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INTRODUCTION: Our goal was to evaluate the potential utility of magnetic resonance imaging (MRI) placental volume as an assessment of placental insufficiency. METHODS: Secondary analysis of a prospective cohort undergoing serial placental MRIs at two academic tertiary care centers. The population included 316 participants undergoing MRI up to three times throughout gestation. MRI was used to calculate placental volume in milliliters (ml). Placental-mediated adverse pregnancy outcome (cAPO) included preeclampsia with severe features, abnormal antenatal surveillance, and perinatal mortality. Serial measurements were grouped as time point 1 (TP1) <22 weeks, TP2 22 0/7-29 6/7 weeks, and TP3 ≥30 weeks. Mixed effects models compared change in placental volume across gestation between cAPO groups. Association between cAPO and placental volume was determined using logistic regression at each TP with discrimination evaluated using area under receiver operator curve (AUC). Placental volume was then added to known clinical predictive variables and evaluated with test characteristics and calibration. RESULTS: 59 (18.7 %) of 316 participants developed cAPO. Placental volume growth across gestation was slower in the cAPO group (p < 0.001). Placental volume was lower in the cAPO group at all time points, and alone was moderately predictive of cAPO at TP3 (AUC 0.756). Adding placental volume to clinical variables had moderate discrimination at all time points, with strongest test characteristics at TP3 (AUC 0.792) with sensitivity of 77.5 % and specificity of 75.3 % at a predicted probability cutoff of 15 %. DISCUSSION: MRI placental volume warrants further study for assessment of placental insufficiency, particularly later in gestation.
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OBJECTIVES: We test whether the level of acculturation is associated with reproductive autonomy among Mexican-origin Latinas in Oregon. STUDY DESIGN: This was a cross-sectional study that used validated reproductive autonomy and language-based acculturation scales and sociodemographic information. We compared maximum reproductive autonomy score, overall and for each subscale (decision-making, freedom from coercion, and communication), by acculturation group. We developed a multivariable logistic regression model adjusted for age, education, and regular income source. RESULTS: Our sample included 434 respondents: 70.7% low, 26.7% bicultural, and 2.5% in the high acculturation group. A higher unadjusted proportion of women in the bicultural/high acculturation group than the low acculturation group had maximum reproductive autonomy scores (13.4% compared with 3.9%; p < 0.001). In adjusted analyses, women in the high/bicultural acculturation group had significantly higher odds of reporting a maximum reproductive autonomy score (adjusted odds ratio = 2.55, 95% CI: 1.08-5.98). CONCLUSIONS: Language-based acculturation was positively associated with reproductive autonomy among a community-dwelling sample of Mexican-origin Latinas in Oregon.
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Aculturación , Lenguaje , Americanos Mexicanos , Autonomía Personal , Humanos , Femenino , Oregon , Adulto , Estudios Transversales , Adulto Joven , Adolescente , Toma de Decisiones , Modelos Logísticos , Hispánicos o Latinos , CoerciónRESUMEN
Prenatal cannabis use is associated with adverse offspring neurodevelopmental outcomes, however the underlying mechanisms are relatively unknown. We sought to determine the impact of chronic delta-9-tetrahydrocannabinol (THC) exposure on fetal neurodevelopment in a rhesus macaque model using advanced imaging combined with molecular and tissue studies. Animals were divided into two groups, control (n = 5) and THC-exposed (n = 5), which received a daily THC edible pre-conception and throughout pregnancy. Fetal T2-weighted MRI was performed at gestational days 85 (G85), G110, G135 and G155 to assess volumetric brain development. At G155, animals underwent cesarean delivery with collection of fetal cerebrospinal fluid (CSF) for microRNA (miRNA) studies and fetal tissue for histologic analysis. THC exposure was associated with significant age by sex interactions in brain growth, and differences in fetal brain histology suggestive of brain dysregulation. Two extracellular vesicle associated-miRNAs were identified in THC-exposed fetal CSF; pathway analysis suggests that these miRNAs are associated with dysregulated axonal guidance and netrin signaling. This data is indicative of subtle molecular changes consistent with the observed histological data, suggesting a potential role for fetal miRNA regulation by THC. Further studies are needed to determine whether these adverse findings correlate with long-term offspring neurodevelopmental health.
