Association of urinary sex hormones with mood and behavior changes in a community adolescent cohort

Philip Hazell; Ben W R Balzer; Frances Garden; David J Handelsman; Karen Paxton; Catherine Hawke; Rebecca Ivers; S Rachel Skinner; Georgina Luscombe; Katharine S Steinbeck

doi:10.1371/journal.pone.0293040

Association of urinary sex hormones with mood and behavior changes in a community adolescent cohort

PLoS One. 2023 Oct 16;18(10):e0293040. doi: 10.1371/journal.pone.0293040. eCollection 2023.

Authors

Philip Hazell¹, Ben W R Balzer^{1

2

3}, Frances Garden⁴, David J Handelsman¹, Karen Paxton¹, Catherine Hawke¹, Rebecca Ivers⁵, S Rachel Skinner^{1

6}, Georgina Luscombe¹, Katharine S Steinbeck^{1

6}

Affiliations

¹ Faculty of Medicine and Health, The University of Sydney School of Medicine, Camperdown, NSW, Australia.
² The University of New South Wales Faculty of Medicine, School of Women's and Children's Health, Randwick, NSW, Australia.
³ Sydney Children's Hospital, Randwick, NSW, Australia.
⁴ Ingham Institute for Medical Research, The University of New South Wales, Liverpool, NSW, Australia.
⁵ The University of New South Wales Faculty of Medicine, School of Public Health and Community Medicine, Kensington, NSW, Australia.
⁶ Specialty of Child and Adolescent Health, The Children's Hospital at Westmead Clinical School, Sydney, NSW, Australia.

Abstract

Objective: To examine the contribution of variation in sex hormone excretion to mood and behavioral changes in adolescent females and males.

Design: Prospective, longitudinal observational cohort study.

Methods: Participants were 342 volunteers aged 10-12 years living in rural Australia. Urinary estradiol and testosterone levels measured by liquid chromatography-mass spectrometry were obtained at three-month intervals for three years. Integrated measures (area-under-curve) of urinary steroid excretion summarised as absolute and variability during each 12-month period of the study. Psychosocial data were gathered annually with the primary outcome of depressive symptomatology. Secondary outcomes were the other subscales of the Youth Self-Report, impulsive-aggression, sleep habits, and self-harm.

Results: 277 (158 male) participants contributed data over the full duration of the study and could be included in the analyses. In females, analyses of absolute urine hormone levels found no relationship between estradiol and any outcome, but higher testosterone was significantly associated with depression and poorer sleep. Greater variability of both urine estradiol and testosterone was associated with lower total psychopathology, anxious/depressed and social problems scores. Greater variability in urine estradiol was associated with lower attention problems and impulsive aggression in females. In males, higher testosterone and estradiol levels were associated with rule-breaking, and poorer sleep, and no associations were found for gonadal hormone variability for males.

Conclusions: Longitudinal measurement of both iso-sexual and contra-sexual gonadal hormones contributes to a more nuanced view of the impact of sex steroids on mood and behavior in adolescents. These findings may enlighten the understanding of the impact of sex steroids during normal male and female puberty with implications for hormone replacement therapies as well as management of common mood and behavioral problems.

Copyright: © 2023 Hazell et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Publication types

Observational Study
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Estradiol
Female
Gonadal Hormones
Gonadal Steroid Hormones*
Humans
Male
Prospective Studies
Testosterone*

Substances

Gonadal Steroid Hormones
Testosterone
Estradiol
Gonadal Hormones

Grants and funding

KS: The ARCHER study was funded by a grant from National Health and Medical Research Council of Australia (1003312) (nhmrc.gov.au). Additional support was received from the Thyne Reid Foundation (playfordtrust.com.au), The Balnaves Foundation (balnavesfoundation.com), Country Women’s Association of New South Wales (cwaofnsw.org.au) and Sydney Medical School (https://www.sydney.edu.au/medicine-health/schools/sydney-medical-school.html). Australian Rotary Health (rotaryaustralia.org.au) and the Sydney Medical School Foundation supported the initial feasibility studies. RI is funded by a National Health and Medical Research Council (NHMRC) Senior Research Fellowship (Grant ID: APP1136430) The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.