The effects of a real-time temperature monitoring non-ablative monopolar radiofrequency technology on vulvovaginal atrophy symptoms in postmenopausal Chinese women.

BACKGROUND: Vulvovaginal atrophy (VVA) includes a wide range of conditions affecting the reproductive and urinary systems, often requiring careful evaluation and management for optimal health. AIMS: This study aims to evaluate the symptom management effects of a real time temperature-monitored non-ablative RF device for the treatment of postmenopausal Chinese women with VVA symptoms. METHODS: This pilot study involved 24 postmenopausal Chinese women with one or more VVA symptoms, who wished to remain sexually active. VHIS, VAS, and FSFI were used to track and evaluate various aspects of the patient's condition. Analyses were conducted at the end of the study to verify the statistical significance of the treatment's results. RESULTS: All patients reported substantial, statistically significant, improvements on every VVA symptom tracked. Approximately 80% of the patients reported total symptom reversal at 12-week post-treatment follow-up. CONCLUSION: This pilot study demonstrated that non-ablative, monopolar RF technology equipped with real time temperature monitoring is feasible and safe in the treatment of postmenopausal women with VVA symptoms, and efficacious at up to 12 weeks post-treatment.

Almanac - Retrieval-Augmented Language Models for Clinical Medicine.

BACKGROUND: Large language models (LLMs) have recently shown impressive zero-shot capabilities, whereby they can use auxiliary data, without the availability of task-specific training examples, to complete a variety of natural language tasks, such as summarization, dialogue generation, and question answering. However, despite many promising applications of LLMs in clinical medicine, adoption of these models has been limited by their tendency to generate incorrect and sometimes even harmful statements. METHODS: We tasked a panel of eight board-certified clinicians and two health care practitioners with evaluating Almanac, an LLM framework augmented with retrieval capabilities from curated medical resources for medical guideline and treatment recommendations. The panel compared responses from Almanac and standard LLMs (ChatGPT-4, Bing, and Bard) versus a novel data set of 314 clinical questions spanning nine medical specialties. RESULTS: Almanac showed a significant improvement in performance compared with the standard LLMs across axes of factuality, completeness, user preference, and adversarial safety. CONCLUSIONS: Our results show the potential for LLMs with access to domain-specific corpora to be effective in clinical decision-making. The findings also underscore the importance of carefully testing LLMs before deployment to mitigate their shortcomings. (Funded by the National Institutes of Health, National Heart, Lung, and Blood Institute.).

Centering equity in a longitudinal health systems science curricula.

What was the educational challenge?Health inequity impedes care at every level of the health care system. Despite this, health equity is not the foundation for most health systems science (HSS) curricula.What was the solution?We reframed our HSS curricula to focus on health equity.How was the solution implemented?We integrated equity concepts into all HSS content areas. First-year content emphasizes structural competency and is delivered through didactics, discussions, interprofessional education, panels, and service-learning requirements. Second-year content applies HSS principles in the clinical space through direct patient care and assignments. Third- and fourth-year content focuses on HSS advocacy and leadership.What lessons were learned that are relevant to a wider global audience?It is crucial to center health equity in medical curricula to improve patient outcomes. Proper faculty development, non-judgmental discussions, and integration with clinical and medical sciences are critical to successful implementation.What are the next steps?We will address feedback, emphasize relevance to patients and populations, and refine outcome measures.

The Society of General Internal Medicine's Recommendations to Improve LGBTQ + Health.

Lesbian, gay, bisexual, transgender, queer, and other sexual and gender minority (LGBTQ +) individuals experience bias in healthcare with 1 in 6 LGBTQ + adults avoiding healthcare due to anticipated discrimination and overall report poorer health status compared to heterosexual and cisgendered peers. The Society of General Internal Medicine (SGIM) is a leading organization representing academic physicians and recognizes that significant physical and mental health inequities exist among LGBTQ + communities. As such, SGIM sees its role in improving LGBTQ + patient health through structural change, starting at the national policy level all the way to encouraging change in individual provider bias and personal actions. SGIM endorses a series of recommendations for policy priorities, research and data collection standards, and institutional policy changes as well as community engagement and individual practices to reduce bias and improve the well-being and health of LGBTQ + patients.

ECHO "Bootcamp": An Innovative Training Model to Onboard Providers in the Care of Gender Diverse Patients.