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Cannabis , MicroARNs , Embarazo , Animales , Femenino , Macaca mulatta , Dronabinol/efectos adversos , Feto , Cannabis/efectos adversos , MicroARNs/genéticaRESUMEN
OBJECTIVE: To assess whether menstrual cycle timing (follicular or luteal phase) of coronavirus disease 2019 (COVID-19) vaccine administration is associated with cycle length changes. METHODS: We used prospectively collected (2021-2022) menstrual cycle tracking data from 19,497 reproductive-aged users of the application "Natural Cycles." We identified whether vaccine was delivered in the follicular or luteal phase and also included an unvaccinated control group. Our primary outcome was the adjusted within-individual change in cycle length (in days) from the average of the three menstrual cycles before the first vaccination cycle (individuals in the unvaccinated control group were assigned a notional vaccine date). We also assessed cycle length changes in the second vaccination cycle and whether a clinically significant change in cycle length (8 days or more) occurred in either cycle. RESULTS: Most individuals were younger than age 35 years (80.1%) and from North America (28.6%), continental Europe (33.5%), or the United Kingdom (31.7%). In the vaccinated group, the majority received an mRNA vaccine (63.8% of the full sample). Individuals vaccinated in the follicular phase experienced an average 1-day longer adjusted cycle length with a first or second dose of COVID-19 vaccine compared with their prevaccination average (first dose: 1.00 day [98.75% CI, 0.88-1.13], second dose: 1.11 days [98.75% CI, 0.93-1.29]); those vaccinated in the luteal phase and those in the unvaccinated control group experienced no change in cycle length (respectively, first dose: -0.09 days [98.75% CI, -0.26 to 0.07], second dose: 0.06 days [98.75% CI, -0.16 to 0.29], unvaccinated notional first dose: 0.08 days [98.75% CI, -0.10 to 0.27], second dose: 0.17 days [98.75% CI, -0.04 to 0.38]). Those vaccinated during the follicular phase were also more likely to experience a clinically significant change in cycle length (8 days or more; first dose: 6.8%) than those vaccinated in the luteal phase or unvaccinated (3.3% and 5.0%, respectively; P <.001). CONCLUSION: COVID-19 vaccine-related cycle length increases are associated with receipt of vaccination in the first half of the menstrual cycle (follicular phase).
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COVID-19 , Progesterona , Femenino , Humanos , Adulto , Vacunas contra la COVID-19 , COVID-19/prevención & control , Ciclo Menstrual , VacunaciónRESUMEN
STUDY OBJECTIVE: To assess preferences for menstrual pattern and acceptability and knowledge about the safety of induced amenorrhea among adolescents and young adults METHODS: We conducted a cross-sectional online survey of US residents aged 14-24 years at least 1 year post-menarche. Online recruitment was conducted via the social media platform TikTok on a teen reproductive health channel. Survey questions focused on menstrual history, menstrual pattern preferences, and demographic characteristics. The primary outcome was the proportion of postmenstrual individuals who would prefer amenorrhea vs scheduled bleeding. RESULTS: From 5113 potential respondents who accessed the eligibility screening, 3001 completed surveys and met the inclusion criteria. Most were aged 14-18 (63.7%), distributed proportionally among all US Census regions. When asked if they could pick their period-bleeding style without any permanent impacts, almost three-quarters chose no bleeding at all (amenorrhea; 71.5%) compared with scheduled periods (28.5%). However, 63.7% agreed or were uncertain when faced with the statement "It might be unsafe if hormone medications stop your period bleeding." After adjusting for age, gender expression, race, religion, heavy bleeding, and frequent bleeding, factors associated with preference for amenorrhea vs regular bleeding were younger age, masculine gender expression, White race, and non-Christian religious background. Baseline bleeding amount and frequency were not associated with preference for amenorrhea. CONCLUSION: More than two-thirds of US adolescents and young adults indicated a preference for medication-induced amenorrhea if the method was assured to not have any permanent effects on the body, despite highly prevalent misconceptions about health and safety.
