I started noticing a pattern in my practice that bothered me.
Women would come to see me already on estrogen therapy, but they were still struggling. They’d arrive with prescriptions for Ambien or Lunesta for sleep. Buspirone, Prozac, or Lexapro for anxiety. Trazodone to help them make it through the night.
These weren’t new patients starting from scratch. These were women who had already sought help, already started hormone therapy, and were still collecting medications to manage individual symptoms.
The missing piece? Progesterone.
This was especially common in women who’d had hysterectomies. Their providers had told them they didn’t need progesterone anymore. Technically true if we’re only thinking about uterine protection. But that narrow view misses how progesterone affects your brain, your bones, your cardiovascular system, and your overall sense of well-being.
How Progesterone Works in Your Brain
Here’s what most women don’t know about progesterone: it’s a powerful modulator of GABA receptors in your brain.
GABA is your brain’s primary calming neurotransmitter. Progesterone enhances GABA activity in two ways. It stimulates the release of GABA from neurons, and it affects how sensitive your receptors are to GABA’s effects.
The result? Natural sedation and relaxation.
This is the same neurotransmitter system that medications like Ambien, benzodiazepines, and many anxiety medications target. But progesterone works with your body’s natural chemistry rather than overriding it.
When I explain this mechanism to patients who’ve been told they need separate medications for sleep and anxiety, the reaction is consistent: relief. Many come to me specifically because they don’t want to be on these medications long-term. Learning that their symptoms could be addressed hormonally changes how they think about treatment.
The Weaning Process Nobody Talks About
Adding progesterone isn’t always a quick fix, and I want to be honest about that.
If you’re already on sleep or anxiety medications, you can’t just stop them abruptly. These medications require a careful weaning process that can take weeks or even months.
But here’s what I’ve observed: progesterone makes that weaning process easier.
As we introduce progesterone and it begins working on your GABA receptors, your body has natural support as we gradually reduce the other medications. You’re not left without anything while we taper down the prescriptions that were filling the gap.
Timing Matters More Than You Think
During your initial consultation, I look for one specific indicator that tells me you’re likely to respond well to progesterone therapy.
I ask: Did you have sleep or anxiety issues before your menopause transition?
If your symptoms started with perimenopause or menopause, that’s a strong sign that progesterone therapy could be highly effective. Your symptoms are directly tied to hormonal changes, and addressing those changes at their source makes sense.
But what if you’ve had anxiety or sleep issues your whole life, and they just got worse during menopause?
If you were already on medications before your transition and they were working well, I might not recommend changing your approach. But if your symptoms are getting worse despite your current medications, progesterone therapy offers an alternative to simply increasing doses of sleep and anxiety medications.
Why Bioidentical Progesterone Is Different
You’ve probably heard the term “bioidentical” thrown around as a marketing buzzword. Let me explain the actual clinical differences I see.
Bioidentical progesterone interacts with GABA receptors in a predictable, positive way. Synthetic progestins interact with these same receptors unpredictably. Some women feel fine on synthetic progestins. Others feel worse.
The differences go beyond brain chemistry:
- Cardiovascular effects: Synthetic progestins can have harmful effects on your cardiovascular system. Bioidentical progesterone is protective.
- Breast cancer risk: The data shows synthetic progestins increase breast cancer risk. Bioidentical progesterone doesn’t increase that risk and may actually be protective.
I’ve had patients switch from synthetic progestins to bioidentical progesterone, and the feedback is consistent: they just feel better. I believe this comes down to supporting your natural hormone environment rather than suppressing it.
The Bone Health Connection You’re Missing
Most women associate estrogen with bone protection during menopause. That’s not wrong, but it’s incomplete.
Progesterone plays a distinct role in bone health that often gets overlooked. It enhances the activity of osteoblasts, the cells that build new bone. At the same time, it decreases the activity of osteoclasts, the cells that break down bone.
Think of it this way: progesterone works on both sides of bone remodeling.
When I talk to patients concerned about osteoporosis or declining bone density, I explain that estrogen and progesterone have a synergistic effect. They work together more effectively than either hormone alone. If you’re only focusing on estrogen for bone health, you’re using half the tools available to you.
The Integrated Approach That Actually Works
Hormone therapy doesn’t exist in a vacuum, and I don’t treat it that way.
Progesterone is naturally anti-inflammatory. When you combine progesterone therapy with anti-inflammatory supplements and an anti-inflammatory diet, you enhance the effectiveness of the hormone therapy itself.
I also recommend that women approach menopause care holistically. That means optimizing thyroid function and adrenal function alongside hormone therapy. Your endocrine system works as an integrated whole. Addressing one piece while ignoring others limits your results.
What to Ask Your Doctor
If you’re considering hormone therapy or already on it but still struggling with symptoms, here’s what I wish every woman would bring up with her healthcare provider:
Ask about both short-term and long-term effects of HRT. The earlier you start hormone therapy, the stronger the benefits for symptom control, quality of life, bone health, cardiovascular protection, cognition, and even colon cancer prevention.
Yes, I said cancer prevention.
This contradicts what you’ve heard for decades, I know. The 2001 Women’s Health Initiative study scared an entire generation of women away from hormone therapy. But the data from that study is now being re-evaluated, and long-term follow-up on those patients tells a different story.
The long-term studies addressing morbidity and mortality have been favorable, with one major exception: synthetic progestins. The literature is also becoming more specific about terminology. When studies say “estrogen” or “progestogens,” you need to know exactly which types they’re referring to. Not all hormones behave the same way.
Rebuilding Trust in Hormone Therapy
When a patient sits in front of me terrified of HRT because of what she heard 20 years ago, I don’t dismiss her concerns.
I show her the current studies. I share the position statement from The Menopause Society. And I explain the specific differences between what was tested in the WHI study and what I would recommend for her.
The WHI study used synthetic progestins and oral estrogen in older women who were years past menopause. That’s not what I prescribe. I use bioidentical progesterone, often with transdermal estrogen, started closer to the onset of menopause when the benefits are strongest.
The details matter.
If your doctor is still making treatment decisions based on outdated interpretations of 20-year-old data, you deserve a conversation about what the current evidence actually shows.
You also deserve treatment that addresses you as a whole person, not just a collection of symptoms to be managed with separate prescriptions. Progesterone therapy, when used appropriately and as part of an integrated approach, can address multiple symptoms through one intervention that works with your body’s natural systems.
That’s not marketing language. That’s what I see in my practice every day.
Kirby Plessala, MD
Kirby Plessala, MD is a board-certified practicing obstetrician and gynecologist with over 30 years of clinical experience. Dr. Plessala was born and raised in Morgan City, Louisiana, earned a Bachelor of Science degree from Tulane University and a Doctor of Medicine degree from Louisiana State University School of Medicine. He continued his medical training, completing his obstetrics and gynecology internship and residency with the University of Alabama at Birmingham School of Medicine.
In 1994, he began practicing in Mobile and, ever since then, has remained committed to serving his patients in the greater Mobile area. He is a Fellow of the American College of Obstetricians & Gynecologists and has maintained his certification with the American Board of Obstetrics & Gynecology.
