Why do antihistamines cause weight gain? And how does hormonal birth control affect metabolism? In my latest podcast and Youtube video, I look at how common medications, including hormonal birth control, affect metabolism and your ability to lose weight.

Welcome back to the podcast. I’m your host Lara Briden, a naturopathic doctor and author of the books Period Repair Manual and Hormone Repair Manual. It’s high summer in New Zealand, and I’m doing lots of walking. Between walks, I’m deep into writing my third book, which is all about troubleshooting metabolism for women. Not just diet and exercise but all the factors, including digestive health, food sensitivities, sleep, chronotype, thyroid, menstrual cycle, and, of course, medications.

So. Which medications are most likely to cause weight gain? Let’s survey the main ones — some of which may surprise you — and then we’ll settle into a discussion of hormonal birth control and natural progesterone.

First, any medication with an antihistamine effect can cause weight gain. That includes antihistamines for hay fever and sleep but also stomach acid medication, anti-nausea medication, and some types of antidepressants such as amitriptyline, nortriptyline, and mirtazapine. There are a couple of things going on. For one thing, histamine normally has an appetite-suppressing effect, so blocking histamine receptors, especially H1 receptors, can increase appetite. Also, blocking histamine receptors at the hypothalamus can induce other downstream metabolic changes such as reduced energy expenditure, reduced fat burning, increased fat deposition, impaired glucose control, and insulin resistance. I’ve put a couple of citations in the show notes.

Other antidepressants that can potentially cause weight gain include some of the SSRIs, especially paroxetine or Paxil. But in that case, it’s probably due to paroxetine’s anticholinergic effect, which means it interacts with—or blocks—acetylcholine receptors. Basically, any medication that blocks histamine, muscarinic, or acetylcholine receptors can potentially cause weight gain via several mechanisms, including increased appetite. Other medications that interact with those receptors and cause weight gain — sometimes dramatic weight gain— include antipsychotic and antiseizure medications.

Of course, do not stop your antidepressant or other medication without first speaking to your doctor.

Moving on. Beta-blockers can cause weight gain. Beta-blockers are calming medications used to treat conditions like high blood pressure, migraines, and anxiety. Mechanisms by which they cause weight gain include increasing appetite, decreasing motivation for exercise, and blocking the effects of adrenaline, which is actually quite an important hormone for fat burning.

Side note, you may be used to thinking of adrenaline and the sympathetic nervous system as bad, but everything has a sweet spot. Some degree of activation of the sympathetic nervous system and adrenaline is good for health, mood, and fat burning.

Now, if you’re a migraine sufferer, you may be relying on amitriptyline, antiseizure medication, or a beta blocker to try to prevent migraines. And if you’re experiencing weight gain from that treatment, you may want to consider some of the natural migraine prevention strategies I provide in both books and my migraine blog post, which I’ll put in the show notes.

Next are oral corticosteroids, such as prednisone, which doctors are usually pretty reluctant to prescribe, but can be required for severe allergies, rashes, and autoimmune conditions like rheumatoid arthritis. If taken long-term — say, longer than a week — oral prednisone can cause pretty dramatic weight gain via several mechanisms including:

• directly increasing appetite,
• disturbing sleep, which then increases appetite, and
• inducing insulin resistance.

See episode 6 of my podcast for a big discussion of insulin resistance. And yes, high levels of endogenous cortisol from chronic stress can also induce insulin resistance.

Fortunately, topical corticosteroid cream and steroid nasal sprays are not likely to cause significant weight gain — although they can increase appetite. Next are some of the medications used to treat diabetes. Not metformin, thank goodness. It usually promotes weight loss. The diabetes medications that can cause weight gain include sulfonylureas, which stimulate the pancreas to release more insulin, and of course, taking insulin as injectable insulin. Which if you have Type 1 diabetes, you obviously need to do. So, once again, I’m not suggesting you stop your medication— especially do not stop insulin if you need insulin.

This is just about information and understanding that although insulin is an essential and highly beneficial hormone, too much insulin — as in, chronically elevated insulin — can cause weight gain via several mechanisms, including increased appetite and deposition of fat, especially visceral fat, which is the bad kind of fat.

Insulin-induced weight gain is potentially a problem if you’re taking insulin but also if you have chronically elevated levels of your own insulin as a result of insulin resistance. Again, see episode 6, plus my new book coming in early 2024.

