Department of Psychology and Centre for Cognitive Neuroscience, University of Salzburg, Salzburg, Austria.
Neurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
JAMA Netw Open. 2023 Sep 5;6(9):e2335957. doi: 10.1001/jamanetworkopen.2023.35957.
Hormonal contraception has been linked to mood symptoms and the ability to recognize emotions after short periods of treatment, whereas the mental health of users of long-term hormonal contraceptives has had limited investigation.
To evaluate whether short-term hormonal withdrawal, which users of combined oral contraceptives (COCs) undergo once a month (pill pause), was associated with altered mood and emotional recognition in long-term users of COCs.
DESIGN, SETTING, AND PARTICIPANTS: This case-control study included a community sample of individuals assigned female sex at birth who identified as women and used COC for 6 months or longer. The control group included women with natural menstrual cycles who otherwise fulfilled the same inclusion criteria. The study was conducted between April 2021 and June 2022 in Salzburg, Austria.
COC users and women with natural menstrual cycles were tested twice within a month, once during their active pill phase or luteal phase and once during their pill pause or menses.
Negative affect, anxiety, and mental health problems were assessed during each session. The percentage increase in mental health symptoms was calculated during the pill pause compared with that during the active intake phase in COC users. How this change compared with mood fluctuations along the menstrual cycle in women with natural menstrual cycles was assessed.
A total of 181 women aged 18 to 35 years (mean [SD] age, 22.7 [3.5] years) were included in the analysis (61 women with androgenic COC use, 59 with antiandrogenic COC use, 60 women with a menstrual cycle not taking COCs). COC users showed a 12.67% increase in negative affect (95% CI, 6.94%-18.39%), 7.42% increase in anxiety (95% CI, 3.43%-11.40%), and 23.61% increase in mental health symptoms (95% CI, 16.49%-30.73%; P < .001) during the pill pause compared with the active intake phase. The effect size of this change did not differ depending on progestin type (negative affect: F1,117 = 0.30, P = .59; state anxiety: F1,117 = 2.15, P = .15; mental health: F1,117 = .16, P = .69) or ethinylestradiol dose (negative affect: F1,57 = .99, P = .32; state anxiety: F1,57 = 2.30, P = .13; mental health: F1,57 = .14, P = .71) was comparable with mood changes along the menstrual cycle in women with natural cycles (negative affect: F2,175 = 0.13, P = .87; state anxiety: F2,175 = 0.14, P = .32; mental health: F2,175 = 0.65, P = .52). Mood worsening during the pill pause was more pronounced in women with higher baseline depression scores (negative affect increase of 17.95% [95% CI, 7.80%-28.10%] in COC users with higher trait depression [BDI >8]). Emotion recognition performance did not differ between active pill phase and pill pause.
In this case-control study of long-term COC users, withdrawal from contraceptive steroids during the pill pause was associated with adverse mental health symptoms similar to those experienced by women during menses with withdrawal from endogenous steroids. These results question the use of the pill pause from a mental health perspective. Long-term COC users may benefit more from the mood-stabilizing effects of COCs in cases of continuous intake.
重要性:激素避孕与短期治疗后的情绪症状和情绪识别能力有关,而长期使用激素避孕药的使用者的心理健康状况则受到限制。
目的:评估长效口服避孕药(COC)使用者每月经历一次的激素撤退(避孕药停药期)是否与 COC 长期使用者的情绪变化和情绪识别能力改变有关。
设计、地点和参与者:这是一项病例对照研究,纳入了出生时被指定为女性的个体,他们认同女性性别,并使用 COC 6 个月或更长时间。对照组包括具有自然月经周期的女性,其他纳入标准相同。该研究于 2021 年 4 月至 2022 年 6 月在奥地利萨尔茨堡进行。
暴露:COC 使用者和具有自然月经周期的女性在一个月内进行两次测试,一次在她们的药物活性期或黄体期,一次在她们的避孕药停药期或月经期。
主要结果和措施:在每次就诊时评估负性情绪、焦虑和心理健康问题。在 COC 使用者中,计算在避孕药停药期与药物活性摄入期之间心理健康症状的百分比增加。与具有自然月经周期的女性在月经周期中情绪波动的比较。
结果:共纳入 181 名年龄在 18 至 35 岁之间的女性(平均[标准差]年龄 22.7[3.5]岁)(61 名使用雄激素 COC,59 名使用抗雄激素 COC,60 名使用非 COC 的月经周期)。与药物活性摄入期相比,COC 使用者的负性情绪增加 12.67%(95%CI,6.94%-18.39%),焦虑增加 7.42%(95%CI,3.43%-11.40%),心理健康症状增加 23.61%(95%CI,16.49%-30.73%;P<0.001)。这种变化的效应大小与孕激素类型(负性情绪:F1,117=0.30,P=0.59;状态焦虑:F1,117=1.55,P=0.22;心理健康:F1,117=0.16,P=0.69)或炔雌醇剂量(负性情绪:F1,57=0.99,P=0.32;状态焦虑:F1,57=1.30,P=0.26;心理健康:F1,57=0.14,P=0.71)无关,与具有自然周期的女性月经周期中的情绪变化相当(负性情绪:F2,175=0.13,P=0.87;状态焦虑:F2,175=0.14,P=0.32;心理健康:F2,175=0.65,P=0.52)。在具有较高基线抑郁评分的女性中,避孕药停药期的情绪恶化更为明显(COC 使用者的负性情绪增加 17.95%[95%CI,7.80%-28.10%],具有较高特质抑郁[BDI>8])。在药物活性期和停药期之间,情绪识别能力没有差异。
结论和相关性:在这项对长效 COC 使用者的病例对照研究中,避孕药停药期停止避孕类固醇与短期治疗后的负面心理健康症状有关,类似于女性在停止内源性类固醇时的月经症状。这些结果从心理健康的角度对避孕药停药期的使用提出了质疑。对于持续摄入 COC 的女性,COC 的稳定情绪作用可能更有益。