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Amenorrea , Medios de Comunicación Sociales , Femenino , Adulto Joven , Adolescente , Humanos , Amenorrea/inducido químicamente , Estudios Transversales , Menstruación , Encuestas y Cuestionarios , HemorragiaRESUMEN
OBJECTIVE: To assess whether coronavirus disease 2019 (COVID-19) is associated with menstrual cycle length changes and, if so, how that compares with those undergoing vaccination or no event (control). METHODS: We conducted a retrospective cohort analysis in which we analyzed prospectively tracked cycle-length data from users of a period tracker application who also responded to a survey regarding COVID-19 symptoms and vaccination. We restricted our sample to users aged 16-45 years, with normal cycle lengths (24-38 days) and regular tracking behavior during the five cycles around COVID-19 symptoms or vaccination or a similar time period for those experiencing no event (control group). We calculated the within-user change in cycle length (days) from the three consecutive cycles preevent average (either vaccination, disease, or neither; cycles 1-3) to the event (cycle 4) and postevent (cycle 5) cycles. We used mixed-effects models to estimate the age- and country-adjusted difference in change in cycle length across the groups. RESULTS: We included 6,514 users from 110 countries representing 32,570 cycles (COVID-19 symptoms: 1,450; COVID-19 vaccination: 4,643; control: 421). The COVID-19 cohort experienced a 1.45-day adjusted increase in cycle length during cycle 4 (COVID-19) compared with their three preevent cycles (95% CI 0.86-2.04). The vaccinated group experienced a 1.14-day adjusted increase in cycle length during cycle 4 (COVID-19 vaccine) compared with their preevent average (95% CI 0.60-1.69). The control group (neither vaccine nor disease) experienced a 0.68-day decrease (95% CI -1.18 to -0.19) in a similar time period. Post hoc tests showed no significant differences in the magnitude of changes between the COVID-19 and vaccination cohorts. In both cohorts, cycle length changes disappeared in the postevent cycle. CONCLUSION: Experiencing COVID-19 is associated with a small change in cycle length similar to COVID-19 vaccination. These changes resolve quickly within the next cycle.
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COVID-19 , Femenino , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , Vacunas contra la COVID-19 , Estudios Retrospectivos , Vacunación , Ciclo MenstrualRESUMEN
OBJECTIVE: We investigated the utility of telehealth instruction versus mail-based written instruction in facilitating high-risk human papillomavirus (hrHPV) self-collection among post-menopausal patients compared with pre-menopausal patients, as well as the impact on acceptability and feasibility. METHODS: We conducted a prospective, randomized study of people eligible for cervical cancer screening, stratified by menopausal status, to undergo standard written or telehealth-based instructions for hrHPV self-collection. English speaking individuals residing in Oregon, with a cervix, eligible for primary hrHPV testing, and with access to a video-capable device were included. Patients with prior hysterectomy, trachelectomy, diagnosis of cervical cancer, or pelvic radiation for gynecologic cancer were excluded. We compared preference for and opinions about self-collection and hrHPV test results, by randomization group and stratified by menopausal status using descriptive statistics. RESULTS: Among 123 patients enrolled, 61 identified as post-menopausal with a median age of 57 years. While the majority of post-menopausal participants who received telehealth instructions found it helpful, only 6.1% considered telehealth instructions necessary to complete self-testing. There was no difference in opinion of telehealth by menopausal status. Overall, 88.5% of post-menopausal participants preferred self-collection to provider-collection. There were no significant differences between pre- and post-menopausal participants in terms of test preference, discomfort, ease of use, or perceptions of self-collection. CONCLUSION: Telehealth instruction did not add significant value to patients participating in hrHPV self-collection, nor did it alter the acceptability of hrHPV-self collection among an English-speaking cohort. Compared with prior experiences with provider-collected screening, hrHPV self-collection was preferred by both pre- and post-menopausal participants. There were no significant differences in preference for provider- versus self-collection when stratified by menopausal status.
