Vitamin D intakes among women living with and without HIV in Canada.

BACKGROUND: Patterns of vitamin D intake are relatively unexplored among women living with HIV, despite its importance for women's health. We compared vitamin D dietary and supplement intakes in women with HIV and population-based national controls and investigated barriers to intake. METHODS: In this case-control study, women with HIV in the Children and Women: AntiRetrovirals and Markers of Aging (CARMA) cohort were matched with Canadian Multicentre Osteoporosis Study (CaMos) controls. Participants were queried for vitamin D in dairy consumption, supplementation/dosage, and sociodemographic variables. We assessed barriers to supplementation and factors associated with dietary intake by regression modelling. RESULTS: Ninety-five women living with HIV were age-matched to 284 controls. Women with HIV had lower income and bone mineral density and were more likely to smoke, take multiple medications and be non-white. Vitamin D dietary intake was lower in women living with HIV versus controls [0.76 vs. 1.79 µg/day; adjusted odds ratio (aOR) for greater than or equal to median intake 0.29 (0.12-0.61), p = 0.002], but any supplementation was higher [62.2% vs. 44.7%; aOR = 3.44 (95% CI: 1.16-11.00), p = 0.03]. Total vitamin D intake was similar between groups. Smoking was associated with no supplementation; non-white ethnicity and low income were related to lower dietary intake. CONCLUSIONS: Women living with HIV showed lower dietary vitamin D intake but higher supplementation rates, suggesting that care providers are promoting supplementation. Women living with HIV who smoke, have low incomes and are non-white may particularly benefit from targeted efforts to improve vitamin D intake.

Combined hormonal contraceptive use is not protective against musculoskeletal conditions or injuries: a systematic review with data from 5 million females.

OBJECTIVE: Assess the association between combined hormonal contraceptives (CHC) use and musculoskeletal tissue pathophysiology, injuries or conditions. DESIGN: Systematic review with semiquantitative analyses and certainty of evidence assessment, guided by the Grading of Recommendations Assessment, Development and Evaluation approach. DATA SOURCES: MEDLINE, EMBASE, CENTRAL, SPORTDiscus, CINAHL searched from inception to April 2022. ELIGIBILITY: Intervention and cohort studies that assessed the association between new or ongoing use of CHC and an outcome of musculoskeletal tissue pathophysiology, injury or condition in postpubertal premenopausal females. RESULTS: Across 50 included studies, we assessed the effect of CHC use on 30 unique musculoskeletal outcomes (75% bone related). Serious risk of bias was judged present in 82% of studies, with 52% adequately adjusting for confounding. Meta-analyses were not possible due to poor outcome reporting, and heterogeneity in estimate statistics and comparison conditions. Based on semiquantitative synthesis, there is low certainty evidence that CHC use was associated with elevated future fracture risk (risk ratio 1.02-1.20) and total knee arthroplasty (risk ratio 1.00-1.36). There is very low certainty evidence of unclear relationships between CHC use and a wide range of bone turnover and bone health outcomes. Evidence about the effect of CHC use on musculoskeletal tissues beyond bone, and the influence of CHC use in adolescence versus adulthood, is limited. CONCLUSION: Given a paucity of high certainty evidence that CHC use is protective against musculoskeletal pathophysiology, injury or conditions, it is premature and inappropriate to advocate, or prescribe CHC for these purposes. PROSPERO REGISTRATION NUMBER: This review was registered on PROSPERO CRD42021224582 on 8 January 2021.

Assessing the role of adolescent hormonal contraceptive use on risk for depression: a 3-year longitudinal study protocol.

