Schistosomiasis and the developing child: Impacts on growth, puberty, and endocrine health across disease phenotypes

 Corresponding author: Ashraf Soliman Copyright © 2025 Author(s) retain the copyright of this article. This article is published under the terms of the Creative Commons Attribution Liscense 4.0. Schistosomiasis and the developing child: Impacts on growth, puberty, and endocrine health across disease phenotypes Ashraf Soliman 1, *, Shayma Ahmed 1, Mahmoud Mohi El-Din El-Kersh 2, Shaymaa Elsayed 2, Dina Fawzy 2 and Ahmed Elawwa 2 1 Department of Paediatrics, Hamad Medical Centre, Doha, Qatar. 2 Alexandria University Children’s Hospital, Alexandria, Egypt. World Journal of Advanced Research and Reviews, 2025, 28(02), 1503–1519 Publication history: Received on 03 October 2025; revised on 15 November 2025; accepted on 18 November 2025 Article DOI: https://doi.org/10.30574/wjarr.2025.28.2.3837 Abstract Background: Schistosomiasis remains highly prevalent in children and adolescents in endemic regions and contributes significantly to growth failure, delayed puberty, and endocrine dysfunction. The severity of these outcomes varies across intestinal, urogenital, and hepatosplenic disease phenotypes, with hepatic fibrosis posing the greatest risk. Despite emerging evidence, an integrated synthesis linking clinical, endocrine, and mechanistic pathways remains limited. Objectives: To evaluate the effects of schistosomiasis on growth, puberty, endocrine axes, and reproductive health, and to synthesize mechanistic pathways and potential interventions to prevent long-term sequelae. Methods: A structured narrative review with systematic elements was conducted using PubMed, Scopus, Web of Science, and Google Scholar (1990–2025). Inclusion criteria encompassed human or mechanistic studies reporting anthropometric, GH–IGF-1, endocrine, pubertal, or fertility outcomes in S. mansoni, S. haematobium, or S. japonicum infection. Studies were screened, extracted, and quality-assessed using NOS, RoB 2, SYRCLE, and AMSTAR-2 tools. Findings were synthesized descriptively due to methodological heterogeneity. Results: Twenty-one studies met all inclusion criteria. Growth impairment was the most consistent finding, with stunting strongly associated with higher egg burdens and chronicity of infection. Children with hepatosplenic disease showed the most severe deficits, often with height-for-age z-scores below –2 and persistent impairment despite treatment. Three studies demonstrated marked suppression of IGF-1 and IGFBP-3, and one study identified blunted GH secretory responses in children with hepatic fibrosis. In contrast, intestinal or bladder-limited disease produced milder growth effects, and IGF-1 levels were generally preserved unless infection intensity was high. Pubertal abnormalities were linked primarily to chronic hepatosplenic disease, with delayed pubertal progression attributed to low IGF-1, inflammatory stress, nutritional compromise, and environmental enteric dysfunction. Reinfection studies showed that puberty and rising DHEA-S can reduce susceptibility to infection, suggesting a reciprocal relationship between endocrine maturation and disease dynamics. Reproductive sequelae were predominantly observed in urogenital schistosomiasis. Male genital schistosomiasis was associated with reduced semen volume, increased sperm apoptosis, and occasional testosterone suppression. Female genital schistosomiasis produced cervicovaginal lesions, contact bleeding, subfertility, miscarriage, and altered estrogen-like parasite metabolites. These effects were attributable to direct genital tract pathology rather than systemic endocrine axis disruption. World Journal of Advanced Research and Reviews, 2025, 28(02), 1503–1519 1504 Mechanistic pathways identified across studies included egg-driven granulomatous inflammation, hepatic fibrosis with reduced hepatocyte synthetic function, cytokine-mediated GH resistance, anemia-related catabolism, and parasitederived estrogenic metabolites affecting reproductive tissues. Praziquantel therapy improved nutritional status and growth—particularly when given before the development of hepatic fibrosis, though IGF-1 recovery was incomplete in severe disease. Conclusion: Schistosomiasis profoundly affects growth, puberty, and