Vitamin D and prebiotics for intestinal health in cystic fibrosis: Rationale and design for a randomized, placebo-controlled, double-blind, 2 x 2 trial of administration of prebiotics and cholecalciferol (vitamin D3) (Pre-D trial) in adults with cystic fibrosis.

Individuals with cystic fibrosis (CF) have dysfunctional intestinal microbiota and increased gastrointestinal (GI) inflammation also known as GI dysbiosis. It is hypothesized that administration of high-dose cholecalciferol (vitamin D3) together with a prebiotic (inulin) will be effective, and possibly additive or synergistic, in reducing CF-related GI and airway dysbiosis. Thus, a 2 x 2 factorial design, placebo-controlled, double-blinded, pilot and feasibility, clinical trial was proposed to test this hypothesis. Forty adult participants with CF were block-randomized into one of four groups: 1) high-dose oral vitamin D3 (50,000 IU weekly) plus oral prebiotic placebo daily; 2) oral prebiotic (12 g inulin daily) plus oral placebo vitamin D3 weekly; 3) combined oral vitamin D3 weekly and oral prebiotic inulin daily; and 4) oral vitamin D3 placebo weekly and oral prebiotic placebo. The primary endpoints included 12-week changes in the microbial bacterial communities, gut and airway microbiota richness and diversity before and after the intervention. This pilot study examined whether vitamin D3 with or without prebiotics supplementation was feasible, changed airway and gut microbiota, and reduced dysbiosis, which in turn, may improve health outcomes and quality of life of patients with CF.

Vitamin D for glycemic control following an acute pulmonary exacerbation: A secondary analysis of a multicenter, double-blind, randomized, placebo-controlled trial in adults with cystic fibrosis.

Individuals with cystic fibrosis (CF) often incur damage to pancreatic tissue due to a dysfunctional cystic fibrosis transmembrane conductance regulator (CFTR) protein, leading to altered chloride transport on epithelial surfaces and subsequent development of cystic fibrosis-related diabetes (CFRD). Vitamin D deficiency has been associated with the development of CFRD. This was a secondary analysis of a multicenter, double-blind, randomized, placebo-controlled study in adults with CF hospitalized for an acute pulmonary exacerbation (APE), known as the Vitamin D for the Immune System in Cystic Fibrosis (DISC) trial (NCT01426256). This was a pre-planned secondary analysis to examine if a high-dose bolus of cholecalciferol (vitamin D3) can mitigate declined glucose tolerance commonly associated with an acute pulmonary exacerbation (APE). Glycemic control was assessed by hemoglobin A1c (HbA1c) and fasting blood glucose levels before and 12 months after the study intervention. Within 72 hours of hospital admission, participants were randomly assigned to a single dose of oral vitamin D3 (250,000 IU) or placebo, and subsequently, received 50,000 IU of vitamin D3 or placebo every other week, beginning at month 3 and ending on month 12. Forty-nine of the 91 participants in the parent study were eligible for the secondary analysis. There were no differences in 12-month changes in HbA1c or fasting blood glucose in participants randomized to vitamin D or placebo. A high-dose bolus of vitamin D3 followed by maintenance vitamin D3 supplementation did not improve glycemic control in patients with CF after an APE.

Vitamin D and Prebiotics for Intestinal Health in Cystic Fibrosis: Rationale and design for a randomized, placebo-controlled, double-blind, 2 × 2 trial of administration of prebiotics and cholecalciferol (vitamin D3) (Pre-D Trial) in adults with cystic fibrosis.

Individuals with cystic fibrosis (CF) have dysfunctional intestinal microbiota and increased gastrointestinal (GI) inflammation also known as GI dysbiosis. It is hypothesized that administration of high-dose cholecalciferol (vitamin D3) together with a prebiotic (inulin) will be effective, and possibly additive or synergistic, in reducing CF-related GI dysbiosis and improving intestinal functions. Thus, a 2 × 2 factorial design, placebo-controlled, double-blind, clinical trial was proposed to test this hypothesis. Forty adult participants with CF will be block-randomized into one of four groups: 1) high-dose oral vitamin D3 (50,000 IU weekly) plus oral prebiotic placebo daily; 2) oral prebiotic (12 g inulin daily) plus oral placebo vitamin D3 weekly; 3) combined oral vitamin D3 weekly and oral prebiotic inulin daily; and 4) oral vitamin D3 placebo weekly and oral prebiotic placebo. The primary endpoints will include 12-week changes in the reduced relative abundance of gammaproteobacteria, and gut microbiota richness and diversity before and after the intervention. This clinical study will examine whether vitamin D3 with or without prebiotics will improve intestinal health and reduce GI dysbiosis, which in turn, should improve health outcomes and quality of life of patients with CF.