Purpose: Extension for Community Health Outcomes (ECHO) is a model of continuing medical education meant to connect academic medical center-based specialists with community providers to increase capacity in managing complex health conditions. The purpose of this study was to evaluate the effectiveness of a shortened "bootcamp" ECHO model in increasing participant competence with topics related to transgender and gender diverse (TGD) health care and the impact of "bootcamp" participation on enrollment in an ongoing ECHO series. Methods: An ongoing monthly ECHO series was instituted on topics of TGD health. After 2 years, the team implemented a four-session "bootcamp" for four consecutive weeks during March 2022 to introduce foundational topics for new participants who had joined or were considering joining the ongoing series. Qualitative and quantitative results were collected from self-reported pre-/post-surveys as well as from in-session quizzes. Results: There were 71 participants in the "bootcamp" including health care providers and support staff. Attendees reported a 10.3% increase (p = 0.02) in self-reported comfort providing care to transgender patients. Pre-/post-knowledge improved in areas of health inequities (50% vs. 74% correct pre/post), surgical requirements (33% vs. 74%), and effects of masculinizing (55% vs. 70%) and feminizing (64% vs. 89%) hormone therapy. Prescribing providers reported a significant change across four areas of practice competency. Among 71 "bootcamp" participants, 15 registered for the ongoing program. Conclusion: Use of a "bootcamp" highlights ways to increase participant comfort and knowledge in providing TGD health care in a shortened timeframe and recruit new participants to an ongoing ECHO curriculum.

Ensuring the future of otitis media research: Interest in and feasibility of a mentoring network program within the otitis media research community.

OBJECTIVES: The goal of this study was to assess the feasibility of the implementation of a mentoring network program based on expressed interest and the diverse composition of the otitis media research community in order to address attrition of the scientific workforce. METHODS: An online survey was sent to basic, translational, and clinical researchers with a known interest in otitis media. RESULTS: Of 509 eligible participants, 119 (23.4%) responded to the survey. Survey respondents had a diverse background by completed education, current job description, and membership in an underrepresented group in science. Most faculty respondents (76.4%) were willing to participate in the proposed program as mentors and faculty lecturers, or had early-career researchers or trainees in their research group who were willing to participate as mentees in the mentoring network. Scientific and non-scientific topics for inclusion in the training program were ranked, with immunology and inflammation, microbiology, science leadership and collaboration, mentoring, and grantsmanship as main foci of interest among respondents. CONCLUSION: Our survey results showed enthusiastic participation among responding otitis media researchers, indicating the feasibility of implementing a mentoring network program that will address workforce attrition, particularly among underrepresented groups in science.

A Transgender Health Information Resource: Participatory Design Study.

BACKGROUND: Despite the abundance of health information on the internet for people who identify as transgender and gender diverse (TGD), much of the content used is found on social media channels, requiring individuals to vet the information for relevance and quality. OBJECTIVE: We developed a prototype transgender health information resource (TGHIR) delivered via a mobile app to provide credible health and wellness information for people who are TGD. METHODS: We partnered with the TGD community and used a participatory design approach that included focus groups and co-design sessions to identify users' needs and priorities. We used the Agile software development methodology to build the prototype. A medical librarian and physicians with expertise in transgender health curated a set of 97 information resources that constituted the foundational content of the prototype. To evaluate the prototype TGHIR app, we assessed the app with test users, using a single item from the System Usability Scale to assess feature usability, cognitive walk-throughs, and the user version of the Mobile Application Rating Scale to evaluate the app's objective and subjective quality. RESULTS: A total of 13 people who identified as TGD or TGD allies rated their satisfaction with 9 of 10 (90%) app features as good to excellent, and 1 (10%) of the features-the ability to filter to narrow TGHIR resources-was rated as okay. The overall quality score on the user version of the Mobile Application Rating Scale was 4.25 out of 5 after 4 weeks of use, indicating a good-quality mobile app. The information subscore received the highest rating, at 4.75 out of 5. CONCLUSIONS: Community partnership and participatory design were effective in the development of the TGHIR app, resulting in an information resource app with satisfactory features and overall high-quality ratings. Test users felt that the TGHIR app would be helpful for people who are TGD and their care partners.

Community Engagement in Research and Design of a Transgender Health Information Resource.

