A very interesting study, which demonstrates that the route of hormonal administration matters quite a bit, at least when it comes to muscle strength and endurance. Namely, when P4 was administered orally during pregnancy in this study, it resulted in increased muscle strength and physical endurance, while topical (vaginal) and injected (intramuscular) routes did not. Interestingly, oral P4 seems to raised plasma pregnenolone (P5), and P5 has already been demonstrated in humans to improve recovery from strenuous physical activity. The human equivalent doses used in the study were 180mg, 800, and 200mg daily for an adult human, as per the study. Now, the study used P4 dissolved in a peanut oil (trade name Urogestan/Utrogestan) and carboxymethylcellulose, which ensures that P4 will undergo heavy first-pass metabolism through the liver. Systemic bioavailability of Urogestan/Utrogestan is in the 12%-14% range and the half-life is less than one hour. However, if P4 is dissolved in vitamin E and some kind of oil (olive oil or MCT), it will largely avoid first pass metabolism, and achieve bioavailability of 65%+, with its half-life being the same as the one for vitamin E (~48 hours). This means that with vitamin E as the main solvent, oral progesterone dosage can probably be cut from 800mg down to less than 175mg daily, while also significantly increasing its half-life, and allow one to achieve the same (or better) ergogenic effects.
https://mednexus.org/doi/10.1097/RD9.0000000000000101
“…The dosages for P4 administration via the different routes were determined with reference to the maximum clinical doses for each route, as summarized by Labarta and Rodriguez[19] and the doses used in clinical trials by Costabile et al.[20], which were converted into animal doses. The human doses for vaginal P4 gel, oral P4, and intramuscular P4 injection are 180[19], 800[19], and 200 mg/day[20], respectively. The doses for rats were calculated using a conversion factor of six. The IG group was administered urogestan capsules prepared as a 20 mg/mL solution of sodium carboxymethylcellulose at a dose of 4 mL/kg, equivalent to 80 mg/kg. The IM group received P4 injections at a concentration of 20 mg/mL, administered at a volume of 1 mL/kg, equivalent to a dose of 20 mg/kg. The VAGIN group received 80 mg/mL of P4 sustained-release vaginal gel at a volume of 0.225 mL/kg, equivalent to 18 mg/kg. Each group was administered the respective dose once daily in the morning for 13 days.”
https://www.eurekalert.org/news-releases/1089855
“…Researchers from Shanghai Institute for Biomedical and Pharmaceutical Technologies randomly classify female rats into four groups based on different administration methods: oral administration, intramuscular injection, vaginal gel application, and a control group with no treatment. P4 was administered daily for 13 consecutive days during the teratogenesis-sensitive period, a vulnerable stage for birth defects. The results showed that offspring from the orally administered P4 group exhibited significantly prolonged swimming times compared to controls, suggesting enhanced physical stamina. In contrast, intramuscular and vaginal routes showed no such effect. Beyond endurance performance, oral administration of P4 also correlated with elevated plasma pregnenolone levels, a neurosteroid tied to exercise adaptation, and reduced non-social behaviors. The gut microbiota analysis also showed differences across groups. Oral and intramuscular methods altered microbial composition, with oral administration uniquely reducing Oligella—a bacterium linked to poorer exercise performance in prior studies.”