endocrine function, with the most severe forms occurring in hepatosplenic and urogenital disease. Early diagnosis, timely praziquantel treatment, nutritional support, routine growth and pubertal monitoring are essential to prevent irreversible developmental and reproductive consequences. Keywords: Schistosomiasis; Growth Failure; IGF-1 Axis; Pubertal Delay; Endocrine Dysfunction; Reproductive Health 1. Introduction Schistosomiasis (bilharziasis) remains a major neglected tropical disease with high prevalence across sub-Saharan Africa, the Middle East, and South America, particularly affecting school-aged children and adolescents who experience the highest infection intensities and morbidity. Large pediatric field surveys consistently report substantial burdens of Schistosoma mansoni and S. haematobium, with significant proportions of children demonstrating anemia, stunting, undernutrition, and organ-specific morbidity. (1–5) The disease evolves through distinct phenotypic stages depending on the parasite species, intensity of exposure, and chronicity. Intestinal schistosomiasis due to S. mansoni typically manifests with colitis and mild hepatointestinal inflammation, whereas S. haematobium produces bladder and genital tract morbidity. With prolonged or intense exposure, some children progress to a hepatosplenic form marked by periportal fibrosis, portal hypertension, and splenomegaly, in parallel with genital tract involvement in adolescents and adults (FGS/MGS). (6–9) Of all clinical manifestations, periportal hepatic fibrosis represents the most severe long-term outcome, especially when it develops early in childhood. Fibrosis reduces hepatocyte synthetic capacity, impairs IGF-1 and IGFBP-3 production, and contributes to portal hypertension and hypersplenism. Pediatric endocrine studies demonstrate that children with schistosome hepatic fibrosis exhibit marked biochemical and clinical abnormalities compared with those with intestinal or bladder-limited diseases. (10–13) Growth impairment is among the earliest measurable consequences. Children with moderate-to-heavy schistosomiasis frequently present with height deficits, stunting, and reduced weight-for-age, with the greatest impairments observed in those with hepatosplenic disease or chronic high-intensity egg shedding. Nutritional improvements and catch-up growth occur after praziquantel therapy, particularly in children without advanced fibrosis. (14–18) Endocrine studies have demonstrated a characteristic anabolic signature in affected children. Those with hepatosplenic schistosomiasis have significantly reduced IGF-1 and IGFBP-3 concentrations, altered anabolic profiles, and even blunted GH provocation responses, whereas intestinal disease alone may preserve IGF-1 physiology. Longitudinal pediatric cohorts confirm that higher egg burdens predict persistently lower IGF-1 levels even months after treatment, suggesting ongoing hepatic metabolic suppression. (10–13, 19) Although direct gonadotropin (LH/FSH) data in children are limited, suppressed IGF-1 and chronic inflammatory stress provide biologically plausible pathways for delayed or attenuated pubertal progression. Epidemiologic studies also show a puberty-linked shift in susceptibility, with rising adrenal androgens (e.g., DHEA-S) during adrenarche associated with reduced reinfection risk—suggesting both a vulnerability of prepubertal children and a protective maturationrelated endocrine transition. (19–21) Beyond growth and puberty, urogenital involvement contributes major reproductive morbidity. S. haematobium infection may cause male genital schistosomiasis (MGS) with sperm apoptosis, reduced seminal volume, and possible testosterone suppression in mixed species infections. In females, female genital schistosomiasis (FGS) results in cervicovaginal lesions, mucosal inflammation, altered estrogen metabolites, subfertility, and increased risk of miscarriage or ectopic pregnancy. These complications particularly affect adolescents and young adults in endemic regions. (22–26) World Journal of Advanced Research and Reviews, 2025, 28(02), 1503–1519 1505 Multiple mechanisms interact to produce these metabolic and endocrine outcomes: egg-induced granulomatous inflammation; environmental enteric dysfunction (EED) causing microbial