Changes in bone turnover after high-dose vitamin D supplementation during acute pulmonary exacerbation in cystic fibrosis.

In people with cystic fibrosis (CF), chronic inflammation and infection increase the risk for low bone mineral density and CF-related bone disease. During acute pulmonary exacerbations (APE), people with CF have increases in markers of bone resorption. Vitamin D has been proposed as a potential nutrient to lower inflammation. In this ancillary analysis of the Vitamin D for the Immune System in CF study, we hypothesized that vitamin D administered at the time of APE would have favorable changes on bone turnover markers compared to placebo. Participants with CF were randomized to receive a single dose of 250,000 IU of vitamin D or placebo during an APE and followed for 1 year for the primary outcome of APE or death after randomization. Bone turnover markers: C-terminal telopeptide (CTX-1) and procollagen type 1 intact N-terminal propetide (P1NP) were assessed at randomization (during APE) and after recovery from the APE in 45 participants. Participants randomized to vitamin D had significant decreases in markers of bone turnover; participants who received placebo had non-significant increases in markers of bone turnover. Vitamin D supplementation during an APE may help reduce the risk for CF-related bone disease.

Prevalence of self-inflicted injuries among transgender and gender diverse adolescents and young adults compared to their peers: an examination of interaction with mental health morbidity.

PURPOSE: Compare occurrence of self-inflicted injuries among transgender and gender diverse (TGD) youth to that of their cisgender peers while accounting for mental health diagnoses. METHODS: Review of electronic health records from three integrated health care systems identified 1087 transfeminine and 1431 transmasculine adolescents and young adults. Poisson regression was used to calculate prevalence ratios comparing the proportion of TGD participants with at least one self-inflicted injury (a surrogate for suicide attempt) before index date (first evidence of TGD status) to the corresponding proportions in presumed cisgender male and female referents matched on age, race/ethnicity, and health plan. Interactions between gender identities and mental health diagnoses were assessed on multiplicative and additive scales. RESULTS: TGD adolescents and young adults were more likely to have a self-inflicted injury, various mental health diagnoses, and multiple mental health diagnoses than their cisgender peers. The prevalence of self-inflicted injuries among TGD adolescents and young adults was high even in the absence of mental health diagnoses. Results were consistent with positive additive interaction and negative multiplicative interaction. CONCLUSIONS: Universal suicide prevention efforts for all youth, including those with no mental health diagnoses, and more intensive suicide prevention efforts for TGD adolescents and young adults and those with at least one mental health diagnosis are warranted.

Effect of Vitamin D Supplementation on Overactive Bladder and Urinary Incontinence Symptoms in Older Men: Ancillary Findings From a Randomized Trial.

PURPOSE: Our goal was to evaluate vitamin D supplementation for preventing or treating overactive bladder and urinary incontinence in men. MATERIALS AND METHODS: Ancillary study of men aged ≥55 years in VITAL (VITamin D and OmegA-3 TriaL). Randomized treatments included: vitamin D3 (cholecalciferol), marine omega-3 fatty acids, or matching placebo. Structured urinary incontinence questions measured the prevalence of overactive bladder at year 5 and urinary incontinence at years 2 and 5, along with incidence and progression of urinary incontinence from years 2 to 5. Prespecified subgroup analyses examined men with low baseline serum 25-hydroxyvitamin D (<20 ng/mL). RESULTS: Among the 11,486 men who provided data at year 2 and 10,474 at year 5, mean age was 68 years at year 2, with 23% racial/ethnic minorities. In primary analyses, vitamin D supplementation compared to placebo did not lower odds of overactive bladder at year 5 (OR 0.97, 95% CI 0.87-1.08) or weekly urinary incontinence at year 2 (OR 0.94, 95% CI 0.83-1.05) or year 5 (OR 0.98, 95% CI 0.88-1.09). We found interactions of baseline serum 25-hydroxyvitamin D level with vitamin D supplementation for overactive bladder (P value for interaction = .001), and secondarily, for any urinary incontinence at year 2 (P value for interaction = .05). Men with baseline 25-hydroxyvitamin D <20 ng/mL, who were assigned to vitamin D supplements, had lower odds of overactive bladder (OR 0.51, 95% CI 0.35-0.76) compared to placebo, yet higher odds of any urinary incontinence (OR 1.24, 95% CI 0.93-1.64). CONCLUSIONS: Overall, vitamin D supplementation did not improve overactive bladder or urinary incontinence compared to placebo. However, specific use of vitamin D in men with lower 25-hydroxyvitamin D levels had inconsistent findings.

