Neurobiology Research Unit, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.
Mental Health Services, Capital Region of Denmark, Copenhagen, Denmark.
Front Endocrinol (Lausanne). 2021 Nov 8;12:731994. doi: 10.3389/fendo.2021.731994. eCollection 2021.
Women who use oral contraceptives (OCs) may have a higher risk of developing a depression, which is associated with both vulnerability to stress and cognitive dysfunction. OCs disrupt the hypothalamic-pituitary-gonadal (HPG) axis by suppressing endogenous sex steroid production including estradiol. The HPG axis and the hypothalamic-pituitary-adrenal (HPA) axis are known to interact, possibly through modulations driven by estradiol. OCs may affect HPA regulation capacity, i.e., disturb cortisol dynamics such as the cortisol awakening response (CAR), and influence cognition such as working memory (WM). We hypothesize that OC use is associated with blunted cortisol dynamics and impaired WM performance relative to non-users.
Data from 78 healthy women in the reproductive age were available from the CIMBI database. We evaluated if CAR and WM differed between OC users (n=25) and non-users (n=53) and if the level of estradiol modulated the OC use effect on CAR or WM in generalized least square models.
We found that OC users had a blunted CAR (p= 0.006) corresponding to a 61% reduction relative to non-users; however, no estradiol-BY-OC use interaction effect was observed on CAR. Also, OC users had higher cortisol levels at awakening compared to non-users (p = 0.03). We observed no effect of OC use or an estradiol-BY-OC use interaction effect on WM. Also, within the OC user group, neither CAR nor WM was associated with suppressed estradiol. CAR was not associated with WM.
Healthy women who use OCs have blunted cortisol dynamics relative to non-users. However, we could not detect OC use effects on working memory in our sample size. We speculate that disrupted cortisol dynamics may be important for the emergence of depressive symptoms in OC users.
使用口服避孕药（OC）的女性可能面临更高的抑郁风险，这与应激易感性和认知功能障碍有关。OC 通过抑制包括雌二醇在内的内源性性激素产生来破坏下丘脑-垂体-性腺（HPG）轴。HPG 轴和下丘脑-垂体-肾上腺（HPA）轴已知相互作用，可能通过雌二醇驱动的调节来实现。OC 可能会影响 HPA 调节能力，即干扰皮质醇动力学，如皮质醇觉醒反应（CAR），并影响认知，如工作记忆（WM）。我们假设 OC 使用与非使用者相比，皮质醇动力学减弱，WM 表现受损。
来自 CIMBI 数据库的 78 名处于生育期的健康女性的数据可用。我们评估了 OC 使用者（n=25）和非使用者（n=53）之间的 CAR 和 WM 是否存在差异，以及在广义最小二乘模型中，雌二醇水平是否调节 OC 使用对 CAR 或 WM 的影响。
我们发现 OC 使用者的 CAR 减弱（p=0.006），与非使用者相比，CAR 减少了 61%；然而，未观察到雌二醇-BY-OC 使用相互作用对 CAR 的影响。此外，OC 使用者在觉醒时的皮质醇水平高于非使用者（p=0.03）。我们未观察到 OC 使用或雌二醇-BY-OC 使用相互作用对 WM 的影响。此外，在 OC 使用者组内，CAR 或 WM 均与雌二醇抑制无关。CAR 与 WM 无关。
与非使用者相比，使用 OC 的健康女性皮质醇动力学减弱。然而，在我们的样本量中，我们无法检测到 OC 使用对工作记忆的影响。我们推测，皮质醇动力学的破坏可能对 OC 使用者出现抑郁症状很重要。