BACKGROUND: The incidence of depression in human females rises steadily throughout adolescence, a critical period of pubertal maturation marked by increasing levels of gonadal hormones including estrogens and progesterone. These gonadal hormones play a central role in social and emotional development and may also contribute to the increased occurrence of depression in females that begins in early adolescence. In this study, we examine whether and how introducing synthetic estrogen and progestin derivatives through the use of combined hormonal contraceptives (CHC), affects adolescent females' risk for developing depression. We further assess potential links between CHC use and alterations in stress responses and social-emotional functioning. METHODS: Using a longitudinal cohort design, we will follow a sample of adolescent females over the span of three years. Participants will be assessed at three time points: once when they are between 13 and 15 years of age, and at approximately 18 and 36 months after their initial assessment. Each time point will consist of two online sessions during which participants will complete a clinical interview that screens for key symptoms of mental health disorders, along with a series of questionnaires assessing their level of depressive symptoms and history of contraceptive use. They will also complete a standardized social-evaluative stress test and an emotion recognition task, as well as provide saliva samples to allow for assessment of their circulating free cortisol levels. DISCUSSION: In this study we will assess the effect of CHC use during adolescence on development of Major Depressive Disorder (MDD). We will control for variables previously found to or proposed to partially account for the observed relationship between CHC use and MDD, including socioeconomic status, age of sexual debut, and CHC-related variables including age of first use, reasons for use, and its duration. In particular, we will discover whether CHC use increases depressive symptoms and/or MDD, whether elevated depressive symptoms and/or MDD predict a higher likelihood of starting CHC, or both. Furthermore, this study will allow us to clarify whether alterations in stress reactivity and social-emotional functioning serve as pathways through which CHC use may result in increased risk of depressive symptoms and/or MDD.

Factors associated with contraceptive use among women living with HIV in Canada: a controlled, cross-sectional study.

BACKGROUND: Multiple contraindications to combined hormonal contraceptives (CHC) use exist. The impact of these factors on contraceptive choice, particularly among women living with HIV (WLWH), is not well understood. We measured and compared the prevalence of contraceptive use and contraindications among WLWH and women not living with HIV (controls). METHODS: We examined cross-sectional survey and medical chart data from 83 WLWH and 62 controls, aged 16-49 and sexually active, from 2013-2017. We compared the age-adjusted prevalence and types of contraceptives used in the last month and the proportion of women with CHC contraindications, including drug interactions, medical comorbidities, and smoking at ≥ 35 years old. All WLWH received care at an interdisciplinary, women-centred HIV clinic. RESULTS: Compared to controls, WLWH were older (median [IQR)] 39 [34-43] vs 31 [23-41] years; p = 0.003), had less post-secondary education (37% vs 73%; p < 0.001), and more often had household income < $15,000/year (49% vs 30%; p = 0.006). WLWH trended to higher contraceptive prevalence than controls (80% vs 63%; p = 0.06 adjusted for age). Overall hormonal contraceptive use was similar. However, despite controlling for age, WLWH used CHC less (4% vs 18%; p = 0.006) than controls, and had more frequently undergone tubal ligation (12% vs 2%; p = 0.03). WLWH also experienced more CHC contraindications (54% vs 13%; p = 0.0001), including smoking at ≥ 35 years old (30% vs 6%; p = 0.0003) or a CHC-related drug interaction (all antiretroviral related) (25% vs 0%; p = 0.0001). CONCLUSIONS: WLWH attending our interdisciplinary clinic used hormonal contraception at similar rates as controls, though with different types. Differences may reflect different distributions of CHC contraindications. CHC contraindications present barriers to accessing the full range of contraceptive choices for WLWH. Guidelines and education for care providers and WLWH regarding contraceptive choices and drug interactions are needed, especially when care is provided without the benefit of an interdisciplinary women-centered healthcare team.

BACKGROUND: There are many reasons why individuals cannot use combined hormonal contraceptives (CHC). The impact of these reasons on contraceptive choice for women living with HIV (WLWH) are poorly understood. We measured and compared the prevalence of contraceptive choice and factors that may preclude their use in WLWH. METHODS: We examined survey and medical chart data from 83 WLWH and 62 controls (women not living with HIV), aged 16­49 and sexually active, from 2013 to 2017. We compared the prevalence and types of contraceptives used in the last month and the proportion of women with factors that would not allow the use of CHC, including drug interactions, medical conditions, and smoking at ≥ 35 years old. All WLWH received care at a women-centred HIV clinic. RESULTS: Compared to controls, WLWH were older, had less post-secondary education, and more often had household income < $15,000/year. WLWH were more likely to use contraception than controls. Overall hormonal contraceptive use was similar. However, even when accounting for age, WLWH used CHC less than controls, and had more frequently undergone tubal ligation. WLWH also had more reasons that would preclude the use of CHC contraindications including smoking at ≥ 35 years old or a CHC-related drug interaction. CONCLUSIONS: WLWH attending our interdisciplinary clinic used combined hormonal contraception at similar rates as controls, though with different types. Differences may reflect the fact that WLWH more often have factors that do not allow the safe use of CHC. Guidelines and education for care providers and WLWH regarding contraceptive choices and drug interactions are needed.

