Longitudinal associations between women's cycle characteristics and sexual motivation using Flo cycle tracking data.

In the current research, we used data from a sample of 16,327 menstrual cycle tracking app users to examine the association between menstrual cycle characteristics and sexual motivation tracked over 10 months of app use. Guided by past work that finds links between menstrual cycle characteristics related to conception risk and sexual motivation, we found that (a) between-women, shorter (r = - 0.04, p = 0.007), more regular cycles predicted small increases in sexual motivation (r = - 0.04, p = 0.001); (b) within-women, shorter cycles predicted greater sexual motivation that month (r = - 0.04, p < 0.001) and (c) the next month (ßs: - 0.10 to - 0.06, ps < 0.001), but (d) changes in sexual motivation did not reliably precede changes in cycle length (ßs: - 0.01 to 0.02, ps > 0.15). Within-woman analyses also revealed that (e) shorter cycles were followed by more frequent reports of fatigue (ß = - 0.06, p < 0.001), insomnia (ß = - 0.03, p < 0.001), and food cravings (ß = - 0.04, p < 0.001). Together, results suggest that menstrual cycles characteristics and sexual motivation may covary together in ways that reflect changing investments in reproduction. Small effect sizes and lack of experimental control warrant cautious interpretations of results.

Chronicling menstrual cycle patterns across the reproductive lifespan with real-world data.

The intricate hormonal and physiological changes of the menstrual cycle can influence health on a daily basis. Although prior studies have helped improve our understanding of the menstrual cycle, they often lack diversity in the populations included, sample size, and the span of reproductive and life stages. This paper aims to describe the dynamic differences in menstrual cycle characteristics and associated symptoms by age in a large global cohort of period-tracking application users. This work aims to contribute to our knowledge and understanding of female physiology at varying stages of reproductive aging. This cohort study included self-reported menstrual cycle and symptom information in a sample of Flo application users aged 18-55. Cycle and period length and their variability, and frequency of menstrual cycle symptom logs are described by the age of the user. Based on data logged by over 19 million global users of the Flo app, the length of the menstrual cycle and period show clear age-associated patterns. With higher age, cycles tend to get shorter (Cycle length: D ¯ = 1.85 days, Cohen's D = 0.59) and more variable (Cycle length SD: D ¯ = 0.42 days, Cohen's D = 0.09), until close to the chronological age (40-44) suggesting menopausal transition, when both cycles and periods become longer (Cycle length: D ¯ = 0.86 days, t = 48.85, Cohen's D = 0.26; Period length: D ¯ = 0.08, t = 15.6, Cohen's D = 0.07) and more variable (Cycle length SD: D ¯ = 2.80 days, t = 111.43, d = 0.51; Period length SD: D ¯ = 0.23 days, t = 67.81, Cohen's D = 0.31). The proportion of individuals with irregular cycles was highest in participants aged 51-55 (44.7%), and lowest in the 36-40 age group (28.3%). The spectrum of common menstrual cycle-related symptoms also varies with age. The frequency of logging of cramps and acne is lower in older participants, while logs of headache, backache, stress, and insomnia are higher in older users. Other symptoms show different patterns, such as breast tenderness and fatigue peaking between the ages of 20-40, or mood swings being most frequently logged in the youngest and oldest users. The menstrual cycle and related symptoms are not static throughout the lifespan. Understanding these age-related differences in cycle characteristics and symptoms is essential in understanding how best to care for and improve the daily experience for menstruators across the reproductive life span.

Efficacy of the Flo App in Improving Health Literacy, Menstrual and General Health, and Well-Being in Women: Pilot Randomized Controlled Trial.

