There’s a conversation more women need to hear — especially if they’re navigating perimenopause or menopause and trying GLP-1 medications for weight loss.
It’s not just about taking hormones or taking a GLP-1. It’s about how these therapies work together.
Because when you stack HRT and GLP-1s, you're not just managing symptoms. You’re supporting your body in a smarter, more complete way.
- GLP-1 meds can slow digestion, which may worsen constipation and interfere with estrogen detox — especially in midlife women.
- Estrogen detox matters. When it’s disrupted, harmful estrogen metabolites can recirculate, throwing hormones even more out of balance.
- HRT supports the terrain. Estrogen, progesterone, and testosterone help stabilize metabolism, improve gut motility, and support detox pathways.
- Starting HRT before or alongside GLP-1s may lead to better results — especially for body composition, insulin resistance, and energy.
- Ask your provider about combining both therapies, supporting liver detox, and tracking beta-glucuronidase — especially if you’re constipated or stuck.
- Join Josie is a top choice for women seeking combined HRT + GLP-1 support – they offer compounded GLP-1s, with real providers and personalized care.
Let’s Start With Digestion
If you’re in perimenopause or menopause, odds are your digestion isn’t what it used to be. Constipation, bloating, and slower motility can all be part of the picture — even before you add in a GLP-1.
Now layer in a medication like semaglutide or tirzepatide. One of the most common side effects? Slower gastric emptying. That means your digestion slows down even more, which can worsen constipation.
This might seem like a minor issue — but it’s not. Because here’s what happens next:
When your body can’t eliminate efficiently, your estrogen detox pathways take a hit.
Your liver is already working hard to metabolize hormones, especially in women who may be relying on things like wine to wind down at night (common, but taxing for the liver). Add sluggish motility, and now your estrogen metabolites get backed up — and some get recirculated.
That’s where beta-glucuronidase comes in.
What’s Beta-Glucuronidase? and Why Does It Matter?
Beta-glucuronidase is an enzyme in your gut that controls how estrogen is processed and cleared. In menopause, this enzyme often rises, especially in women who are already prone to constipation.
When beta-glucuronidase is elevated, it can lead to recycling estrogen back into the bloodstream — which is not what you want, especially if your liver is trying to clear it out. That recirculation can throw off hormonal balance and increase toxic burden.
Women in midlife are already in a hormonal transition — and without the right supports, systems like detoxification and elimination can get overwhelmed quickly.
The combo of:
- A sluggish gut (from GLP-1s and hormonal shifts)
- A stressed liver (often from lifestyle load)
- Rising beta-glucuronidase …can create the perfect storm.
But There’s a Smarter Way to Support the Body
This is where HRT — especially balanced estrogen, progesterone, and testosterone in menopause — comes in.
These hormones aren’t just for reproductive health. They influence mitochondrial function, insulin signaling, inflammation, fat storage, and gut health. Estrogen in particular supports the microbiome and helps maintain digestive motility. Testosterone can support muscle mass and energy, while progesterone helps calm the nervous system and promotes regularity.
When these hormones are brought back online through bioidentical HRT, they help stabilize the terrain.
Add GLP-1s After That Terrain Is Supported
When HRT is in place — and you’ve stabilized estrogen’s impact on tissues, glucose, and fat metabolism — GLP-1s become more effective.
That’s what emerging research is showing. In fact, there’s early data suggesting that women who start HRT and GLP-1s together may experience better body composition outcomes than women using either one alone.
It makes sense:
- Estrogen affects GLUT4 transporters (key for moving glucose into the mitochondria)
- Estrogen reduces visceral fat
- Estrogen and testosterone improve insulin sensitivity
So when GLP-1s are layered on top of this hormonal support, you’re not fighting an uphill battle. You’re working with your body.
Real-World Example
Let’s say you’re a 48-year-old woman in perimenopause. You’re struggling with belly fat, sleep, and digestion. You start a GLP-1 — and the weight begins to shift.
But you’re still constipated, foggy, and tired. That’s because you haven’t addressed what’s happening hormonally.
Now imagine supporting your liver, lowering beta-glucuronidase, restoring estrogen, testosterone, and progesterone — and then adding in a GLP-1.
That’s where real transformation happens.
What to Ask Your Provider
Not all providers understand this synergy — but some do.
If you're considering this approach, ask about:
- Testing your beta-glucuronidase levels (especially if constipated)
- Supporting phase 1 and 2 liver detox
- Bioidentical HRT tailored to your symptoms
- Timing HRT and GLP-1s together for metabolic synergy
Many of my clients I coach use Join Josie for both HRT and GLP-1s — because we’ve seen how powerful the combination can be when done thoughtfully.
And we’re just getting started.
Still Have Questions? Here’s What Women Ask Me Most
Yes, many women do — but it's important to work with a provider who understands both. Some emerging research suggests that combining hormone therapy with GLP-1s may support better outcomes for weight, metabolism, and overall well-being. Always consult with your healthcare provider to decide what’s best for you.
Because they work on different — but complementary — systems. HRT can help restore hormonal balance, while GLP-1s target appetite regulation and insulin resistance. Together, they may support a more complete metabolic picture for women in midlife.
No. Everyone’s body and health history is different. What works well for one woman might not be ideal for another. That’s why it’s essential to work with a qualified medical provider who can evaluate your labs, symptoms, and goals.
You’re allowed to start the conversation. Many women are surprised to learn how much hormones impact things like weight, energy, sleep, and mood. It’s okay to ask questions and explore your options with a provider who listens.
There are a few platforms now offering support for both GLP-1s and HRT in women. One of my top recommendations is Join Josie — many of my clients have had positive experiences there.