Vertebral Fractures: Which Radiological Criteria Are Better Associated With the Clinical Course of Osteoporosis?

STUDY PURPOSE: Morphometric methods categorize potential osteoporotic vertebral fractures (OVF) on the basis of loss of vertebral height. A particular example is the widely used semiquantitative morphometric tool proposed by Genant (GSQ). A newer morphologic algorithm-based qualitative (mABQ) tool focuses on vertebral end-plate damage in recognizing OVF. We used data from both sexes in the Canadian Multicentre Osteoporosis Study (CaMos) to compare the 2 methods in identifying OVF at baseline and during 10 years of follow-up. MATERIALS AND METHODS: We obtained lateral thoracic and lumbar spinal radiographs (T4-L4) 3 times, at 5-year intervals, in 828 participants of the population-based CaMos. Logistic regressions were used to study the association of 10-year changes in bone mineral density (BMD) with incident fractures. RESULTS: At baseline, 161 participants had grade 1 and 32 had grade 2 GSQ OVF; over the next 10 years, only 9 of these participants had sustained incident GSQ OVF. Contrastingly, 21 participants at baseline had grade 1 and 48 grade 2 mABQ events; over the next 10 years, 79 subjects experienced incident grade 1 or grade 2 mABQ events. Thus, incident grades 1 and 2 morphologic fractures were 8 times more common than morphometric deformities alone. Each 10-year decrease of 0.01 g/cm2 in total hip BMD was associated with a 4.1% (95% CI: 0.7-7.3) higher odds of having an incident vertebral fracture. CONCLUSIONS: This analysis further suggests that morphometric deformities and morphologic fractures constitute distinct entities; morphologic fractures conform more closely to the expected epidemiology of OVF.

Cyclic Progesterone Therapy in Androgenic Polycystic Ovary Syndrome (PCOS)-A 6-Month Pilot Study of a Single Woman's Experience Changes.

Background and Objectives: Women with androgenic Polycystic Ovary Syndrome (PCOS) have increased endometrial cancer risk that cyclic progesterone will prevent; it may also reverse PCOS's neuroendocrine origins. This pilot study's purpose was to document 6-month experience changes in a woman with PCOS taking cyclic progesterone therapy because she was intolerant of combined hormonal contraceptive therapy, the current PCOS standard of care. A 31-year-old normal-weight woman with PCOS had heavy flow, irregular cycles, and was combined hormonal contraceptives-intolerant. She was prescribed cyclic oral micronized progesterone (OMP) (300 mg/h.s. cycle days 14-27). She kept Menstrual Cycle Diary© (Diary) records, starting with the 1st treatment cycle for six cycles; she was on no other therapy. Statistical analysis a priori hypothesized progesterone decreases high estradiol (E2) experiences (flow, cervical mucus, fluid retention, front-of-the-breast tenderness and anxiety); analysis focused on these. Our objectives: (1) changes from cycles 1 to 6 in E2-related experiences; and (2) follicular phase E2-related changes from cycle 1 (no therapy) to cycles 3 and 6. Materials and Methods: Data from consecutive Diaries were entered into an SPSS database and analyzed by Wilcoxon Signed Rank Test (Objective #1) within-person whole cycle ordinal data, and (Objective #2 follicular phase) repeated measures ANOVA. Results: Cyclic OMP was associated with regular, shorter cycles (±SD) (28.2 ± 0.8 days). Comparison of cycles 1-6 showed decreased fluid retention (p = 0.001), breast tenderness (p = 0.002), and cervical mucus (p = 0.048); there were no changes in flow or anxiety. Fluid retention in the follicular phase also significantly decreased over time (F (1.2, 14.7) = 6.7, p = 0.017). Conclusions: Pilot daily Diary data suggest women with PCOS have improved everyday experiences on cyclic progesterone therapy. Larger prospective studies with more objective outcomes and randomized controlled trials of this innovative PCOS therapy are needed.

Adolescent use of combined hormonal contraception and peak bone mineral density accrual: A meta-analysis of international prospective controlled studies.

