Progesterone

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Progesterone
Skeletal formula for Progesterone; a progestogen and GnRH agonist.
Drug class: Progestogen
Dosage range:
Oral
100–200 mg/day
Injection
50-200 mg/day
Rectal
100-200 mg/day
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
Skeletal formula for Progesterone; a progestogen and GnRH agonist.
Drug class: Progestogen
Dosage range:
Oral
100–200 mg/day
Injection
50-200 mg/day
Rectal
100-200 mg/day
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 (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.

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

Antigonadotropin effects

Progesterone inhibits gonadotropin-releasing hormone (GnRH) secretion in the HPG axis.

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. [1] 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.[1][2] 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.

5α-Reductase inhibition

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.[3][4] 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.[5][6] 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.[7][8] 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. [9]

Lobuloalveolar maturation and lactation

Progesterone is essential for lobuloalveolar maturation of the mammary glands during pregnancy, and [10] thus progesterone is an important addition for any transgender woman that wants to lactate or breastfeed.[11] 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.[12][13] Lobuloalveolar development reversed with discontinuation of cypro, however, which suggests that continued progestogen exposure is necessary to maintain the tissue.[12]

Side Effects

The use of progesterone may result in the following side effects...

  • Mood swings.
  • Irritability.
  • 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.

Dosage

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.

Oral

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.

Rectal

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.[14] 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.

Injection

Intramuscular

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.

Subcutaneous

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

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%.[15][16] 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.[17] 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.[17][18]

Breast Application

When transdermal progesterone is applied to the breasts, high concentrations within breast tissue have been observed.[15] 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.

Brand Names

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.

Sources

Online Pharmacies

Progesterone Capsules

Product Price Bulk Website Shipping
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

Progesterone Gel

Product Price Bulk Website Shipping
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 Injections

Product Price Bulk Website Shipping
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 6.90$ 6.21$ UnitedPharmacies (US-Centric)
Progesterone 50mg/1ml 5.67€ 5.10€ UnitedPharmacies-UK (UK-Centric)
Progesterone 50mg/1ml 2.80$ 2.08$ WebOrderPharmacy Ships from India
Progesterone 50mg/1ml x 5 27.00€ Shape Shifter Ships from Turkey

Alibaba

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.

See also

External links

References

  1. 1.0 1.1 Engel, J., Schally, A. Drug Insight: clinical use of agonists and antagonists of luteinizing-hormone-releasing hormone. Nat Rev Endocrinol 3, 157–167 (2007). https://www.nature.com/articles/ncpendmet0399
  2. Conn PM, Crowley WF (January 1991). "Gonadotropin-releasing hormone and its analogues". N. Engl. J. Med. 324 (2): 93–103. PMID 1984190. https://www.nejm.org/doi/full/10.1056/NEJM199101103240205
  3. Mari S. Golub Farla L. Kaufman Marlissa A. Campbell Ling‐Hong Li James M. Donald (October 2006). "“Natural” progesterone: information on fetal effects" https://onlinelibrary.wiley.com/doi/abs/10.1002/bdrb.20089
  4. Kincl F.A. (1990) Control of Reproductive Function in the Adult. In: Hormone Toxicity in the Newborn. Monographs on Endocrinology, vol 31. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-83794-4_2
  5. A. Gompel (2012) Micronized progesterone and its impact on the endometrium and breast vs. progestogens, Climacteric, 15:sup1, 18-25, DOI: 10.3109/13697137.2012.669584
  6. J. Dinny Graham, Christine L. Clarke, Physiological Action of Progesterone in Target Tissues, Endocrine Reviews, Volume 18, Issue 4, 1 August 1997, Pages 502–519, https://doi.org/10.1210/edrv.18.4.0308
  7. 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
  8. Katrien Wierckx, MD, Louis Gooren, MD, PhD, Guy T'Sjoen, MD, PhD (MAY 01, 2014) "Clinical Review: Breast Development in Trans Women Receiving Cross-Sex Hormones" DOI:https://doi.org/10.1111/jsm.12487
  9. Citation Needed
  10. Macias, H. and Hinck, L. (2012), Mammary gland development. WIREs Dev Biol, 1: 533-557. doi:10.1002/wdev.35
  11. Tamar Reisman and Zil Goldstein.Transgender Health.Dec 2018.24-26. http://doi.org/10.1089/trgh.2017.0044
  12. 12.0 12.1 Kanhai, Robert C.J. M.D.; Hage, J. Joris M.D., Ph.D.; van Diest, Paul J. M.D., Ph.D.; Bloemena, Elisabeth M.D., Ph.D.; Mulder, J. Wiebe M.D., Ph.D. Short-Term and Long-Term Histologic Effects of Castration and Estrogen Treatment on Breast Tissue of 14 Male-to-Female Transsexuals in Comparison With Two Chemically Castrated Men, The American Journal of Surgical Pathology: January 2000 - Volume 24 - Issue 1 - p 74 https://journals.lww.com/ajsp/Fulltext/2000/01000/Short_Term_and_Long_Term_Histologic_Effects_of.9.aspx
  13. Lawrence A.A. (2007) Transgender Health Concerns. In: Meyer I.H., Northridge M.E. (eds) The Health of Sexual Minorities. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-31334-4_19
  14. Vittorio Unfer, Gian C. di Renzo, Sandro Gerli and Maria L. Casini, “ The Use of Progesterone in Clinical Practice: Evaluation of its Efficacy in Diverse Indications Using Different Routes of Administration”, Current Drug Therapy (2006) 1: 211. https://doi.org/10.2174/157488506776930923
  15. 15.0 15.1 Régine Sitruk-Ware, M.D (JANUARY 01, 1989) "Transdermal delivery of steroids" DOI: https://doi.org/10.1016/0010-7824(89)90012-7
  16. J. De Boever, C. Verheugen, G. Van Maele, and D. Vandekerckhove (1983) "Steroid Concentrations in Serum, Glandular Breast Tissue, and Breast Cyst Fluid of Control and Progesterone-Treated patient" http://hormonebalance.org/images/documents/DeBoerer%2083%20Steroid%20Conc%20Br%20Tissue%20Pg%20ECBD.PDF
  17. 17.0 17.1 Stanczyk, Frank Z. PhD; Paulson, Richard J. MD; Roy, Subir MD Percutaneous administration of progesterone: blood levels and endometrial protection, Menopause: March-April 2005 - Volume 12 - Issue 2 - p 232-237 https://journals.lww.com/menopausejournal/Abstract/2005/12020/Percutaneous_administration_of_progesterone__blood.19.aspx
  18. F. Z. Stanczyk (2014) Treatment of postmenopausal women with topical progesterone creams and gels: are they effective?, Climacteric, 17:sup2, 8-11, DOI: 10.3109/13697137.2014.944496