Thyroid function, sex hormones and sexual function: a Mendelian randomization study

Alisa D. Kjaergaard*, Eirini Marouli, Areti Papadopoulou, Panos Deloukas, Aleksander Kuś, Rosalie Sterenborg, Alexander Teumer, Stephen Burgess, Bjørn O. Åsvold, Daniel I. Chasman, Marco Medici, Christina Ellervik

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

6 Citations (Scopus)

Abstract

Hypothyroidism and hyperthyroidism are observationally associated with sex hormone concentrations and sexual dysfunction, but causality is unclear. We investigated whether TSH, fT4, hypo- and hyperthyroidism are causally associated with sex hormones and sexual function. We used publicly available summary statistics from genome-wide association studies on TSH and fT4 and hypo- and hyperthyroidism from the ThyroidOmics Consortium (N ≤ 54,288). Outcomes from UK Biobank (women ≤ 194,174/men ≤ 167,020) and ReproGen (women ≤ 252,514) were sex hormones (sex hormone binding globulin [SHBG], testosterone, estradiol, free androgen index [FAI]) and sexual function (ovulatory function in women: duration of menstrual period, age at menarche and menopause, reproductive lifespan, and erectile dysfunction in men). We performed two-sample Mendelian randomization (MR) analyses on summary level, and unweighted genetic risk score (GRS) analysis on individual level data. One SD increase in TSH was associated with a 1.332 nmol/L lower (95% CI: − 0.717,− 1.946; p = 2 × 10–5) SHBG and a 0.103 nmol/l lower (− 0.051,V0.154; p = 9 × 10–5) testosterone in two-sample MR, supported by the GRS approach. Genetic predisposition to hypothyroidism was associated with decreased and genetic predisposition to hyperthyroidism with increased SHBG and testosterone in both approaches. The GRS for fT4 was associated with increased testosterone and estradiol in women only. The GRS for TSH and hypothyroidism were associated with increased and the GRS for hyperthyroidism with decreased FAI in men only. While genetically predicted thyroid function was associated with sex hormones, we found no association with sexual function.

Original languageEnglish
Pages (from-to)335-344
Number of pages10
JournalEuropean Journal of Epidemiology
Volume36
Issue number3
DOIs
Publication statusPublished - Mar 2021

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