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WARNING: Always start with lower doses due to differences between individual body weight, tolerance, metabolism, and personal sensitivity. See responsible use section.
DISCLAIMER: PW's dosage information is gathered from users and resources for educational purposes only. It is not a recommendation and should be verified with other sources for accuracy.
Pregn-4-ene-3,20-dione, also known as Progesterone or P4 is a steroid sex hormone of the progestogen class. It occurs naturally and is the bodies major progestogen.
Progesterone was first discovered in 1929 by George W. Corner and Willard M. Allen. By 1934 pure crystalline material was achieved by Adolf Butenandt at the Chemisches Institut of Technical University in wikipedia:Gdańsk. Synthesis was accomplished later that year.
[2]
In a 2012 study higher levels of progesterone were linked to lower affinity to competitive behavior in women.[3][4]
Chemistry
Progesterone is a naturally occurring pregnane steroid and is also known as pregn-4-ene-3,20-dione. It has a double bond (4-ene) between the C4 and C5 positions and two ketone groups (3,20-dione), one at the C3 position and the other at the C20 position.[5]
Progesterone is mainly metabolised in the liver, therefore the route of administration significantly influences the intensity of experienced effects. The most important metabolites are allopregnanolone, pregnanolone, isopregnanolone and epipregnanolone.[7]
Allopregnanolone and Pregnanolone are documented to have antidepressant, anxiolytic, stress reducing, antiagressive, sedative, sleep aiding, analgesic, amnesic, anesthetic, anticonvulsant & neuroprotective effects.[8][9]Allopregnanolone and Pregnanolone act as positive allosteric modulators of GABAA whereas isopregnanolone and epipregnanolone selectively counteract GABAA as well as the sedative and anesthetic effects.[7]
Subjective effects
Disclaimer: The effects listed below cite the Subjective Effect Index (SEI), an open research literature based on anecdotal user reports and the personal analyses of PsychonautWikicontributors. As a result, they should be viewed with a healthy degree of skepticism.
It is also worth noting that these effects will not necessarily occur in a predictable or reliable manner, although higher doses are more liable to induce the full spectrum of effects. Likewise, adverse effects become increasingly likely with higher doses and may include addiction, severe injury, or death ☠.
Physical effects
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The observed LD50 in mice was 100mg/kg via intravenous, 327mg/kg intraperitoneal and > 200mg/kg orally, anasthetic effects were observed at 16mg/kg intraperitoneal.[10]
Tolerance and addiction potential
Dependence potential of Progesterone has been sparsely reported by transfeminine people. There is one case report of a women on post menopausal HRT that documents addiction.[11]
Tolerance to the offects of Progesterone metabolites on GABA will build within a few years and return to baseline within a few months after cessation.[citation needed]
Interactions
Combining oral progesterone with food leads to a two fold increase in absorptions. [12] Since oral progesterone is a oil soluable reports of increased effects when combined with fatty foods do seem plausible.
Warning:Many psychoactive substances that are reasonably safe to use on their own can suddenly become dangerous and even life-threatening when combined with certain other substances. The following list provides some known dangerous interactions (although it is not guaranteed to include all of them).
Always conduct independent research (e.g. Google, DuckDuckGo, PubMed) to ensure that a combination of two or more substances is safe to consume. Some of the listed interactions have been sourced from TripSit.
Depressants Taking oral progesterone together with alcohol or barbiturates will increase absorption rates and peak potentially leading to black out intervals or loss of motor control, anesthetic levels in humans are not documented, but might be reachable. Other dangerous depressants are benzodiazepines and opioids since their absorption can be increased, resulting in a higher risk of overdose.[13]
As such, it may contain incomplete or wrong information. You can help by expanding it.
Progesterone is widely available as prescription medication or in some cases over the counter and generally not controlled. Taking transgender HRT is not as widely accepted and may be prosecuted. [14]
↑Piosik, Romuald (2003). "Adolf Butenandt und sein Wirken an der Technischen Hochschule Danzig". CHEMKON. 10 (3): 135–138. doi:10.1002/ckon.200390038. ISSN0944-5846.
↑ 7.07.1Kolatorova, Lucie; Vitku, Jana; Suchopar, Josef; Hill, Martin; Parizek, Antonin (2022-07-20). "Progesterone: A Steroid with Wide Range of Effects in Physiology as Well as Human Medicine". International Journal of Molecular Sciences. 23 (14): 7989. doi:10.3390/ijms23147989. ISSN1422-0067. PMID35887338.
↑Diviccaro, Silvia; Cioffi, Lucia; Falvo, Eva; Giatti, Silvia; Melcangi, Roberto Cosimo (2022). "Allopregnanolone: An overview on its synthesis and effects". Journal of Neuroendocrinology. 34 (2). doi:10.1111/jne.12996. ISSN0953-8194. PMID34189791.
↑Simon, James A.; Robinson, Denise E.; Andrews, Mason C.; Hildebrand, James R.; Rocci, Mario L.; Blake, Richard E.; Hodgen, Gary D. (1993). "The absorption of oral micronized progesterone: the effect of food, dose proportionality, and comparison with intramuscular progesterone". Fertility and Sterility. 60 (1): 26–33. doi:10.1016/S0015-0282(16)56031-2.
. ISSN 1673-5374. PMC 7513974