Progesterone vs. Progestin: Why the Difference Matters for Your Perimenopause Treatment

Two Words That Mean Very Different Things

If you have been researching hormone therapy, you have probably seen the words progesterone and progestin used almost interchangeably, sometimes by doctors, sometimes in articles, sometimes on pharmacy labels. They are not the same thing. Understanding the difference matters because the type of progestogen in your HRT formulation can affect your side effects, your sleep, your mood, and your risk profile in meaningful ways.

Progesterone refers to the exact hormone your body makes. When it is used in a medication, it is called micronized progesterone or bioidentical progesterone. The most commonly prescribed form in the United States is a capsule called Prometrium, and it is also available as a component in some combination HRT products. Bioidentical progesterone has the same molecular structure as the progesterone your ovaries produce.

Progestins are synthetic compounds created in a lab to mimic some of progesterone's effects. They were developed partly because natural progesterone was hard to stabilize in older drug formulations, and partly because pharmaceutical companies needed patentable compounds. Different progestins have somewhat different effects in the body, and they behave differently than natural progesterone in ways that have real clinical consequences. Common progestins include medroxyprogesterone acetate (MPA), norethindrone, and levonorgestrel.

Why Both Are Used in HRT

Progesterone and progestins are used in hormone therapy for one primary reason: to protect the uterine lining. Estrogen, when used alone and without any progestogen, stimulates the endometrium and increases the risk of endometrial cancer over time. Adding a progestogen counteracts that stimulation and keeps the lining stable. If you have had a hysterectomy and no longer have a uterus, you generally do not need a progestogen at all, and many providers offer estrogen-only therapy in that case.

For women who do have a uterus, the question shifts to which progestogen to use and in what dose and schedule. There are several different regimens: sequential (taking progestogen for part of the month, which often produces a withdrawal bleed), continuous combined (taking both estrogen and progestogen daily, which typically stops periods after a few months of adjustment), or cyclic approaches. The specific progestogen used interacts with both the regimen and the side effect profile in ways that differ between individual women.

It is also worth noting that some providers use intrauterine devices such as the levonorgestrel IUD as the progestogen component for women using systemic estrogen. This approach delivers the progestogen directly to the endometrium while keeping systemic levels very low. Whether that approach is right for you depends on your overall treatment goals and your provider's experience.

The Breast Cancer Risk Conversation

The Women's Health Initiative (WHI) study in 2002 generated headlines that scared many women away from hormone therapy entirely. One of the key findings was an increased breast cancer risk in the combination HRT arm of the study. What is often not discussed is that the specific progestogen used was medroxyprogesterone acetate (MPA), a synthetic progestin, paired with conjugated equine estrogen.

Subsequent research, particularly large observational studies from France and Scandinavia, has suggested that natural micronized progesterone paired with estrogen does not carry the same elevated breast cancer risk as MPA. A major French study published in Climacteric followed tens of thousands of women and found that women using estrogen plus micronized progesterone had no increased breast cancer risk compared to non-users, while women using estrogen plus synthetic progestins did show increased risk.

This distinction matters enormously for women making decisions about HRT. The risk profile is not uniform across all forms of hormone therapy. However, it is important to acknowledge that the French and Scandinavian data are observational, not randomized controlled trials, which means there are limitations in how definitively we can attribute the difference to progesterone type versus other factors. What the data does support is that the type of progestogen is a clinically meaningful variable worth discussing with your provider.

Sleep and Mood: Where Micronized Progesterone Stands Out

One of the most clinically interesting differences between natural progesterone and synthetic progestins is the effect on sleep and mood. Progesterone, the natural form, is metabolized in the brain into compounds called neurosteroids, particularly allopregnanolone. Allopregnanolone acts on GABA receptors in the brain, producing a calming, sedating effect similar to benzodiazepines. This is why Prometrium, when taken at night, often helps women sleep. Many women notice a genuine improvement in sleep quality after starting micronized progesterone.

Synthetic progestins do not convert to the same neurosteroids and do not produce the same GABA-enhancing effect. In fact, some women report that progestins worsen mood, increase irritability, or cause PMS-like symptoms. This is part of why some women who had difficult experiences with birth control pills (which contain synthetic progestins) are sometimes pleasantly surprised when they switch to natural progesterone in their perimenopausal HRT.

If sleep disruption and mood are significant issues for you in perimenopause, this pharmacological difference between progesterone and progestins is worth bringing up explicitly with your prescriber. It is not always the first variable providers optimize, but it can make a meaningful difference in how you feel on a day-to-day basis.

Which Formulations Use Which

Knowing which products contain natural progesterone versus synthetic progestins helps you navigate this with your prescriber. Prometrium is oral micronized progesterone and is the most widely prescribed bioidentical option in the United States. Utrogestan is the equivalent in the UK and much of Europe. Crinone is a vaginal progesterone gel used more often in fertility contexts but occasionally in menopause care.

Synthetic progestins appear in many combination HRT tablets and patches. CombiPatch, for example, contains estradiol and norethindrone acetate. Activella contains similar ingredients. The Mirena IUD uses levonorgestrel. Prempro, one of the most widely researched HRT products but also the one used in the WHI study, contains conjugated equine estrogen plus MPA.

Some compounded HRT products also exist, combining estradiol or estriol with progesterone in customized formulations. These are prepared by compounding pharmacies and are not FDA-approved products. The quality and consistency of compounded hormones varies and is a topic of some debate in menopause medicine. For most women, FDA-approved micronized progesterone products are the preferred option when natural progesterone is the goal.

What to Ask Your Doctor

The Bottom Line on Progestogen Choice

The difference between progesterone and progestins is not just marketing language. It reflects real differences in molecular structure, how each compound acts in your brain and tissues, and what the clinical evidence suggests about long-term outcomes. Progestogens are not interchangeable, and the type you take as part of HRT is worth understanding and discussing with your care team.

For most women with a uterus who are considering combined hormone therapy, natural micronized progesterone is generally considered the preferred option by current menopause specialty guidelines, based on its superior side effect profile, sleep benefits, and more favorable breast cancer data. That said, individual circumstances vary, and some women do well on specific synthetic progestins or progestogen-releasing IUDs depending on their full clinical picture.

Knowing that this variable exists puts you in a better position to have an informed conversation. Your hormonal health during perimenopause is worth treating with that level of specificity.

Medical Disclaimer

This article is for informational purposes only and does not constitute medical advice. Hormone therapy decisions are complex and depend on individual health history, risk factors, and preferences. The information about breast cancer risk represents one area of ongoing research and should be interpreted in the context of your full clinical picture, not as a blanket reassurance or warning. Speak with a qualified healthcare provider before making any changes to your hormone therapy.

Information in this article reflects clinical research and guidance available as of early 2026.