Bone Measures by Dual-Energy X-Ray Absorptiometry and Peripheral Quantitative Computed Tomography in Young Women With Type 1 Diabetes Mellitus.

Understanding bone fragility in young adult females with type 1 diabetes mellitus (T1DM) is of great clinical importance since the high fracture risk in this population remains unexplained. This study aimed to investigate bone health in young adult T1DM females by comparing relevant variables determined by dual-energy X-ray absorptiometry (DXA), peripheral quantitative computed tomography (pQCT) at the tibia and pQCT-based finite element analysis (pQCT-FEA) between T1DM subjects (n = 21) and age-, height- and weight-matched controls (n = 63). Tibial trabecular density (lower by 7.1%; 228.8 ± 33.6 vs 246.4 ± 31.8 mg/cm3, p = 0.02) and cortical thickness (lower by 7.3%; 3.8 ± 0.5 vs 4.1 ± 0.5 cm, p = 0.03) by pQCT were significantly lower in T1DM subjects than in controls. Tibial shear stiffness by pQCT-FEA was also lower in T1DM subjects than in controls at both the 4% site (by 17.1%; 337.4 ± 75.5 vs 407.1 ± 75.4 kN/mm, p < 0.01) and 66% site (by 7.9%; 1113.0 ± 158.6 vs 1208.8 ± 161.8 kN/mm, p = 0.03). These differences remained statistically significant after adjustment for confounding factors. No difference between groups was observed in DXA-determined variables (all p ≥ 0.08), although there was a trend towards lower aBMD at the lumbar spine in T1DM subjects than in controls after adjustment for confounders (p = 0.053). These novel findings elicited using pQCT and pQCT-FEA suggest a clinically significant impact of T1DM on bone strength in young adult females with T1DM. Peripheral QCT and pQCT-FEA may provide more information than DXA alone on bone fragility in this population. Further longitudinal studies with a larger sample size are warranted to understand the evolution and causes of bone fragility in young T1DM females.

Polycystic ovarian syndrome: Prevalence and impact on the wellbeing of Australian women aged 16-29 years.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is the most common condition among reproductive-aged women. However, its exact prevalence is unknown. AIMS: To determine the prevalence of PCOS in Australian women aged 16-29 years using the National Institutes of Health (NIH) criteria compared to self-reported PCOS, to compare co-morbidities between the groups and to determine the most distressing aspect of a diagnosis of PCOS for these young women. MATERIALS AND METHODS: Participants were recruited from the Young Female Health Initiative (YFHI) and Safe-D studies. Participants completed questionnaires, physical examinations and blood tests from 2012 to 2016. In March 2016, two supplementary questionnaires were distributed: the first, comprising questions on reproductive health and impact of diagnosis, was sent to participants who self-reported having PCOS in the original studies. The second, comprising general reproductive health questions, was sent to the remainder. RESULTS: The prevalence of PCOS, according to the NIH criteria, was 12% (31/254), while the prevalence of self-reported PCOS was 8% (23/300). Only 35% (8/23) of those with self-reported PCOS actually fulfilled the NIH criteria for PCOS. Comorbidities were relatively similar among groups. Finally, approximately 65% (15/23) were unhappy or worried about their initial PCOS diagnosis, with 72% (13/18) stating fertility concerns were the most distressing aspect of their diagnosis. CONCLUSIONS: The lack of consistent and accurate diagnosis of PCOS in young women potentially leads to over-diagnosis. This creates unnecessary fears of health complications, particularly infertility. Therefore, we recommend the development of standardised criteria with set parameters that allow for better diagnosis of PCOS.

Predictors and correlates of serum 25-hydroxyvitamin D concentrations in young women: results from the Safe-D study.

