Noachtar, I. A., Frokjaer, V. G., & Pletzer, B. (2023). Mental Health Symptoms in Oral Contraceptive Users During Short-Term Hormone Withdrawal. JAMA network open, 6(9), e2335957. https://doi.org/10.1001/jamanetworkopen.2023.35957
Noachtar IA, Frokjaer VG, Pletzer B. Mental Health Symptoms in Oral Contraceptive Users During Short-Term Hormone Withdrawal. JAMA network open. 2023;6(9):e2335957. doi:10.1001/jamanetworkopen.2023.35957
Noachtar, Isabel A., et al. "Mental Health Symptoms in Oral Contraceptive Users During Short-Term Hormone Withdrawal." JAMA network open, vol. 6, no. 9, 2023, pp. e2335957.
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Long-term pill users report worse mood and anxiety in the pill pause
Long-term pill users reported more negative mood and anxiety during the pill pause, a case-control study of young women in Austria found. Women with natural cycles had a similar rise at menses. The pill pause is the week without hormones in a combined oral contraceptive (COC) cycle.
Key Findings
In the pill pause, negative affect among COC users was up 12.67% (95% CI, 6.94%-18.39%) and anxiety was up 7.42% (95% CI, 3.43%-11.40%).
Mental health symptoms among COC users rose 23.61% (95% CI, 16.49%-30.73%; P < .001) in the pill pause, relative to the days of active pills.
Women with natural cycles had negative affect up 12.93% (95% CI, 3.37%-22.49%) and anxiety up 6.83% (95% CI, 1.61%-12.06%) from luteal phase to menses.
Mental health symptoms in women with natural cycles increased by 33.80% (95% CI, 21.56%-46.05%) from the luteal phase to menses.
Among COC users scoring above 8 on the Beck Depression Inventory (BDI), negative affect rose 17.95% (95% CI, 7.80%-28.10%). At 8 or below, it rose 8.48% (95% CI, 2.04%-14.93%).
Interpretation
The authors call this a case-control study. Pill users were compared with a control group of women with natural cycles. Each woman was tested twice within a month. The design shows association only. The analysis covered 61 women on androgenic COCs, 59 on antiandrogenic COCs, and 60 with natural cycles, mean age 22.7 years. All pill users had taken the pill for 6 months or longer. Results may not extend to women who had mood problems early in use. The authors say physical discomfort during withdrawal bleeding may explain the rise. Emotion recognition did not differ between the two phases.
RRM Context
COCs are suppressive medications. They hold hormone levels steady and replace the cycle's own rise and fall with a scheduled withdrawal bleed. Women with natural cycles showed a similar mood pattern at menses, which fits the restorative reproductive medicine view that cycle-related mood change deserves recording. Cycle charting records symptom timing day by day.
Our editorial summary of this paper, not the article's abstract.
Abstract
Importance
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.
Objective
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.
Exposure
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.
Main Outcomes and Measures
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.
Results
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.
Conclusions and Relevance
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.
