The association between reproductive hormones and asthma-related outcomes in boys in the rural Western Cape Province, South Africa
DOI:
https://doi.org/10.7196/SAMJ.2025.v115i11.3050Keywords:
asthma, Sex disparity, boys, reproductive hormones, testosterone, rural settingAbstract
Background. Asthma is more prevalent and severe among boys than girls, but this pattern reverses after puberty. It has been suggested that reproductive hormones may play a role in explaining these sex differences after puberty. However, the evidence for this relationship remains limited, as there have been no previous studies conducted on children in low- and middle-income countries on several reproductive endocrine hormones.
Objective. To investigate the association between reproductive endocrine hormones and asthma-related outcomes among boys residing in a rural setting.
Methods. Data on asthma outcomes and hormone levels were analysed from a cross-sectional study of 314 boys (aged 6 - 18 years) in the rural Western Cape Province, South Africa (SA). These were collected using an abbreviated International Study of Asthma and Allergies in Childhood questionnaire. Testosterone (total serum testosterone (TST) and free testosterone (FT)), luteinising hormone (LH), serum follicle- stimulating hormone (FSH), oestradiol and serum hormone-binding globulin (SHBG) were assessed using electrochemiluminescence immunoassays.
Results. Current wheezing (CW), asthma symptom score ≥2 and parental-reported asthma (PA) prevalence were 6.1%, 6.7% and 8.0%, respectively. Multivariate analysis showed that increasing levels of detected TST were significantly negatively associated with CW (odds ratio (OR) 0.66, 95% confidence interval (CI) 0.45 - 0.98) and asthma symptom score (OR 0.64, 95% CI 0.43 - 0.95), while no statistically significant association was observed for PA (OR 0.86, 95% CI 0.59 - 1.25). FT levels showed an inverse association with all asthma- related outcomes, with a statistically significant association with asthma symptom score. Similar associations were found for FSH, while associations with LH were less consistent across outcomes, and no association was observed for oestradiol and SHBG.
Conclusion. Our findings suggest that increasing serum testosterone levels (including those in the normal range and those above the normal range) detected among boys from rural settings in the Western Cape Province, SA, are associated with a reduced risk of asthma after adjusting for important underlying risk factors.
References
1. Bulkhi AA, Shepard KV, Casale TB, Cardet JC. Elevated testosterone is associated with decreased likelihood of current asthma regardless of sex. J Allergy Clin Immunol 2020;8(9):3029-3035.e4. https:// doi.org/10.1016/j.jaip.2020.05.0222
2. Leynaert B, Sunyer J, Garcia-Esteban R, et al. Gender differences in prevalence, diagnosis and incidence of allergic and non-allergic asthma: A population-based cohort. Thorax 2012;67(7):625-631. https://doi.org/10.1136/thoraxjnl-2011-201249
3. Koper I, Hufnagl K, Ehmann R. Gender aspects and influence of hormones on bronchial asthma – secondary publication and update. World Allergy Org J 2017;10(1):46. https://www.10.1186/s40413- 017-0177-9
4. Naeem A, Silveyra P. Sex differences in paediatric and adult asthma. Euro Med J 2019;4(2):27-35.
https://doi.org/10.33590/emj/10312930
5. Holguin F. Sex hormones and asthma. Am J Respir Crit Care Med 2020;201(2):127-128. https://doi.
org/10.1164/rccm.201910-1923ED
6. DeBoer MD, Phillips BR, Mauger DT, et al. Effects of endogenous sex hormones on lung function and symptom control in adolescents with asthma. BMC Pulmonary Med 2018;18(1):58. https://doi. org/10.1186/s12890-018-0612-x
7. Han Y-Y, Forno E, Celedón JC. Sex steroid hormones and asthma in a nationwide study of US adults. Am J Respir Crit Care Med 2020;201(2):158-166. https://doi.org/10.1164/rccm.201905-0996OC
8. Han Y-Y, Yan Q, Yang G, Chen W, Forno E, Celedon JC. Serum free testosterone and asthma, asthma hospitalisations and lung function in British adults. Thorax 2020;75(10):849-854. https://doi. org/10.1136/thoraxjnl-2020-214875
9. Arathimos R, Granell R, Haycock P, et al. Genetic and observational evidence supports a causal role of sex hormones on the development of asthma. Thorax 2019;74(7):633-642. https://doi.org/10.1136/ thoraxjnl-2018-212207
10. Fuseini H, Newcomb DC. Mechanisms driving gender differences in asthma. Curr Allergy Asthma Rep 2017;17(3):19. https://doi.org/10.1007/s11882-017-0686-1
11. Chetty-Mhlanga S, Basera W, Fuhrimann S, et al. A prospective cohort study of school-going children investigating reproductive and neurobehavioral health effects due to environmental pesticide exposure in the Western Cape, South Africa: Study protocol. BMC Public Health 2018;18(1):1-13. https://doi. org/10.1186/s12889-018-5783-0
12. Soldin OP, Hoffman EG, Waring MA, Soldin SJ. Pediatric reference intervals for FSH, LH, oestradiol, T3, free T3, cortisol, and growth hormone on the DPC IMMULITE 1000. Clin Chim Acta 2005;355(1- 2):205-210. https://doi.org/10.1016/j.cccn.2005.01.006
13. Galloway PJ, Donaldson MDC, Wallace AM. Sex hormone binding globulin concentration as a prepubertal marker for hyperinsulinaemia in obesity. Arch Dis Childhood 2001;85(6):489. https://doi. org/10.1136/adc.85.6.489
14. Sunyer J, Pekkanen J, Garcia-Esteban R, et al. Asthma score: Predictive ability and risk factors. Euro J Allergy Clin Immunol 2007;62(2):142-148. https://doi.org/10.1111/j.1398-9995.2006.01184.x
15. World Medical Association. World Medical Association Declaration of Helsinki ethical principles for medical research involving human subjects. JAMA 2013;310(20):2191-2194. https://doi.org/10.1001/ jama.2013.281053
16. World Health Organization. The WHO Child Growth Standards. Geneva: WHO, 2007. https:// www.who.int/tools/growth-reference-data-for-5to19-years/indicators/weight-for-age-5to10-years (accessed 17 June 2024).
