articles and reports examining exposure to Fe via inhalation in the past 10 years. These were sequentially analyzed by title, abstract and full-text to identify 87 articles publishing results on the toxicity of Fe-containing PM by inhalation or instillation to the respiratory system. The remaining 87 papers were examined to summarize research dealing with in vitro, in vivo and epidemiological studies involving PM containing Fe or iron oxide following inhalation or instillation. The major findings from these investigations are summarized and tabulated. Epidemiological studies showed that exposure to Fe oxide is correlated with an increased incidence of cancer, cardiovascular diseases, and several respiratory diseases. Iron PM was found to induce inflammatory effects in vitro and in vivo and to translocate to remote locations including the brain following inhalation. A potential pathway for the PM-containing Fe-mediated toxicity by inhalation is via the generation of ROS which leads to lipid peroxidation and DNA and protein oxidation. Our recommendations include an expansion of epidemiological, in vivo and in vitro studies, integrating research improvements outlined in this review, such as the method of particle preparation, cell line type, and animal model, to enhance our understanding of the complex biological interactions of these particles.

Iron insufficiency among young Australian women: a population-based survey.

BACKGROUND: Although serum ferritin is considered a reliable indicator of iron stores, there are few data documenting the prevalence of low ferritin in representative samples of young women. AIMS: To estimate the prevalence of low ferritin and to identify factors associated with low ferritin in young Australian women. METHODS: Women, aged 18-39 years, living in the eastern states of Australia were recruited by email to a cross-sectional, online questionnaire-based study between November 2016 and July 2017. Participants not pregnant, breast feeding, taking hormonal contraception, using assisted reproduction or postmenopausal were invited to provide a blood sample. RESULTS: Of the 3689 invited participants, 761 (23.1%) provided a sample and 736 women, mean (SD) age 31.7 (±5.6) years, were included in the analyses. The overall prevalence of serum ferritin <30 µg/L was 34.8% (95% confidence interval (CI) 31.4-38.3%), with 41.4% (35.1-48.0%) in NSW, 31.5% (26.4-37.1%) in Victoria and 32.6% (26.8-39.0%) in Queensland. Serum ferritin <30 µg/L was positively associated with the reporting of >2 days of heavy menstrual bleeding (adjusted odds ratio (AOR) 1.73, 95% CI 1.15-2.59), living in New South Wales (AOR 1.57, 95% CI 1.07-2.30), not working outside home (AOR 1.58, 95% CI 1.01-2.49), and inversely associated with never experiencing heavy menses (AOR 0.46, 95% CI 0.23-0.93) and obesity (AOR 0.32, 95% CI 0.21-0.50). CONCLUSIONS: This study demonstrates that serum ferritin below 30 µg/L is common amongst young Australian women. Healthcare professionals should note the association between low ferritin and heavy bleeding.

Hormonal contraceptive use in Australian women: Who is using what?

BACKGROUND: In Australia many hormonal contraceptives are not Pharmaceutical Benefits Scheme (PBS) supported, hence the use of different formulations have not been quantified. OBJECTIVES: To document the use of hormonal contraceptives and factors associated with their use. MATERIALS AND METHODS: Cross-sectional, online questionnaire-based study of 6986 Australian women, aged 18-39 years, recruited by email invitation from two large, representative databases. Main outcome measures were the prevalence of use of hormonal contraceptives and associated socio-demographic characteristics. RESULTS: Of the 6600 potential hormone contraceptive users, 43.2% were current users. Most (63.6%) reported using a combined oral contraceptive (COC) of which 30.9% were non-PBS-supported anti-androgenic progestin-containing COCs. Use of long-acting reversible contraceptives (LARC) or an injectable contraceptive was reported by 26.8%. Education beyond secondary school, being Australian born, rural residency, normal body mass index, age <25 years and nulliparity were significantly associated with hormonal contraceptive use. Women who reported polycystic ovary syndrome or acne were more likely to be taking a third or fourth generation COC (P < 0.0001) and endometriosis was significantly associated with intrauterine system (IUS) use. Third or fourth generation COC use was reported by 12.1% of obese, current smokers. CONCLUSION: An estimated one-third of Australian women aged 18-39 are taking a non-PBS-supported anti-androgenic progestin COC, highlighting inequity in access to COC options. That hormonal contraceptive use is higher in rural areas is a novel finding and the proportion of LARC or injectable use suggests that uptake in Australia is higher than previously reported.

The benefits of adding metformin to tamoxifen to protect the endometrium-A randomized placebo-controlled trial.

BACKGROUND: We investigated whether metformin prevents tamoxifen-induced endometrial changes and insulin resistance (IR) after a diagnosis of breast cancer. METHODS: This was a single-centre, randomized, double-blind, placebo-controlled, parallel group trial. Postmenopausal women with hormone receptor-positive breast cancer taking tamoxifen were randomly allocated to metformin 850 mg or identical placebo, twice daily, for 52 weeks. Outcome measures included double endometrial thickness (ET) measured by transvaginal ultrasound, fasting insulin, glucose and IR estimated by the homeostasis model of assessment (HOMA-IR). RESULTS: A total of 112 women were screened and 102 randomized. Results are presented as median (range). The 101 women who took at least one dose of medication were aged 56 (43-72) years, with 5(0.5-28) years postmenopause, and had taken tamoxifen for 28.9 (0-367.4) weeks. The baseline ET was 2.9 mm (1.4-21.9) for the placebo group (n = 52) and 2.5 mm (1.3-14.8) for the metformin group (n = 50). At 52 weeks, the median ET was statistically significantly lower for the metformin (n = 36) than for the placebo group (n = 45) (2.3 mm (1.4-7.8) vs 3.0 (1.2-11.3); P = 0.05). 13.3% allocated to placebo had an ET greater than 4 mm vs 5.7% for metformin (P = 0.26). There was no endometrial atypia or cancer. Compared with placebo, metformin resulted in significantly greater baseline-adjusted reductions in weight (P < 0.001), waist circumference (0.03) and HOMA-IR (P < 0.001). CONCLUSIONS: Metformin appears to inhibit tamoxifen-induced endometrial changes and has favourable metabolic effects. Further research into the adjuvant use of metformin after breast cancer and to prevent EH and cancer is warranted.