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OBJECTIVE: We describe awareness about the modified "public charge" rule among Oregon's Mexican-origin Latino/a population and whether concerns about the rule influenced disenrollment from state-funded programs, which do not fall under the public charge. METHODS: We conducted a cross-sectional survey of adults (ages 18-59) recruited at the Mexican consulate and living in the state of Oregon. Our outcomes were awareness (of the public charge, source of knowledge, and confidence in knowledge of the public charge) and disenrolling self or family members from state-funded public healthcare programs due to concerns about the rule. We described outcomes and used logistic regression and calculated adjusted probabilities to identify factors associated with awareness of the public charge. RESULTS: Of 498 Latino/a respondents, 48% reported awareness of the public charge. Among those who knew about the public charge, 14.6% had disenrolled themselves or family members from public healthcare programs and 12.1% were hesitant to seek care due to concerns about the public charge. Younger respondents had a lower adjusted probability of awareness of the public charge (18-24 years: 15.6% (95% CI 3.1-28.2); 30-39 years 54.9% (95% CI 47.7-62.0). Higher education was associated with a higher adjusted probability of awareness of the public charge; ability to speak English was not associated with awareness of the public charge. CONCLUSION: Our study reveals limited awareness about the public charge among Mexican-origin Oregon Latino/as. Outreach and advocacy are essential to ensure Latino/as know their rights to access available state-funded healthcare programs.
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Atención a la Salud , Conocimientos, Actitudes y Práctica en Salud , Hispánicos o Latinos , Práctica de Salud Pública , Adulto , Humanos , Estudios Transversales , Atención a la Salud/etnología , Familia , Oregon , México/etnología , Concienciación , Conocimientos, Actitudes y Práctica en Salud/etnología , Adolescente , Adulto Joven , Persona de Mediana Edad , Accesibilidad a los Servicios de Salud , Programas de GobiernoRESUMEN
STUDY OBJECTIVE: To compare menstrual health literacy among adolescents and young adults on the basis of family religious background and United States region METHODS: We conducted a cross-sectional online survey of post-menarcheal US adolescents and young adults aged 14-24 years who identified their family religious background, including Christian or non-religious, with recruitment via the social media platform TikTok. We asked participants several questions to assess their health literacy regarding common myths about the use of gonadal steroid hormones for menstrual suppression. RESULTS: From 3250 online survey respondents, 2997 met the criteria for analysis, with 1989 identifying their family as Christian (66.4%) and 1008 identifying their family as non-religious (33.6%), with equal representation by US region. Health literacy was lower among those with a Christian family background, with concerns that menstrual suppression is unhealthy (16.4% vs 10.5% with non-religious background, P < .01), is unsafe (31.4% vs 24.2%, P < .01), and could lead to infertility (32.6% vs 20.0%, P < .01). Similarly, adolescents and young adults from the US South were worried that menstrual suppression is unhealthy (31.5%; P < .01) and would lead to infertility (33.8%; P < .01). CONCLUSION: Health literacy is lower among adolescents and young adults with a Christian family background and those who live in the South. These results demonstrate a need for an evidence-based national curriculum that addresses the safe and effective use of hormonal medications for menstrual suppression.