Vitamin D supplements and prevalent overactive bladder in women from midlife through older ages.

OBJECTIVE: The objective of this study is to determine if vitamin D supplementation is associated with prevalent overactive bladder (OAB) in women across the aging spectrum. METHODS: We used the Nurses' Health Study (NHS) I (initiated in 1976) and NHS II (initiated in 1989) cohorts to evaluate the association of vitamin D supplements with prevalent OAB, all of which were reported by participants in 2019 in both NHS cohorts. OAB was defined as the self-reported need to rush to toilet to urinate at least sometimes. Further, OAB/wet included incontinence at least monthly because of urgency, whereas OAB/dry included incontinence once per month or less, or stress-predominant incontinence. Multivariable-adjusted odds ratios and 95% confidence intervals of OAB/dry and OAB/wet subtypes were estimated using logistic regression models. RESULTS: Among the 75,316 women (age range, 55-98 y) from NHS and NHS II OAB prevalence was 26%. Increasing prevalence was observed across each older age group, with 41% of women 85 years or older reporting OAB symptoms. OAB/dry was more common (18%) than OAB/wet (8%). After multivariable adjustment, no clinically significant association between vitamin D supplementation and prevalent OAB or OAB type was observed. CONCLUSIONS: OAB symptoms are highly prevalent across adult women, including the oldest old, who are often excluded from treatment trials. Despite interest in vitamin D supplementation as a low-cost strategy to address OAB, our findings indicate oral vitamin D is not associated with prevalent OAB in middle-aged and older women.

Is There a Link Between Hormone Use and Diabetes Incidence in Transgender People? Data From the STRONG Cohort.

BACKGROUND: Risk of type 2 diabetes mellitus (T2DM) in transgender and gender diverse (TGD) persons, especially those receiving gender-affirming hormone therapy (GAHT) is an area of clinical and research importance. METHODS: We used data from an electronic health record-based cohort study of persons 18 years and older enrolled in 3 integrated health care systems. The cohort included 2869 transfeminine members matched to 28 300 cisgender women and 28 258 cisgender men on age, race/ethnicity, calendar year, and site, and 2133 transmasculine members similarly matched to 20 997 cisgender women and 20 964 cisgender men. Cohort ascertainment spanned 9 years from 2006 through 2014 and follow-up extended through 2016. Data on T2DM incidence and prevalence were analyzed using Cox proportional hazards and logistic regression models, respectively. All analyses controlled for body mass index. RESULTS: Both prevalent and incident T2DM was more common in the transfeminine cohort relative to cisgender female referents with odds ratio and hazard ratio (95% CI) estimates of 1.3 (1.1-1.5) and 1.4 (1.1-1.8), respectively. No significant differences in prevalence or incidence of T2DM were observed across the remaining comparison groups, both overall and in TGD persons with evidence of GAHT receipt. CONCLUSION: Although transfeminine people may be at higher risk for T2DM compared with cisgender females, the corresponding difference relative to cisgender males is not discernable. Moreover, there is little evidence that T2DM occurrence in either transfeminine or transmasculine persons is attributable to GAHT use.

Effect of vitamin D supplementation on urinary incontinence in older women: ancillary findings from a randomized trial.