Vitamin D deficiency is a global public health concern. Studies of serum 25-hydroxyvitamin D (25(OH)D) determinants in young women are limited and few include objective covariates. Our aims were to define the prevalence of vitamin D deficiency and examine serum 25(OH)D correlates in an exploratory study of women aged 16-25 years. We studied 348 healthy females living in Victoria, Australia, recruited through Facebook. Data collected included serum 25(OH)D assayed by liquid chromatography-tandem MS, relevant serum biochemistry, soft tissue composition by dual-energy X-ray absorptiometry, skin melanin density, Fitzpatrick skin type, sun exposure using UV dosimeters and lifestyle factors. Mean serum 25(OH)D was 68 (sd 27) nmol/l and 26 % were vitamin D deficient (25(OH)D 2 h in the sun in summer daily, holidaying in the most recent summer period, serum Fe levels, height and multivitamin use were positively associated with 25(OH)D. Fat mass and a blood draw in any season except summer was inversely associated with 25(OH)D. Vitamin D deficiency is common in young women. Factors such as hormonal contraception, sun exposure and sun-related attitudes, as well as dietary supplement use are essential to consider when assessing vitamin D status. Further investigation into methods to safely optimise vitamin D status and to improve understanding of the impact of vitamin D status on long-term health outcomes is required.

HPV16/18 prevalence in high-grade cervical lesions in an Australian population offered catch-up HPV vaccination.

OBJECTIVES: Using laser capture microdissection (LCM) and sensitive human papillomavirus (HPV) genotyping, we aimed to determine the distribution of vaccine-preventable types in cervical intraepithelial neoplasia grade 3 (CIN3) lesions and adenocarcinoma in situ (AIS) in young women in Victoria, Australia, offered catch-up HPV vaccination, as a baseline for ongoing vaccine impact monitoring. We also compared findings with available pre-vaccination estimates from women with HPV detected on concurrently-collected cytology samples. METHODS: Consecutive histologically-confirmed CIN3/AIS biopsies were collected between May 2011 and December 2014 from vaccine-eligible women (born after 30th June 1981). Genotypes present in whole tissue sections (WTS) were determined by a sensitive reverse hybridisation assay; RHA kit HPV SPF10-LiPA25, v1 (Labo Bio-medical Products). Where multiple genotypes were detected, lesions were isolated using LCM and genotyped. Cervical cytology samples from a pre-vaccine cohort had been previously collected and genotyped using HPV Linear Array HPV Genotyping Test (Roche Diagnostics). Mixed-genotype detections in this cohort were resolved to single-lesion-attributable genotypes using hierarchical attribution. RESULTS: Overall, 213 and 530 cases were included from pre- and post-vaccine time-periods, respectively. In 18-25 year-olds, the proportion of HPV16/18-positive CIN3/AIS decreased significantly over time from 69% in 2001-2005 (pre-vaccine), to 62% in 2011-2012 (post-vaccine), to 47% in 2013-2014 (p-trend = 0.004). There was no significant change in HPV16/18 in 26-32 year-olds (p-trend = 0.15). In 2013/14, nonavalent vaccine types accounted for 80% of CIN3/AIS in 18-25 year old women and 90% in 26-32 year old women. CONCLUSION: Four to 8 years following implementation of HPV vaccination in Australia, approximately 70% of CIN3/AIS in young women was due to HPV16/18. Our data, despite some limitations due to change in methods between pre- and post-vaccine periods, suggests that for vaccine-eligible women aged 18-25 at the time of biopsy, the proportion of HPV16/18-attributable CIN3/AIS lesions is significantly declining post-vaccination.

Assessment of attribution algorithms for resolving CIN3-related HPV genotype prevalence in mixed-genotype biopsy specimens using laser capture microdissection as the reference standard.