17. Jassal MS. Pediatric asthma and ambient pollutant levels in industrializing nations. Int Health 2014;7(1):7-15. https://doi.org/10.1093/inthealth/ihu081
18. To T, Stanojevic S, Moores G, et al. Global asthma prevalence in adults: Findings from the cross- sectional world health survey. BMC Public Health 2012;12:204. https://doi.org/10.1186/1471-2458- 12-204
19. Olaniyan T, Dalvie MA, Röösli M, et al. Asthma-related outcomes associated with indoor air pollutants among schoolchildren from four informal settlements in two municipalities in the Western Cape Province of South Africa. Indoor Air 2019;29(1):89-100. https://doi.org/10.1111/ina.12511
20. Shirinde J, Wichmann J, Voyi K. Association between wheeze and selected air pollution sources in an air pollution priority area in South Africa: A cross-sectional study. Environ Health 2014;13(1):32. https://doi.org/10.1186/1476-069X-13-32
21. Kistnasamy EJ, RobinsTG, Naidoo R, et al. The relationship between asthma and ambient air pollutants among primary school students in Durban, South Africa. Int J Environ 2008;2(3-4):365-385. https:// doi.org/10.1504/IJEnvH.2008.020929
22. Toskala E, Kennedy DW. Asthma risk factors. Int Forum Allergy Rhinol 2015;5(Suppl 1):S11-S16.
https://doi.org/10.1002/alr.21557
23. Baard CB, Franckling-Smith Z, Munro J, Workman L, Zar HJ. Asthma in South African adolescents: A time trend and risk factor analysis over two decades. ERJ Open Res 2021;7(2):00576-2020. https:// doi.org/10.1183/23120541.00576-2020
24. Zacharasiewicz A. Maternal smoking in pregnancy and its influence on childhood asthma. ERJ Open Res 2016;2(3):00042-2016. https://doi.org/10.1183/23120541.00042-2016
25. Grabenhenrich LB, Gough H, Reich A, et al. Early-life determinants of asthma from birth to age 20 years: A German birth cohort study. J Allergy Clin Immunol 2014;133(4):979-988. https://doi. org/10.1016/j.jaci.2013.11.035
26. Ehrlich RI, Jordaan E, du Toit D, Volmink JA, Weinberg E, Zwarenstein M. Underrecognition and undertreatment of asthma in Cape Town primary school children. S Afr Med J 1998;88(8):986-994. 27. Fuseini H, Yung JA, Cephus JY, et al. Testosterone decreases house dust mite-induced type 2 and
IL-17A-mediated airway inflammation. J Immunol 2018;201(7):1843-1854. https://doi.org/10.4049/
jimmunol.1800293
28. Bridges NA, Hindmarsh PC, Pringle PJ, Matthews DR, Brook CG. The relationship between endogenous testosterone and gonadotrophin secretion. Clin Endocrinol 1993;38(4):373-378. https:// doi.org/10.1111/j.1365-2265.1993.tb00517.x
29. Babu SR, Sadhnani MD, Swarna M, Padmavathi P, Reddy PP. Evaluation of FSH, LH and testosterone levels in different subgroups of infertile males. Indian J Clin Biochem 2004;19(1):45-49. https://doi. org/10.1007/bf02872388
30. Pasquali R. Obesity and androgens: Facts and perspectives. Fertil Steril 2006;85(5):1319-1340. https:// doi.org/10.1016/j.fertnstert.2005.10.054
31. SelbyC.Sexhormonebindingglobulin:Origin,functionandclinicalsignificance.AnnClinBiochemistry 1990;27(6):532-541. https://doi.org/10.1177/000456329002700603
32. Diamanti-Kandarakis E, Bourguignon J-P, Giudice LC, et al. Endocrine-disrupting chemicals: An Endocrine Society scientific statement. Endocrine Rev 2009;30(4):293-342. https://doi.org/10.1210/ er.2009-0002
33. Suárez B, Vela-Soria F, Castiello F, et al. Organophosphate pesticide exposure, hormone levels, and interaction with PON1 polymorphisms in male adolescents. Sci Total Environ 2021;769:144563. https://doi.org/10.1016/j.scitotenv.2020.144563
34. World Health Organization. Annex H: Sexual maturity rating (Tanner staging) in adolescents. In: Antiretroviral Therapy for HIV Infection in Infants and Children: Recommendations for a Public Health Approach: 2010 Revision. Geneva: WHO, 2010.
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