BACKGROUND: Observational studies among older women have associated vitamin D insufficiency with a greater prevalence and incidence of urinary incontinence. However, little is known about the effect of vitamin D supplementation in reducing urinary incontinence. OBJECTIVE: This study aimed to evaluate the effects of vitamin D supplementation in reducing the frequency of urinary incontinence in older women. STUDY DESIGN: We conducted an ancillary study of women aged ≥55 years in the Vitamin D and Omega-3 Trial, a randomized trial with a 2×2 factorial design. Recruitment of participants started from 2011 to 2014 across 50 US states, and the follow-up of participants ended in January 2018. Randomized treatments in the parent study included (1) vitamin D3 (cholecalciferol) at a dosage of 2000 IU/d, (2) marine omega-3 fatty acids at a dosage of 1 g/d, and (3) matching placebo. Here, we analyzed women according to their randomization to vitamin D supplementation or placebo, regardless of treatment with omega-3 fatty acid supplementation. Validated frequency of urinary incontinence questions were added in year 2 of the study and were used again in year 5 at the end of trial. Prespecified ancillary outcomes included the prevalence of urinary incontinence at years 2 and 5, along with incident incontinence and progression of incontinence (from lower to higher frequency) from year 2 to year 5. Preplanned subgroup analyses examined the following outcomes: prerandomization of low serum levels of vitamin D (serum 25-hydroxyvitamin D<20 ng/mL), incontinence types, weight categories, and African American race. RESULTS: Among the randomized women who provided urinary incontinence data, 11,646 women at year 2 and 10,527 women at year 5, the mean age was 70 years at year 2, with 29% racial and ethnic minorities. The prevalence of urinary incontinence that occurred at least weekly was 29% at year 2 and increased to 37% at year 5. Vitamin D supplementation compared to with placebo was not associated with lower odds of urinary incontinence occurring at least weekly at year 2 (odds ratio, 1.08; 95% confidence interval, 0.99-1.19) or year 5 (odds ratio, 1.04; 95% confidence interval, 0.94-1.15). Vitamin D supplementation compared to placebo was not associated with lower incidence or progression of urinary incontinence from year 2 to year 5: incidence (odds ratio, 1.06; 95% confidence interval, 0.83-1.35) or progression (odds ratio, 0.94; 95% confidence interval, 0.82-1.08). Women with prerandomization of low serum levels of vitamin D (n=836) did not have lower odds of the prevalence, incidence, or progression of urinary incontinence. The findings were null in subgroups according to incontinence type, women with obesity, and African American women. Only women with healthy weight randomized to vitamin D had lower odds of progression of urinary incontinence (odds ratio, 0.78; 95% confidence interval, 0.63-0.95; P=.01). CONCLUSION: Vitamin D supplementation compared to placebo for 2 to 5 years was not associated with differences in the prevalence, incidence, or progression of urinary incontinence in older women with and without adequate serum vitamin D levels, with inconsistent differences among subgroups. The findings showed that the broad use of moderate doses of vitamin D supplementation did not reduce urinary incontinence in older women.

Randomized trial of two maintenance doses of vitamin D in children with chronic kidney disease.

BACKGROUND: Correction of nutritional vitamin deficiency is recommended in children with chronic kidney disease (CKD). The optimal daily dose of vitamin D to achieve or maintain vitamin D sufficiency is unknown. METHODS: We conducted a phase III, double-blind, randomized trial of two doses of vitamin D3 in children ≥ 9 years of age with CKD stages 3-5 or kidney transplant recipients. Patients were randomized to 1000 IU or 4000 IU of daily vitamin D3 orally. We measured 25-hydroxvitamin D (25(OH)D) levels at baseline, 3 months and 6 months. The primary efficacy outcome was the percentage of patients who were vitamin D replete (25(OH)D ≥ 30 ng/mL) at 6 months. RESULTS: Ninety-eight patients were enrolled: 49 randomized into each group. Eighty (81.6%) patients completed the study and were analyzed. Baseline plasma 25(OH)D levels were ≥ 30 ng/mL in 12 (35.3%) and 12 (27.3%) patients in the 1000 IU and 4000 IU treatment groups, respectively. At 6 months, plasma 25(OH)D levels were ≥ 30 ng/mL in 33.3% (95% CI: 18.0-51.8%) and 74.4% (95% CI: 58.8-86.5%) in the 1000 IU and 4000 IU treatment groups, respectively (p = 0.0008). None of the patients developed vitamin D toxicity or hypercalcemia. CONCLUSIONS: In children with CKD, 1000 IU of daily vitamin D3 is unlikely to achieve or maintain a plasma 25(OH)D ≥ 30 ng/mL. In children with CKD stages 3-5, a dose of vitamin D3 4000 IU daily was effective in achieving or maintaining vitamin D sufficiency. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01909115.

A Clinician's guide to vitamin D supplementation for patients with cystic fibrosis.