Finally, we come to hormonal birth control and the big question of, “does hormonal birth control cause weight gain?” And if so, which types are more likely to do so? Well, it’s tricky because, for decades, women have observed weight gain on hormonal birth control. Only to be told by experts that it’s not a thing. Which is similar, by the way, to how, for decades, women observed depression on hormonal birth control. Only to be told by experts that it was not a thing. Until 2016, of course, when scientists discovered that depression from hormonal birth control is a thing.

But back to weight gain from hormonal birth control. Here’s what we know so far:

1. The evidence — so far— seems to be that combined estrogen methods, like the pill, patch, and Nuvaring, do not cause significant weight gain. That’s probably thanks to the fact that estrogen, even synthetic estrogen, is insulin-sensitizing, so potentially reduces visceral fat.
2. Combined estrogen methods do, however, alter body composition by causing more fluid retention and impairing muscle gain from exercise. So big picture, I think some combined estrogen methods do impair metabolism and cause weight gain. But the whole data set is confused by the fact that some combined estrogen methods (namely those with antiandrogen progestins like drospirenone) are likely to cause weight loss.

And that brings us to point number 3, which is that antiandrogen progestins (i.e. progestins that suppress testosterone) are likely to cause weight loss, while androgenic progestins (i.e. progestins that stimulate androgen receptors) are likely to cause abdominal weight gain, especially when taken on their own without estrogen.

Why do androgenic progestins cause abdominal weight gain? Because, in women, too much testosterone causes insulin resistance. That’s true for PCOS; it’s also true for some types of hormonal birth control.

And yes, an antiandrogen progestin such as drospirenone (which is a close cousin of the antiandrogen medication spironolactone) can potentially promote weight loss, but only for as long as you take it. Stopping drospirenone can, unfortunately, lead to rebound weight gain, which I discuss in episode 8 — all about post-pill acne, hair loss, and weight gain.

Back to androgenic progestins and how they potentially cause weight gain, especially when taken on their own without estrogen. Examples of progestins on their own include the progestin-only pill, the Depo-Provera injection, and implants. And, indeed. According to a 2021 randomized trial, Depo-Provera and a levonorgestrel implant were found to cause significant weight gain after 18 months. That study is in the show notes.

Levonorgestrel is the progestin in most implants and hormonal IUDs, and it is definitely androgenic or testosterone-like — hence the tendency for weight gain, even potentially weight gain from hormonal IUDs, although they were not included in the study.

The progestin in the contraceptive injection is medroxyprogesterone acetate or Depo-Provera, which is also androgenic at the androgen receptor, so, in women, can cause androgen side effects like acne, facial hair, and weight gain. Provera is a little confusing, though, because, at high doses in men, it’s sometimes used to shut down testicular function and therefore function as an anti-androgen treatment. But high-dose use in men is not what we’re talking about here.

The other mechanism by which Depo-Provera can cause weight gain is by interacting with cortisol receptors, thereby causing weight gain in the same way corticosteroids do, as we just discussed. That’s possibly why one study found Depo-Provera to cause “unstoppable weight gain” in young women — i.e. weight gain that doesn’t plateau or level out.

Let’s now talk about natural progesterone, also called oral micronized progesterone, or the brand names Prometrium and Utrogestan. Does it cause weight gain? Well, according to a 2019 systematic review (link in the show notes), natural progesterone given together with estrogen to healthy menopausal women caused either weight loss or no change. Interestingly, the paper lists all the mechanisms by which progesterone should cause weight loss, including:

• progesterone is diuretic,
• it increases core body temperature
• it increases thyroid hormone, and
• it supports sleep and, therefore, growth hormone.

I would point out that natural progesterone also has beneficial antiandrogen properties, which is why it’s used as part of cyclic progesterone therapy for PCOS. Link the show notes. Lots of links today.

Okay. As always, there’s a section in my forum at LaraBriden.com to discuss the episode. You can chime in there with your knowledge, experience, and questions.

I hope that’s been helpful, and thanks so much for listening. Please share and leave a review. And I’ll see you next time when I’ll discuss a gut condition called SIBO, or small intestinal bacterial overgrowth, and how it can be an underlying driver of endometriosis, PCOS, mood problems, and even weight gain.