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Progesterone (P4) is an endogenous steroid and progestogen sex hormone involved in the menstrual cycle and pregnancy of humans and other species. Progesterone plays an important role in breast development for cis women at the end of puberty. In conjunction with prolactin, it mediates maturation of the mammary glands during pregnancy to allow for milk production and thus lactation and breastfeeding of offspring following childbirth. It belongs to a group of steroid hormones called progestogens, and is the most common progestogen in the body. Progesterone has a variety of important functions in the body.
|Brand names:||Prometrium, Endogest, Microgest, Susten, Progestan, Utrogestan|
|Elimination half-life||Oral: 5 hours (with food)
Sublingual: 6–7 hours
Vaginal/Rectal: 14–50 hours
Transdermal: 30–40 hours
IM: 20–28 hours
SC: 13–18 hours
IV: 3–90 minutes
Progesterone is prescribed to MtF patients to assist in breast maturation, helping users reach Tanner stages 4 and 5, as well as to provide feminizing fat redistribution, increase libido, and assist in a decrease of testosterone production. It is not universally prescribed and many people are under the impression that it serves no vital role in a person's transition.
Method of Action
GnRH is a hormone made by a part of the brain called the hypothalamus. GnRH causes the pituitary gland in the brain to make and secrete the hormones luteinizing hormone (LH) and follicle-stimulating hormone (FSH). In those born AMAB, these hormones cause the testicles to make testosterone.
Progesterone accomplishes this by overstimulating the GnRH receptor in such a way that it desensitizes it to the point where it becomes non-functional.  GnRH is normally released in pulses throughout the day, secreting LH and FSH consistently with each pulse. When GnRH agonists are continuously present, this results in excessive downregulation of the receptor and a complete loss of function. When taken rectally, progesterone has a very long elimination half-life and thus acts as an agonist for much longer.
As a result of this process, progesterone can help inhibit LH and FSH secretion, thus preventing the testicles from producing testosterone. This makes it an effective antiandrogen option for transgender women.
Progesterone has been found to act as a competitive inhibitor of the enzyme 5α-Reductase types 1 and 2. In this case, it may possess antiandrogenic properties, but the effect has been found to be very weak and has only been demonstrated in vitro and at supraphysiological concentrations. Progesterone at regular circulating physiological levels has not been found to influence circulating DHT concentrations to any large degree.
Antiestrogenic effects and breast growth hindrance
Progestogens have some antiestrogenic effects in the breasts. They do this by decreasing expression of the estrogen receptor and increasing expression of estrogen-metabolizing enzymes. Progesterone does not normally start to produce in the cis female's pubertal cycle until near the end of puberty, by which point breast development has already been completed. There is a theory that premature exposure to progestogens during the process of breast development may compromise final breast growth outcome, although this is only a theory and has not been proven yet. The idea behind this is that lobular tissue penetrates stromal layers and spurs further glandular growth. If these are prematurely stimulated into maturation, it could limit potential growth.
For now, think of it like you're baking a cake. Starting estrogen administration is like putting the cake in the oven, while adding progesterone is the act of browning the top and sides. Adding progesterone too early is like browning the outside before the inside is finished cooking. 
Lobuloalveolar maturation and lactation
Progesterone is essential for lobuloalveolar maturation of the mammary glands during pregnancy, and  thus progesterone is an important addition for any transgender woman that wants to lactate or breastfeed. There have been studies that show transgender women taking high doses of cyproterone acetate, which is a popular antiandrogen in Europe that is also a progestin, were found to have full lobuloalveolar maturation of the mammary glands. Lobuloalveolar development reversed with discontinuation of cypro, however, which suggests that continued progestogen exposure is necessary to maintain the tissue.
The use of progesterone may result in the following side effects...
- Mood swings.
- Enhances skin elasticity and bone strength.
- Raises epidermal growth factor-1 (EGF-1) levels.
- Reduces spasm and relaxes smooth muscle.
- Acts as an anti-inflammatory agent and regulates the immune response.
- Reduces gall-bladder activity.
- Normalizes blood clotting and vascular tone, zinc and copper levels, cell oxygen levels, and use of fat stores for energy.
- Plays an important role in the signaling of insulin release and pancreatic function, and may affect the susceptibility to diabetes or gestational diabetes.
Intake dosages of progesterone may vary, but the majority of transgender women will be prescribed 100 mg to 200 mg taken orally. Whether you take these pills orally or rectally is your choice, but be sure that you are able to take progesterone meant for oral administration rectally, as a few brands of oral progesterone are powdered on the inside of the pill. See the Rectal administration section below for how to work around this.
Routes of Administration
Progesterone can be acquired in many different forms with each one having unique administration methods. The most common forms prescribed to transgender women are oral capsules, however, some users may opt to take these pills rectally as well. Listed below are the different forms of progesterone with accompanying information regarding their administration methods.