BACKGROUND: Reproductive health literacy and menstrual health awareness play a crucial role in ensuring the health and well-being of women and people who menstruate. Further, awareness of one's own menstrual cycle patterns and associated symptoms can help individuals identify and manage conditions of the menstrual cycle such as premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD). Digital health products, and specifically menstrual health apps, have the potential to effect positive change due to their scalability and ease of access. OBJECTIVE: The primary aim of this study was to measure the efficacy of a menstrual and reproductive health app, Flo, in improving health literacy and health and well-being outcomes in menstruating individuals with and without PMS and PMDD. Further, we explored the possibility that the use of the Flo app could positively influence feelings around reproductive health management and communication about health, menstrual cycle stigma, unplanned pregnancies, quality of life, work productivity, absenteeism, and body image. METHODS: We conducted 2 pilot, 3-month, unblinded, 2-armed, remote randomized controlled trials on the effects of using the Flo app in a sample of US-based (1) individuals who track their cycles (n=321) or (2) individuals who track their cycles and are affected by PMS or PMDD (n=117). RESULTS: The findings revealed significant improvements at the end of the study period compared to baseline for our primary outcomes of health literacy (cycle tracking: D̄=1.11; t311=5.73, P<.001; PMS or PMDD: D̄=1.20; t115=3.76, P<.001) and menstrual health awareness (D̄=3.97; t311=7.71, P<.001), health and well-being (D̄=3.44; t311=5.94, P<.001), and PMS or PMDD symptoms burden (D̄=-7.08; t115=-5.44, P<.001). Improvements were also observed for our secondary outcomes of feelings of control and management over health (D̄=1.01; t311=5.08, P<.001), communication about health (D̄=0.93; t311=2.41, P=.002), menstrual cycle stigma (D̄=-0.61; t311=-2.73, P=.007), and fear of unplanned pregnancies (D̄=-0.22; t311=-2.11, P=.04) for those who track their cycles, as well as absenteeism from work and education due to PMS or PMDD (D̄=-1.67; t144=-2.49, P=.01). CONCLUSIONS: These pilot randomized controlled trials demonstrate that the use of the Flo app improves menstrual health literacy and awareness, general health and well-being, and PMS or PMDD symptom burden. Considering the widespread use and affordability of the Flo app, these findings show promise for filling important gaps in current health care provisioning such as improving menstrual knowledge and health. TRIAL REGISTRATION: OSF Registries osf.io/pcgw7; https://osf.io/pcgw7 ; OSF Registries osf.io/ry8vq; https://osf.io/ry8vq.

Assessment of a Digital Symptom Checker Tool's Accuracy in Suggesting Reproductive Health Conditions: Clinical Vignettes Study.

BACKGROUND: Reproductive health conditions such as endometriosis, uterine fibroids, and polycystic ovary syndrome (PCOS) affect a large proportion of women and people who menstruate worldwide. Prevalence estimates for these conditions range from 5% to 40% of women of reproductive age. Long diagnostic delays, up to 12 years, are common and contribute to health complications and increased health care costs. Symptom checker apps provide users with information and tools to better understand their symptoms and thus have the potential to reduce the time to diagnosis for reproductive health conditions. OBJECTIVE: This study aimed to evaluate the agreement between clinicians and 3 symptom checkers (developed by Flo Health UK Limited) in assessing symptoms of endometriosis, uterine fibroids, and PCOS using vignettes. We also aimed to present a robust example of vignette case creation, review, and classification in the context of predeployment testing and validation of digital health symptom checker tools. METHODS: Independent general practitioners were recruited to create clinical case vignettes of simulated users for the purpose of testing each condition symptom checker; vignettes created for each condition contained a mixture of condition-positive and condition-negative outcomes. A second panel of general practitioners then reviewed, approved, and modified (if necessary) each vignette. A third group of general practitioners reviewed each vignette case and designated a final classification. Vignettes were then entered into the symptom checkers by a fourth, different group of general practitioners. The outcomes of each symptom checker were then compared with the final classification of each vignette to produce accuracy metrics including percent agreement, sensitivity, specificity, positive predictive value, and negative predictive value. RESULTS: A total of 24 cases were created per condition. Overall, exact matches between the vignette general practitioner classification and the symptom checker outcome were 83% (n=20) for endometriosis, 83% (n=20) for uterine fibroids, and 88% (n=21) for PCOS. For each symptom checker, sensitivity was reported as 81.8% for endometriosis, 84.6% for uterine fibroids, and 100% for PCOS; specificity was reported as 84.6% for endometriosis, 81.8% for uterine fibroids, and 75% for PCOS; positive predictive value was reported as 81.8% for endometriosis, 84.6% for uterine fibroids, 80% for PCOS; and negative predictive value was reported as 84.6% for endometriosis, 81.8% for uterine fibroids, and 100% for PCOS. CONCLUSIONS: The single-condition symptom checkers have high levels of agreement with general practitioner classification for endometriosis, uterine fibroids, and PCOS. Given long delays in diagnosis for many reproductive health conditions, which lead to increased medical costs and potential health complications for individuals and health care providers, innovative health apps and symptom checkers hold the potential to improve care pathways.

