What We Can Learn From the Placebo Effect

A few weeks ago, I saw a patient for a follow-up visit. She had started taking testosterone, and she reported feeling better the very first day she used it. Then she laughed and noted that that probably wasn’t possible, that it had to be the placebo effect. She was referring to the idea that when a patient knows they are taking a new medication, they might observe changes before the medication could possibly have kicked in.

I agreed with her. It typically takes some time for testosterone levels to rise. Trials usually show an effect after about four weeks. But, as I reminded her, the placebo effect is real. People do get relief from their symptoms when they know they are being treated. And it is a significant factor in many trials looking at treatments for perimenopause symptoms.

Take me to the bottom line

What is the placebo effect?

When we want to see if an intervention like a medication has an effect, we treat a group with the medication and look for our desired outcome. Say we want to see if a new medication lowers blood pressure. We give people the medication and see if their blood pressure is lower after taking it. But we don’t know if their blood pressure fell because of the medication or if it would have gotten better on its own. Maybe something else about the study participants caused their lower blood pressure at the follow-up visit.

So, to get around this, we can add a control group (a group of participants who don’t get the medication or any intervention) to our study. This is called a controlled trial. We give the study group the medication and see if their blood pressure is lower than the group that didn’t get the medication. But it raises the question, what if the people who got the medication got better because they knew they were getting treatment, not because the medication was effective?

Enter the placebo-controlled trial. In this type of trial, both groups get a treatment. One group gets the medication and one group gets a sugar pill. Participants don’t know which group they are in (this is the key difference between a controlled trial and a placebo-controlled trial). If the group taking the medication has lower blood pressure and the group that took the sugar pills doesn’t, you can say that the medication was effective at lowering blood pressure.

However, in many trials we see that the group that got the sugar pills also has some improvement. In the case of the blood pressure medication, the people who got the sugar pills have lower blood pressure than before they took the sugar pills. Their blood pressure wasn’t as low as the people who got the medication, but they still saw some improvement. This improvement may be because they believed they were being treated. That is the placebo effect.

The placebo effect and perimenopause treatments

Many trials of treatments for perimenopausal symptoms have shown strong placebo effects. This may be because in many trials, the outcome we are looking for is a perceived improvement in symptoms. For example, there is no lab test to tell us if testosterone is improving women’s sexual desire. We have to rely on the women’s reports of their symptoms.

We see a great example of this in one of the largest trials of testosterone for decreased sexual desire and arousal. The group that was given a testosterone spray reported having more than twice as many satisfactory sexual encounters after taking the testosterone compared with before taking the testosterone. But the group that received the placebo spray also had a big increase in the number of satisfying sexual events during the trial. They had 70% more satisfying sexual encounters after taking the placebo spray. The testosterone spray was better than the placebo spray, but the placebo spray was significantly better than nothing.

And it isn’t just with testosterone for hypoactive sexual desire where we see this kind of strong placebo effect. Fezolinetant (Veozah) is a non-hormonal treatment for hot flushes and night sweats. In the clinical trial that the manufacturer submitted to the FDA to get the medication approved, women who took fezolinetant had a 60% reduction in their hot flushes.

The women who took the placebo also saw a significant improvement in their hot flushes. In fact, nearly 61% of the women who were given a placebo reported some degree of improvement of their symptoms. Fezolinetant was better than a placebo, but the placebo also had a significant effect on participants’ symptoms. There is a way to objectively measure hot flushes, but it is cumbersome and so it is not typically used in larger trials. Again we are typically relying on women’s perceptions of their symptoms.

Why does the placebo effect matter?

Understanding the placebo effect is important for interpreting clinical trials and understanding not just whether medications and other interventions are effective, but also just how effective they are. After all, one of our goals is to objectively treat symptoms. Knowing that there is a large placebo effect tells us that at least some of the effects patients are experiencing are not from the medication itself, even if the effect seen in the treatment group is bigger than the effect in the placebo group.

But I think there is something else important to consider when we repeatedly see a strong placebo effect in trials in a specific area, like perimenopause. In a world where women’s symptoms are often dismissed, just validating a woman’s symptoms and offering a treatment provides some relief, even before the treatment takes effect. These improvements are real, in that patients really are feeling better. In my mind, that has value.

In fact, psychologists often report a similar phenomenon. People with anxiety and depression report that just scheduling an appointment with a therapist improves their symptoms. This makes sense. Both mood changes and perimenopause symptoms can leave people feeling isolated. Knowing that what you are feeling is common and there is treatment available gives people hope, and that can go a long way toward relieving symptoms.

I want to offer my patients the best evidence-based medicine. My goal in doing so is to help them feel their best. Trials like the ones above serve as a reminder that the first step in helping patients is to listen to them, validate that what they are feeling is real, and then, whenever possible, offer them an evidence-based treatment for their symptoms.

The bottom line

The placebo effect is when patients see improvements in symptoms from taking a treatment they believe will work, despite the fact that what they are taking doesn’t contain an effective medication.
Trials of testosterone for decreased desire for sex have shown strong placebo effects. So did the trial of the non-hormonal treatment for hot flushes, fezolinetant.
While understanding the placebo effect is important when interpreting trial results, it also reminds us that validating women’s symptoms and offering treatment provides relief even before medications take effect.