Vitamin D deficiency is common in the general population, and even more so in patients with cystic fibrosis. Deficiency is exacerbated in cystic fibrosis patients because of a myriad of causes including malabsorption, decreased fat mass, reduced 25-hydroxylation of vitamin D, reduced exposure to sunlight, decreased vitamin D binding protein, and exposure to drugs that increase catabolism. In turn, vitamin D deficiency can contribute to poor bone health. Additionally, it may contribute to pulmonary decline in the form of worsening pulmonary function, increased colonization with pathogens, and increased pulmonary exacerbation. Because vitamin D deficiency is correlated with negative clinical effects in multiple organ systems of patients with cystic fibrosis, it is important to screen for and treat deficiency in these patients. The Cystic Fibrosis Foundation has issued guidelines for the treatment of vitamin D deficiency, targeting serum levels of 25-hydroxyvitamin D of at least 30 ng/ml. The guidelines offer age-specific escalating dose regimens depending on serum vitamin D levels, with monitoring at 12- week intervals after changing therapy. They address the literature on alternative vitamin D sources, such as UV lamps, ideal formulations (cholecalciferol in preference to ergocalciferol), and optimal vehicles of administration. Despite these detailed recommendations, most centers are still unable to achieve in-target serum vitamin D levels for many of their patients. Future research examining ideal treatment regimens to achieve serum targets and maximize clinical effects are needed. Moreover, it is unknown whether vitamin D sufficiency will be easier to achieve on new triple therapy cystic fibrosis drug combinations, and how these drugs will contribute to vitamin D-related clinical outcomes.

Findings from a feasibility study of estradiol for hypogonadal women with cystic fibrosis-related bone disease.

BACKGROUND: Advancements in therapies for patients with cystic fibrosis (CF) have decreased mortality, leading to increased prevalence of chronic complications including bone disease. CF-related bone disease (CFBD) is characterized by low bone mineral density (BMD) and fragility fractures. Estrogen deficiency increases bone resorption, resulting in decreased BMD that can be restored with estrogen replacement. Current CF guidelines recommend treating female hypogonadal patients with CFBD with estrogen replacement, but no prospective study has investigated the effects of estrogen supplementation on CFBD. Estrogen is known to modulate inflammatory markers and autoimmune diseases. We proposed to test the hypothesis that estrogen status plays a critical role in optimizing bone health, modulating inflammation, preserving lung function, and maximizing quality of life in premenopausal women with CF. METHODS: We planned a randomized, placebo-controlled, investigator- and patient-blinded, pilot trial with two parallel arms. Eligible subjects were women with CF 18-50 years old with hypogonadism and low BMD who were not taking systemic glucocorticoids, had not had a prior transplant, and did not have contraindications to oral estradiol. Subjects would be block randomized to receive oral estradiol or placebo for 6 months. The primary outcome was feasibility metrics. Secondary outcomes included relative changes in estradiol, bone turnover markers, lung function, inflammatory markers, and quality of life metrics. The study was funded through departmental funds. RESULTS: Of 233 subjects screened, 86 subjects were women with CF 18-50 years old and none were eligible for participation. Most subjects were excluded due to absent DXA report (24%), normal BMD (22%), or use of systemic estrogen (16%). Due to difficulty recruiting the planned 52 subjects, the trial was closed for recruitment and no subjects were randomized. CONCLUSION: This study was designed to investigate the feasibility of a safety and efficacy trial of estrogen therapy for women with CF. Unfortunately, due to eligibility criteria, the study was unable to recruit subjects. This feasibility study highlights the need for improved BMD screening in young women with CF. Future study designs may require the incorporation of a screening DXA as part of subject recruitment. TRIAL REGISTRATION: The study was registered on ClinicalTrials.gov ( NCT03724955 ).

Longitudinal Changes in Liver Enzyme Levels Among Transgender People Receiving Gender Affirming Hormone Therapy.

