Pill pause for combined oral contraceptive use worsens mental health


In a recent study, negative mental health symptoms such as increased anxiety were observed among combined oral contraceptive users when treatment was paused.

Pill pause for combined oral contraceptive use worsens mental health | Image Credit: © Antonioguillem - © Antonioguillem - stock.adobe.com.

Pill pause for combined oral contraceptive use worsens mental health | Image Credit: © Antonioguillem - © Antonioguillem - stock.adobe.com.

Withdrawal from long-term combined oral contraceptive (COC) is associated with adverse mental health effects, according to a recent study published in JAMA Network Open.


  • A recent study in JAMA Network Open found that withdrawal from long-term combined oral contraceptives (COC) is associated with adverse mental health effects.
  • Data suggests an increased risk of depression and suicide attempts in the first few months of COC use, but it's unclear if these effects are due to COC initialization or pausing treatment.
  • The study aimed to determine changes in mental health symptoms among long-term COC users and included participants with no other underlying health conditions.
  • During the pill pause phase, COC users experienced an increase in anxiety and mental health symptoms, while negative affect increased and positive affect decreased.
  • These results suggest that long-term COC users may experience adverse mental health effects during the pill pause phase, raising questions about the benefits of continuous COC intake for mood stabilization.

Approximately 407 million women worldwide use hormonal contraceptives, and data has indicated a 1.8-fold increased risk of a first depression diagnosis or antidepressant use in the first few months of COC use, as well as a 2-fold increased risk of a suicide attempt. However, this data is minimal, and it is unclear if the mental health impact is caused by initialization of COCs or pausing treatment.

Mental health issues associated with endogenous hormonal change are most commonly observed during phases of hormonal withdrawal. However, studies have not evaluated whether mental health symptoms are associated with COC application or COC withdrawal.

To determine changes in mental health symptoms among long-term COC users, investigators conducted a case-control study. Participants were long-term COC users aged 18 to 35 years old with no other medication use or endocrinologic, psychiatric, or neurologic illnesses.

Androgenic COC users and antiandrogenic COC users were selected for intervention groups. Women with natural menstrual cycles (NCs) were selected for the control group.

The procedure occurred from April 2021 to June 2022, during which COC users received 2 tests. The first test occurred during the second or third week of COC intake while the second occurred between the fourth and seventh day of pill pause.

State and trait measures, such as the Premenstrual Symptom Screening Tool, Beck Depression Inventory, and Beck Anxiety Inventory, were used to evaluate mood. Other measures included the Positive and Negative Affect Schedule, Daily Rating of Severity of Problems, and State-Trait Anxiety Inventory.

There were 180 women included in the final analysis, aged a mean 22.7 years. Androgenic COC use was reported in 61 women, antiandrogenic COC use in 59, and no COC use in 60. Sixty NC participants with a mean menstrual cycle length of 28.7 days were included. Most participants were nonsmoking, nulliparous, and heterosexual.

Significant differences in trait measures of mental health were not observed between the COC groups and NC group. Additionally, emotion recognition did not differ between the active and pill pause phase conditions.

Among COC users, a 7.42% increase in anxiety and 23.61% increase in mental health symptoms was observed during the pill pause. Negative affect was increased by 12.67%, while positive affect was decreased by 1.76%.

NC women were not a significant moderator of self-reported mood changes across phases. Anxiety in NC women increased by 6.83%, mental health symptoms by 33.80%, and negative affect by 12.93%.

These results indicated adverse mental health effects from pill pause among long-term COC users. Investigators concluded it should be explored whether the mood-stabilizing effects of COCs benefits long-term COC users more in cases of continuous intake.


Noachtar IA, Frokjaer VG, Pletzer B. Mental health symptoms in oral contraceptive users during short-term hormone withdrawal. JAMA Netw Open. 2023;6(9):e2335957. doi:10.1001/jamanetworkopen.2023.35957

Related Videos
Understanding combined oral contraceptives and breast cancer risk | Image Credit: health.ucdavis.edu
Matthew Zerden, MD
Marci Bowers, MD | Image Credit: Marcibowers.com
Angela Dempsey
Related Content
© 2024 MJH Life Sciences

All rights reserved.