OBJECTIVE: Many women use combined hormonal contraceptives (CHC) during adolescence during which they are accruing peak areal bone mineral density (BMD) that relates to lifetime fracture risk. To build BMD requires formation with which CHC-related exogenous oestrogen may interfere. We compared peak BMD accrual in adolescents using and not using CHC. DESIGN/PARTICIPANTS: We performed literature searches for prospective published peer-reviewed articles providing 12- to 24-month BMD change in adolescent (12- to 19-year-old) women using CHC vs CHC-unexposed control women. METHODS: Meta-analyses used random-effects models to assess BMD change rate at lumbar spine (LS) and other sites in adolescent CHC users vs CHC nonusers. RESULTS: Literature searches yielded 84 publications of which nine were eligible. Adolescent-only data were sought from cohorts with wider age inclusions. The 12-month LS meta-analysis with eight paired comparisons in 1535 adolescents showed a weighted mean BMD difference of -0.02 (95% confidence interval [CI]: -0.05 to 0.00) g/cm2 in CHC-exposed adolescents (P = 0.04). The 24-month LS meta-analysis with five paired comparisons in 885 adolescents showed a highly significant weighted mean BMD difference of -0.02 (95% CI: -0.03 to -0.01) g/cm2 in CHC-exposed adolescents (P = 0.0006). Heterogeneities by I2 were 96% and 85%, respectively. Insufficient data for other bone sites precluded quantitative analysis. CONCLUSION: Given that adolescent exposure to CHC appears to be increasing, this evidence for potential impairment of peak spinal BMD accrual is of concern and suggests a potential public health problem. Randomized controlled trial data are needed to determine CHC effects on adolescent bone health.

Combined hormonal contraceptives use and bone mineral density changes in adolescent and young women in a prospective population-based Canada-wide observational study.

OBJECTIVES: To assess combined hormonal contraceptives (CHC) use and adolescent women's peak areal bone mineral density (BMD) accrual. METHODS: We enrolled 527 randomly selected women across Canada (2004-6) divided by age into adolescents (16-19) and young adults (20-24) and by CHC use to ever (E-CHC)/never (N-CHC) users. At baseline and year 2 we measured height, weight, and BMD at lumbar spine (L1-4), femoral neck, and total hip sites. Interviewer-administered questionnaires addressed menarche age, cigarette and alcohol use, calcium/vitamin D intakes, physical activity and estrogen dose (≤30/>30 micrograms). Linear regression models examined associations of CHC use with 2-year BMD change adjusted for bone-related variables. RESULTS: Of 307 women with complete data, 229 (75%) used CHC. N-CHC adolescents gained significantly more unadjusted total hip BMD +0.012 g/cm2/2-y (95% C.I.: 0.001, 0.023) with similar trends at all sites. N-CHC adolescents tended to have greater adjusted femoral neck BMD gain: mean difference +0.009 g/cm2 (95% CI: -0.002; 0.021). In young women N-CHC, however, adjusted femoral neck BMD decreased significantly more -0.021 g/cm2 (95%CI: -0.006; -0.036) with similar trends at other sites. BMD changes were unrelated to estrogen dose and age at starting CHC. CONCLUSIONS: Adolescent CHC users in a random population demonstrated less hip region peak BMD accrual than non-users. This requires randomized control trial confirmation.

Endocrine abnormalities in HIV-infected women are associated with peak viral load - the Children and Women: AntiRetrovirals and Markers of Aging (CARMA) Cohort.

OBJECTIVES: To investigate the prevalence of endocrine disturbances in a group of HIV-positive (HIV+) women and to identify factors affecting presence of these disorders. To examine specifically whether cellular ageing, as measured by leukocyte telomere length (LTL), is correlated with the presence of endocrine disturbance. DESIGN: A cross-sectional retrospective substudy of an ongoing prospective cohort study. PATIENTS: Adult HIV+ (≥19 years) women enrolled in the CARMA (Children and Women: AntiRetrovirals and Markers of Aging) cohort study (N = 192). Prevalences of T2DM, glucose intolerance, dyslipidaemia, thyroid disorders, adrenal insufficiency, hypogonadism, primary ovarian insufficiency (POI), demographics, HIV and hepatitis C virus (HCV) infection status, baseline LTL, combined antiRetroviral therapy (cART) and substance exposures were collected. Statistical analysis included univariable followed by multivariable Poisson regression and step-wise reduction to refine the multivariable model. RESULTS: Prevalence of any endocrine abnormality was 58% (dyslipidaemia 43%, glucose intolerance/T2DM 13%, thyroid disorders 15%). In multivariable analysis, age was associated with number and type (any, glucose, lipid) of abnormality, while increasing body mass index (BMI) was associated with number of diagnoses and with glucose metabolism disorders. Interestingly, peak HIV pVL ≥100 000 copies/ml was associated with any abnormality, total number of disorders and presence of a thyroid disorder, while any disorder, glucose abnormalities and dyslipidaemia were negatively associated with alcohol use. LTL was not associated with number or type of endocrine abnormalities in this study. CONCLUSION: Further studies examining the relationship between duration and extent of exposure to HIV viraemia in relation to developing abnormal endocrine function are warranted.