BACKGROUND: The effect of gender affirming hormone therapy (GAHT) on clinical laboratory parameters, including levels of liver enzymes alanine aminotransferase (ALT) and aspartate transaminase (AST), is an area of uncertainty in transgender health. AIM: We sought to estimate the distribution parameters of liver enzyme levels among transmasculine (TM) and transfeminine (TF) persons receiving GAHT relative to the corresponding measures in cisgender reference groups, and to evaluate longitudinal changes in these laboratory measures following GAHT initiation. METHODS: The data for this longitudinal study included 624 TF and 438 transmasculine (TM) people as well as 4,090 cisgender males and 4,797 cisgender females enrolled in 3 integrated health systems. Time under observation was divided into 2 intervals: from the first blood test to the date of the first filled GAHT prescription and from GAHT initiation to the most recent ALT or AST measurement. Linear mixed models were used to compare changes in log-transformed ALT and AST values among transgender cohort members before and after GAHT initiation, and relative to the reference groups. The results were expressed as relative differences (in %) and the ratios of these differences (ratios-of-ratios) along with the 95% confidence intervals (CIs). OUTCOMES: Changes in ALT and AST levels among transgender people over time and relative to the corresponding changes in cisgender referents. RESULTS: Among TM study participants, the post GAHT ratios-of-ratios for AST were 1.61 (95% CI: 1.13, 2.31) and 1.57 (95% CI: 1.06, 2.31) relative to cisgender males and females respectively. For ALT, the corresponding comparisons yielded the ratios-of-ratios (95% CIs) of 2.06 (1.67, 2.54) and 1.90 (1.50, 2.40). No statistically significant changes were observed among TF participants. Other factors associated with higher liver enzyme levels included alcohol use/abuse and obesity. CLINICAL IMPLICATIONS: TM persons may experience modest increases in ALT and AST concentrations following testosterone initiation; however, clinical significance of the observed association remains unclear and requires further investigation. By contrast, feminizing GAHT is unlikely to induce appreciable changes in liver enzyme levels. STRENGTH AND LIMITATIONS: The strengths of this study are the longitudinal design and the ability to assemble an unselected cohort nested within large health systems. The main limitations include the lack of information on hormone levels and the inability to take into account GAHT doses and routes of administration. CONCLUSION: The influence of long-term GAHT on ALT and AST levels appears modest and not likely to reflect clinically meaningful changes in liver function. Hashemi L, Zhang Q, Getahun D, et al. Longitudinal Changes in Liver Enzyme Levels Among Transgender People Receiving Gender Affirming Hormone Therapy. J Sex Med 2021;18:1662-1675.

Changes in Size and Demographic Composition of Transgender and Gender Non-Binary Population Receiving Care at Integrated Health Systems.

OBJECTIVE: To examine temporal changes in the number and demographic composition of transgender/gender non-binary (TGNB) population using data from integrated health care systems. METHODS: Electronic health records from Kaiser Permanente health plans in Georgia and Northern and Southern California were used to identify TGNB individuals, who sought care from January 2006 to December 2014, and the data were analyzed by year, site, age, and sex assigned at birth. RESULTS: In 2006, the number of TGNB people (and corresponding 95% CI) per 100 000 population were 3.5 (1.9, 6.3) in Georgia, 5.5 (4.8, 6.4) in Southern California, and 17 (16, 19) in Northern California. In 2014, these frequencies increased to 38 (32, 45), 44 (42, 46), and 75 (72, 78) per 100 000 population, respectively. When analyzed by age, the most rapid increase was observed among persons 18 to 25 years old, and this increase accelerated after 2010. The ratio of transmasculine to transfeminine persons also changed from 1:1.7 in 2006 to 1:1 in 2014 overall and from 1:1 in 2006 to 1.8:1 in 2014 among persons <18 years of age. CONCLUSION: This analysis confirms previous observations that the proportion of TGNB people is growing, especially among young adults. The composition of the TGNB population is also changing from predominantly transfeminine to roughly 1:1 overall and to predominantly transmasculine in children and adolescents.

Factors Contributing to Vitamin D Status at Hospital Admission for Pulmonary Exacerbation in Adults With Cystic Fibrosis.

BACKGROUND: Individuals with cystic fibrosis (CF) have difficulty maintaining optimal vitamin D status due to pancreatic insufficiency-induced malabsorption, inadequate sunlight exposure, and poor intake of vitamin D containing foods. Vitamin D deficiency may increase the risk of pulmonary exacerbations of CF. The objective of this study was to assess factors impacting vitamin D status in patients with CF recently hospitalized for a pulmonary exacerbation of CF. METHODS: This was a pre-planned analysis of vitamin D intake in patients enrolled in a multi-center, double-blind, randomized controlled study examining vitamin D therapy for pulmonary exacerbation of CF. Demographic information, responses from a habitual sun exposure questionnaire and food frequency questionnaire, and vitamin D supplement usage were queried and compared to serum 25-hydroxyvitamin D (25(OH)D) concentrations. RESULTS: A total of 48 subjects were included in this analysis. Subjects were taking approximately 1,200 IU of vitamin D daily. Reported vitamin D intake, age, race, employment, and education were not significantly associated with vitamin D status in this population. However, smoking status, sunlight exposure in the last 3 years, and skin type (in the bivariate model) were all significantly associated with vitamin D status (all p<0.05). CONCLUSIONS: Sunlight exposure was the most predictive determinant of vitamin D status in patients with CF prior to pulmonary exacerbation. Subjects reported vitamin D intake below the recommended amounts. The role and mode of optimizing vitamin D status prior to a pulmonary exacerbation needs further investigation.