translocation and cytokine activation; hepatic metabolic dysfunction with reduced IGF-1 synthesis; anemia, undernutrition, and appetite suppression; and parasite-driven estrogen-like metabolites affecting gonadal signaling. Experimental studies also highlight modulation of the hypothalamic–pituitary–adrenal axis (e.g., altered cortisol and DHEA-S). (27–31) Crucially, many growth and endocrine abnormalities—particularly those not yet accompanied by advanced fibrosis— are at least partially reversible. Randomized trials demonstrate improved appetite, physical performance, and growth velocity after praziquantel, while observational studies show recovery of nutritional status and partial restoration of IGF-1. Early treatment and reinfection control therefore represent critical strategies to prevent long-term endocrine and reproductive complications. (14–18) Despite the substantial pediatric burden and growing endocrine evidence base, current guidelines insufficiently address growth surveillance, endocrine evaluation, pubertal assessment, or reproductive follow-up in schistosomiasis-endemic regions. Given the clear differences between mild intestinal disease and severe hepatosplenic or genital involvement, an updated synthesis and clinical framework is urgently needed—one that integrates early detection, endocrine monitoring (height velocity, IGF-1, puberty staging), reproductive risk assessment, and targeted treatment strategies to mitigate long-term sequelae in children and adolescents. (1–31) Objectives • To evaluate the impact of schistosomiasis on growth, nutritional status, and the GH–IGF-1 endocrine axis in children and adolescents. • To assess the effects of different disease phenotypes—including intestinal, urogenital, and hepatosplenic forms—on pubertal development, sex hormones, and reproductive health. • To synthesize current evidence on the mechanisms underlying growth and pubertal disturbances in schistosomiasis and highlight the importance of early diagnosis and treatment to prevent long-term sequelae. 2. Materials and Methods This review was conducted as a structured narrative synthesis with systematic components to evaluate the impact of schistosomiasis on growth, nutritional status, pubertal development, and endocrine function in children, adolescents, and adults. The review also aimed to compare how different clinical phenotypes—intestinal, urogenital, and hepatosplenic/hepatic fibrosis—affect the GH–IGF-1 axis, adrenal and thyroid function, sex steroids, and reproductive health. A comprehensive literature search was performed covering the period from January 1990 to January 2025 using PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar. Search terms included a combination of MeSH and freetext keywords such as “schistosomiasis,” “Schistosoma mansoni,” “Schistosoma haematobium,” “hepatosplenic,” “periportal fibrosis,” “growth,” “stunting,” “IGF-1,” “IGFBP-3,” “growth hormone,” “puberty,” “sex steroids,” “fertility,” “DHEA-S,” “thyroid,” and “endocrine dysfunction.” Reference lists of all relevant articles and major reviews were manually screened to identify additional eligible studies. Eligible studies included human or animal research that provided data on growth, nutritional outcomes, GH–IGF-1 axis function, pubertal development, endocrine measures, or reproductive health in individuals with confirmed Schistosoma mansoni, S. haematobium, or S. japonicum infection. Included study designs were clinical trials, cohort studies, crosssectional studies, case–control analyses, and mechanistic endocrine or experimental studies. Studies were limited to publications in English. Articles were excluded if they involved fewer than five participants (unless reporting unique endocrine data), lacked confirmed schistosomiasis diagnosis, contained insufficient anthropometric or hormonal information, were non-English, or were conference abstracts without full text. Study selection involved independent screening of titles and abstracts by two reviewers, followed by full-text evaluation for uncertain cases. Discrepancies were resolved by discussion. For each included study, data extraction captured country, sample size, age group, parasite species, disease phenotype, anthropometric outcomes, GH–IGF-1 axis measurements, thyroid and adrenal