Negative spinal bone mineral density changes and subclinical ovulatory disturbances--prospective data in healthy premenopausal women with regular menstrual cycles.

Subclinical ovulatory disturbances (anovulation or short luteal phases within normal-length menstrual cycles) indicate lower progesterone-to-estrogen levels. Given that progesterone plays a bone formation role, subclinical ovulatory disturbances may be associated with bone loss or less than expected bone gain. Our purpose was to perform a meta-analysis of prospective studies in healthy premenopausal women to determine the overall relationship of subclinical ovulatory disturbances to change in bone mineral density. Two reviewers independently identified from serial literature searches 6 studies meeting inclusion criteria: a 2-year study in 114 young adult women, 2006-2009, Vancouver, Canada; a 2-year study in 189 premenopausal women, 2000-2005, Toronto, Canada; a single-cycle study in 14 young women, 1996-1997, Melbourne, Australia; an 18-month study in 53 women, 1990-1995, Santa Clara, California; a 4-year study in 27 women, 1988-1995, Vancouver, Canada; and a 1-year study in 66 women, 1985-1988, Vancouver, Canada. This meta-analysis included a combined sample size of 473 observations in 436 premenopausal women studied over 1-4 years and aged 14-47 years. The percentage of women with ovulatory disturbances varied significantly from 13% to 82%. Women with more frequent ovulatory disturbances had more negative percentage changes in spine bone mineral density (weighted mean difference = -0.86; P = 0.040) for random-effects analysis. There was significant heterogeneity among these 6 studies (I(2) = 80%). In summary, these data show that regularly menstruating women with more frequent ovulatory disturbances experience more negative changes in bone (approximately -0.9% per year). These cycles with silent estrogen/progesterone imbalance may be clinically important.

Prospectively measured 10-year changes in health-related quality of life and comparison with cross-sectional estimates in a population-based cohort of adult women and men.

PURPOSE: To prospectively assess changes in health-related quality of life (HRQOL) over 10 years, by age and sex, and to compare measured within-person change to estimates of change based on cross-sectional data. METHODS: Participants in the Canadian Multicentre Osteoporosis Study completed the 36-item short form (SF-36) in 1995/1997 and 2005/2007. Mean within-person changes for domain and summary components were calculated for men and women separately, stratified by 10-year age groups. Projected changes based on published age- and sex-stratified cross-sectional data were also calculated. Mean differences between the two methods were then estimated, along with the 95 % credible intervals of the differences. RESULTS: Data were available for 5,569/9,423 (59.1 %) of the original cohort. Prospectively collected 10-year changes suggested that the four physically oriented domains declined in all but the youngest group of men and women, with declines in the elderly men exceeding 25 points. The four mentally oriented domains tended to improve over time, only showing substantial declines in vitality and role emotional in older women, and all four domains in older men. Cross-sectional estimates identified a similar pattern of change but with a smaller magnitude, particularly in men. Correspondence between the two methods was generally high. CONCLUSIONS: Changes in HRQOL may be minimal over much of the life span, but physically oriented HRQOL can decline substantially after middle age. Although clinically relevant declines were more evident in prospectively collected data, differences in 10-year age increments of cross-sectional data may be a reasonable proxy for longitudinal changes, at least in those under 65 years of age. Results provide additional insight into the natural progression of HRQOL in the general population.

Longitudinal Assessment of Bone Mineral Density in Women Living With and Without HIV Across Reproductive Phases.

