Nobody Tells You What GLP-1s Do to Your Sex Drive | GLS #213

0:00Dr. Gabrielle Lyon:The GLP-1 receptor might be hurting your sex life. Women are experiencing a sexual side effect signal that is being systematically missed because nobody is measuring it. The evidence for safety in women is not weak. It's non-existent. The FDA's reporting system only captures 1 % and 10 % of side effects that happen. And sexual side effects are among the most underreported in all of medicine. Now, let me explain why the same drug can help men and potentially hurt women. And this is where it becomes so interesting. It's not the specific drug that matters most. It's the receptor, the lock that all these drugs fit into.

0:41And this argument is simple. Does this class of medication harm sexual health or is it a positive? I'm going to start with the scariest version of this story. the strongest case that GLP-1 drugs are causing sexual problems. And I'm going to give it to you at full strength. Let's look at what we know.

1:06If a medication could kill your cravings for pancakes and your craving for sex, would you still take it? That's the question millions of people on Ozempic, Moderno, and the rest of the GLP-1 class are asking. Okay, so it's either pancakes or you put in the other P word. Here's what should bother you about it. The receptors these drugs hit to switch off appetite is the same receptor sitting in your reward circuitry, your hormones, and the smooth muscle of your body. Think about this, appetite and arousal running on one wire. If we turn down appetite, what happens to arousal? And for most people the drug, well, they didn't really think about this.

1:54No one ever checked what happened to the other. I'm going to give you a breakdown so that you have a clear decision landscape. Let's use a case similar to what I see in my own medical practice. Okay. Imagine this, a 35-year-old woman sitting across from you in clinic. She's a marketing director, two kids under five. Her life is absolutely insane. She's been on an SSRI for postpartum anxiety for two years. And frankly, it's working. She feels level-headed. She doesn't have anxiety. She doesn't want to touch it. Six months ago, her primary care doctor started her on a GLP-1 for weight. Her BMI was 33.

2:34She did not have diabetes. She does not have PMOS, formerly known as PCOS. She's down 28 pounds. Blood pressure is better. On paper, a total success story. That's not why she's here. It took her three visits to say these words out loud. Are you ready? It has nothing to do with the in-laws. It is. The interest in sex is almost gone. When it happens, it takes me a million years to feel aroused. And orgasm, which had never been a problem before is now absolutely unreliable. And sometimes it doesn't even happen. She assumed it was the SSRI medication. So she dropped the dose. Nothing changed. Now she's wondering, is there something wrong with her marriage?

3:26And then she gets the courage to ask you the question, could it be the weight loss drug? The honest answer is we don't know. Can you imagine that? We don't know. And it wouldn't matter which GLP she was on because the question itself has never been answered for many of them. Same drug class. Think about that. Pancakes or penis? You turn down the desire for pancakes because it's on that same reward circuitry. What happens to the desire for sex? Well, I'm going to argue both sides with myself. Again, and it's just another Tuesday, to come up with a conclusion for you. What does her doctor do? Her doctor switches her to semaglutide, also known as Ozempic or Wagovi.

4:14No change. Then they try a different medication, which is Terzepatide, the drug also known as Mondiorno or Zepbound. And her sex drive and ability to orgasm comes back. Meanwhile, in a completely different study, Get this. Men with obesity and low testosterone are put on the same class of the drug. Their testosterone goes up. Their erections improve and their sex lives get better. Same family of drugs, opposite outcomes. Just think about that for a second. A woman, a 35-year-old woman is put on these medications. A male, roughly the same age, is also put on these medications. his testosterone goes up, his erections get better, and his sex drive improves while hers is totally turned off.

5:05And I'm going to share both sides. And this argument is simple. Does this class of medication harm sexual health or is it a positive? The case that these drugs might be hurting your sex life. I'm going to start with the scariest version of this story. The strongest case that GLP-1 drugs are causing sexual problems. And I'm going to give it to you at full strength because if I can't be honest about the concern, you shouldn't trust me when I get to the reassurance. Let's look at what we know. A database study looked at young and middle-aged men,

5:39Dr. Gabrielle Lyon:non-diabetic, just overweight, who were prescribed semaglutide for weight loss compared to similar men not on the drug. And they were roughly, those on the drug, they were roughly four and a half times more likely to be diagnosed with erectile dysfunction and about twice as likely to be diagnosed with low testosterone. It's not just one drug. The FDA keeps a database where doctors and patients can report side effects. It's called FAIRS. The FDA adverse event reporting system, FAIRS, is the FDA's primary post-marketing safety surveillance database. It's been operational since 1969. You can read into that how you want and modernized into its current form in 2012.