BACKGROUND: Access to credible and relevant health care information is an unmet need for the transgender and gender-diverse (TGD) community. This paper describes the community engagement methods and resulting community priorities as part of a codesign process for the development of a Transgender Health Information Resource (TGHIR) application. METHODS: A lesbian, gay, bisexual, transgender, and queer advocacy organization and an academic health sciences team partnered to establish a community advisory board (CAB) of TGD individuals, parents of TGD individuals, and clinicians with expertise in transgender health to inform the project. The analytic-deliberative model and group facilitation strategies based on Liberating Structures guided procedures. Affinity grouping was used to synthesize insights from CAB meeting notes regarding roles and perspectives on the design of the TGHIR application. We used the Patient Engagement in Research Scale (PEIRS) to evaluate CAB members' experience with the project. RESULTS: The CAB emphasized the importance of designing the application with and for the TGD community, including prioritizing intersectionality and diversity. CAB engagement processes benefited from setting clear expectations, staying focused on goals, synchronous and asynchronous work, and appreciating CAB member expertise. TGHIR application scope and priorities included a single source to access relevant, credible health information, the ability to use the app discreetly, and preserving privacy (i.e., safe use). An out-of-scope CAB need was the ability to identify both culturally and clinically competent TGD health care providers. PEIRS results showed CAB members experienced moderate to high levels of meaningful engagement (M[standard deviation] = 84.7[12] out of 100). CONCLUSION: A CAB model was useful for informing TGHIR application priority features. In-person and virtual methods were useful for engagement. The CAB continues to be engaged in application development, dissemination, and evaluation. The TGHIR application may complement, but will not replace, the need for both culturally and clinically competent health care for TGD people.

Co-design of the Transgender Health Information Resource: Web-Based Participatory Design.

BACKGROUND: There is an urgent and unmet need for accessible and credible health information within the transgender and gender-diverse (TGD) community. Currently, TGD individuals often seek and must find relevant resources by vetting social media posts. A resource that provides accessible and credible health-related resources and content via a mobile phone app may have a positive impact on and support the TGD population. OBJECTIVE: COVID-19 stay-at-home orders forced a shift in the methods used in participatory design. In this paper, we aimed to describe the web-based participatory methods used to develop the Transgender Health Information Resource. We also described and characterized the web-based engagement that occurred during a single session of the overall design process. METHODS: We planned and conducted web-based design sessions to replace the proposed in-person sessions. We used web-based collaborative tools, including Zoom (Zoom Video Communications), Mural (Mural), REDCap (Research Electronic Data Capture; Vanderbilt University), and Justinmind (Justinmind), to engage the participants in the design process. Zoom was used as an integrated platform for design activities. Mural was used to perform exercises, such as free listing, brainstorming, and grouping. REDCap allowed us to collect survey responses. Justinmind was used to create prototypes that were shared and discussed via Zoom. Recruitment was led by one of our community partners, One Colorado, who used private Facebook groups in which web-based flyers were dispersed. The design process took place in several workshops over a period of 10 months. We described and characterized engagement during a single design session by tracking the number of influential interactions among participants. We defined an influential interaction as communication, either verbal or web-based content manipulation, that advanced the design process. RESULTS: We presented data from a single design session that lasted 1 hour and 48 minutes and included 4 participants. During the session, there were 301 influential interactions, consisting of 79 verbal comments and 222 web-based content manipulations. CONCLUSIONS: Web-based participatory design can elicit input and decisions from participants to develop a health information resource, such as a mobile app user interface. Overall, participants were highly engaged. This approach maintained the benefits and fidelity of traditional in-person design sessions, mitigated deficits, and exploited the previously unconsidered benefits of web-based methods, such as enhancing the ability to participate for those who live far from academic institutions. The web-based approach to participatory design was an efficient and feasible methodological design approach.

What Happened and Why: Responding to Racism, Discrimination, and Microaggressions in the Clinical Learning Environment.