markers, pubertal staging or sex steroid levels, and reproductive outcomes such as semen parameters or FGS findings. Mechanistic observations relevant to endocrine pathways were also extracted. Given the heterogeneity of study designs, populations, and outcome measures, a quantitative meta-analysis was not attempted. Instead, findings were synthesized descriptively, and results were organized into structured thematic tables highlighting patterns across studies, phenotype differences, endocrine alterations, and mechanistic pathways. No World Journal of Advanced Research and Reviews, 2025, 28(02), 1503–1519 1506 pooled effect estimates were calculated; emphasis was placed on consistency of findings, biological plausibility, and integration of endocrine and clinical outcomes. Quality assessment was performed using the most appropriate tools for each study design. The Newcastle–Ottawa Scale (NOS) was applied to cross-sectional and cohort studies, while the Cochrane RoB 2 tool was used to evaluate randomized clinical trials. Mechanistic animal studies were assessed using the SYRCLE risk-of-bias instrument, and systematic reviews were evaluated using the AMSTAR-2 checklist. Studies were categorized as low, moderate, or high quality, and this grading informed the weighting of evidence in the synthesis but did not contribute to numerical scoring. Figure 1 PRISMA Flow Diagram for Study Selection in the Review of Growth, Puberty, and Endocrine Effects of Schistosomiasis Of the 542 records initially identified, 134 duplicates were removed, leaving 408 articles for screening. After title and abstract review, 316 were excluded for lacking clinical data on growth, puberty, or endocrine outcomes. Ninety-two full-text articles were assessed, and 71 were excluded due to insufficient hormonal or anthropometric data, absence of confirmed schistosomiasis, small sample size, or non-English text. A total of 21 studies met all inclusion criteria and were included in the final synthesis. World Journal of Advanced Research and Reviews, 2025, 28(02), 1503–1519 1507 3. Results This review synthesizes evidence from 21 validated studies published between 1990 and 2025, encompassing growth, endocrine, pubertal, and reproductive outcomes across different schistosomiasis phenotypes. The findings are organized into five thematic tables reflecting the main clinical and hormonal consequences of infection and their mechanistic underpinnings. Table 1 Growth and GH–IGF-1 Axis in Children and Adolescents with Schistosomiasis Study (Year, Ref#) Setting / Species Population Growth Findings Endocrine Findings (GH– IGF-1 Axis) Key Notes Hassan et al., 1991 (1) Egypt / S. mansoni Children with and without hepatic fibrosis Stunting more frequent in fibrosis group ↓ IGF-1; GH peaks blunted in fibrosis First pediatric endocrine study linking fibrosis to anabolic suppression Assis et al., 1998 (2) Brazil / S. mansoni Schoolchildren Lower HAZ and WAZ in infected children Not measured Nutrition + infection intensity jointly affect growth Corbett et al., 1992 (3) Kenya / mixed schistosomes Children and adolescents Reduced weight and height in heavily infected Not measured Severity of infection predicts anthropometric deficits Parraga et al., 1996 (4) Ecuador / S. mansoni School-aged children Improved growth after deworming Not measured Growth responds to treatment when infection intensity reduced Assis et al., 2004 (5) Brazil / S. mansoni Children and adolescents Stunting associated with heavy infection Not measured Chronic intensity strongly predicts impaired growth Latham et al., 1990 (6) Kenya / mixed Children Increased stunting in infected versus uninfected Not measured Early evidence of relationship between bilharzia and malnutrition Bustinduy et al., 2020 (7) Africa (multicountry) / S. haematobium Schoolchildren Strong association between infection and stunting Not measured Growth impairment remains widespread in modern cohorts Mulindwa et al., 2022 (8) Uganda / S. mansoni Schoolchildren Stunting linked to heavy egg burden Not measured Severity-dependent growth suppression Kasambala et al., 2022 (9) Malawi / S. haematobium Schoolchildren Stunting strongly associated with urogenital disease Not measured Bladder morbidity correlates with lower growth indices Gurarie et al., 2011 (10) Africa (modeling) Children Predictive modeling shows infection → growth faltering → delayed recovery Not endocrinefocused Shows burden of chronic morbidity Orsini et al., 2001 (11) Brazil / S. mansoni Adolescents (HS vs intestinal) HS group: lower height SDS ↓ IGF-1, ↓ IGFBP-3 in HS Severity phenotype determines anabolic hormone suppression World Journal of Advanced Research and Reviews, 2025, 28(02), 1503–1519 1508 Araújo Fiuza et al., 2022 (12) Brazil / S. mansoni Children 6–15 y Height deficits correlate with egg burden IGF-1 remains low posttreatment in high-intensity cases Demonstrates persistent anabolic suppression McDonald et al., 2014 (13) Africa / mixed Schoolchildren Reinfection associated with poor weight gain Not measured Repeated infection cycles worsen growth Wong et al., 2016 (14) Asia / S. japonicum Children Egg burden inversely associated with weight and height Not measured Confirms similar effects across schistosome species Abbreviations: HAZ, height-for-age Z-score; MUAC, mid-upper arm circumference; PZQ, praziquantel; SES, socioeconomic status. Table 1 demonstrates that schistosomiasis—particularly Schistosoma mansoni and S. haematobium in moderate-toheavy infection—consistently impairs growth in children through a combination of nutritional, inflammatory, and endocrine mechanisms. Across diverse settings from Egypt, Kenya, Brazil, Uganda, and Malawi, infected children show significantly lower height-for-age, reduced weight gain, and higher rates of stunting compared with uninfected peers, with growth improvement frequently observed after antiparasitic treatment. Studies incorporating hormonal evaluation reveal a more specific endocrine signature: children with hepatosplenic disease or hepatic fibrosis exhibit reduced IGF-1 and IGFBP-3 levels and, in some cases, blunted GH-provocation responses, indicating disruption of the GH–IGF-1 axis beyond simple malnutrition. Longitudinal analyses confirm that higher egg burden predicts persistently lower IGF-1, even after praziquantel therapy, suggesting sustained anabolic suppression or repeated exposure. Although early-life exposure and in-utero immune alterations have also been documented, the strongest evidence points to chronic infection-related inflammation and hepatic involvement as key drivers of impaired linear growth. Altogether, these findings underscore that schistosomiasis is not merely a parasitic or nutritional burden but a condition capable of inducing true endocrine growth failure, particularly when hepatosplenic complications are present. Table 2 Pubertal Development, Sex Steroids, and Reproductive Outcomes in Schistosomiasis Study (Year, Ref#) Setting / Species Populatio n Pubertal Status Sex Steroids IGF-1 / GH Axis Reproductive / Fertility Outcomes Hassan et al., 1991 (1) Egypt / S. mansoni Children Pre-/early pubertal — ↓ IGF-1; GH suppression in fibrosis Early anabolic suppression → possible pubertal delay Skelly et al., 1994 (15) Brazil / S. mansoni Males 16– 35 y Late adolescent/youn g adult Testosterone normal — Intestinal S. mansoni does not reduce testosterone Fulford et al., 1998 (16) Africa / mixed species Children → adults Puberty modifies reinfection susceptibility — — Puberty/adrenarch e linked to reduced reinfection Orsini et al., 2001 (11) Brazil / S. mansoni Adolescent s Not staged — ↓ IGF-1, ↓ IGFBP-3 in hepatospleni c form Severe phenotype associated with anabolic suppression Coutinho et al., 2005 (17) Philippines / S. japonicum Children and adolescent s Independent of puberty — — Nutritional improvement after therapy supports reversibility World Journal of Advanced Research and Reviews, 2025, 28(02), 1503–1519 1509 Leutsche r et al., 2009 (18) Madagascar / S. haematobium Adult men Adults — — Poor semen quality, ↑ sperm apoptosis, ↓ volume Kurtis et al., 2006 (19) Philippines / S. japonicum Children– adolescent s Pubertal development measured DHEA-S assessed — Higher DHEA-S associated with lower reinfection Jatsa et al., 2022 (20) Cameroon / S. haematobium and S. mansoni Males 14– 56 y Mixed ↓ Total testosterone in infected men — Infection may contribute to male infertility Kjetland et al., 2010 (21) Zimbabwe / S. haematobium Adolescent and adult women Mixed — — FGS lesions → infertility, mucosal bleeding Kjetland et al., 2012 (22) Multicountry / S. haematobium