Cross-Cultural Disparities in Psychosocial Research with Individuals with Classical Congenital Adrenal Hyperplasia: A Scoping Review

Classical congenital adrenal hyperplasia (CAH) refers to a group of conditions characterized by autosomal recessive enzyme deficiencies that interfere with cortisol production in the adrenal cortex. CAH may result in medical complications such as atypical genital appearance and the inability to retain sodium [1]. Families of individuals with CAH are tasked with making complex medical decisions and daily medication management. As such, those with conditions affecting sex development and their families are at risk for psychosocial adaptation difficulties throughout development secondary to factors such as atypical genital appearance, genital surgery, gender identity, sexual functioning, reduced fertility, psychological distress, and impaired quality of life [2].

Clinical care recommendations call for including specialized psychosocial providers on the CAH healthcare team to aid in navigating various aspects of this management (e.g., assigning sex of rearing, engaging in surgical decision-making, experiencing stigma, coping with long-term adjustment outcomes; [2, 3]). Providers are encouraged to engage in patient-centered care and consider the individual’s and their family’s cultural values, as well as the broader sociocultural context, particularly as they pertain to issues concerning gender [4]. Moreover, it has been suggested that much of the psychosocial research conducted is not cross-culturally representative [5]. Recent meta-analysis findings also indicate that geographic areas with the highest CAH rates are indeed in non-Western parts of the world [6]. In other words, empirically based recommendations and standards of psychosocial care may not generalize worldwide.

Although previous studies have directed attention to the clinical implications related to cultural differences in psychosocial adjustment among individuals with CAH [5], to our knowledge, no studies have attempted to systematically and empirically review the CAH literature to quantify any disparity between rates of CAH and psychosocial research arising from different geographic regions. Therefore, the current scoping review is preferable to other types of reviews (e.g., systematic review), as the present aim is to systematically map the existing research, identify gaps in the literature, and determine areas for future research [7]. This scoping review aims to: (1) identify rates of CAH by geographic region, and rates of psychosocial research by geographic region, and (2) compare those rates by respective geographic region.

Data sources for this project were pulled from 6 electronic article databases, including PubMed (biomedical), Scopus/Elsevier (multidisciplinary), CINAHL Complete/EBSCO (nursing and allied health), PsycINFO/ProQuest (psychology and behavioral sciences), PsycArticles/ProQuest (psychology), and Health Source Nursing and Academic Edition/EBSCO (nursing and allied health). These databases were selected because of their comprehensive coverage of biomedical, behavioral sciences, health, and nursing literature. Initial searches in these databases were performed on January 8, 2021, followed by a second round of searching on November 11, 2021, and a third round of searching on August 2, 2022, to collect additional articles that were published in 2022.

Given the scope of this project, the search strategy contained two phases. Phase one targeted psychosocial research that addressed individuals with CAH. A query was developed that included a targeted range of terms as follows: (“psychosocial adjustment” OR “emotional adjustment” OR “psychological adjustment” OR “quality of life” OR “adjustment” OR “depression” OR “anxiety” OR “posttraumatic stress” OR “distress” OR “mental health”) AND (“congenital adrenal hyperplasia” OR “21-hydroxylase deficiency” OR “Classic CAH salt losing” OR “disorder of sex development” OR “difference of sex development”). Phase two aimed to look for studies that addressed CAH in relation to birth/prevalence rates. A second query was built that included a targeted range of terms as follows: (“birth rate” OR “prevalence rate” OR “incidence”) AND (“congenital adrenal hyperplasia” OR “21-hydroxylase deficiency” OR “Classic CAH salt losing” OR “disorder of sex development” OR “difference of sex development”).

These search queries were applied separately to the aforementioned electronic article databases. No limits were set on publication dates for searching within these databases. However, searches were limited to academic journal articles in the English language. While it is typical for a scoping review to identify both published and unpublished sources, given the research questions and the time constraint, the decision was made at the outset to include only peer-reviewed evidence published in academic journal articles.

The online supplementary Material (for all online suppl. material, see https://doi.org/10.1159/000531167) presents a summary of data sources, searches, and search findings. A total number of 1,102 articles were retrieved from the six databases for psychosocial research on CAH, and 918 articles reporting birth rates and CAH were discovered. The citation management software EndNote was used to import sources from the databases to EndNote. Duplicates were removed using a function available in EndNote which reduced the number of sources to 608 rate studies and 765 psychosocial articles. Resulting data were then imported into Microsoft Excel spreadsheets for the next step of screening.

Inclusion criteria were as follows: (1) written in English, (2) a peer-reviewed published article, (3) includes at least CAH, 21-hydroxylase deficiency, or classic CAH salt losing, and (4) includes birth/prevalence rate.