BACKGROUND: Women living with HIV commonly experience low areal bone mineral density (BMD), but whether this is affected by low ovarian hormonal states (prolonged amenorrhea or menopause) is unknown. We compared rates of BMD loss between women living with HIV and HIV-negative control women and investigated its association with low ovarian hormonal states. SETTING: Women living with HIV were enrolled from Vancouver Canada and controls from 9 Canadian sites. METHODS: This longitudinal analysis included age-matched women living with HIV in the Children and Women: AntiRetrovirals and Markers of Aging cohort and controls in the population-based Canadian Multicentre Osteoporosis Study. Rate of change/year in BMD at the total hip and lumbar spine (L1-L4) between 3 and 5 years was compared between groups, adjusting for sociodemographic and clinical variables. RESULTS: Ninety-two women living with HIV (median [interquartile range] age: 49.5 [41.6-54.1] years and body mass index: 24.1 [20.7-30.8] kg/m 2 ) and 278 controls (age: 49.0 [43.0-55.0] years and body mass index: 25.8 [22.9-30.6] kg/m 2 ) were included. Total hip BMD loss was associated with HIV (ß: -0.003 [95% CI: -0.006 to -0.0001] g/cm 2 /yr), menopause (ß: -0.007 [-0.01 to -0.005] g/cm 2 /yr), and smoking (ß: -0.003 [-0.006 to -0.0002] g/cm 2 /yr); BMD gain was linked with higher body mass index (ß: 0.0002 [0.0007-0.0004] g/cm 2 /yr). Menopause was associated with losing L1-L4 BMD (ß: -0.01 [-0.01 to -0.006] g/cm 2 /yr). Amenorrhea was not associated with BMD loss. CONCLUSIONS: HIV and menopause negatively influenced total hip BMD. These data suggest women living with HIV require hip BMD monitoring as they age.

Sedentary behavior does not predict low BMD nor fracture-population-based Canadian Multicentre Osteoporosis Study.

Sedentary behavior (SB) or sitting is associated with multiple unfavorable health outcomes. Bone tissue responds to imposed gravitational and muscular strain with there being some evidence suggesting a causal link between SB and poor bone health. However, there are no population-based data on the longitudinal relationship between SB, bone change, and incidence of fragility fractures. This study aimed to examine the associations of sitting/SB (defined as daily sitting time), areal BMD (by DXA), and incident low trauma (fragility) osteoporotic fractures (excluding hands, feet, face, and head). We measured baseline (1995-7) and 10-yr self-reported SB, femoral neck (FN), total hip (TH), and lumbar spine (L1-L4) BMD in 5708 women and 2564 men aged 25 to 80+ yr from the population-based, nationwide, 9-center Canadian Multicentre Osteoporosis Study. Incident 10-yr fragility fracture data were obtained from 4624 participants; >80% of fractures were objectively confirmed by medical records or radiology reports. Vertebral fractures were confirmed by qualitative morphological methods. All analyses were stratified by sex. Multivariable regression models assessed SB-BMD relationships; Cox proportional models were fit for fracture risk. Models were adjusted for age, height, BMI, physical activity, and sex-specific covariates. Women in third/fourth quartiles had lower adjusted FN BMD versus women with the least SB (first quartile); women in the SB third quartile had lower adjusted TH BMD. Men in the SB third quartile had lower adjusted FN BMD than those in SB first quartile. Neither baseline nor stable 10-yr SB was related to BMD change nor to incident fragility fractures. Increased sitting (SB) in this large, population-based cohort was associated with lower baseline FN BMD. Stable SB was not associated with 10-yr BMD loss nor increased fragility fracture. In conclusion, habitual adult SB was not associated with subsequent loss of BMD nor increased risk of fracture.

The number of hours of sitting in a day (often called "sedentary behavior") is currently understood to be "bad for bone health" both because of increased bone loss and a higher risk for fractures. Very few studies in randomly sampled men and women from a whole population have consistently asked about hours of sitting and examined baseline bone density. Fewer still have compared hours of sitting and its changes over 10 yr with changes in bone density and the number of new fractures that occurred. The Canadian Multicentre Osteoporosis Study obtained sitting hours from 5708 women and 2564 men aged 25 to 80+ yr and compared it with the spine, total hip (TH), and femoral neck (FN) bone density values. The average sitting at 7.4 h in men was associated with slightly lower adjusted femoral neck bone density; in women, sitting 6.7 h/d was associated with slightly lower adjusted FN and TH bone density. Ten-year follow-up data (now in about 5000 people) showed no relationship between the slightly longer sitting (an increase of 18% in men and 22% in women) and bone loss or new bone fractures. In this large country-wide population-based study, hours of sitting each day were not associated with 10-yr BMD loss in women or men nor did sitting more associate with new bone fractures. These data are reassuring; women and men who walk regularly and have some moderate-vigorous physical activity each day, despite more sitting, do not seem to be at greater risk for osteoporosis.

