It’s not discussed as often as other side effects of GLP-1 receptor agonists, but one adverse effect is the drugs’ potential to interfere with patients’ libido, causing a dulling or dampening effect.
Good news for patients, however, is that the issue can be mitigated.
About 4% of Americans were taking GLP-1 receptor agonists in 2024 for either overweight, obesity, or type 2 diabetes, one research paper found. That figure shows a skyrocketing 600% growth since 2018 that shows little sign of abating, despite the gastrointestinal adverse effects some encounter when taking these medications.
The Active Mechanisms Behind GLP-1s
These drugs act primarily in the gut but also work on pathways in the brain that influence appetite regulation and reward processing, said Bronwyn Holmes, MD, a member of the medical advisory board at Eden, an online weight loss clinic that prescribes GLP-1s. It’s difficult to pinpoint exactly how they behave, because the mechanisms by which they work are still not exactly known.
Bronwyn Holmes, MD
“These drugs are thought to dampen dopamine-driven reward signals, which help reduce the cravings for food and other compulsive behaviors. This can indirectly affect mood and motivation, useful for weight loss but potentially relevant to other reward-driven activities like intimacy or alcohol use,” Holmes said.
Emerging research suggests the medications may enhance serotonin receptors that are known to blunt sexual desire in another context, Holmes said.
The combination of reduced dopamine signaling and elevated serotonin could contribute to a muted reward response, she said. But, she said, definitive human trials are limited.
Psychiatrist Ryan S. Sultan, MD, said a closer look at current studies that show how GLP-1s may be useful in addiction treatment highlights the effects this class of medication has on patients’ brain chemistry. In this sense, he agreed with Holmes.
Ryan S. Sultan, MD
New research has shown GLP-1s could be the next treatment to reduce cravings and improve recovery in alcohol and opioid addiction, Sultan, an assistant professor of clinical psychiatry at Columbia University’s Irving Medical Center, New York City, and the founder and medical director of Integrative Psychiatry in Chelsea, New York, and Miami, said.
GLP-1 receptor agonists can increase dopamine release in the mesolimbic pathway, ultimately increasing baseline dopamine levels and reducing the spike that leads to cravings, he said. Other studies have shown that GLP-1 receptor activation can lead to a drop in dopamine and food cravings. In serotonin pathways, activation of GLP-1 receptors also aids in appetite regulation.
As reproduction and eating are both drives that are wired into the human system by evolution, Sultan said it “makes complete biological sense” that both of these needs are tied to the brain’s reward pathways. An overabundance of food in Western society creates what Sultan characterized as “major dysfunction in the reward system pathways associated with food.”
“Sex is based on drive and reward as well, and many neuronal networks involved in food and sex drives overlap,” he said.
“When we take GLP-1s, we are essentially dampening the internal processes that drive us to address our evolutionary needs. By inhibiting the pathways that drive us towards food acquisition, we are subsequently affecting the overlapping systems that drive us to have sex.”
Holmes said that the physical side effects that some patients experience when taking these medications, including nausea, constipation, and fatigue, can also lead to a reduced desire for intimacy.
On the Upside
Holmes pointed out that some patients experience enhanced sexual desire as the result of weight loss and improved self-perception, so there are some benefits to the libido from taking GLP-1s — or at least, benefits are experienced by some patients.
“The majority of people experience better sexual desire and function after weight loss because their mood improves, together with their self-esteem and hormonal balance,” she said. “The drug-induced libido reduction does not always outweigh the benefits of weight-loss improvements, which are most pronounced in menopausal women and men with low testosterone levels.”
Hormonal Fluctuations
Given that GLP-1s work on the patient’s hormones, it’s natural that they affect the functioning of the body’s overall hormonal system. The mechanism through which they help patients with type 2 diabetes manage their blood sugar levels is predicated on stimulating insulin release and slowing glucagon, in addition to slowing gastric emptying.
Two decades after the introduction of the first medication in this class, it can be hard to remember that weight loss was originally just a side effect. As a result, a patient’s hormonal changes before, during, and after taking the medication can combine with the medication’s effects on libido, too.
“Weight loss enhances insulin sensitivity while lowering leptin resistance, which leads to positive changes in testosterone and estrogen levels in people with metabolic dysfunction at the beginning (of treatment),” Holmes said.
For a provider to know what hormonal fluctuations are occurring, having baseline measurements would be imperative.
“Recent preliminary research indicates that long-term GLP-1 therapy can lead to increased testosterone levels in male patients,” she said. “People who already have hormone-related libido changes, such as menopausal women or men with low testosterone, will be more sensitive to the neurochemical effects of GLP-1s. Their fundamental hormonal alterations will make any minor dopamine or serotonin variations more noticeable.”
Hayley Miller, MD
Overall, more research needs to be done on the area of interconnectedness between GLP-1, hormones, and sexual desire, said Hayley Miller, MD, obesity medicine specialist and metabolic health director at Nurx, an online women’s health clinic.
Mitigating Decreased Libido
All the doctors said patients and clinicians should work together to discuss changes to the medication regimen in the face of disturbances in libido. Holmes said there are many ways a doctor can alter a prescription or help in other ways to lessen the impact of this side effect, or what’s behind it.
“These include adjusting the dose, addressing related symptoms like fatigue or nausea, and supporting sexual health through hormone optimization, counseling, or lifestyle changes,” she said. “In most cases, libido or mood-related side effects are reversible after stopping the medication. However, the timeline and completeness of reversal vary based on the individual and the presence of other contributing factors.”