Inclusion criteria were as follows: (1) written in English, (2) a peer-reviewed published article, (3) includes at least CAH, 21-hydroxylase deficiency, or classic CAH salt losing, and (4) assesses psychosocial adjustment (broadly defined).

Abstracts of 608 unique articles were reviewed by authors K.T., N.B., T.D., and R.F. Two authors reviewed each abstract to evaluate it for inclusion criteria. Classification discrepancies between two reviewers were resolved by re-rating content and consulting with senior authors until raters agreed on final classifications. Abstract review resulted in 126 studies for full-text review. The full-text review followed identical procedures as for the abstract review (i.e., 2 authors screening each study for inclusion criteria and jointly resolving disagreements). An additional 58 studies were excluded in the full-text review stage upon not meeting inclusion criteria (e.g., did not uniquely examine rates for classical CAH, was a case study or series). Therefore, 68 articles met inclusion criteria upon full-text review. See Figure 1 for flow chart depicting CAH rate article review process. For each article, CAH rate information and country/geographic region were collected and validated within rater pairs.

Review of psychosocial studies was conducted in an identical manner, such that 765 abstracts were identified for abstract review. Upon classification by author pairs, 187 studies were included for full-text review. Full-text review resulted in excluding an additional 94 studies for not meeting criteria (e.g., did not examine psychosocial data, did not separately report outcomes for classical CAH). Due to their specific nature, studies solely examining factors such as sexual satisfaction and gender identity were excluded. Therefore, 93 articles met inclusion criteria upon full-text review. See Figure 2 for flow chart depicting psychosocial article review process. For each article, country/geographic region were collected and validated within rater pairs.

The final sample consisted of 68 empirical studies focusing on CAH birth/incidence/prevalence rates. The regions with the highest reported rates of CAH were Thailand, Ghana, and India. Of note, some rates varied within a given region due to multiple studies’ findings. For these regions, the average of the reported rates was calculated. See Figure 3 for a summary of findings. All final included CAH rate articles are included in the online supplementary Material. Of note, there was wide variation in the number of studies reporting CAH rate information by geographic region. For example, there were several publications from which to glean CAH rates for the USA (n = 7), Japan (n = 7), Brazil (n = 6), and Italy (n = 6), whereas only one publication was found to meet inclusion criteria for 17 other countries/regions.

The final sample consisted of 93 empirical studies focusing on psychosocial factors among individuals with CAH and their families. The regions with the highest number of studies were the USA, Germany, and the UK. Some examples of psychosocial findings reported include quality of life, body image, self-esteem, and anxious and depressive symptoms. Regions were sorted based on their proportion of the total number of publications. See Figure 3 for a summary of findings. All final included CAH psychosocial articles are included in the online supplementary Material.

The present study aimed to use scoping review techniques to further identify the gap between regions with higher CAH rates and those with the greater proportion of psychosocial research. Findings reveal a disparity between those countries with the greatest proportion of individuals affected (i.e., Thailand, Ghana, and India) and those countries with the highest representation in the psychosocial literature (i.e., USA, Germany, and UK). In other words, psychosocial findings that intend to inform evidence-based practices are likely not globally culturally representative.

Understanding psychosocial factors that impact those with CAH and their families not only informs interventions [8], but also has the potential to impact medical decision-making [3, 9‒11], clinical recommendations [3], and policy changes [1]. However, broader systems-level psychosocial factors such as cultural norms, traditions, values, beliefs, healthcare policies and resources, and educational/occupational opportunities are heterogenous both within and across cultures; importantly, they exert significant influence over the management of CAH [4, 12]. Clinical recommendations and policies based on extant psychosocial research may not be universally appropriate given the diverse, respective cultural contexts of individuals with CAH [3, 13]. Indeed, present findings identify a gap between those regions conducting research that informs care recommendations and those regions in which there appear to be the highest rates of diagnosis.

Similarly, a review from Zainuddin and colleagues [5] highlights the disparities in research on the quality of life in female patients with CAH, noting several culturally bound considerations unique to some non-Western nations. These considerations include societal discrimination and stigma of conditions involving sex development; cultural preference for sons; inadequate prenatal treatment, prenatal counseling, and newborn screening; absent or minimal government support for long-term medical care; and variation in the quality and accessibility of genitoplasty surgery. As the disparity presently reported in this study [11] suggests, much of the psychosocial care recommendations are guided by research findings from Western nations and may not adequately translate to patients in other regions of the world [3]. In general, psychosocial research has been critiqued for being predominantly Western, educated, industrialized, rich, and democratic and lacking cultural representativeness [14, 15], and CAH research is no exception. Therefore, there is a need for more culturally representative and collaborative research to best inform psychosocial support for those affected by CAH and their families when navigating medical care and rearing decisions.

