What is natural progesterone cream and how does it work?

Natural progesterone cream contains bioidentical progesterone — a hormone molecularly identical to the progesterone your body produces naturally.

There are various strengths of progesterone cream on the market. Natpro is a 3.33% cream, meaning you get 33.33mg of progesterone per gram or milliliter of cream. A 5% cream would mean you are getting 50mg of progesterone per g/ml and so on. Measuring the correct dose of progesterone will depend on the strength of the cream you are using.

When natural progesterone is applied to the skin in the form of a cream or gel, it is absorbed through the skin and enters the capillaries of the dermis. From there, it binds to proteins in the blood and is delivered to tissues.

Here is an overview:

1. Absorption through the skin
Progesterone is lipophilic, meaning it dissolves in fat. This allows it to move through the stratum corneum, the outermost layer of skin. Absorption occurs not just by diffusion through skin layers, but also via the hair follicles and sebaceous glands, which provide a direct pathway inward.

2. Bypassing the liver
Unlike oral progesterone, which is rapidly broken down in the liver, transdermal progesterone avoids this ‘first-pass metabolism’. This means more intact hormone can reach tissues before being metabolised.

3. Distribution to tissues:
Once in circulation, progesterone delivered via a cream behaves the same as endogenous progesterone. It binds to receptors in the uterus, brain, breast, bone, skin, and other tissues. Importantly, the skin itself expresses progesterone receptors — so some benefits occur locally at the site of application before the hormone even reaches the bloodstream.

4. Metabolism and excretion
After exerting its effects, transdermally delivered progesterone undergoes the same metabolic pathways as natural progesterone, eventually being transformed into neuroactive and inactive metabolites, conjugated, and excreted in urine and bile.

Clinical studies show that topical progesterone raises levels in capillary blood and saliva, even if serum blood levels do not always reflect the increase. This is why conventional lab testing sometimes underestimates the effectiveness of creams — serum reflects only one compartment, whereas tissue and saliva levels often tell a different story.

The skin, particularly sebaceous glands and hair follicles, expresses 5α-reductase. This enzyme is best known for converting testosterone into DHT. It can also convert progesterone into 5α-dihydroprogesterone, a precursor of allopregnanolone.

While some progesterone is metabolized locally in the skin, research shows that a significant fraction still passes through intact, entering systemic circulation.
In fact, measurable rises in progesterone are found in tissues, saliva, and capillary blood after topical application.
Most conversion into neuroactive metabolites like allopregnanolone happens after absorption, in the liver and nervous system — not primarily in the skin.

It is important to understand that natural progesterone is not the same as synthetic progestins or progestogens, nor is it the same as wild yam extract. Progestins have an altered molecular structure and behave very differently in the body, carrying a range of known side effects. Wild yam extracts contain diosgenin but the body cannot convert this into progesterone. 

For more in depth information and research papers visit these pages: progesterone metabolism and transdermal application.