Bone health and prevalent fractures in women with polycystic ovary syndrome: a meta-analysis and endocrine-context pathophysiology review.

INTRODUCTION: Bone health in those with Polycystic Ovary Syndrome (PCOS) is complex, but the general consensus is that cortical areal bone mineral density (aBMD) sites will be higher in PCOS than in age- and BMI-similar controls. However, spine aBMD sites may be lower, especially in non-obese PCOS. Whether or not incident fracture risk is increased in PCOS is currently controversial; no meta-analysis has yet assessed prevalent fractures. AREAS COVERED: We assessed the bone effects of PCOS-related ovarian hormone alterations, e.g. androgen excess, tonically normal/higher estradiol, and lower-than-normal progesterone levels. We also highlighted evidence that common PCOS medications (e.g. combined hormonal contraceptives [CHC], metformin, and spironolactone) have important bone effects. In adolescents, meta-analysis of CHC showed significant negative aBMD changes. Inflammation has negative PCOS bone effects and is linked with CHC use. EXPERT OPINION: Is fracture risk altered by PCOS? Our meta-analysis showed a 25% increased risk of prevalent fracture in PCOS versus controls; this did not reach statistical significance. Future prospective research needs to collect and evaluate ovulation characteristics, progesterone exposure, and adolescent CHC use, in addition to the complex variables that may influence risks for prevalent or incident fragility fractures and/or for cortical and cancellous aBMD values in PCOS.

Experiences of women living with Polycystic Ovary Syndrome: A pilot case-control, single-cycle, daily Menstrual Cycle Diary study during the SARS-CoV-2 pandemic.

Polycystic Ovary Syndrome (PCOS) affects many people and is often distressing. Much medical literature about diagnosis and treatment exists, but little is known about PCOS menstrual cycle-related experiences except that cycles tend to be far-apart and unpredictable. Our purpose was to examine the menstrual cycle and daily life experiences in those with PCOS having approximately month-apart cycles compared with age and BMI-matched cohort controls using data from the Menstruation & Ovulation Study 2 (MOS2) during the first 1.5 years of SARS-CoV-2 pandemic. We hypothesized that those with PCOS would experience lower self-worth and more negative moods. This is a single-cycle prospective case-control study in community-dwelling women ages 19-35 years. Eight reported physician-diagnosed PCOS and were matched (1:3 ratio) with controls by age (within .6 years) and BMI (within .19 BMI units). Experiences were recorded daily (Menstrual Cycle Diary©, Diary). All kept daily morning temperatures to assess luteal phase lengths by the validated Quantitative Basal Temperature© analysis method. From 112 in MOS2, 32 women were compared: eight with PCOS versus 24 controls. Demographic, socioeconomic, comorbidities and lifestyle variables were not different between the two groups. Cycle lengths were similar in PCOS and controls (one PCOS and control each had oligomenorrhea; most lengths were 21-35 days, P = .593). Unexpectedly, luteal phase lengths were also similar between PCOS and controls (P = .167); anovulation occurred in 5 with PCOS, and in 9 controls. There were no significant Diary differences between the two groups except for greater "outside stress" in the PCOS group (P = .020). In contrast to our hypotheses, there were no significant differences in feelings of self-worth, anxiety nor depression. The SARS-CoV-2 pandemic was a stressful time for women. MOS2 captured granular menstrual cycles, ovulation and daily experiences in women with PCOS compared with age- and BMI-matched controls. These pilot data in women with milder PCOS are the first of more research required to understand the daily experiences in those living with PCOS.

Oral micronized progesterone for perimenopausal night sweats and hot flushes a Phase III Canada-wide randomized placebo-controlled 4 month trial.

This study tested progesterone for perimenopausal hot flush ± night sweat (vasomotor symptom, VMS) treatment. It was a double-blind, randomized trial of 300 mg oral micronized progesterone@bedtime versus placebo for 3-months (m) after a 1-m untreated baseline during 2012/1-2017/4. We randomized untreated, non-depressed, screen- and baseline-eligible by VMS, perimenopausal women (with flow within 1-year), ages 35-58 (n = 189). Participants aged 50 (± SD = 4.6) were mostly White, educated, minimally overweight with 63% in late perimenopause; 93% participated remotely. The 1° outcome was 3rd-m VMS Score difference. Participants recorded VMS number and intensity (0-4 scale)/24 h on a VMS Calendar. Randomization required VMS (intensity 2-4/4) of sufficient frequency and/or ≥ 2/week night sweat awakenings. Baseline total VMS Score (SD) was 12.2 (11.3) without assignment difference. Third-m VMS Score did not differ by therapy (Rate Difference - 1.51). However, the 95% CI [- 3.97, 0.95] P = 0.222, did not exclude 3, a minimal clinically important difference. Women perceived progesterone caused decreased night sweats (P = 0.023) and improved sleep quality (P = 0.005); it decreased perimenopause-related life interference (P = 0.017) without increased depression. No serious adverse events occurred. Perimenopausal night sweats ± hot flushes are variable; this RCT was underpowered but could not exclude a minimal clinically important VMS benefit. Perceived night sweats and sleep quality significantly improved.