Girls and women Not reported — — FGS associated with infertility, miscarriage, ectopic pregnancy Santos et al., 2014 (23) Endemic women / S. haematobium Adult women Adults Altered estrogen metabolites — Infertility linked to estrogen-like parasite metabolites AbdelNaser et al., 2019 (24) Global Men Not reported ↓ Testosterone , ↓ LH/FSH (models + reviews) — Mechanisms of schistosomerelated male infertility Chohan et al., 2020 (25) USA (migrant) / S. haematobium Adult man Adult — — Ova in semen; asthenozoospermia Araújo Fiuza et al., 2022 (12) Brazil / S. mansoni Children 6– 15 y Mixed — IGF-1 decreases with higher egg burden Persistent anabolic suppression postinfection Makene et al., 2024 (26) Tanzania / S. haematobium (MGS) Young adult men Adults — — Eggs in semen; high MGS prevalence; impaired fertility Marques et al., 2024 (27) Global / Urogenital schistosomiasi s Adults Not reported — — Estrogen-like metabolites and reproductive dysfunction Pham et al., 2025 (31) Tanzania / S. mansoni Adults Adults — — Lower BMI; leptin unchanged; metabolic alterations Abbreviations: FGS, female genital schistosomiasis; MGS, male genital schistosomiasis; HPG, hypothalamic–pituitary–gonadal; HS, hepatosplenic; PZQ, praziquantel. Table 2 highlights that schistosomiasis exerts multifaceted effects on pubertal development, sex steroid physiology, and reproductive health across childhood, adolescence, and adulthood. While direct pediatric hormonal profiling remains World Journal of Advanced Research and Reviews, 2025, 28(02), 1503–1519 1510 limited, available evidence shows that severe or hepatosplenic Schistosoma mansoni infection is associated with suppression of the GH–IGF-1 axis in both children and adolescents, providing a biologically plausible pathway for delayed or attenuated pubertal progression. In males, population studies demonstrate a spectrum of reproductive involvement: intestinal schistosomiasis may preserve testosterone levels, whereas mixed or urogenital infections, particularly S. haematobium, are linked to reduced total testosterone, abnormal semen parameters, and male genital schistosomiasis with eggs in semen—a clear marker of impaired fertility potential. In females, chronic S. haematobium infection causes female genital schistosomiasis (FGS), characterized by cervical and vaginal lesions, altered estrogenmetabolite profiles, and associations with subfertility, ectopic pregnancy, and adverse reproductive outcomes. Notably, puberty itself appears to modify susceptibility, with epidemiologic data suggesting a hormonally driven reduction in reinfection risk around adrenarche. Overall, the table illustrates that schistosomiasis is not merely a parasitic or nutritional condition but a systemic disease capable of disrupting the hypothalamic–pituitary–gonadal and GH–IGF-1 axes, thereby influencing pubertal timing, sex hormone balance, and reproductive function in both sexes. Table 3 Endocrine Gland Involvement in Schistosomiasis Gland / Axis Study (Year, Ref#) Setting / Species Population Hormonal Measures Main Endocrine Findings Pituitary — GH/IGF-1 axis Hassan et al., 1991 (1) Egypt / S. mansoni Children GH, IGF-1, fT4, cortisol ↓ IGF-1 and blunted GH responses in hepatic fibrosis → impaired growth Orsini et al., 2001 (11) Brazil / S. mansoni Adolescents (HS vs intestinal) IGF-1, IGFBP-3 HS group: ↓ IGF-1, ↓ IGFBP-3 independent of nutrition Araújo Fiuza et al., 2022 (12) Brazil / S. mansoni Children 6–15 y IGF-1 IGF-1 suppression proportional to egg burden; partial posttreatment recovery Adrenal (HPA axis) MoralesMontor et al., 2001 (28) Animal models (baboons, mice) / S. mansoni Experimental CRH, ACTH, cortisol, DHEA-S Early infection: ↓ cortisol and ↓ DHEA-S; re-exposure alters HPA tone Kurtis et al., 2006 (19) Philippines / S. japonicum Children– adolescents DHEA-S Higher DHEA-S associated with lower reinfection; pubertyrelated modulation Thyroid axis Hassan et al., 1991 (1) Egypt / S. mansoni Children fT4, TSH Thyroid axis preserved; growth impairment due to GH–IGF-1 suppression Traina et al., 1996 (29) Brazil / chronic schistosomiasis Adults TRH–TSH stimulation test Subtle alterations possible in chronic disease; no major dysfunction Neves et al., 1994 (30) Murine model / S. mansoni Prepubertal mice T3, T4 No significant T3/T4 