Introduction: Within clinical learning environments, medical students are uniquely faced with power differentials that make acts of racism, discrimination, and microaggressions (RDM) challenging to address. Experiences of microaggressions and mistreatment are correlated with higher rates of positive depression screening and lower satisfaction with medical training. We developed a curriculum for medical students beginning clerkship rotations to promote the recognition of and response to RDM. Methods: Guided by generalized and targeted needs assessments, we created a case-based curriculum to practice communication responses to address RDM. The communication framework, a 6Ds approach, was developed through adaptation and expansion of established and previously learned communication upstander frameworks. Cases were collected through volunteer submission and revised to maintain anonymity. Faculty and senior medical students cofacilitated the small-group sessions. During the sessions, students reviewed the communication framework, explored their natural response strategies, and practiced all response strategies. Results: Of 196 workshop participants, 152 (78%) completed the evaluation surveys. Pre- and postsession survey cohort comparison demonstrated a significant increase in students' awareness of instances of RDM (from 34% to 46%), knowledge of communication strategies to mitigate RDM (presession M = 3.4, postsession M = 4.6, p < .01), and confidence to address RDM (presession M = 3.0, postsession M = 4.4, p < .01). Discussion: Students gained valuable communication skills from interactive sessions addressing RDM using empathy, reflection, and relatability. The workshop empowered students to feel prepared to enter professional teams and effectively mitigate harmful discourse.

A Novel Multidisciplinary Model of Care for Transgender and Gender Diverse Adults: Program Description and Patient Perspectives.

Transgender and gender diverse (TGD) adults face significant health care disparities stemming from systematic discrimination and stigma in health care. We created the UCHealth Integrated Transgender Program to provide culturally responsive and clinically competent care to TGD adults in Colorado. This article outlines the clinic model and summarizes results from a qualitative patient survey to assess patients' impressions and recommendations for improvement. A multidisciplinary integrated clinic is a feasible and desired step toward improving health care for the TGD population.

The ACLGIM LEAD Program: a Leadership Program for Junior-Mid-Career Faculty.

BACKGROUND: Junior to mid-career medical faculty often move into administrative and leadership roles without formal leadership training. Many national leadership training programs target senior rather than junior faculty. AIM: To address the leadership development needs of junior and mid-career faculty. SETTING: Sessions at annual meetings combined with online learning, independent work, and leadership coaching. PARTICIPANTS: 79 junior-mid-career general internal medicine (GIM) faculty enrolled in five consecutive annual cohorts from 2014 to 2018. PROGRAM DESCRIPTION: LEAD scholars participate in a full-day anchor session followed by selected workshops during the annual meeting. They then participate in monthly online sessions, complete a project, interview a senior leader, and receive leadership coaching from senior GIM faculty. PROGRAM EVALUATION: Post-program evaluation indicated the LEAD program was effective in helping participants understand what it means to be a good leader (93%, 37/40), become a more reflective leader (90%, 35/39), and apply principles of leadership to increase effectiveness in their role (88%, 34/39). DISCUSSION: LEAD provides junior-mid-career medical faculty an opportunity to learn effective leadership skills and build a network.

Early Intervention for LGBTQ Health: A 10-Hour Curriculum for Preclinical Health Professions Students.

Introduction: Individuals who identify as lesbian, gay, bisexual, transgender, or queer (LGBTQ) face significant health disparities and barriers to accessing care. Patients have reported provider lack of knowledge as one of the key barriers to culturally responsive, clinically competent care. Many US and Canadian medical schools still offer few curricular hours dedicated to LGBTQ-related topics, and medical students continue to feel unprepared to care for LGBTQ patients. Methods: We developed a 10-hour LGBTQ health curriculum for preclinical medical and physician assistant students. The curriculum included lectures and case-based small-group discussions covering LGBTQ terminology, inclusive sexual history taking, primary care and health maintenance, and transition-related care. It also included a panel discussion with LGBTQ community members and a small-group practice session with standardized patients. Students were surveyed before and after completing the curriculum to assess for increases in confidence and knowledge related to LGBTQ-specific care. Results: Forty first- and second-year medical students completed the sessions and provided valid responses on pre- and postcourse surveys. Nearly all students initially felt unprepared to sensitively elicit information, summarize special health needs and primary care recommendations, and identify community resources for LGBTQ individuals. There was significant improvement in students' confidence in meeting these objectives after completion of the five sessions. Knowledge of LGBTQ health issues increased minimally, but there was a significant increase in knowledge of LGBTQ-related terminology. Discussion: Our 10-hour LGBTQ health curriculum was effective at improving medical students' self-confidence in working with LGBTQ patients but was less effective at increasing LGBTQ-related medical knowledge.

Measuring the Health of an Invisible Population: Lessons from the Colorado Transgender Health Survey.

