Placebo pills found to significantly reduce premenstrual syndrome symptoms

Placebo pills found to significantly reduce premenstrual syndrome symptoms | Image Credit: © Farknot Architect - © Farknot Architect - stock.adobe.com.

Introduction

Placebo pills reduce the intensity and debilitating effect of premenstrual syndrome (PMS) symptoms even when recipients are told they do not contain any active medication, according to a recent study published in BMJ Evidence-Based Medicine.¹

Reproductive-aged women with PMS often experience significant distress and psychological symptoms such as depressed mood, irritability, and mood swings. Physical symptoms such as joint pain, breast tenderness, and bloating may also occur in these patients. This can lead to depression, eating disorders, migraines, and suicidal thoughts.

“Thus, PMS has detrimental consequences at an individual and economic level,” wrote investigators.² “Although the etiology of PMS is not yet fully understood, inadequate responses to hormone fluctuation have been discussed.”

Limitations of traditional options and potential of placebo

This has led to multiple therapy options such as selective serotonin reuptake inhibitors and hormonal agents. However, these treatments may lead to side effects such as tremors and nausea, leading 69%of patients to discontinue treatment.

Efficacy against multiple psychological and somatic conditions has been reported from open-label placebos (OLP), defined as placebos provided with full transparency. Therefore, investigators conducted a randomized controlled trial to determine the efficacy of OLP against PMS.

Study design and methodology

Recruitment occurred between March 2018 and December 2020, with eligibility criteria including being aged 18 to 45 years, having moderate to severe PMS or premenstrual dysphoric disorder, a regular menstrual cycle (MC), and at least 1 impairing psychological or somatic PMS symptom. Any medication use was reported.

The trial began with a screening phase, where participants reported premenstrual symptoms and underwent daily monitoring of PMS. This occurred for 1 MC and was followed by an intervention phase for 2 MCs, where participants were randomized 1:1:1 to receive OLP with treatment rationale (OLP+), OLP without treatment rationale (OLP–), or standard treatment.

Intervention and randomization

Randomization occurred during the first half of the second MC. This was followed by 2 subsequent contacts and online surveys. At 3 weeks, the OLP+ group repeated the treatment rationale.

In the OLP+ and OLP- groups, participants took 2 placebo pills per day for 6 weeks. This treatment was labelled as placebo in both groups, with the OLP+ group being told about how PMS symptoms may be reduced by placebo treatment. This included watching a short video about the first OLP trial on irritable bowel syndrome.

In comparison, women in the OLP- group were only told they would receive placebo intervention. The changes in symptom intensity and interference of PMS since baseline were reported in all participants as primary outcomes.

These outcomes were assessed at the second and third luteal phase of the MCs through daily online surveys. Scores ranged from 0 to 135 for symptom intensity and 0 to 15 for interference. Subscales of the symptom intensity scale were used to measure psychological and somatic symptom intensity.

Study results

There were 150 women aged a mean 25.3±5.7 years included in the final analysis, with 50 placed in each group. Trial completion was reported by 96.7%. Meeting the criteria for premenstrual dysphoric disorder was reported in 52.7% and taking medicine at baseline in 40%.

From the first MC to the last MC, participants in the OLP+ group reported a mean change in symptom intensity of 18.00±18.56, indicating a 79.3% reduction. In the OLP- group, this change was an average of 12.89±20.27, indicating a 50.4% reduction.

Patients with standard care had the smallest reduction of 33%. For symptom interference, rates of decline were 82.5%, 50.3%, and 45.7%, respectively.

Comparing the treatment groups

Additionally, reduced symptom intensity was reported in the OLP+ group at the final MC compared to the OLP- and standard care groups. However, differences were not reported between the latter 2 groups. The OLP- and standard care groups also reported similar interference at the last MC, vs a significant decrease among OLP+ patients.

Safety outcomes were also assessed, with 4 women reporting non serious adverse events following OLP initiation. Differences in the rate of adverse events were not reported between groups, and none occurred after 6 weeks. Overall, the data indicated success in reducing the symptom intensity and interference among women with PMS.

“Considering our results as much as the individual and societal burden of PMS, OLP treatment could serve as an acceptable, efficacious, and safe intervention for PMS,” investigators concluded.

1. Open-label placebo appears to reduce premenstrual symptoms, study suggests. BMJ Group. March 25, 2025. Accessed March 27, 2025. https://www.eurekalert.org/news-releases/1077758
2. Nascimento AF, Gaab J, Degen B, et al. Efficacy of open-label placebos for premenstrual syndrome: a randomised controlled trial. BMJ Evidence-Based Medicine. 2025. doi:10.1136/bmjebm-2024-112875