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Alfabetización en Salud , Infertilidad , Humanos , Adolescente , Adulto Joven , Estados Unidos , Estudios Transversales , Menstruación , CristianismoRESUMEN
Importance: There are well-documented racial and ethnic disparities in effective contraceptive use due to multiple factors. A key contributor may be differential insurance coverage and patient costs. The Oregon Reproductive Health Equity Act (RHEA), enacted in 2017, ensures full coverage of reproductive health care without cost sharing for all Oregonians with low income. Objective: To assess whether removing financial barriers to accessing contraceptive care is associated with an improvement in use of moderately and highly effective contraceptive methods among Latina women compared with non-Latina women. Design, Setting, and Participants: This cohort study included women aged 12 to 51 years who sought contraceptive care in the Oregon Health Authority Reproductive Health Program from April 2016 to March 2020. Patients using permanent contraception, those missing data on ethnicity, and non-Oregon residents were excluded. Data analysis was performed in January 2021. Exposures: Contraceptive care in the Reproductive Health Program after RHEA implementation. Main Outcomes and Measures: The main outcome was prevalence of use of moderately effective methods (contraceptive pills, patch, ring, or injection) or highly effective methods (long-acting reversible contraceptives) at the time of the contraceptive visit. Difference-in-differences analysis was used to compare moderately and highly effective contraception use between Latina and non-Latina patients. Secondary outcomes were proportions of adoption or continuation of moderately and highly effective methods, prevalence of highly effective methods, and adoption or continuation of highly effective methods. The unit of analysis was at the clinic visit level. Results: The study sample consisted of 295â¯604 evaluable clinic visits, in which 28.4% of individuals identified as Latina and 71.6% of individuals identified as non-Latina. The mean (SD) age was 25.5 (8.1) years. With difference-in-differences analysis, there was a significant adjusted 1.9 percentage point (95% CI, 0.2-3.6 percentage points) increase in prevalence of moderately or highly effective contraceptive methods for Latina patients compared with non-Latina patients. There were no significant differences for other outcomes of interest. Conclusions: This cohort study found that in Oregon, legislation removing financial barriers to accessing contraceptive care was associated with significant mitigation in disparate moderately and highly effective contraceptive method prevalence for Latina patients compared with non-Latina patients. The findings suggest that state funds successfully supplanted federal funds to enable continued robust comprehensive family planning services after withdrawal from Title X.
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Anticoncepción , Salud Reproductiva , Humanos , Femenino , Estudios de Cohortes , Anticoncepción/métodos , Anticonceptivos/uso terapéutico , Servicios de Planificación FamiliarRESUMEN
We developed and validated the use of ultra-high-performance liquid chromatography-heated electrospray ionization-tandem triple quadrupole mass spectrometry to simultaneously analyze serum concentrations of ethinylestradiol, dienogest, norelgestromin, norethindrone, gestodene, levonorgestrel, etonogestrel, segesterone acetate, medroxyprogesterone acetate, and drospirenone. The calibration range for all targets was 0.009-10 ng/mL, with lower limit of quantification of 0.009 ng/mL for all analytes except gestodene (0.019 ng/mL). We used our assay to check compliance among participants in a clinical trial, confirmed the use of drospirenone in 11 of 13 study participants, and evidence of noncompliant progestins in 2 (levonorgestrel = 1, norethindrone = 1). We conclude that this approach provides an accurate method to check protocol compliance in contraceptive clinical trials. IMPLICATIONS: The availability of a liquid chromatography-tandem triple quadrupole mass spectrometry multiprogestin analysis panel for simultaneous evaluation of the most common contraceptive steroids approved worldwide could improve monitoring of compliance and protocol adherence in clinical trials.
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Anticonceptivos , Progestinas , Humanos , Cromatografía Liquida/métodos , Adhesión a Directriz , Levonorgestrel , Espectrometría de Masas , Noretindrona , Reproducibilidad de los Resultados , Ensayos Clínicos como AsuntoRESUMEN
OBJECTIVE: To assess whether coronavirus disease 2019 (COVID-19) vaccination impacts menstrual bleeding quantity. DESIGN: Retrospective cohort. SETTING: Five global regions. POPULATION: Vaccinated and unvaccinated individuals with regular menstrual cycles using the digital fertility-awareness application Natural Cycles°. METHODS: We used prospectively collected menstrual cycle data, multivariable longitudinal Poisson generalised estimating equation (GEE) models and multivariable multinomial logistic regression models to calculate the adjusted difference between vaccination groups. All regression models were adjusted for confounding factors. MAIN OUTCOME MEASURES: The mean number of heavy bleeding days (fewer, no change or more) and changes in bleeding quantity (less, no change or more) at three time points (first dose, second dose and post-exposure menses). RESULTS: We included 9555 individuals (7401 vaccinated and 2154 unvaccinated). About two-thirds of individuals reported no change in the number of heavy bleeding days, regardless of vaccination status. After adjusting for confounding factors, there were no significant differences in the number of heavy bleeding days by vaccination status. A larger proportion of vaccinated individuals experienced an increase in total bleeding quantity (34.5% unvaccinated, 38.4% vaccinated; adjusted difference 4.0%, 99.2% CI 0.7%-7.2%). This translates to an estimated 40 additional people per 1000 individuals with normal menstrual cycles who experience a greater total bleeding quantity following the first vaccine dose' suffice. Differences resolved in the cycle post-exposure. CONCLUSIONS: A small increase in the probability of greater total bleeding quantity occurred following the first COVID-19 vaccine dose, which resolved in the cycle after the post-vaccination cycle. The total number of heavy bleeding days did not differ by vaccination status. Our findings can reassure the public that any changes are small and transient.