Long-Term Change in Bone Mineral Density in Women Living With HIV: A 10-Year Prospective Controlled Cohort Study.

Women living with HIV (WLWH) may be at higher risk for osteoporosis and fragility fractures. However, limited prospective data describe long-term trajectories of bone mineral density (BMD) in WLWH versus women without HIV. Thus, in this prospective study, we aimed to compare 10-year change in areal BMD (aBMD) between WLWH (n = 49; 36.8 ± 8.8 years; 96% pre/perimenopausal) and HIV-negative women (population-based controls; n = 49; 41.9 ± 9.2 years; 80% pre/perimenopausal). In an exploratory analysis, we compared fracture history between WLWH and controls. Outcomes were lumbar spine (L1 to L4), total hip, and femoral neck aBMD at baseline and follow-up, which occurred at 13 and 10 years in WLWH and controls, respectively. We fit multivariable regression models to compare baseline and 10-year change in aBMD between groups, adjusting for osteoporosis risk factors. Within WLWH, we examined associations between aBMD and HIV-related factors, including combination antiretroviral therapy (cART) duration. WLWH were diagnosed 6.5 ± 3.7 years before baseline, 80% were on cART for 241 ± 142 weeks, and 49% had HIV plasma viral load <40 copies/mL. Before and after adjusting for osteoporosis risk factors, baseline and 10-year change in aBMD did not differ between WLWH and controls at any site. At baseline, more WLWH than controls reported a history of low-trauma fracture (30% versus 10%, p < 0.05) and major osteoporotic fracture (17% versus 4%, p < 0.05). During follow-up, the number of WLWH and controls with incident fragility fracture was not significantly different. Lifetime cART duration and tenofovir use were not associated with aBMD 10-year percent change. Higher CD4 count at baseline was positively associated with femoral neck aBMD 10-year percent change. Long-term aBMD change in this small WLWH cohort paralleled normal aging, with no evidence of influence from cART use; however, these results should be interpreted with caution given the small sample size. Larger cohort studies are needed to confirm these findings. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Lower anti-Müllerian hormone levels are associated with HIV in reproductive age women and shorter leukocyte telomere length among late reproductive age women.

OBJECTIVES: We sought to better understand factors associated with ovarian aging in women with HIV (WWH). DESIGN: HIV has been associated with diminished fertility, younger age at menopause, and shorter leukocyte telomere length (LTL), a marker of cellular aging. We herein examine cross-sectional and longitudinal associations between LTL, anti-Müllerian hormone (AMH), and HIV. METHODS: We included WWH and HIV-negative women 12-50 years of age in the CARMA cohort with one or more study visit(s). LTL and AMH were measured by qPCR and ELISA, respectively. Women were analyzed in peak reproductive (<35 years) vs. late reproductive (≥35 years) life phases. Using multivariable mixed-effect linear or logistic regressions, we assessed factors associated with AMH and ΔAMH/year while adjusting for relevant confounders. RESULTS: WWH had shorter LTL and lower AMH levels compared to HIV-negative controls despite being of similar age. After adjusting for relevant factors, HIV was associated with 20% lower AMH levels in women under 35 years of age and shorter LTL was associated with AMH levels below 2 ng/ml among women aged 35 years or older. Longitudinally, ΔAMH/year was largely related to initial AMH level among older women, and to age in younger women. CONCLUSIONS: Factors associated with AMH change across women's reproductive lifespan. Lower AMH among peak reproductive aged WWH suggests that HIV may have an initial detrimental effect on ovarian reserve, an observation that may warrant counseling around pregnancy planning. In women aged 35 years or older, the association between shorter LTL and lower AMH suggests that the immune and reproductive aging connections are more important in this age group.