Characterization of Self-reported Improvements in Knowledge and Health Among Users of Flo Period Tracking App: Cross-sectional Survey.

BACKGROUND: Research shows that poor knowledge and awareness of menstrual and pregnancy health among women are associated with adverse reproductive health and pregnancy outcomes. Menstrual cycle- and pregnancy-tracking mobile apps are promising tools for improving women's awareness of and attitudes toward their reproductive health; however, there is little information about subscribers' perceptions of app functionality and its impact on their knowledge and health. OBJECTIVE: This study aimed to explore knowledge and health improvements related to menstrual cycle and pregnancy, as well as improvements in general health among Flo app users. We also investigated what components of the Flo app were associated with the abovementioned improvements and evaluated whether those improvements differed based on education level, country of residence (low- and middle-income vs high-income countries), free or premium subscription to the app, short- or long-term use of the app, and frequency of use. METHODS: Flo subscribers who had been using the app for no less than 30 days, completed a web-based survey. A total of 2212 complete survey responses were collected. The survey included demographic questions and questions about motivations guiding the use of the Flo app and which components of the app improved their knowledge and health, as well as to what extent. RESULTS: Most study participants reported improvements in menstrual cycle (1292/1452, 88.98%) and pregnancy (698/824, 84.7%) knowledge from Flo app use. Participants with higher levels of education and those from high-income countries reported using the app predominantly for getting pregnant (χ21=4.2, P=.04; χ21=52.3, P<.001, respectively) and pregnancy tracking (χ21=19.3, P<.001; χ21=20.9, P=.001, respectively). Participants with less education reported using the app to avoid pregnancy (χ21=4.2; P=.04) and to learn more about their body (χ21=10.8; P=.001) and sexual health (χ21=6.3; P=.01), while participants from low- and middle-income countries intended to mainly learn more about their sexual health (χ21=18.2; P<.001). Importantly, the intended use of the app across education levels and country income levels matched areas in which they had gained knowledge and achieved their health goals upon use of the Flo app. Period, fertile days, and ovulation predictions as well as symptom tracking were consistently the top 3 components in the app that helped users with their cycle knowledge and general health. Reading articles or watching videos helped with users' education regarding their pregnancy. Finally, the strongest improvements in knowledge and health were observed in premium, frequent, and long-term users. CONCLUSIONS: This study suggests that menstrual health apps, such as Flo, could present revolutionary tools to promote consumer health education and empowerment on a global scale.

A large-scale RNAi screen reveals that mitochondrial function is important for meiotic chromosome organization in oocytes.

In prophase of the first meiotic division, chromatin forms a compact spherical cluster called the karyosome within the enlarged oocyte nucleus in Drosophila melanogaster. Similar clustering of chromatin has been widely observed in oocytes in many species including humans. It was previously shown that the proper karyosome formation is required for faithful chromosome segregation, but knowledge about its formation and maintenance is limited. To identify genes involved in karyosome formation, we carried out a large-scale cytological screen using Drosophila melanogaster oocytes. This screen comprised 3916 genes expressed in ovaries, of which 106 genes triggered reproducible karyosome defects upon knockdown. The karyosome defects in 24 out of these 106 genes resulted from activation of the meiotic recombination checkpoint, suggesting possible roles in DNA repair or piRNA processing. The other genes identified in this screen include genes with functions linked to chromatin, nuclear envelope, and actin. We also found that silencing of genes with mitochondrial functions, including electron transport chain components, induced a distinct karyosome defect typically with de-clustered chromosomes located close to the nuclear envelope. Furthermore, mitochondrial dysfunction not only impairs karyosome formation and maintenance, but also delays synaptonemal complex disassembly in cells not destined to become the oocyte. These karyosome defects do not appear to be mediated by apoptosis. This large-scale unbiased study uncovered a set of genes required for karyosome formation and revealed a new link between mitochondrial dysfunction and chromatin organization in oocytes.

Menstrual cycle-associated symptoms and workplace productivity in US employees: A cross-sectional survey of users of the Flo mobile phone app.