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Vacunas contra la COVID-19 , COVID-19 , Femenino , Humanos , Estudios Retrospectivos , Vacunas contra la COVID-19/efectos adversos , COVID-19/epidemiología , COVID-19/prevención & control , Hemorragia , Vacunación , Estudios de CohortesRESUMEN
Career development awards are a successful strategy to facilitate the advancement of physician-scientists trained in obstetrics and gynecology (OBGYN) toward a path of investigative independence. While these funding mechanisms can be effective approaches to developing the career of future OBGYN scientists, optimizing the probability of obtaining these awards requires determining the appropriate career development award for the applicant. There are many details and opportunities that need to be considered when deciding on the appropriate award. Some of the most sought-after awards are those that integrate career development and applied research, such as the K-series awards supported by the National Institutes of Health (NIH). A quintessential example of an NIH-funded mentor-based career development award to support the scientific training of an OBGYN physician-scientist is the Reproductive Scientist Development Program (RSDP). In this study, we provide data on the academic achievements of past and present RSDP scholars and discuss the structure, impact, and future of the RSDP, a federally funded K12 program dedicated to women's health for OBGYN scientific investigators. As healthcare is changing and physician-scientists comprise a unique and valuable part of the biomedical workforce, programs such as the RSDP are critical to maintaining a well-trained pipeline of OBGYN scientists to maintain and challenge the leading edge of medicine, science, and biology.
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Investigación Biomédica , Ginecología , Obstetricia , Médicos , Estados Unidos , Humanos , Femenino , National Institutes of Health (U.S.)RESUMEN
BACKGROUND: Some users of the etonogestrel contraceptive implant experience bothersome bleeding, which can reduce contraceptive satisfaction and continuation. Few strategies exist to manage this bleeding. The exact mechanism of progestin-induced bleeding is unknown, but it is likely multifactorial (eg, impaired angiogenesis, "leaky" fragile vasculature, and inflammation). Curcumin, the active ingredient in turmeric, has anti-inflammatory, antiproliferative, and antiangiogenic properties, which may make it a useful agent for implant-associated bothersome bleeding. OBJECTIVE: This study aimed to evaluate whether curcumin decreases frequent or prolonged bleeding or spotting in contraceptive implant users. STUDY DESIGN: The study was a randomized, double-blind, placebo-controlled trial. Here, etonogestrel implant users with frequent or prolonged bleeding or spotting were enrolled and randomized to either 600-mg Theracurmin HP (Immunovites, Las Vegas, NV) or placebo daily for 30 days. The term "frequent" was defined as ≥2 independent bleeding or spotting episodes, and the term "prolonged" was defined as ≥7 consecutive days of bleeding or spotting in a 30-day interval. Implant use was confirmed by clinical examination and negative gonorrhea and chlamydia and pregnancy tests. Enrolled participants initiated study treatment after 3 consecutive days of bleeding or spotting; if no bleeding or spotting occurred within 30 days of enrollment, the participants were withdrawn from the study. Study treatments were encapsulated to maintain a similar appearance. Participants used text messages to record daily bleeding patterns and study drug compliance. Bleeding was defined as a day that required the use of protection with a pad, tampon, or liner, and spotting was defined as a day with minimal blood loss that did not require the use of any protection. Our primary outcome was the total number of days without bleeding or spotting during the 30 days of study drug or placebo exposure. The secondary outcomes included total number of bleeding-free days, bleeding episodes, and satisfaction. A sample size of 22 per group provided 80% power at an alpha level of .05 to demonstrate a 6-day difference between groups. RESULTS: From February 2021 to November 2022, 58 individuals enrolled in the study with 54 