TY - JOUR

T1 - Thyroid function, sex hormones and sexual function

T2 - a Mendelian randomization study

AU - Kjaergaard, Alisa D.

AU - Marouli, Eirini

AU - Papadopoulou, Areti

AU - Deloukas, Panos

AU - Kuś, Aleksander

AU - Sterenborg, Rosalie

AU - Teumer, Alexander

AU - Burgess, Stephen

AU - Åsvold, Bjørn O.

AU - Chasman, Daniel I.

AU - Medici, Marco

AU - Ellervik, Christina

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

KW - Erectile dysfunction

KW - Mendelian randomization

KW - Reproductive lifespan

KW - SHBG

KW - Testosterone

KW - Thyroid function

U2 - 10.1007/s10654-021-00721-z

DO - 10.1007/s10654-021-00721-z

M3 - Journal article

C2 - 33548002

AN - SCOPUS:85100575662

VL - 36

SP - 335

EP - 344

JO - European Journal of Epidemiology

JF - European Journal of Epidemiology

SN - 0393-2990

ER -