Relationship Between Estrogen Treatment and Skeletal Health in Women With Cystic Fibrosis.

BACKGROUND: Patients with cystic fibrosis (CF) are at risk for CF-related bone disease. Women with CF may use estrogen supplementation for reasons other than skeletal health. It is unknown whether estrogen therapy has a beneficial impact on skeletal health in women with CF. METHODS: In this retrospective cohort study of women with CF followed at a single CF center, the lumbar spine bone mineral density (BMD) of women with CF exposed to supplemental and not exposed to supplemental estrogen were compared. Spline function models included the main effect of estrogen exposure and the interaction between age and estrogen supplementation. RESULTS: Of the 145 subjects analyzed, 44 subjects were exposed to supplemental estrogen. The baseline characteristics of estrogen exposed and unexposed subjects were similar except for use of CF transmembrane conductance regulator modulators and anti-osteoporosis medications. Women exposed to estrogen reached peak BMD around 21 years of age, but women not exposed to estrogen reached peak BMD around 25 years of age. A significant interaction of age and estrogen supplementation indicated that the lumbar spine BMD trajectories differed by exposure group. CONCLUSIONS: Our study demonstrates that few women with CF of reproductive age are prescribed estrogen therapy. Furthermore, estrogen exposure up to age 21 is associated with improved BMD, but estrogen exposure after age 21 does not appear to be associated with improved BMD. Further studies are needed to understand the reasons for the low rates of estrogen use in young women with CF and the optimal timing, dose and formulation of estrogen prescription.

Suicide Attempts Among a Cohort of Transgender and Gender Diverse People.

INTRODUCTION: Transgender and gender diverse people often face discrimination and may experience disproportionate emotional distress that leads to suicide attempts. Therefore, it is essential to estimate the frequency and potential determinants of suicide attempts among transgender and gender diverse individuals. METHODS: Longitudinal data on 6,327 transgender and gender diverse individuals enrolled in 3 integrated healthcare systems were analyzed to assess suicide attempt rates. Incidence was compared between transmasculine and transfeminine people by age and race/ethnicity and according to mental health status at baseline. Cox proportional hazards models examined rates and predictors of suicide attempts during follow-up. Data were collected in 2016, and analyses were conducted in 2019. RESULTS: During follow-up, 4.8% of transmasculine and 3.0% of transfeminine patients had at least 1 suicide attempt. Suicide attempt rates were more than 7 times higher among patients aged <18 years than among those aged >45 years, more than 3 times higher among patients with previous history of suicide ideation or suicide attempts than among those with no such history, and 2-5 times higher among those with 1-2 mental health diagnoses and more than 2 mental health diagnoses at baseline than among those with none. CONCLUSIONS: Among transgender and gender diverse individuals, younger people, people with previous suicidal ideation or attempts, and people with multiple mental health diagnoses are at a higher risk for suicide attempts. Future research should examine the impact of gender-affirming healthcare use on the risk of suicide attempts and identify targets for suicide prevention interventions among transgender and gender diverse people in clinical settings.

Oral ethinyl estradiol treatment in women with cystic fibrosis is associated with lower bone mineral density.