BACKGROUND: Transgender people, those whose gender identity does not match their sex assigned at birth, face barriers to receiving health care. These include discrimination, prohibitive cost, and difficulty finding transgender-inclusive providers. As transgender identities are not typically recognized in public health research, the ability to compare the health of the transgender population to the overall population is limited. OBJECTIVE: The Colorado Transgender Health Survey sought to explore current disparities and their effects on the health of transgender people in Colorado. DESIGN AND PARTICIPANTS: The Colorado Transgender Health Survey, based on the Behavioral Risk Factor Surveillance System (BRFSS), was developed by the Colorado Department of Public Health and Environment, transgender advocates, and transgender community members. Outreach was targeted to transgender-inclusive events and organizations. MAIN MEASURES: Responses to the 2014 Colorado Transgender Health Survey were compared side by side to Colorado 2014 BRFSS data. RESULTS: Results from 406 transgender or gender-nonconforming adults who live in Colorado were included in the analysis. Forty percent of respondents report delaying medical care due to cost, inadequate insurance, and/or fear of discrimination. Respondents report significant mental health concerns, with 43% reporting depression, 36% reporting suicidal thoughts, and 10% attempting suicide in the past year. Respondents with a transgender-inclusive provider were more likely to receive wellness exams (76 versus 48%), less likely to delay care due to discrimination (24 versus 42%), less depressed (38 versus 54%), and less likely to attempt suicide (7 versus 15%) than those without. CONCLUSIONS: The transgender community in Colorado faces significant disparities, especially around mental health. However, a transgender-inclusive provider is associated with improved mental and physical health and health behaviors. Further population-level research and provider education on transgender health should to be incorporated into national efforts to eliminate health disparities.

Development of a formula for estimating plasma free cortisol concentration from a measured total cortisol concentration when elastase-cleaved and intact corticosteroid binding globulin coexist.

Cortisol bound to corticosteroid binding globulin (CBG) contributes up to 90% of the total cortisol concentration in circulation. Therefore, changes in the binding kinetics of cortisol to CBG can potentially impact on the concentration of free cortisol, the only form that is responsible for the physiological function of the hormone. When CBG is cleaved into elastase-cleaved CBG (eCBG) by the activity of neutrophil elastase, its affinity for cortisol is reduced. Therefore, when eCBG coexists with intact CBG (iCBG) in plasma, the calculation of free cortisol concentration based on the formulae that considers only one CBG pool with the same affinity for cortisol may be inappropriate. In this study, we developed in vivo and in vitro models of cortisol partitioning which considers two CBG pools, iCBG and eCBG, with different affinities for cortisol, and deduce a new formula for calculating plasma free cortisol concentration. The formula provides better estimates of free cortisol concentration than previously used formulae when measurements of the concentrations of the two CBG forms are available. The model can also be used to estimate the affinity of CBG and albumin for cortisol in different clinical groups. We found no significant difference in the estimated affinity of CBG and albumin for cortisol in normal, sepsis and septic shock groups, although free cortisol was higher in sepsis and septic shock groups. The in vivo model also demonstrated that the concentration of interstitial free cortisol is increased locally at a site of inflammation where iCBG is cleaved to form eCBG by the activity of elastase released by neutrophils. This supports the argument that the cleavage of iCBG at sites of inflammation leads to more lower-affinity eCBG and may be a mechanism that permits the local concentration of free cortisol to increase at these sites, while allowing basal free cortisol concentrations at other sites to remain unaffected.

The role of enzyme compartmentalization on the regulation of steroid synthesis.