This is the most common administration method of progesterone that is prescribed for transgender women. Many doctors following the WPATH method that will allow the use of progesterone recommend taking this medication orally. When administered in this way, progesterone is poorly metabolized in the gastrointestinal tract and undergoes first-pass metabolism in the liver, therefor lowering the efficacy of the drug severally. About 80-90% of it is metabolized into allopregnanolone and pregnanolone by the enzymes 5α- and 5β-reductase and 3α-hydroxysteroid dehydrogenase in the liver. With this administration route, there will be more allopregnanolone and pregnanolone circulating the body than progesterone.
The neurosteroid metabolites of progesterone have a relatively short half-life and can cause dramatic and highly supraphysiological spikes in allopregnanolone and pregnanolone concentrations followed by steep declines with each oral intake of progesterone. If one eats food with oral progesterone, this will increase the absorption of the progesterone and may further amplify the fluctuations in the levels of neurosteroid levels. These fluctuations in neurosteroid levels can cause central depressant effects in some individuals.
In contrast to oral administration, taking progesterone rectally (or vaginally) avoids the first-pass metabolism in the liver, thus avoiding supraphysiological levels of neurosteroid metabolites or fluctuations in neurosteroid levels. Levels of progesterone peak after 6 to 8 hours and then gradually decrease, making this administration method more effective at inhibiting GnRH for a longer period of time.
Progesterone is delivered directly into the circulation when it is absorbed by the lower portion of the rectum and transported by the inferior and middle rectal veins. Conversely, if it is absorbed by the upper portion of the rectum, progesterone is subject to hepatic first-pass metabolism due to entry into the hepatic portal system via the superior rectal vein. As such, although rectal administration is a parenteral route, it may still be subject to some first-pass metabolism similarly to oral progesterone.
Rectal administration has been becoming more popular among transgender women because of the longer GnRH inhibition, which helps reduce the creation of gonadal androgens through LH and FSH. Many users that take their progesterone rectally recommend taking extra steps to ensure the pill dissolves properly inside the rectum. These users will put the pill in their mouth for a short while, using their saliva to begin dissolving the outer layer before insertion. Another option is to take a push-pin and poke a small hole in the pill to ensure drainage into the rectum. If your progesterone pill is filled with powder instead of an oil, you may take a syringe with oil in it (castor oil, olive oil, omega 3 cod liver oil, canola oil) and inject a small amount into the pill to dissolve the powder for rectal use.
When progesterone is administered via intramuscular injections, it bypasses first-pass metabolism in the intestines and liver, meaning one can achieve a higher circulating level of progesterone overall when compared to oral administration. Due to a depot effect, IM progesterone can be administered once every 1 to 3 days. Intramuscular injections of progesterone are best done in the gluteal muscles of the buttocks, as the half-life is much longer this way.
This method of administration is known to be less painful than intramuscular injections. It is also considered safer and easier due to less risk of injection site reactions. Subcutaneous injections of progesterone has an elimination half-life of 13 to 18 hours, which is much shorter than the 20 to 28 hours that intramuscular injections in oil solutions can provide. It is for these reasons that transgender women prefer to take progesterone injections intramuscularly over subcutaneous administration.
Transdermal progesterone is not widely used in transgender women's hormone replacement therapy. Progesterone creams and gels are widely available over the counter and online as a component of menopausal hormone therapy, however little clinical testing has been done on them and they are mostly ineffective at increasing circulating levels of progesterone.
The transdermal bioavailability of progesterone applied to the breasts is approximately 10%. Progesterone creams are more lipophilic, meaning they dissolve easier into fats, oils and lipids, and may have a preference for uptake into the fatty layer under the skin. Alcohol-based gels are more water-soluble, and this helps them distribute into the microcirculation of the skin and then into general circulation, making them more effective at increasing systemic circulating levels of progesterone.
When transdermal progesterone is applied to the breasts, high concentrations within breast tissue have been observed. Progesterone applied in this way has been found to inhibit estrogen-induced proliferation of breast epithelial cells. This effect is the reason why progesterone is used to treat breast disorders, as it possesses antiestrogenic effects in the breasts. However, due to progesterone's potential to be absorbed into the fatty layer under the skin, this has shown to be effective at fat redistribution and may help even the size of the breasts out. Dr. Powers prescribes his patients with an extra strength progesterone cream that is to be applied locally to the breasts, among other areas, to assist with this. If you would like to learn how to create your own extra strength progesterone cream, refer to the article DIY Extra Strength Progesterone Cream where we have detailed instructions on how to create your own DMSO carrier lotion with high levels of progesterone for this purpose.
Progesterone is marketed under a large number of brand names throughout the world. Some of the major brand names are: Prometrium, Crinone, Cyclogest, Endogest, Endometrin, Luteina, Microgest, Progestan, among many others.
