Everyone lucky enough to be prescribe progesterone in the form of oral micronised progesterone capsules has probably been told to ensure they take them on an empty stomach. This isn’t that uncommon with medications, eating can affect the way they are absorbed. Out of curiosity I wondered what the problems are, in case I forget and have a snack just before taking it.

First, a caution. Always take medication in the manner prescribed by your doctor. This information is just for curiosity.

It turns out there was a study done in 1993. Micronised progesterone for oral administration came to the market in 1980, so it’s been around a while and a lot of the studies are fairly old. It’s a well understood product.

The study¹ handily titled “The absorption of oral micronized progesterone: the effect of food, dose proportionality, and comparison with intramuscular progesterone” was performed on 15 post-menopausal women, so it’s a very small sample size. To quote their results:

Concomitant food ingestion increased the area under the serum P concentration versus time curve (AUC_{0 to 24}) and the maximum serum P concentration (C_max) without affecting time to maximum serum concentration (T_max) (P < 0.05). Micronized P absorption and elimination were first-order processes and exhibited dose-independent pharmacokinetics between 100 and 300 mg.

So to translate that - taking your progesterone with food increases your absorption of progesterone, over the 24 hour period more total progesterone was absorbed, higher blood progesterone levels were measured, but the time taken to get to the maximum progesterone level was the same as for fasting. Secondly, the absorption of progesterone scales directly with dose, it doesn’t seem to drop down or rapidly increase.

But how much more progesterone is absorbed? From the paper’s conclusion:

Absorption of micronized P was enhanced twofold in the presence of food.

So taking progesterone with food results in twice the absorption rate compared to fasting. The peak is higher but the rate of metabolism is unaffected, so the end result is a consistently higher serum progesterone level (you can look at the paper to see the graphs and numbers)

Why are we told to take progesterone on an empty stomach? I can’t find an answer. It could be to avoid the peak - nearly six times higher when taken with food - or there could be other interactions not documented in this paper. If I find out more I’ll post an update!