Pill pause linked to adverse mental health symptoms in long-term contraceptive users

For long-term users of combined oral contraceptives (COC), short-term hormonal withdrawal that occurs during the once-a-month pill pause appears to be accompanied by a significant increase in negative affect, anxiety, and mental health symptoms, regardless of COC type, as reported in a study.

Data from 181 women (mean age 22.7 years) showed that those who had been using COC for at least 6 months experienced a 12.67-percent increase in negative affect (95 percent confidence interval [CI], 6.94–18.39), 7.42-percent increase in anxiety (95 percent CI, 3.43–11.40), and 23.61-percent increase in mental health symptoms (95 percent CI, 16.49–30.73) during the pill pause compared to the active intake phase. Emotion recognition performance remained stable. [JAMA Netw Open  2023;6:e2335957]

Of the women, 61 were using androgenic COC, 59 were using antiandrogenic COC, and 60 were not taking COCs. The mean cycle length of non-COC-user controls was 28.7 days.

The mood changes that occurred during the pill pause did not differ by the type of progestin used (androgenic vs antiandrogenic COC; p=0.69) and by ethinylestradiol dose (p=0.71), suggesting that the type of progestin does not play a role in mental health symptoms associated with hormone withdrawal, as the investigators pointed out.

Also of note, mood worsening during the pill pause was comparable to the mood changes experienced by women with natural menstrual cycles during their menses—a period where the levels of endogenous steroids drop sharply. This similarity, according to the investigators, indicates similar effects of both synthetic and endogenous hormonal withdrawal.

“Given that any type of hormone withdrawal appears to elicit similar symptom strength, it is also possible that the increase in mental health symptoms was not a direct result of hormone withdrawal but was associated with the physical discomfort during withdrawal bleeding,” they added.

Finally, baseline depression moderated the mood changes during the pill pause, such that mood worsening was more pronounced in women with higher baseline depression scores as assessed by the Beck Depression Inventory (BDI). Specifically, negative affect increased by 17.95 percent among COC users with BDI score of >8 at baseline.

Overall, the data presented here are “in line with the assumption of a mood-stabilizing effect of COCs in long-term users and questions the usefulness of frequent (ie, monthly) pill pauses from a mental health perspective,” the investigators said. [J Affect Disord 2002;70:229-240; Open Access J Contracept 2019;10:27-39]

“It is possible that this mood worsening is related to previously observed changes in brain structure and resting state connectivity during the pill pause. Adverse mood symptoms during the pill pause may also explain why results on the effectiveness of COCs as a treatment for premenstrual dysphoric disorder are mixed,” they added. [Neurobiol Stress 2020;13:100276; Brain Res 2015;1624:275-285; Neuroimage 2014;90:24-32; J Clin Psychiatry 2020;81:6789]

The investigators called for more studies to explore whether long-term COC users benefit more from the mood-stabilizing effects of COCs in cases of continuous intake.