participants (93%) completing 30 days of treatment (26 in the curcumin group and 28 in the placebo group). Of note, 1 individual in the curcumin arm did not experience a qualifying bleeding event and, thus, never initiated treatment and, per protocol, was withdrawn from the study. Participant characteristics did not differ between groups, including length of implant use at study enrollment (placebo, 521±305 days; curcumin, 419±264 days). The study groups did not differ concerning any bleeding-related outcome (mean days without bleeding or spotting: curcumin, 16.7±6.9; placebo, 17.5±4.8; P=.62; mean bleeding-free days: curcumin, 23.4±4.9; placebo, 22.4±4.5; P=.44; bleeding episodes: curcumin, 2.0±0.8; placebo, 2.1±0.8; P=.63). In addition, satisfaction with the implant as contraception and acceptability of bleeding over the study period did not differ by study group (P=.54 and P=.30, respectively). CONCLUSION: Daily use of curcumin did not improve bleeding patterns in users of the etonogestrel contraceptive implant experiencing frequent or prolonged bleeding patterns.
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Anticonceptivos Femeninos , Curcumina , Metrorragia , Embarazo , Femenino , Humanos , Hemorragia Uterina/inducido químicamente , Hemorragia Uterina/tratamiento farmacológico , Curcumina/uso terapéutico , Anticonceptivos Femeninos/efectos adversos , Metrorragia/inducido químicamente , Metrorragia/tratamiento farmacológico , Anticoncepción , Levonorgestrel/uso terapéuticoRESUMEN
OBJECTIVE: To determine whether discontinuation of delta-9-tetrahydrocannabinol (THC) use mitigates THC-associated changes in male reproductive health using a rhesus macaque model of daily THC edible consumption. DESIGN: Research animal study. SETTING: Research institute environment. PATIENT(S): Adult male rhesus macaques (age, 8-10 years; n = 6). INTERVENTION(S): Chronic daily THC edible administration at medically and recreationally relevant contemporary doses followed by cessation of THC use. MAIN OUTCOME MEASURE(S): Testicular volume, serum male hormones, semen parameters, sperm deoxyribonucleic acid (DNA) fragmentation, seminal fluid proteomics, and whole genome bisulfite sequencing of sperm DNA. RESULT(S): Chronic THC use resulted in significant testicular atrophy, increased gonadotropin levels, decreased serum sex steroid levels, changes in seminal fluid proteome, and increased DNA fragmentation with partial recovery after discontinuation of THC use. For every increase of 1 mg/7 kg/day in THC dosing, there was a significant decrease in the total testicular volume bilaterally by 12.6 cm3 (95% confidence interval [CI], 10.6-14.5), resulting in a 59% decrease in volume. With THC abstinence, the total testicular volume increased to 73% of its original volume. Similarly, with THC exposure, there were significant decreases in the mean total testosterone and estradiol levels and a significant increase in the follicle-stimulating hormone level. With increasing THC dose, there was a significant decrease in the liquid semen ejaculate volume and weight of coagulum; however, no other significant changes in the other semen parameters were noted. After discontinuing THC use, there was a significant increase in the total serum testosterone level by 1.3 ng/mL (95% CI, 0.1-2.4) and estradiol level by 2.9 pg/mL (95% CI, 0.4-5.4), and the follicle-stimulating hormone level significantly decreased by 0.06 ng/mL (95% CI, 0.01-0.11). Seminal fluid proteome analysis revealed differential expression of proteins enriched for processes related to cellular secretion, immune response, and fibrinolysis. Whole genome bisulfite sequencing identified 23,558 CpGs differentially methylated in heavy-THC vs. pre-THC sperm, with partial restoration of methylation after discontinuation of THC use. Genes associated with altered differentially methylated regions were enriched for those involved in the development and function of the nervous system. CONCLUSION(S): This is the first study demonstrating that discontinuation of chronic THC use in rhesus macaques partially restores adverse impacts to male reproductive health, THC-associated sperm differentially methylated regions in genes important for development, and expression of proteins important for male fertility.