When attempting to address this gap, it is important to also consider factors that contribute to the varying rates of CAH worldwide, as well as the wide range of psychosocial research being conducted. Rates of CAH differ across the world due to factors such as consanguinity impacting inheritance rates [16‒18], and inadequate diagnostic tools [12]. Of particular note, nationwide newborn screening requirements vary considerably across countries [19], likely biasing the field’s understanding of CAH with regard to detected rates and medical outcomes [20, 21]. Rates of CAH in India and Saudi Arabia are reported to be some of the highest in the world [20, 22]. Additionally, a recent meta-analysis identified countries in the Eastern Mediterranean and South-East Asia as those having the highest rates of CAH [6]. Although our results focus on similar regions, our findings also suggest that inconsistent newborn screening practices and peer-reviewed publication of rates of CAH make it difficult to be certain about which areas have the highest rates of CAH.

The present study did not aim to examine or draw conclusions from specific psychosocial findings. However, in conducting the article review, the authors noted considerable variability in the type of psychosocial research conducted. This range encompasses larger multisite studies whose a priori aim was to systematically examine psychosocial functioning [23], as well as those employing chart review methodologies to examine clinical data [24]. The range of methodologies is warranted and adds to the richness of research findings available. However, it is important to note systemic factors, such as funding, that are available to support different levels of research efforts, and how methodologies inform the psychosocial outcomes being examined (i.e., clinical vs. research surveys, quantitative vs. qualitative methods). An argument can be made for both standardizing some aspects of psychosocial research worldwide to allow for cross-cultural comparisons, and using idiographic, culturally informed measures and approaches to examining psychosocial functioning. The present review can be interpreted to support either rationale, yet it is likely both approaches will provide unique informative aspects to understand the wide array of individual and family experiences and inform standards of care.

Although the current scoping review takes an important preliminary step to quantify existing disparities, it is not without limitations. In limiting the searches to classical CAH, articles that collapsed across other differences in sex development diagnoses were excluded from the review. As such, findings may be biased against countries/regions/institutions that may not have resources to collect large classical CAH sample and publish such findings. Additionally, our CAH rate search includes birth, incidence, and prevalence rates together which differ from an epidemiological measurement perspective. However, in casting a wider search for rates of congenital conditions like classical CAH, we are likely capturing the most comprehensive rates without changing the interpretability of results, particularly as some regions do not have systematic newborn screening processes and patients are identified through different avenues, if ever. For example, Janejei et al. [25] report that the initially detected rate of 144 samples out of 58,563 newborns could not all be confirmed due to lack of follow-up. Lastly, by limiting the review to only include publications written in English, we likely excluded important research and biased our findings.

Despite these limitations, the present study takes a critical preliminary step in quantifying the cross-cultural disparities in psychosocial CAH research that have often been implied [5, 12, 13]. These findings highlight the need for more international collaborative cross-cultural psychosocial research, particularly in those countries with the highest rates of CAH. Some such national and international coordinated efforts and data repositories are active (e.g., [26, 27]) and provide a framework for continued and expanded efforts. Future directions might include comparing rates of CAH based on country/region with newborn screening programs. Additionally, collaborative efforts might examine ways to integrate standardized and culturally bound psychosocial measurement approaches. In all, to enhance evidence-based psychosocial interventions within CAH, more culturally representative research is needed to better understand patients’ experiences within their unique sociocultural context.

An ethics statement is not applicable because this study is based exclusively on published literature.

The authors have no conflicts of interest to declare.

The authors have no funding to declare.

Katherine A. Traino, M.S., developed design, coordinated review of and reviewed individual abstracts and full-text articles for inclusion/exclusion criteria, drafted the manuscript, and reviewed final version for submission. Nathan L. Basile, M.A., Rachel S. Fisher, M.S., and Taylor M. Dattilo, M.S., reviewed individual abstracts and full-text articles for inclusion/exclusion criteria, assisted with drafting of the manuscript, and reviewed final version for submission. Hui-Fen Chang, M.A., MLIS, conducted search of literature, assisted with drafting of the manuscript, and reviewed final version for submission. Larry L. Mullins, Ph.D., Annastasia Ediati, Ph.D., and Amy B. Wisniewski, Ph.D., developed design, provided feedback throughout review process, and reviewed final version for submission.

The authors confirm that the data supporting the findings of this study are available within the article and its supplementary materials. Further inquiries can be directed to the corresponding author.