To make accurate determinations regarding potential and actual impact of HPV vaccine programs, precise estimates of genotype-specific contributions to disease are required for pre- and post-vaccine populations. Definitive determination of lesion-specific genotypes, particularly where multiple genotypes are detected in a sample, can be technically demanding and resource intensive; therefore, most prevalence studies use mathematical algorithms to adjust for multiple genotype detections. There are currently several algorithms, which can produce genotype estimates within a wide range of variability. The use of these for cervical cytology samples has recently been assessed for accuracy against a definitive reference standard, but none have yet been assessed for multiple-genotype-containing whole biopsy specimens. Using laser capture microdissection (LCM) on biopsy samples, lesion-specific genotype prevalence data were generated for a cohort of 516 young Australian women (aged 18-32 years) with cervical intraepithelial neoplasia grade 3 or adenocarcinoma in situ. Using whole tissue section genotype data from the same cohort, including 71 (13.7%) with multiple genotypes, lesion-associated genotype prevalence was estimated using four different attribution algorithms. The proportion of lesions attributable to HPV16 and HPV18 by LCM were 58.4% and 5%, respectively; hierarchical, proportional, single type/minimum and any type/maximum attribution estimates were comparable across genotypes. For analyses utilising whole tissue biopsy cervical specimens, attribution estimates are appropriate for estimating the proportional contribution of individual genotypes to lesions in a population.

Associations between 25-hydroxyvitamin D levels, body composition and metabolic profiles in young women.

BACKGROUND/OBJECTIVES: Cardiovascular disease (CVD) is a major cause of mortality and morbidity globally. Results from previous studies are inconsistent and it remains unclear whether low-serum 25 OHD levels are associated with an increased risk of CVD. These associations have been little studied in young women. The aim of this study was to assess the relationship between serum 25 OHD and obesity, body composition, metabolic profiles and blood pressure in young women. SUBJECTS/METHODS: Women aged 16-25 years living in Victoria, Australia, were recruited through Facebook advertising in this cross-sectional study. Participants completed an online survey and attended a site visit in a fasted state, where parameters, including blood pressure, anthropometry, metabolic profiles, serum 25 OHD levels and body composition (using dual energy X-ray absorptiometry) were measured. RESULTS: A total of 557 participants were recruited into this study. Multiple linear regression analysis showed that after adjusting for visceral fat, season, smoking, physical activity, age, alcohol intake, oral contraceptive use, country of birth, taking multivitamins and taking vitamin D supplement, a 10 nmol/L increase in 25 OHD levels was associated with 0.65% greater HDL levels (p = 0.016) and 0.92% greater triglyceride levels (p = 0.003). It was also associated with 0.48% lower BMI (p < 0.001), 0.50% lower total fat percentage (p < 0.001), 0.09% lower visceral fat percentage (p < 0.001), 0.14% lower visceral fat to total fat ratio (p < 0.001) and 0.36% lower trunk fat to total fat ratio (p < 0.001), after adjustment for season, smoking, physical activity, age, alcohol intake, oral contraceptive use, country of birth, taking multivitamins and taking vitamin D supplements. Although these associations were statistically significant, they were very small in magnitude and of uncertain clinical significance. CONCLUSIONS: These findings may help to explain an association between 25 OHD levels and CVD risk factors through associations with HDL, BMI, total body and visceral fat mass. Possible underlying mechanisms warrant further investigation.

Bone turnover marker determinants in young women: results from the Safe-D study.

Background Bone turnover markers (BTMs) may provide insight into bone health in young women, but have been little studied in this demographic. We aimed to explore the association between body composition, hormonal contraception, bone mineral density and biochemical parameters and BTMs in young women. Methods Participants were community-dwelling females aged 16-25 years, living in Victoria, Australia. Carboxy-terminal cross-linking telopeptide of type 1 collagen (CTX) and total procollagen type 1 N-propeptide (P1NP) were analysed on the Roche Elecsys automated analyzer. A total of 305 were evaluated, after excluding participants with medical conditions or medications (except hormonal contraceptives), which may affect bone metabolism. Results Median (Q1, Q3) BTM values were 540 (410, 690) ng/L for CTX and 61.7 (46.2, 83.7) µg/L for P1NP. Serum CTX and P1NP were inversely associated with chronological age ( P < 0.001), transferrin ( P < 0.020) and serum dehydroepiandrosterone sulphate concentration ( P < 0.001). BTM values were up to 22% lower in combined oral contraceptive (COC) pill users ( P < 0.001). Serum CTX was inversely associated with per cent body fat ( P = 0.009) and tibial cortical volumetric bone mineral density (vBMD; P = 0.003). Serum P1NP concentrations were 23 µg/L higher in participants who reported using an osteopath in the previous year ( P = 0.007). Conclusions These data suggest that BTMs are influenced by age, COC use, body composition, iron status and hormonal profiles. Higher CTX values were associated with lower tibial cortical vBMD. Examining BTMs in relation to interventions aimed at improving bone health in young women is warranted.