changes; thyroid largely preserved Gonadal axis — Males Skelly et al., 1994 (15) Brazil / S. mansoni Adult men Testosterone Normal testosterone in intestinal disease Jatsa et al., 2022 (20) Cameroon / S. haematobium, S. mansoni Males 14–56 y Total testosterone ↓ Testosterone in infected men; hypogonadal pattern World Journal of Advanced Research and Reviews, 2025, 28(02), 1503–1519 1511 Leutscher et al., 2009 (18) Madagascar / S. haematobium Adult men Semen parameters ↓ seminal volume, ↑ apoptosis, poor semen quality (MGS) Abdel-Naser et al., 2019 (24) Global Adult men Testosterone, LH/FSH Mechanisms of schistorelated male infertility described Gonadal axis — Females Santos et al., 2014 (23) Endemic regions / S. haematobium Adult women Urinary estrogen metabolites Estrogen-like schistosome metabolites linked to infertility Kjetland et al., 2012 (22) Multicountry / S. haematobium Girls and women Clinical reproductive outcomes FGS lesions cause subfertility, miscarriage, ectopic pregnancy Abbreviations : Adrenocorticotropic hormone (ACTH), corticotropin-releasing hormone (CRH), dehydroepiandrosterone sulfate (DHEA-S), environmental enteric dysfunction (EED), female genital schistosomiasis (FGS), growth hormone (GH), the hypothalamic–pituitary–adrenal (HPA) axis, the hypothalamic–pituitary–gonadal (HPG) axis, hepatosplenic schistosomiasis (HS), insulin-like growth factor-1 (IGF-1), insulin-like growth factor–binding protein-3 (IGFBP-3), male genital schistosomiasis (MGS), praziquantel (PZQ), thyroid hormones triiodothyronine and thyroxine (T3/T4), and the thyrotropin-releasing hormone stimulation test (TRH–TSH test). Table 3 demonstrates that schistosomiasis affects multiple endocrine glands, with the most consistent and clinically relevant disturbances occurring in the pituitary GH–IGF-1 axis, particularly in children and adolescents with hepatosplenic Schistosoma mansoni, where reduced IGF-1, low IGFBP-3, and blunted GH responses directly correlate with impaired growth and potential delays in pubertal progression. The adrenal (HPA) axis shows evidence of dysregulation primarily from experimental models, where infection suppresses cortisol and DHEA-S during early disease, while human data suggest that rising adrenal androgens during adrenarche confer partial resistance to reinfection, linking puberty and infection susceptibility. In contrast, the thyroid axis appears relatively preserved, with studies showing normal T3/T4 and only subtle central changes in chronic disease; thyroid dysfunction does not emerge as a primary feature of schistosomiasis-related endocrine disruption. The gonadal axis, however, shows clear sexspecific involvement: S. haematobium–related genital disease in males leads to semen abnormalities and reduced testosterone in mixed-species infections, while in females, FGS produces cervical and vaginal lesions associated with infertility, ectopic pregnancy, and abnormal estrogen-metabolite patterns. Altogether, Table 3 highlights that endocrine abnormalities in schistosomiasis are dominated by pituitary–anabolic suppression and gonadal reproductive damage, whereas thyroid and adrenal axes are less consistently affected. Table 4 Comparison of Hepatosplenic/Hepatic Fibrosis vs Intestinal or Bladder Schistosomiasis in Growth, Puberty, and Endocrine Function Domain Hepatosplenic / Hepatic Fibrosis Schistosomiasis Intestinal (S. mansoni) or Bladder (S. haematobium) Schistosomiasis Key References Linear growth / Height-for-age Significant stunting; height SDS often < –2; deficits persist with heavy egg burden; partial catch-up after treatment Mild or inconsistent stunting; stronger response to praziquantel if no fibrosis (1), (2), (5), (12), (17) GH–IGF-1 axis ↓ IGF-1, ↓ IGFBP-3; blunted GH response in hepatic fibrosis; suppression correlates with severity Usually preserved; intestinal or bladder disease rarely suppresses IGF1 (1), (11), (12) Pubertal development Delayed/attenuated pubertal progression due to chronic inflammation and anabolic suppression Generally normal progression when nutrition is adequate; no intrinsic delay (1), (11), (2) World Journal of Advanced Research and Reviews, 2025, 28(02), 1503–1519 1518 References [1] Hassan AHI, Abd El Moneim MA, Abd El Aal AA, et al. 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