6:27It's a passive spontaneous reporting system. This collects adverse event reports that are voluntarily submitted by healthcare providers, patients, and consumers and mandatorily submitted by drug manufacturers. Then what happens? A research team pulled every sexual side effect reported that's been linked to GLP-1 drugs. They found 182 of them. All of the tides, semaglutide was second, lariglutide, trisepatide, they were all represented. This isn't a one drug problem. It showed up across the entire class. Now, here's the part that should make you pay attention.

7:06Dr. Gabrielle Lyon:I know it made me pay attention. These drugs work by mimicking a hormone called GLP-1. And the receptors for that hormone aren't just in your gut and your pancreas, they're in your brain. Specifically, they're in parts of your brain that control reward. The same circuits that make food taste good, hence when we're talking about pancakes. It's the same circuits that make a glass of wine feel relaxing that also make sex feel pleasurable. That's why these drugs are being studied for things like alcohol addiction, for gambling, for opioid use. They turn down the volume on reward and sex for your brain is a reward.

7:49Okay, what do we know about humans versus animals? In animal studies, when researchers activated these receptors directly, the GLP-1, the animals lost interest in mating.

8:01Dr. Gabrielle Lyon:The brain chemicals needed for desire and orgasm, dopamine, norepinephrine, went down. Surprisingly, there's also a plumbing problem. Sexual arousal in both men and women, and we've talked about this before, that both get their forms of erections, depend on blood flow. Blood vessels in genitalia need to relax and open up, but GLP-1 receptor activation can do the opposite in some of these tissues. It can tighten blood vessels. And if the blood vessels that need to be open are being told to close, arousal doesn't work. It just doesn't work the way it should. And then there's a hormone problem that almost nobody is explaining.

8:46When you lose weight rapidly from any cause, from, I don't know, the grapefruit diet, your body makes more of a protein called SHBG, sex hormone binding globulin. Think of SHBG as a sponge that soaks up testosterone in your blood. Hormones are like children. Yes, I have two of them. They need to go with a chaperone everywhere. The more SHBG you have, the less free testosterone is available to do its job.

9:14Dr. Gabrielle Lyon:So a man can lose 30 pounds on one of these drugs, get his blood work done, see a quote normal testosterone number and still feel sexually flat because the total number looked fine, but the free testosterone, the part that actually matters, dropped and nobody measured it. For women who already have a fraction of the testosterone, men do, that same effect can push their free testosterone into a real deficit. And listen, women have less testosterone and we have no standard protocol for checking this. Here's the part that should make you a little pissed. Maybe it makes you a little angry. Women are 60 to 70 % of the people taking these drugs in this country.

9:55And the entire evidence base for what these drugs do to women's sexual function is two

10:01Dr. Gabrielle Lyon:case reports, not two clinical trials, two individual patients, two. Not a single major trial of any GLP-1 drug has ever given women a validated sexual function questionnaire. They measured weight. They measured blood sugar. they measured heart attacks. They never measured this. We called a darkened room empty. This is my metaphor. A darkened room empty without ever turning on the lights. How do you know? So that's my case against. And I have not softened it, but I want to give you my perspective. Well, let me first give you the counterpoint. Let me show you the case four. The case that these drugs are sexually safe, maybe even helpful.

10:50Now, I want you to notice something about every scary study. Notice who was studied. Notice how they measured things. The four and a half fold increase in erectile dysfunction that I mentioned earlier, where'd it come from? Well, it came from a database identified ED, erectile dysfunction, using billing codes. For those who are physicians or work in healthcare, you know what these billing codes are. And the database that identified erectile dysfunction using billing codes and Viagra prescriptions, not by actually asking men, hey, how was your sex life? Rather, the billing codes.

11:29Dr. Gabrielle Lyon:Here's why this matters. Men who are on somaglutide see their doctors more often than men who are not on medication. More doctor visits means more chances to be asked about sexual function or more chances to just talk about sex. More questions means more diagnoses. More diagnoses means more billing codes, even if the actual rate of problems is exactly the same in both groups. That's a lot. I know. This is a well-known problem in research. It's called detection bias. You find more of what you're looking for in the group you're looking at more closely. And when a more careful study tried to confirm that 4.5 times number, using better statistical methods to account for these kinds of biases, the signal shrank to nothing.

