Progesterone Creams for HRT: How They Work & Usage

Around 70,000 women in the U.S. start hormone replacement therapy (HRT) every year, and for many, that includes progesterone cream.

Individuals exploring HRT may frequently hear about progesterone creams as a more natural or gentle option. But how do these creams work, and are they effective at protecting the uterus when estrogen is part of treatment?

This article explains what progesterone creams are, how to use them, their benefits, and the important safety details to know when considering them as part of HRT.

Understanding Progesterone's Role in HRT

Progesterone is a hormone the body makes naturally. During the menopause transition, progesterone levels drop. This can cause symptoms like hot flashes, trouble sleeping, and changes in the uterus. Using HRT can help bring hormone levels back into balance. Estrogen is usually the main hormone prescribed, but for women with a uterus, progesterone is added to protect the endometrium (the lining of the uterus) from becoming too thick, which could raise the risk of certain cancers.⁽¹⁾

In addition to protecting the endometrium, progesterone may also help with sleep and mood. However, these effects are more strongly linked with oral forms.

HRT can come in many forms: pills, capsules, patches, gels, sprays, vaginal rings, and creams. Topical progesterone creams are one option for delivering progesterone through the skin.⁽²⁾

What are progesterone creams? 

Progesterone creams are topical products that contain the hormone progesterone, which is applied directly to the skin. These creams are usually made with (natural) bioidentical progesterone, meaning they’re identical to the hormone made in the body.

Common cream ingredients include:

Moisturizers – Ingredients like glycerin, olive oil, and triglycerides that hydrate and soften the skin

Skin Smoothers – Emollients and fatty acids that protect the skin barrier and help the hormone medication absorb through the skin

Stabilizers – Ingredients that keep the cream fresh, well-mixed, and safe to use

Types of Progesterone Creams Available

• Over-the-counter (OTC) creams are available without a prescription and are often marketed as natural. This type typically has lower concentrations of progesterone.

• Pharmaceutical creams are mass-produced medications manufactured by large pharmaceutical companies. They follow standardized formulas and are dispensed at regular pharmacies.

• Compounded progesterone creams are individually prepared by compounding pharmacies based on a physician’s specific prescription. They are customized to each patient’s needs and made with FDA-approved ingredients.

Bioidentical Progesterone Cream

The term bioidentical refers to hormones that have the exact same molecular structure as those produced naturally by the human body. This differs from synthetic hormones, which are structurally similar but not identical and may behave differently in the body. Bioidentical progesterone is often preferred for its closer alignment with the body’s natural hormone activity.⁽³⁾⁽⁴⁾

Many pharmaceutical and compounded creams use bioidentical progesterone. However, it’s important to understand that natural does not automatically mean safer. All forms of hormone therapy — whether bioidentical or synthetic — should be prescribed and monitored by a medical professional to ensure the correct dose, delivery method, and treatment plan.

The U.S. Food and Drug Administration (FDA) does not formally recommend compounded hormone therapy, due to variability in quality among some compounding pharmacies. However, reputable providers use accredited compounding pharmacies that follow strict quality-control standards. With compounding, each formulation can be customized to the patient’s needs and prescribed under medical supervision, allowing for more precise dosing and better hormone balance.⁽⁴⁾

This personalized approach not only enhances safety but also increases effectiveness — particularly for women who may not respond well to mass-produced, one-size-fits-all treatments.

How do progesterone creams work?

Progesterone creams deliver hormone through transdermal absorption, meaning the hormone passes through the skin and enters the bloodstream. Once in circulation, progesterone can bind to hormone receptors throughout the body, including in the uterus, brain, and breast tissue. This allows it to help regulate hormonal cycles, reduce estrogen-driven tissue growth, and support hormonal balance during the menopause transition.^(2)(3)(5)

Several factors influence how well progesterone cream is absorbed and how much reaches the bloodstream:

• Application site – Areas with thinner skin and better blood flow allow for more efficient absorption.

• Skin condition – Thicker or dehydrated skin may reduce how much hormone is absorbed.

• Cream concentration – Higher-strength formulas typically deliver more hormone per dose.

• Amount used – Larger amounts generally provide more progesterone, but only up to a point — skin saturation and individual differences also matter.

Although transdermal delivery avoids the digestive system and liver (unlike oral forms), research shows that absorption can vary from person to person. This makes careful dosing and regular follow-up with a healthcare provider essential when using hormone therapy.⁽²⁾

Oral Progesterone vs. Cream

Oral and transdermal progesterone each have advantages. Oral progesterone is processed in the liver and converted into metabolites like allopregnanolone, which may support sleep and mood. Because of this metabolism, oral progesterone is often preferred for its systemic effects and for protecting the uterine lining. However, it may also carry a higher risk of certain side effects for some people.⁽³⁾

Topical creams bypass the liver completely and tend to cause fewer systemic effects. They also offer steady hormone levels when applied consistently. One scientific review reported that progesterone creams can counteract estrogen’s effects on the uterine lining and offer endometrial protection when used in appropriate doses.⁽³⁾⁽⁶⁾

Because absorption can be less predictable with creams, working with a physician trained in menopause care is the best way to ensure the right dose and delivery method.

How to Use Progesterone Creams Effectively

Application: Where and How to Apply

Creams are usually applied to soft, thin areas of skin where hormones can be absorbed easily. The best places to apply progesterone cream for HRT include the following:⁽³⁾

• Inner wrists

• Inner arms

• Inner thighs

• Behind the knees

• Lower abdomen

Always follow a physician’s or pharmacist's instructions for when and where to apply the cream.