Bone turnover marker reference intervals in young females.

Background The use of bone turnover markers in clinical practice and research in younger people is limited by the lack of normative data and understanding of common causes of variation in bone turnover marker values in this demographic. To appropriately interpret bone turnover markers, robust reference intervals specific to age, development and sex are necessary. This study aimed to determine reference intervals of bone turnover markers in females aged 16-25 years participating in the Safe-D study. Methods Participants were recruited through social networking site Facebook and were asked to complete an extensive, online questionnaire and attend a site visit. Participants were tested for serum carboxy-terminal cross-linking telopeptide of type 1 collagen and total procollagen type 1 N-propeptide using the Roche Elecsys automated analyser. Reference intervals were determined using the 2.5th to 97.5th percentiles of normalized bone turnover marker values. Results Of 406 participants, 149 were excluded due to medical conditions or medication use (except hormonal contraception) which may affect bone metabolism. In the remaining 257 participants, the reference interval was 230-1000 ng/L for serum carboxy-terminal cross-linking telopeptide of type 1 collagen and 27-131 µg/L for procollagen type 1 N-propeptide. Both marker concentrations were inversely correlated with age and oral contraceptive pill use. Therefore, intervals specific to these variables were calculated. Conclusions We defined robust reference intervals for cross-linking telopeptide of type 1 collagen and procollagen type 1 N-propeptide in young females grouped by age and contraceptive pill use. We examined bone turnover markers' relationship with several lifestyle, clinical and demographic factors. Our normative intervals should aid interpretation of bone turnover markers in young females particularly in those aged 16 to 19 years where reference intervals are currently provisional.

Serum 25-hydroxyvitamin D and mental health in young Australian women: Results from the Safe-D study.

BACKGROUND: While there is evidence linking vitamin D status with mood, this association and its clinical significance remain uncertain. Moreover, few studies have focused on young, community-dwelling females. The Safe-D study examined the association between serum 25-hydroxyvitamin D (25OHD) levels and mental health in young women. METHODS: Participants completed an online questionnaire, wore a UV dosimeter to measure personal sun exposure and underwent a comprehensive health assessment. Serum 25OHD was measured by liquid chromatography-tandem mass spectrometry in 353 healthy women aged 16-25 years, living in Victoria, Australia. Mental health measures included: Patient Health Questionnaire (PHQ-9), 7-item Generalized Anxiety Disorder Scale (GAD-7), Kessler psychological distress scale (K10) and 12-item short-form health survey (SF-12), plus any self-reported mental disorder diagnoses or medication use. RESULTS: The prevalence of self-reported mental disorder was 26% and of vitamin D deficiency 27%. The median (Q1, Q3) scores for the PHQ-9, GAD-7, K10 and SF-12 MCS were 6 (3, 9), 5 (2, 8), 19 (15, 25) and 43 (34, 49), respectively. Serum 25OHD levels were not associated with mental health scores. Vitamin D status was not associated with a reported diagnosis of depression or anxiety. LIMITATIONS: There was a low prevalence of severe vitamin D deficiency and mental health symptoms, which may reduce study power. CONCLUSION: Our findings do not support an association between serum 25OHD levels and mental health status in young women. Longitudinal studies and randomized clinical trials investigating vitamin D and mood in young women are needed to confirm and extend these results.