Objective: Mood and physical symptoms related to the menstrual cycle affect women's productivity at work, often leading to absenteeism. However, employer-led initiatives to tackle these issues are lacking. Digital health interventions focused on women's health (such as the Flo app) could help fill this gap. Methods: 1867 users of the Flo app participated in a survey exploring the impact of their menstrual cycle on their workplace productivity and the role of Flo in mitigating some of the identified issues. Results: The majority reported a moderate to severe impact of their cycle on workplace productivity, with 45.2% reporting absenteeism (5.8 days on average in the previous 12 months). 48.4% reported not receiving any support from their manager and 94.6% said they were not provided with any specific benefit for issues related to their menstrual cycle, with 75.6% declaring wanting them. Users stated that the Flo app helped them with the management of menstrual cycle symptoms (68.7%), preparedness and bodily awareness (88.7%), openness with others (52.5%), and feeling supported (77.6%). Users who reported the most positive impact of the Flo app were 18-25% less likely to report an impact of their menstrual cycle on their productivity and 12-18% less likely to take days off work for issues related to their cycle. Conclusions: Apps such as Flo could equip individuals with tools to better cope with issues related to their menstrual cycle and facilitate discussions around menstrual health in the workplace.

Premenstrual symptoms across the lifespan in an international sample: data from a mobile application.

Premenstrual symptoms, including physical and mood symptoms, affect a large proportion of women worldwide. Data on premenstrual symptoms across nations and age groups is limited. In the present study, we leveraged a large international dataset to explore patterns in premenstrual symptom frequency with age. A survey was administered to users of the Flo mobile application (app), aged 18 to 55. The survey queried app users about a range of premenstrual symptoms. Respondents were asked whether they experienced each symptom every menstrual cycle, some cycles, or never. Age was also captured and categorized as 18-27, 28-37, 38-47, 48-55. Data was summarized and Pearson's chi square test for count data assessed differences in symptom frequency by age group. A sample of 238,114 app users from 140 countries responded to the survey. The most common symptoms reported were food cravings (85.28%), mood swings or anxiety (64.18%), and fatigue (57.3%). Absentmindedness, low libido, sleep changes, gastrointestinal symptoms, weight gain, headaches, sweating or hot flashes, fatigue, hair changes, rashes, and swelling were significantly more frequent with increasing age (p's < 0.001). Mood swings and anxiety did not vary by age group. Of the respondents, 28.61% reported that premenstrual symptoms interfered with their everyday life each menstrual cycle. In a large international sample, the majority of women reported premenstrual food cravings, mood changes, and fatigue every menstrual cycle. Mood symptoms did not vary by age group, suggesting that premenstrual mood changes are a persistent issue among women of reproductive age.

Rates of self-reported postpartum depressive symptoms in the United States before and after the start of the COVID-19 pandemic.

BACKGROUND: This study aimed to determine the relationship between the start of the COVID-19 pandemic and changes in postpartum depressive symptoms (PDS) in individuals in the United States. Further analyses explored how these changes related to state-level measures of pandemic severity, economic hardship, and social isolation. METHODS: Data were collected from users of the Flo mobile health application who completed a survey about their mood within 90 days of giving birth. Analyses assessed changes in national and state-level self-reported PDS from a pre-pandemic period (N = 159,478) to a pandemic period (N = 118,622). Linear regression determined which state-level pandemic severity or economic factors were associated with changes in PDS. RESULTS: National rates of PDS increased from 6.5% (pre-pandemic) to 6.9% (pandemic). There was a significant increase in PDS over the course of the pandemic timeframe. Linear regressions revealed a negative association between percent change in PDS across states and COVID-19 deaths per 100 K residents as well as 2020 women's unemployment rate. There was no association between change in PDS and COVID-19 cases per 100 K residents, percent job loss, percent change in women's unemployment rate, or percentage of population staying at home. CONCLUSIONS: There was a national increase in PDS that worsened over the course of a year following the start of the COVID-19 pandemic. States with a greater increase in PDS tended to show overall fewer deaths from COVID-19 and lower women's unemployment rates. Further work is needed to identify what individual-level factors may be driving these differences.

Risk factors associated with postpartum depressive symptoms: A multinational study.

