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In a recent study published in JAMA Network Open, researchers investigated whether the short-term hormone withdrawal that users of combination oral contraceptive agents (COCs) experience one time per month (pill break) was connected with mood changes and emotional identification among long-term COC users.

Study: Mental Health Symptoms in Oral Contraceptive Users During Short-Term Hormone Withdrawal. Image Credit: Kotcha K/


Research has indicated that hormonal contraception, particularly COC, can raise women's risk of depression and suicidal thoughts. Long-term COC usage, on the other hand, has been related to a lower incidence of panic disorder, depression, clinda m retin a and suicide, particularly among teenagers.

The mental health consequences of COC usage are unknown and may be altered by lifestyle changes or socioeconomic levels.

About the study

In the present case-control study, researchers investigated whether short-term hormone withdrawal, or pill pause, was related to changes in psychiatric symptoms among long-term COC users depending on estrogen dosage, progestin type, and mental health symptoms at study initiation.

The study, which took place in Austria from April 2021 to June 2022, sought to determine the influence of pill pause on mental health symptoms among long-term COC users and whether these changes were mediated by progestin type, estrogen dosage, and prior mental health symptoms.

The research comprised 18 to 35-year-old community members who had used COC for at least six months, spoke German fluently, and had no neurologic, psychiatric, or endocrinologic illnesses.

There was also a control group of women with regular menstrual periods. Both groups were evaluated two times monthly, during the luteal/active pill phase and the pill break or menses phase.

Anxiety, negative affect, and mental well-being issues were measured throughout each session as outcome measures. In COC users, the proportionate increase in psychiatric symptomatology was measured during the oral contraceptive pill break vs. the active consumption period.

The researchers also compared mood changes during the menstrual periods among women with regular menstrual cycles. To examine characteristics, the Beck Depression Inventory (BDI-II), Beck Anxiety Inventory (BAI), and Premenstrual Symptom Screening Tool (PSST) were utilized.

Throughout each session, the Positive and Negative Affect Schedule (PANAS), an emoticon scale assessing negative and positive affect, the State-Trait Anxiety Inventory (STAI), and the Daily Rating of Severity of Problems (DRSP) were all administered.

Participants conducted a health check and three cognitive tests (verbal fluency, navigation, mental rotation, an emotion detection task, mood surveys, and three saliva samples) over 90 minutes at each session.

Users of COC containing progestins such as desogestrel, levonorgestrel, etonogestrel, norelgestromin, or gestodene were categorized as androgenic-type COC users (COC-A). Users of COCs comprising drospirenone, dienogest, cyproterone acetate, nomegestrol acetate, or chlormadinone acetate were categorized as anti-androgenic-type COC users (COC-AA). Linear mixed effects modeling was performed for the analysis.


The study comprised 181 females aged between 18 and 35 years, with a mean age of 23 years, among whom 61 reported androgenic COC usage, 59 said anti-androgenic COC usage, and 60 did not use COCs.

The majority of participants were nulliparous, heterosexual, nonsmokers, had completed university admission examinations, and were unemployed.

Compared to the active intake period, COC users demonstrated 13%, 7.4%, and 24% increases in the negative affect, anxiety, and psychiatric symptoms in the pill break phase, respectively.

The magnitude of this shift was equivalent to mood changes during the menstrual cycles among women with regular cycles, regardless of progestin type or ethinylestradiol dosage. The increase in the negative effect of 18% among depressed COC users (BDI scores above 8.0) was more severe in the pill break phase.

There were no significant differences in the emotional identification performance between the luteal and the pill break phases. There were no significant differences in psychiatric health aspects between COC groups and NC women throughout the pill discontinuation.

Among COC consumers with lower trait depression, negative affect rose 8.5%, whereas anxiety increased by 6.8% in women with natural menstrual cycles. The presence of trait anxiety did not affect state anxiety variations in the pill break phase.


Based on the study findings, the pill pause, a period of withdrawal from contraceptives, has been linked to adverse psychiatric symptoms among long-term combined oral contraceptive consumers.

These symptoms are similar to the ones experienced during menstruation after withdrawing from endogenous-type steroids. The study findings indicate that long-term COC users might benefit continuous consumers more due to the mood-stabilizing properties.

The findings indicated significantly increased anxiety, negative effects, and psychiatric symptoms in the pill break period, influenced by depression scores.

The worsening mood may be related to brain structural alterations and connectivity during the resting state in the pill break phase. Adverse mood symptoms in the pill break phase might explain the mixed findings on COC efficacy in managing premenstrual dysphoric disorders.

It is possible that the worsening of psychiatric symptoms may not result directly from hormonal withdrawal but could be linked to physical discomfort at the time of withdrawal bleeding.

Journal reference:
  • Isabel A. Noachtar, MSc; Vibe G.Frokjaer, MD, PhD; Belinda Pletzer, PhD., (2023) 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.,with%20the%20active%20intake%20phase.

Posted in: Medical Science News | Medical Research News | Women's Health News | Pharmaceutical News

Tags: Anxiety, Bleeding, Brain, Contraception, Contraceptive, Depression, Efficacy, Estrogen, Hormone, Levonorgestrel, Menstruation, Mental Health, Panic Disorder, Progestin, Research

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Pooja Toshniwal Paharia

Dr. based clinical-radiological diagnosis and management of oral lesions and conditions and associated maxillofacial disorders.

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