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Dronabinol , Semen , Animales , Masculino , Macaca mulatta , Epigenoma , Proteoma , Espermatozoides/fisiología , Testosterona , Hormona Folículo Estimulante , Fertilidad , Estradiol , ADN , Recuento de EspermatozoidesRESUMEN
IMPORTANCE: There are limited data to determine the change in severity, efficacy, and mechanism of action of yoga-Pilates in the treatment of stress urinary incontinence (SUI). OBJECTIVES: The primary objective was to evaluate the effect of an 8-week web-based home yoga-Pilates exercise program on SUI severity and to evaluate the potential mechanism of action through ultrasound examination of the urethral rhabdosphincter cross-sectional area. STUDY DESIGN: This was a prospective cohort study of women with SUI. Participants underwent visits pre- and post-intervention, completed quality of life/severity surveys, and underwent pelvic examination and 3-dimensional transperineal ultrasonography to determine the urethral cross-sectional area. Pre- and post-intervention 24-hour voiding diaries were also collected. The intervention was an 8-week online yoga-Pilates video that tracked and prompted participation. RESULTS: Sixty women completed the study; they were predominantly premenopausal (67%) and vaginally parous (65%) and had done yoga (76%) and/or Pilates (44%). Seventy-three percent performed the exercises ≥3 times per week. For the primary outcome, the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form score improved from 9.5 (95% confidence interval [CI], 8.7-10.4) to 7.1 (95% CI, 6.3-7.9) (P < 0.001). The median (interquartile range) number of incontinence episodes per 24 hours decreased from 1 (1-3) to 1 (0-1) (P < 0.001). The Brink pelvic floor strength score improved from 7.1 (95% CI, 6.6-7.7) to 7.7 (95% CI, 7.2-8.2) (P = 0.01). Eighty-three percent reported that they were "better" on Patient Global impression of Improvement. There were no significant changes in urethral measurements. CONCLUSIONS: Although it did not meet the minimal clinically important difference, this 8-week web-based yoga-Pilates exercise program improved SUI symptoms and decreased the number of incontinence episodes in women with SUI.
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Incontinencia Urinaria de Esfuerzo , Incontinencia Urinaria , Yoga , Femenino , Humanos , Estudios Prospectivos , Calidad de Vida , Incontinencia Urinaria/terapia , Incontinencia Urinaria de Esfuerzo/diagnóstico por imagen , InternetAsunto(s)
Aborto Inducido , Aborto Espontáneo , Embarazo , Femenino , Humanos , Aborto Legal , Accesibilidad a los Servicios de SaludRESUMEN
Cannabis use in pregnancy is associated with adverse perinatal outcomes, which are likely mediated by the placenta. However, the underlying mechanisms and specific vasoactive effects of cannabis on the placenta are unknown. Our objective was to determine the impact of chronic prenatal delta-tetrahydrocannabinol (THC, main psychoactive component of cannabis) exposure on placental function and development in a rhesus macaque model using advanced imaging. Animals were divided into two groups, control (CON, n = 5) and THC-exposed (THC, n = 5). THC-exposed animals received a THC edible daily pre-conception and throughout pregnancy. Animals underwent serial ultrasound and MRI at gestational days 85 (G85), G110, G135 and G155 (full term is ~ G168). Animals underwent cesarean delivery and placental collection at G155 for histologic and RNA-Seq analysis. THC-exposed pregnancies had significantly decreased amniotic fluid volume (p < 0.001), placental perfusion (p < 0.05), and fetal oxygen availability (p < 0.05), all indicators of placental insufficiency. Placental histological analysis demonstrated evidence of ischemic injury with microinfarctions present in THC-exposed animals only. Bulk RNA-seq demonstrated that THC alters the placental transcriptome and pathway analysis suggests dysregulated vasculature development and angiogenesis pathways. The longer-term consequences of these adverse placental findings are unknown, but they suggest that use of THC during pregnancy may deleteriously impact offspring development.