Males have a lower prevalence of depression than females and testosterone may be a contributing factor. A comparison of opposite-sex and same-sex twins can be used indirectly to establish the role of prenatal testosterone exposure and the risk of depression. We therefore aimed to explore differences in depression risk using opposite-sex and same-sex twins.

We included 126 087 opposite-sex and same-sex twins from the Danish Twin Registry followed in nationwide Danish registers. We compared sex-specific incidences of depression diagnosis and prescriptions of antidepressants between opposite-sex and same-sex twins using Cox proportional hazard regression.

During follow-up, 2664 (2.1%) twins were diagnosed with depression and 19 514 (15.5%) twins had purchased at least one prescription of antidepressants. First, in male twins, we found that the opposite-sex male twins had the same risk of depression compared to the same-sex male twins {hazard ratio (HR) = 1.01 [95% confidence interval (CI) 0.88–1.17)]}. Revealing the risk of use of antidepressants, the opposite-sex male twins had a slightly higher risk of 4% (HR = 1.04 (95% CI 1.00–1.11)) compared with the same-sex male twins. Second, in the female opposite-sex twins, we revealed a slightly higher, however, not statistically significant risk of depression (HR = 1.08 (95% CI 0.97–1.29)) or purchase of antidepressants (HR = 1.01 (95% CI 0.96–1.05)) when compared to the same-sex female twins.

We found limited support for the hypothesis that prenatal exposure to testosterone was associated with the risk of depression later in life.

男性抑郁症患病率低于女性，睾丸激素可能是一个影响因素。异性和同性双胞胎的比较可间接用于确定产前睾酮暴露的作用和抑郁症风险。因此，我们的目的是利用异性和同性双胞胎来探讨抑郁风险的差异。

我们纳入了丹麦双胞胎登记处的 126 087 名异性和同性双胞胎，随后在丹麦全国登记处进行了登记。我们使用 Cox 比例风险回归比较了异性和同性双胞胎之间抑郁症诊断和抗抑郁药处方的性别特异性发生率。

在随访期间，2664 名（2.1%）双胞胎被诊断患有抑郁症，19514 名（15.5%）双胞胎购买了至少一种抗抑郁药处方。首先，在男性双胞胎中，我们发现异性男性双胞胎与同性男性双胞胎相比具有相同的抑郁风险{风险比（HR）= 1.01 [95％置信区间（CI）0.88–1.17）] }。揭示使用抗抑郁药的风险，与同性男性双胞胎相比，异性男性双胞胎的风险略高，为 4%（HR = 1.04（95% CI 1.00–1.11））。其次，在女性异性双胞胎中，我们发现患抑郁症（HR = 1.08（95% CI 0.97–1.29））或购买抗抑郁药（HR = 1.01（95% CI 0.96）的风险略高，但没有统计学意义。 –1.05)) 与同性女性双胞胎相比。

我们发现对产前接触睾酮与晚年抑郁风险相关这一假设的支持有限。