Adverse mental health symptoms with repeated short-term hormonal contraceptive withdrawal

Key takeaways:

• Oral contraceptive users reported increases in negative feelings, anxiety and mental health symptoms during pill pause vs. active phase weeks.
• Symptoms were similar to mood changes during menses.

Repeated withdrawal from contraceptive steroids during monthly pill pause was linked to adverse mental health symptoms, according to study findings published in JAMA Network Open.

“Interestingly, mental health problems associated with endogenous hormonal changes appear most commonly during phases of hormonal withdrawal, like the premenstrual or postpartum period or menopause. Also, withdrawal from hormone replacement therapy results in negative mood symptoms,” Isabel A. Noachtar, MSc, researcher PhD candidate in the department of psychology and the Centre for Cognitive Neuroscience at the University of Salzburg, Austria, and colleagues wrote. “However, neither randomized clinical trials nor cohort studies have the necessary temporal resolution to identify whether mental health symptoms occur in response to combined oral contraceptive application or during combined oral contraceptive withdrawal.”

Noachtar and colleagues conducted a case-control study in Austria from April 2021 to June 2022 with 181 women aged 18 to 35 years (mean age, 22.7 years) who used only combined oral contraceptives for 6 months or longer. Researchers also evaluated a control group of 60 women with a mean natural cycle length of 28.7 days who did not take any combined oral contraceptives in the past 6 months.

The primary outcome was negative feelings, anxiety and mental health problems assessed during the active pill phase or luteal phase and once during the pill pause or menses.

Overall, 61 women had androgenic combined oral contraceptive use, 59 had antiandrogenic use and 60 had menses without taking combined oral contraceptives.

Combined oral contraceptive users had a 12.67% increase in negative feelings (P = .009), 7.42% increase in anxiety (P = .003) and 23.61% increase in mental health symptoms (P < .001) during the pill pause compared with the active pill phase. The effect size did not differ by progestin type or ethinylestradiol dose. These adverse mental health symptoms were comparable with mood changes observed along the menstrual cycle in the control group.

In addition, researchers observed more pronounced mood worsening during the pill pause among women with higher baseline depression scores. Recognition of emotions did not differ between the active pill phase and the pill pause.

“These results question the usefulness of pill pauses from a mental health perspective and it should be explored whether long-term combined oral contraceptive users benefit more from the mood-stabilizing effects of combined oral contraceptives in cases of continuous intake,” the researchers wrote.