Vitamin D Status, Bone Mineral Density and Mental Health in Young Australian Women: The Safe-D Study.

BACKGROUND: Vitamin D deficiency has been associated with both poor bone health and mental ill-health. More recently, a number of studies have found individuals with depressive symptoms tend to have reduced bone mineral density. To explore the interrelationships between vitamin D status, bone mineral density and mental-ill health we are assessing a range of clinical, behavioural and lifestyle factors in young women (Part A of the Safe-D study). DESIGN AND METHODS: Part A of the Safe-D study is a cross-sectional study aiming to recruit 468 young females aged 16-25 years living in Victoria, Australia, through Facebook advertising. Participants are required to complete an extensive, online questionnaire, wear an ultra-violet dosimeter for 14 consecutive days and attend a study site visit. Outcome measures include areal bone mineral measures at the lumbar spine, total hip and whole body, as well as soft tissue composition using dual energy x-ray absorptiometry. Trabecular and cortical volumetric bone density at the tibia is measured using peripheral quantitative computed tomography. Other tests include serum 25-hydroxyvitamin D, serum biochemistry and a range of health markers. Details of mood disorder/s and depressive and anxiety symptoms are obtained by self-report. Cutaneous melanin density is measured by spectrophotometry. EXPECTED IMPACT: The findings of this cross-sectional study will have implications for health promotion in young women and for clinical care of those with vitamin D deficiency and/or mental ill-health. Optimising both vitamin D status and mental health may protect against poor bone health and fractures in later life. Significance for public healthVitamin D deficiency, depression and osteoporosis are all major public health issues. Vitamin D deficiency has been associated with both reduced bone mineral density and depressive symptoms. Moreover, cohort studies have found that subjects with depression have lower bone mineral density when compared to healthy controls. Early adulthood is a critical time in young woman's lives as their independence, behaviours and lifestyle choices are established. These choices made as a young adult lay down the foundation for future health trajectories for not only for themselves but also for their potential partners and families. Addressing vitamin D deficiency, poor bone health and mental ill-health at a younger age may ultimately improve their wellbeing, productivity and long-term health outcomes. This study is of particular significance as the interplay between vitamin D, depression and bone health is currently uncertain and such knowledge is crucial for understanding, prevention and treatment of these conditions.

How best to interpret mixed human papillomavirus genotypes in high-grade cervical intraepithelial neoplasia lesions.

OBJECTIVES: This study aimed to determine human papillomavirus (HPV) genotypes present in biopsy sections from young women of vaccine eligible age living in Victoria, Australia, with confirmed cervical intraepithelial neoplasia grade 3 (CIN3) or adenocarcinoma in situ (AIS) using laser capture microdissection (LCM). METHODS: Histologically confirmed CIN3 or AIS positive biopsies from vaccine eligible women (born after 30th June 1981, n=169), between May 2011 and March 2013, were identified. CIN3 or AIS lesions were isolated from biopsy material using LCM, and the HPV genotypes present in whole tissue sections (WTS) as well as LCM-isolated lesion tissue were determined by a sensitive reverse hybridisation assay; RHA kit HPV SPF10-LiPA25, version 1 (Labo Bio-medical Products, Rijswijk, The Netherlands). RESULTS: One hundred and sixty-eight cases were shown to be HPV positive (99%), of which 20 (12%) had more than one HPV genotype detected using WTS-PCR. Evaluation by LCM of individual biopsies with mixed infections showed 18 cases (90%) had only one HPV genotype associated with each CIN3 lesion. HPV 16 was the most common HPV type, found in 95/168 cases (57%). CONCLUSION: LCM-PCR allowed us to confirm the presence of a single HPV genotype associated with each biologically separate CIN3 lesion, supporting the theory that only one virus type causes each independent CIN lesion. LCM will provide an important tool in assessing vaccine effectiveness in HPV vaccine programs.