|Endogest 100mg x30||29.40$||23.25$||InHousePharmacy||Ships from Vanuatu|
|Endogest 200mg x30||39.80$||31.50$||InHousePharmacy||Ships from Vanuatu|
|Microgest 100mg x 50||20.24$||18.48$||WebOrderPharmacy||Ships from India|
|Microgest 100mg x50||31.04$||27.93$||UnitedPharmacies||(US-Centric)|
|Microgest 100mg x50||25.52£||22.97£||UnitedPharmacies-UK||(UK-Centric)|
|Microgest 100mg x50||28.11€||25.29€||UnitedPharmacies-NL||(NL-Centric)|
|Microgest 200mg x 50||34.32$||30.80$||WebOrderPharmacy||Ships from India|
|Microgest 200mg x50||59.02$||54.89$||UnitedPharmacies||(US-Centric)|
|Microgest 200mg x50||48.53£||45.13£||UnitedPharmacies-UK||(UK-Centric)|
|Pragisan 100mg x 30||20.55$||Pilloid||Ships from Russia|
|Progestan 100mg x30||22.00€||Shape Shifter||Ships from Turkey|
|Progestan 100mg x30||32.00$||25.60$||AllRealMedications||Ships from Turkey|
|Progestan 100mg x30||28.00$||21.56$||InHousePharmacy||Ships from Vanuatu|
|Progestan 100mg x30||18.70€||Aphrodite's||Ships from Portugal|
|Progestan 200mg x 30||24.00€||DIYHRT||Ships from EU|
|Progestan 200mg x30||30.00€||Shape Shifter||Ships from Turkey|
|Progestan 200mg x30||34.90$||27.92$||AllRealMedications||Ships from Turkey|
|Progestan 200mg x30||38.50$||30.00$||InHousePharmacy||Ships from Vanuatu|
|Progestan 200mg x30||24.40€||Aphoridite's||Ships from Portugal|
|Progesterone 100mg x 30||12.00$||OTC-Online-Store||Ships from Russia|
|Progesterone 200mg x 15||12.00$||OTC-Online-Store||Ships from Russia|
|Susten 100mg x30||19.00$||15.00$||AllDayChemist||Various fulfilment centers|
|Susten 200mg x30||32.50$||28.17$||AllDayChemist||Various fulfilment centers|
|Utrogestan 100mg x 28||26.25$||Pilloid||Ships from Russia|
|Utrogestan 100mg x 30||22.90€||PharmaOnline||Ships from Germany|
|Utrogestan 100mg x30||47.00$||33.17$||InHousePharmacy||Ships from Vanuatu|
|Utrogestan 100mg x30||15.00€||EU-Aibolit||Ships from EU|
|Utrogestan 100mg x30||38.00$||Amazon4Health||Ships from Thailand|
|Utrogestan 200mg x 15||24.00€||PharmaOnline||Ships from Germany|
|Darstin 80g 1% - 800mg||29.20€||PharmaOnline||Ships from Germany|
|Progestogel 80g 1% - 800mg||38.35$||Pilloid||Ships from Russia|
|Progestogel 80g 1% - 800mg||26.00$||OTC-Online-Store||Ships from Russia|
|Sustene Gel 1.35g 8% - 108mg||5.00$||4.50$||UnitedPharmacies||(US-Centric)|
|Sustene Gel 1.35g 8% - 108mg||4.11£||3.70£||UnitedPharmacies-UK||(UK-Centric)|
|Sustene Gel 1.35g 8% - 108mg||4.53€||4.07€||UnitedPharmacies-NL||(NL-Centric)|
|Progesterone 200mg/2ml x 10||96.00$||89.00$||InHousePharmacy||Ships from Vantuatu|
|Progesterone 25mg/1ml x 10||24.85$||Pilloid||Ships from Russia|
|Progesterone 25mg/1ml x 10||18.00$||OTC-Online-Store||Ships from Russia|
|Progesterone 500mg/10ml||20.00$||15.00$||Otokonoko Pharmaceuticals||Ships from Brazil|
|Progesterone 50mg/1ml||2.80$||2.08$||WebOrderPharmacy||Ships from India|
|Progesterone 50mg/1ml x 5||27.00€||Shape Shifter||Ships from Turkey|
Progesterone can be purchased in tablet form through a variety of sources such as online pharmacies. However, it can also be purchased in bulk powdered form through vendors on websites such as Alibaba. From personal experience, Alibaba is substantially cheaper and some vendors will often go to great lengths to get your product to you by deliberately mislabelling packages in order to more easily get them through customs. We have personally had good luck with this particular vendor. It is also worth noting that in order to purchase products from these sites, you will need to personally contact the vendor and negotiate a price with them.
- DIY Extra Strength Progesterone Cream
- DIY Rectal Progesterone Solution
- Hormone Replacement Therapy
- Breast growth advice
- Powers Method of HRT
- 9channel /hrt/ Spreadsheet of Hormones and Prices
- Pharmacodynamics of Progesterone (Wikipedia.org)
- Pharmacokinetics of Progesterone (Wikipedia.org)
- Progesterone Is Important for Transgender Women’s Therapy—Applying Evidence for the Benefits of Progesterone in Ciswomen
- Antiestrogen action of progesterone in breast tissue
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- RANDOLPH, JOHN F. Jr MD Gender-Affirming Hormone Therapy for Transgender Females, Clinical Obstetrics and Gynecology: December 2018 - Volume 61 - Issue 4 - p 705-721 doi: 10.1097/GRF.0000000000000396
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- Tamar Reisman and Zil Goldstein.Transgender Health.Dec 2018.24-26. http://doi.org/10.1089/trgh.2017.0044
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