Steno Diabetes Center Aarhus, Aarhus University Hospital, Hedeager 3, Aarhus, Denmark.
Barts and The London School of Medicine and Dentistry, William Harvey Research Institute, Queen Mary University of London, London, UK.
Eur J Epidemiol. 2021 Mar;36(3):335-344. doi: 10.1007/s10654-021-00721-z. Epub 2021 Feb 6.
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) SHBG and a 0.103 nmol/l lower (- 0.051,V0.154; p = 9 × 10) 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.
甲状腺功能减退症和甲状腺功能亢进症与性激素浓度和性功能障碍有关，但因果关系尚不清楚。我们研究了 TSH、游离甲状腺素、甲状腺功能减退症和甲状腺功能亢进症是否与性激素和性功能有关。我们使用了甲状腺代谢组学联盟（ThyroidOmics Consortium）中 TSH 和游离甲状腺素以及甲状腺功能减退症和甲状腺功能亢进症的全基因组关联研究的公开汇总统计数据（N≤54288）。英国生物银行（女性≤194174/男性≤167020）和 ReproGen（女性≤252514）的结果是性激素（性激素结合球蛋白[SHBG]、睾丸激素、雌二醇、游离雄激素指数[FAI]）和性功能（女性排卵功能：月经周期持续时间、初潮和绝经年龄、生殖寿命，以及男性勃起功能障碍）。我们在汇总水平上进行了两样本 Mendelian 随机化（MR）分析，并在个体水平数据上进行了未加权遗传风险评分（GRS）分析。TSH 增加一个标准差与 SHBG 降低 1.332 nmol/L（95%CI：-0.717，-1.946；p=2×10）和睾丸激素降低 0.103 nmol/L（-0.051，V0.154；p=9×10）相关，两样本 MR 和 GRS 分析均支持这一结果。两种方法都表明，甲状腺功能减退症的遗传易感性与 SHBG 和睾丸激素降低有关，而甲状腺功能亢进症的遗传易感性与 SHBG 和睾丸激素增加有关。fT4 的 GRS 仅与女性的睾丸激素和雌二醇增加有关。TSH 的 GRS 和甲状腺功能减退症与男性的 FAI 增加有关，而 GRS 与甲状腺功能亢进症与男性的 FAI 减少有关。虽然遗传预测的甲状腺功能与性激素有关，但我们没有发现与性功能有关的结果。