Rotating application sites helps prevent concentration in one area. Apply creams on clean, dry skin and rub it in thoroughly until fully absorbed. 

It’s important to wash hands right after application. This avoids transferring the hormone to unwanted parts of the body, other people, food, or pets.

Timing and Frequency of Use

Most regimens call for applying progesterone cream once daily. Evening is a common choice, especially if the patient finds that progesterone has a calming effect.⁽³⁾

Depending on whether a woman is still menstruating, the cream may be used on a cyclical (e.g., 14 days per month with a rest period) or continuous (indefinite, daily) schedule. The prescribing doctor will help decide what’s best.⁽³⁾

Dosage Considerations: Finding the Right Amount

The amount of progesterone in each cream varies, and each person's needs are different. Prescription and compounded creams are dosed based on a person’s hormone levels and treatment goals. Some products use pumps, while others come with an applicator.

Doses are often measured in milligrams (mg). Compounded creams typically contain 50–200 mg per dose. Over-the-counter creams often contain lower doses of progesterone and may not be strong enough to offer full endometrial protection.^(1)(2)(3)

For HRT, it’s crucial that enough progesterone is absorbed to protect the endometrium. This is where guidance from a physician, plus high-quality products, is key.

Over-the-Counter (OTC) vs. Prescription Progesterone Creams

Over-the-counter (OTC) progesterone creams are widely available, but they’re not held to the same quality or dosing standards as prescription formulations — they’re manufactured products, not carefully formulated medications. Because they are often classified as cosmetics, OTC creams are not required to undergo rigorous testing for hormone content or absorption.⁽⁵⁾⁽⁷⁾

In contrast, prescription and compounded progesterone creams are made in licensed pharmacies and carefully prepared to meet medical standards. A doctor decides the right dose and checks that it’s working well. This medical guidance helps make sure the treatment is both safe and effective. Because of this, prescription creams are regarded as the safer choice.

Potential Benefits of Progesterone Creams

Endometrial Protection (The Primary Goal with Estrogen)

Reminder: Progesterone’s most important job in HRT is protecting the uterus. This only works if levels in the body stay high enough throughout the month. While some women may absorb enough hormone from creams, others may not, so careful monitoring is essential.

Menopause Symptom Relief

Many women report that progesterone cream, when part of an HRT regimen, helps with these symptoms:⁽³⁾

• Hot flashes

• Night sweats

• Sleep disturbances

• Mood shifts

• Vaginal dryness and discomfort

However, most studies on menopause management have been done with oral progesterone, which is generally considered to be more reliably absorbed.

Advantages of Topical Delivery

Compared to oral pills, topical progesterone comes with the following benefits:⁽³⁾

• Often feels gentler for those who have trouble tolerating oral hormones

• Suitable for women who prefer a non-pill option

• Bypasses the liver, which may reduce certain systemic side effects

• Less likely to cause digestive issues 

• Works well when monitored by a provider who can adjust dosing based on individual response

Risks, Side Effects, and Limitations of Progesterone Cream

Common Side Effects of Progesterone

Most women tolerate progesterone cream well, but side effects can include the following:⁽³⁾

• Skin irritation at the application site

• Drowsiness or dizziness

• Bloating

• Breast tenderness

• Mood changes (especially if too much is absorbed)

These side effects typically resolve on their own after the body adjusts to HRT treatment.

Potential Risks and Contraindications

Like many medications, progesterone carries some potential risks. While these risks are not guaranteed, it's important to be aware of them. Some women, particularly those with a history of the following, may decide to forgo progesterone when considering HRT:⁽³⁾

• Breast cancer

• Blood clots

• Cardiovascular disease

• Liver disease

While these risks are lower with transdermal hormones than with oral treatments, it’s still important to discuss o

ptions with a menopause specialist. 

This is especially important because absorption can vary depending on the individual and the way the cream is applied. Without careful medical guidance, dosing may not be accurate. If too little progesterone is absorbed, the uterus may not be adequately protected, which can increase the risk of complications. Despite these concerns, many women respond well to customized progesterone cream regimens, especially when treatment is monitored and supported by a physician.

Talking to a Doctor About Progesterone Creams

Before starting progesterone cream, it’s important to talk with a knowledgeable provider. Some helpful questions to ask include the following:

• Is progesterone cream the right option for my needs?

• How can we make sure I’m getting enough to protect my uterus?

• Are there more effective alternatives for my specific case?

• What are the risks based on my health history?

• How will we monitor its effects?

The Gentler Option for Symptom Relief

Progesterone creams provide a non-oral way to take bioidentical progesterone. For some women, they may offer gentle symptom relief or serve as part of a custom HRT plan. However, getting enough progesterone through the skin to protect the uterus can be tricky.

The key is working with a physician who can prescribe high-quality creams and monitor how well they’re working. With the right guidance, progesterone creams can help manage hormone imbalance and menopause as part of a safe, balanced treatment plan.

Experiencing menopausal symptoms? Discover if HRT is right for you.

If you’ve entered the menopause transition or are struggling with hormone imbalance symptoms, you don’t have to suffer in silence. Take our brief quiz to see if you’re an eligible candidate for HRT. Get started with Winona to take the first step toward feeling better.