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Maternal androgen excess increases the risk of pre-diabetes mellitus in male offspring in later life: a long-term population-based follow-up study

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Abstract

Purpose

Prenatal androgen exposure could be a source of early programming, leading to the development of cardiometabolic diseases in later life. In this study, we aimed to examine cardiometabolic disturbances in males exposed to maternal androgen excess during their prenatal life.

Methods

In this prospective population-based study, 409 male offspring with maternal hyperandrogenism (MHA), and 954 male offspring without MHA, as controls, were included. Both groups of male offspring were followed from the baseline to the date of the incidence of events, censoring, or end of the study period, whichever came first. Age-scaled unadjusted and adjusted Cox regression models were applied to assess the hazard ratios (HR) and 95% confidence intervals (CIs) for the association between MHA with pre-diabetes mellitus (Pre-DM), type 2 diabetes mellitus (T2DM), pre-hypertension (Pre-HTN), hypertension (HTN), dyslipidemia, overweight, and obesity in the offspring of both groups. Statistical analysis was performed using the STATA software package; the significance level was set at P < 0.05.

Results

A higher risk of Pre-DM (adjusted HR: 1.46 (1.20, 1.78)) was observed in male offspring with MHA after adjustment for potential confounders, including body mass index, education, and physical activity. However, no significant differences were observed in the risk of T2DM, Pre-HTN, HTN, dyslipidemia, overweight, and obesity in males with MHA compared to controls in both the unadjusted and adjusted models.

Conclusion

Maternal androgen excess increases the risk of Pre-DM in male offspring in later life. More longitudinal studies with long enough follow-up are needed to clarify the effects of MHA on the cardiometabolic risk factors of male offspring in later life.

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Funding

This work was financially supported by the project (No. 19868) of the Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

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Authors and Affiliations

  1. Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, 23 Arabi, Yaman Street, VelenjakTehran, 1985717413, Iran

    M. Farhadi-Azar, M. Noroozzadeh, M. Rahmati, M. Saei Ghare Naz & F. Ramezani Tehrani

  2. Department of Obstetrics and Gynecology, Education Program in Reproduction and Development, Monash University, Melbourne, VIC, Australia

    M. Ghahremani

  3. Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    F. Azizi

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  1. M. Farhadi-Azar
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Contributions

M.F.A. contributed substantially to the conception and design, interpretation of data, drafted the article and revised and approved the final version to be published. M.N. contributed substantially to the conception and design, interpretation of data, drafted the article and revised and approved the final version to be published. M.G. contributed substantially to interpretation of data, drafted the article and revised and approved the final version to be published. M.R. contributed substantially to analysis data, drafted the article, and revised and approved the final version to be published. M.S.G.N. contributed substantially to the draft of the article and revised and approved the final version to be published. F.A. contributed substantially to conception and design, revised and approved the final version to be published. F.R.T contributed substantially to conception and design, interpretation of data, drafting the article, and revising and approving the final version to be published.

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Correspondence to M. Noroozzadeh.

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The ethics review board of the Research Institute for Endocrine Sciences approved the study proposal (approval number: IR.SBMU.ENDOCRINE.REC.1398.125).

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Written informed consent was signed by all participants after a full explanation of the purpose of the study to them. Written consent was obtained from their parents if they were under 18 years old.

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Farhadi-Azar, M., Noroozzadeh, M., Ghahremani, M. et al. Maternal androgen excess increases the risk of pre-diabetes mellitus in male offspring in later life: a long-term population-based follow-up study. J Endocrinol Invest 46, 1775–1785 (2023). https://doi.org/10.1007/s40618-022-01972-7

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