Steroidogenic enzymes can be compartmentalized at different levels, some by virtue of being membrane bound in specific intra-cellular compartments. Although both 3ß-hydroxysteroid dehydrogenase/Δ(5)-Δ(4) isomerase (3ß-HSD) and 17α-hydroxylase/17,20-lyase cytochrome P450 (P450c17) are expressed in the endoplasmic reticulum (ER) membrane, these proteins may still be spatially separated within this membrane system. Side chain cleavage cytochrome P450 (P450scc) is anchored to the inner mitochondrial membrane and this organelle is the major source of pregnenolone (P5) feeding steroidogenesis. Furthermore, steroidogenic enzymes can also be partitioned in different cells. Although well recognized, the effect of enzyme compartmentalization on the rate of steroid production and the balance of different steroids is unclear. This study uses mathematical modeling to investigate the effect of enzyme compartmentalization on steroid synthesis in a human-ovine-bovine model of steroid synthesis. The study shows that the spatial separation of steroidogenic enzymes within the ER has a minimal effect on the rate of steroid synthesis. The compartmentalization of the enzymes into different organelles of a cell creates cellular steroid gradients and can affect the balance of the different steroid products. The partitioning of steroidogenic enzymes in different cells reduces the rate of steroid synthesis. The greater is the distance between the cells that contain different enzymes, the more the rate of steroid synthesis is reduced. Additionally, when 3ß-HSD is not in the same cell with P450scc (the P5 source) and P450c17, the ratio of the Δ(5)-pathway products' concentrations to the Δ(4)-pathway products' concentrations is increased. However, none of these levels of compartmentalization of steroidogenic enzymes alter the qualitative behaviors of steroid synthesis in response to variation in an enzyme activity or P5 supply.

Multilevel regulation of steroid synthesis and metabolism in the bovine placenta.

Steroid hormones play critical roles in almost all physiological processes in male and female reproduction. In a normal pregnancy, the concentrations of steroid hormones in maternal and foetal blood vary with gestation in response to changing needs. The placenta plays a central role in producing the appropriate steroids to support the pregnancy by coordinating its own steroidogenic activity with that of the corpus luteum and responding to foetal signals. Although much is known about the steroidogenic potential of the bovine placenta, far less is known about how the placenta integrates the synthesis of steroids with their subsequent metabolism and clearance to achieve appropriate local and peripheral concentrations of steroids in maternal and foetal blood at each stage of gestation. This review focuses on the current knowledge of the temporal and spatial regulation and compartmentalization of the biochemical pathways by which potent steroid hormones are synthesized and metabolized in the bovine placenta. The aim is to increase our understanding of how the balance of synthesis and metabolism determines placental steroid output as it changes with development and differentiation, and how this is regulated in response to the variations in the foetal signals and luteal secretory activity. The review highlights knowledge gaps and suggests that mathematical modelling can help understand the effect of different levels of regulation on the steroidogenic output of an organ, such as the bovine placenta.

Variation in 3ß-hydroxysteroid dehydrogenase activity and in pregnenolone supply rate can paradoxically alter androstenedione synthesis.

The 3ß-hydroxysteroid dehydrogenase/Δ(5)-Δ(4) isomerase (3ß-HSD) and 17α-hydroxylase/17,20-lyase cytochrome P450 (P450c17) enzymes are important in determining the balance of the synthesis of different steroids such as progesterone (P4), glucocorticoids, androgens, and estrogens. How this is achieved is not a simple matter because each of the two enzymes utilizes more than one substrate and some substrates are shared in common between the two enzymes. The two synthetic pathways, Δ(4) and Δ(5), are interlinked such that it is difficult to predict how the synthesis of each steroid changes when any of the enzyme activities is varied. In addition, the P450c17 enzyme exhibits different substrate specificities among species, particularly with respect to the 17,20-lyase activity. The mathematical model developed in this study simulates the network of reactions catalyzed by 3ß-HSD and P450c17 that characterizes steroid synthesis in human, non-human primate, ovine, and bovine species. In these species, P450c17 has negligible 17,20-lyase activity with the Δ(4)-steroid 17α-hydroxy-progesterone (17OH-P4); therefore androstenedione (A4) is synthesized efficiently only from dehydroepiandrosterone (DHEA) through the Δ(5) pathway. The model helps to understand the interplay between fluxes through the Δ(4) and Δ(5) pathways in this network, and how this determines the response of steroid synthesis to the variation in 3ß-HSD activity or in the supply of the precursor substrate, pregnenolone (P5). The model simulations show that A4 synthesis can change paradoxically when 3ß-HSD activity is varied. A decrease in 3ß-HSD activity to a certain point can increase A4 synthesis by favouring metabolism through the Δ(5) pathway, though further decrease in 3ß-HSD activity beyond that point eventually limits A4 synthesis. The model also showed that due to the competitive inhibition of the enzymes' activities by substrates and products, increasing the rate of P5 supply above a certain point can suppress the synthesis of A4, DHEA, and 17OH-P4, and consequently drive more P5 towards P4 synthesis.