12:13It didn't show up. It didn't hold up. Now, those 182 side effect reports from the FDA database,

12:20Dr. Gabrielle Lyon:but the case against left out the most important number in that same study. The researchers calculated something called a reporting odds ratio. Basically, how sexual side effects were reported for GLP-1 drugs. Compared to all other drugs in the database, the number was 0.4, which means below 1. That means GLP-1 drugs had fewer sexual side effects reports than the average medication. The study's own authors called it a weak association. The case against gave you that scary number, the 4.5, and hid the context. Now let me tell you what happens when someone actually measure sexual function properly, not with billing codes, not with side effect reports, but with validated questionnaires and blood tests.

13:06Dr. Gabrielle Lyon:Multiple studies looked at 10 trials involving 639 men on various GLP-1 drugs. You know what they found? Testosterone went up. The hormones that drive testosterone production, LH, FSH, were preserved or went up too. Sperm quality improved. The drug wasn't one drug. It was across laraglutide, semaglutide, dulaglutide, and exonatide. A head-to-head trial compared laraglutide against testosterone replacement therapy in men with obesity-related low testosterone. Yes, it's a thing. Both groups improved. Erectile function scores went up, libido went up, and on some measures, the GLP-1 drug matched, which again, this is a little crazy, or beat testosterone injections.

13:53Dr. Gabrielle Lyon:We don't have time to talk about that. We'll come back to that in a different episode. The largest and longest study called Rewind followed nearly 10 ,000 men for over five years. They use validated erectile function questionnaire. Men on dulaglutide had a modest reduction in new erectile dysfunction compared to placebo. In men who already had heart disease, remember plumbing is plumbing, the group with the worst blood vessel function, the benefit was even larger. They had about a 19 % reduction. And here's a point that matters enormously. If you're a man who still wants to have children, testosterone replacement therapy is not on the table for you.

14:35It shuts down your body's own testosterone production. It suppresses LH and FSH, the hormones that tell your testicles to make sperm.

14:43Dr. Gabrielle Lyon:And that's why men on testosterone therapy often become infertile. Now, enter GLP-1 drugs. GLP-1 drugs do the opposite. They raise testosterone, i.e. indirectly, while keeping LH and FSH intact. Your body's own system, and this is very important for fertility, stays on. For a 35-year-old man who wants better sexual function and the option to have kids, this distinction is everything. And almost nobody is framing it that way. On social media, you just hear about GLP-1 and weight loss and Skeletor and all this stuff, but you're not hearing the sexual side effects or the sexual benefits. Now, let me explain why the same drug can help men and potentially hurt women.

15:28And this is where it becomes so interesting, men versus women, because it is the key to the whole conversation. It's not the specific drug that matters most. It's the receptor, the lock that all these drugs fit into. The GLP-1 receptor, they're everywhere. It's in your pancreas. It's in your gut. It's in your brain reward system. It's probably even under my bed, just, you know, whatever. Your blood vessels, your smooth muscle.

15:54Dr. Gabrielle Lyon:Every GLP-1 drug, semaglutide, laraglutide, dulaglutide, terazepatide, hits the same receptor. This is the mic drop moment. So the question isn't which drug. The question is which body. In a man with obesity, the math works like this. He loses visceral fat, probably loses some muscle fat, which was converting his testosterone to estrogen. His blood vessels improve, his inflammation drops, his testosterone goes up. All of those benefits outweigh whatever dampening the drug might do to his reward circuits. In my opinion, it's a net positive. In a lean woman or a postmenopausal woman or any woman whose sexual function was already working fine before she started the drug, the math, friends, is completely different.

16:44There's no testosterone deficit to fix. There's no obesity-driven vascular disease to reverse. but the reward circuit dampening is still there. The blood vessels tighten, that's still there. The SHBG rise, dropping her already free low testosterone, it's all still there. Without the metabolic upside to offset those effects, the net results could be negative. Where does that leave us. How do we examine both sides?

17:16Dr. Gabrielle Lyon:The case four rests on the question, if that mechanism that helps men is metabolic repair, what is the mechanism in a lean woman with normal lads who can no longer orgasm? And why have we never looked at it before? Round three, the cross-examination. Putting both sides to the test. The thing that makes the show different from every other podcast you listen to. I'm going to poke holes in both sides, including the one I just argued, because if I only attack the argument I don't like and protect the one I do, I'm not being honest. I'm just being persuasive. And persuasion without honesty, well, is just marketing.

17:54Dr. Gabrielle Lyon:The case against first, the four and a half fold number, it's not fabricated. It's a real finding in a real database. But it's the kind of study that you can't tell whether the drug caused the problem or whether of the men on the drug were just being watched more closely. And the one attempt to confirm it with better methods came back flat. This doesn't mean that the signal is fake. It means that it's unproven. The case against presented it as settled. It isn't. The 182 side effects, that report sounds alarming until you learn the study's own math showed GLP-1 drugs were actually, yes I said actually underrepresented for sexual side effects.