OBJECTIVE: To evaluate the association between maternal age, parity, gestational number (singleton vs twin), newborn gender and self-reported postpartum depressive symptoms (PDS) in a large multinational sample using survey data from a digital telephone application. METHODS: Women using the Flo app answered a survey (available in 10 languages) from January 2018 to April 2020. A survey question asking about emotional state was used to determine the presence of PDS. Chi-squared statistics were used to compare groups. A weighted mean prevalence was calculated based upon the socioeconomic status and reproductive population of each country in 2020. RESULTS: Over a million women from 138 countries participated. Of all respondents, 9.4% endorsed PDS. The weighted mean prevalence of PDS was 11%. We found that PDS decreased with advancing age. First-time mothers reported higher rates of PDS. Twin births were associated with a higher symptom burden than singleton births and mothers of twins in the oldest age group reported the greatest burden. We did not find a clinically significant difference in rates of PDS between mothers of singleton girls and boys. CONCLUSIONS: To our knowledge, this study is the first to examine risk factors for postpartum symptoms using the same survey across a large international population. These results can further research and clinical aims to identify and treat maternal depression more effectively. LIMITATIONS: Data was aggregated, thereby limiting analysis of individual associations. The survey was self-report and not diagnostic for postpartum depression. Generalizability of risks of postpartum depression should be approached with caution.

Characterization of polycystic ovary syndrome among Flo app users around the world.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex and multi-faceted endocrine disorder that affects 5-20% of women. Literature is limited regarding potentially differing PCOS phenotypes among women around the world. OBJECTIVE: To use Flo app technology to understand the multifaceted characteristics of PCOS across several countries and identify contributing risk factors to the development of this condition. STUDY DESIGN: Flo is a widely used female health and wellbeing app with period tracking functionality that provides a globally representative and medically unbiased perspective on PCOS symptomatology. A chatbot dialog on PCOS was subsequently administered on the Flo application (app) to users from 142 countries (with at least 100 respondents) who have the app running in English during September-October 2019. RESULTS: For analyses, we selected the five countries with the greatest number of respondents: US (n = 243,238), UK (n = 68,325), India (n = 40,092), Philippines (n = 35,131), and Australia (n = 29,926). Bloating was the most frequently reported symptom among PCOS-positive women and appeared to be the main predictor of PCOS in our model (odds ratio 3·76 [95% CI 3·60-3·94]; p < 0·0001). Additional top predictors of PCOS are high blood cholesterol and glucose levels. As BMI increased, the percentage of women who reported a physician-confirmed PCOS diagnosis also increased. However, women in India did not follow this trend. CONCLUSION: Our findings are based on the largest known PCOS dataset and indicate that symptoms are more complex than previously understood. The most frequently reported symptoms (bloating, facial hirsutism, irregular cycles, hyperpigmentation, and baldness) are broader than those included in the Rotterdam criteria. Future work should reevaluate and refine the criteria utilized in PCOS diagnosis.

SCF-Fbxo42 promotes synaptonemal complex assembly by downregulating PP2A-B56.

Meiosis creates genetic diversity by recombination and segregation of chromosomes. The synaptonemal complex assembles during meiotic prophase I and assists faithful exchanges between homologous chromosomes, but how its assembly/disassembly is regulated remains to be understood. Here, we report how two major posttranslational modifications, phosphorylation and ubiquitination, cooperate to promote synaptonemal complex assembly. We found that the ubiquitin ligase complex SCF is important for assembly and maintenance of the synaptonemal complex in Drosophila female meiosis. This function of SCF is mediated by two substrate-recognizing F-box proteins, Slmb/ßTrcp and Fbxo42. SCF-Fbxo42 down-regulates the phosphatase subunit PP2A-B56, which is important for synaptonemal complex assembly and maintenance.

Kdm5/Lid Regulates Chromosome Architecture in Meiotic Prophase I Independently of Its Histone Demethylase Activity.

During prophase of the first meiotic division (prophase I), chromatin dynamically reorganises to recombine and prepare for chromosome segregation. Histone modifying enzymes are major regulators of chromatin structure, but our knowledge of their roles in prophase I is still limited. Here we report on crucial roles of Kdm5/Lid, one of two histone demethylases in Drosophila that remove one of the trimethyl groups at Lys4 of Histone 3 (H3K4me3). In the absence of Kdm5/Lid, the synaptonemal complex was only partially formed and failed to be maintained along chromosome arms, while localisation of its components at centromeres was unaffected. Kdm5/Lid was also required for karyosome formation and homologous centromere pairing in prophase I. Although loss of Kdm5/Lid dramatically increased the level of H3K4me3 in oocytes, catalytically inactive Kdm5/Lid can rescue the above cytological defects. Therefore Kdm5/Lid controls chromatin architecture in meiotic prophase I oocytes independently of its demethylase activity.