OBJECTIVE: The purpose of this study was to determine whether estrogen supplementation primarily from oral contraceptive pills compared to no estrogen supplementation is associated with differences in mean bone mineral density (BMD) measured by DXA in a cross-sectional study of women with cystic fibrosis (CF). METHODS: In this cross-sectional study of women with CF followed at a single center, we analyzed 49 women with CF ages 18-50 years with a documented DXA. BMD of women with CF taking estrogen supplementation was compared to BMD of women with CF not taking estrogen supplementation. RESULTS: Twelve women with CF were taking estrogen supplementation with mean dose of 23.3 mcg/day (SD 6.9 mcg/day) of ethinyl estradiol. There were no statistically significant differences between demographics of the 12 women with CF taking estrogen supplementation compared to the 37 women with CF not taking estrogen supplementation. Women taking estrogen had lower mean lumbar spine Z-score: -0.7 ± 0.7, compared to women not taking estrogen, Z-score: -0.04 ± 1.0 (p-value 0.046). Women taking estrogen had lower mean BMD at the lumbar spine: 0.952 ± 0.086 g/cm2, compared to women not taking estrogen: 1.023 ± 0.105 g/cm2 (p-value 0.038). Similar trends were seen at the total hip and femoral neck. CONCLUSION: Low-dose estrogen supplementation in premenopausal women with CF was associated with lower BMD compared to no estrogen supplementation in a similar group of premenopausal young women with CF. Future studies are needed to investigate the optimal formulation, route of administration, and dose to accrue and preserve bone mass in premenopausal women with CF.

Vitamin D intake and the 10-year risk of urgency urinary incontinence in women.

Evidence indicates that higher serum 25-hydroxy vitamin D levels may be associated with decreased prevalence of urgency urinary incontinence (UI), but the impact of vitamin D consumption on development of urgency and mixed UI is unclear. The objective was to assess whether greater vitamin D intake was associated with decreased risk of incident urgency and mixed UI over 10 years using 2 large prospective cohorts of middle-aged and older women. We analyzed 38,101 women from the Nurses' Health Study I (NHS I) and 35,190 women from NHS II who were free of UI at baseline. We followed incident UI, defined as new UI occurring at least monthly, separately by subtype (urgency, mixed, stress UI), from 2002-2012. We categorized vitamin D intake from supplements and diet. We estimated relative risk for developing UI according to vitamin D intake using Cox-proportional hazard models with adjustment for covariates. Median vitamin D intake was 580IU in the older women in NHS I (age range 56-71 at baseline) and 487IU in middle-aged women in NHS II (age range 40-57). Among women taking ≥1000IU of vitamin D, median intake in the older women was 1252IU and 1202IU in the middle-aged women. Among the older women, we found no relation of vitamin D intake to risk of developing UI, across all UI subtypes. In multivariable-adjusted analysis for middle-aged women, the relative risk of developing mixed UI among women taking >1000IU was 0.79 (0.63, 0.99) and for urgency UI was 0.88 (0.71, 1.07), versus <200IU. Risks of developing stress UI were not related to vitamin D intake categories. Overall, we did not find a relationship between vitamin D intake and UI incidence in middle-aged and older women; however, the reported intake was moderate.

Longitudinal Changes in Hematologic Parameters Among Transgender People Receiving Hormone Therapy.

CONTEXT: The effect of gender-affirming hormone therapy (HT) on erythropoiesis is an area of priority in transgender health research. OBJECTIVE: To compare changes in hematologic parameters and rates of erythrocytosis and anemia among transgender people to those of cisgender controls. DESIGN: Longitudinal observational study. PARTICIPANTS AND SETTING: We compared 559 transfeminine (TF) and 424 transmasculine (TM) people enrolled in 3 integrated health care systems to matched cisgender referents. INTERVENTIONS AND OUTCOME: Hormone therapy receipt was ascertained from filled prescriptions. Hemoglobin (Hb) and hematocrit (Hct) levels were examined from the first blood test to HT initiation, and from the start of HT to the most recent blood test. Rates of erythrocytosis and anemia in transgender participants and referents were compared by calculating adjusted hazard ratios and 95% confidence intervals (CI). RESULTS: In the TF group, there was a downward trend for both Hb and Hct. The corresponding changes in the TM cohort were in the opposite direction. TM study participants experienced a 7-fold higher rate (95% CI: 4.1-13.4) of erythrocytosis relative to matched cisgender males, and an 83-fold higher rate (95% CI: 36.1-191.2) compared to cisgender females. The corresponding rates for anemia were elevated in TF subjects but primarily relative to cisgender males (hazard ratio 5.9; 95% CI: 4.6-7.5). CONCLUSIONS: Our results support previous recommendations that hematological parameters of transgender people receiving HT should be interpreted based on their affirmed gender, rather than their sex documented at birth. The clinical significance of erythrocytosis following testosterone therapy, as well as anemia following feminizing HT, requires further investigation.