18:35But this is an important thing to consider.

18:38Dr. Gabrielle Lyon:The FDA's reporting system only captures somewhere between 1 % and 10 % of side effects that happen. And sexual side effects are among the most underreported in all of medicine, and for obvious reasons, because people are embarrassed to bring them up. So the reporting odds ratio favoring the case for these medications, it doesn't end the conversation. It just unfortunately makes it more complicated. The animal data, mice losing interest in sex when these receptors are activated is real biology. The last time I checked, mice are not people. And when researchers tested whether these drugs caused a general flattening of pleasure in humans in a clinical trial of semaglutide in people with depression, the group you'd expect to be most vulnerable, those that were depressed, found no effect.

19:33Dr. Gabrielle Lyon:The drug that supposedly blunts all reward didn't blunt reward in people most likely to show it. The case against, two case reports, the women who lost sexual function are real and they matter. But two patients are two patients. They tell you something is possible. They don't tell you how common it is or whether the drug was definitely the cause. Now, my own defense, same treatment, the systematic review showing testosterone improvements, it's made up of a small study and small studies have well-known problem. They tend to exaggerate whatever effect they're looking for. You hear this in nutrition all the time.

20:14Dr. Gabrielle Lyon:The study was small. The positive results may be real or they may be inflated. We can't be sure. The trial showing laraglutide-matched testosterone therapy, well, I don't know what I think about this. Nobody was blinded. Both the doctors and the patients knew which treatment they were getting, and sexual function is one of the most placebo-responsive things in medicine. If you believe a drug is going to help your sex life, it often does. Whether the drug is actually doing anything or not, an unblinded study of sexual function, because we know sex in the brain, go hand in hand, has to be taken with a grain of salt.

20:50Dr. Gabrielle Lyon:The Rewind trial, the big one, 10 ,000 men, five years, is the best evidence we have. But the sexual function analysis wasn't the main point of the trial. It was a secondary look at the data after the fact. And the benefit was modest. And when they looked at whether the improvement lasted, the effect shrank to non-significant. The defense presented the best number from the best subgroup and called it the headline. We see this all the time in medicine and reporting. We'll just call them the prosecution because I don't have a better name yet, but in future episodes, I will. That's the same move that the case against made with the 4.5 number.

21:32Dr. Gabrielle Lyon:Different direction, same technique. The only blinded controlled human trial that directly measures sexual function on a GLP-1 drug, dulaglutide, in 24 healthy men, found nothing, no harm. But it was four weeks long, and sexual side effects from antidepressants, the closest comparison we have, I did psych for a handful of years, often take six to 12 weeks to show up. Four weeks may simply not be long enough to catch a slow developing problem. And here's a complication that cuts across both arguments, the argument for and the argument against. Not all of these drugs may be the same. A 2026 study compared side effect profiles across six different GLP-1 drugs.

22:13Dr. Gabrielle Lyon:Semaglutide, the drug, you know, Ozempic, Wagovi, that stood out. It had significantly higher reporting for formerly called polycystic ovarian syndrome and menstrual problems than the other drugs. It also had a higher reporting for depression in two separate international databases, while Trisepetide, despite causing more weight loss and more nausea, did not. If this were a pure class effect, meaning all GLP-1 drugs do the same thing, every drug would trend the same direction. They don't. This tells you something important. Lumping all these drugs together may be hiding real differences between them.

22:49Dr. Gabrielle Lyon:The floor of concern is case-wide same receptor, same brain region, but somatilatide might be sitting on a higher floor, whether that's real biology or just the fact that somatilatide has the biggest market share because, again, it has just been the most widely used, generating the most reports is genuinely unknown. Though terzepatide also has enormous market share and doesn't show the same signal. I will say in our medical clinic, Strong Medical, we typically use terzepatide more. Just say that. Which makes the market share harder to sustain. Where does this leave us? Do we want pancakes or the alternative?

23:29It leaves us in this uncomfortable place where honest conversations live, where transparent

23:35Dr. Gabrielle Lyon:conversations live. The evidence for sexual benefit in men with obesity and metabolic disease is real. Multiple types of studies point the same direction. If you're a man with weight-related low testosterone, these drugs are probably helping your sex life, not hurting it. The evidence for sexual harm in any population is weak. Case reports, a database study that didn't hold up under scrutiny, and animal data that hasn't been confirmed in humans, not so great. The evidence for safety in women is not weak. It's non-existent. No trial, no questionnaire, no systemic measurement, nada, a big zero. And non-existent is not the same as reassuring.