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Estrone/progesterone
Estrone (top) and
progesterone (bottom)
Combination of
EstroneEstrogen
ProgesteroneProgestogen
Clinical data
Trade namesSynergon[1][2]
Other namesE1/P4
Routes of
administration		Intramuscular injection

Estrone/progesterone (E1/P4), sold under the brand name Synergon, is a combination medication formulation of estrone, an estrogen, and progesterone, a progestogen. E1/P4 is used as an injectable preparation to induce withdrawal bleeding in women with non-pregnancy-related amenorrhea (absence of menstruation).[3][1][2][4] [5][6][7] It has also sometimes been used off-label as an abortifacient.[5][6][8] The medication comes in a three-ampoule pack, contains 1 mg estrone and 10 mg progesterone per ampoule, and is administered by intramuscular injection.[3][5][6][9] The usual dose of the medication is three injections, each two days apart, with the treatment duration not exceeding one week.[3] E1/P4 is or has been available in France, Monaco, and Turkey, as well as in some French-speaking African countries such as Benin and Cameroon.[1][2][4][10][6][8] The medication has been marketed since at least 1952.[11]

Progesterone (P4) is a steroid that is required for the regulation of the reproductive system. It is categorized with a group of hormones called progestogens and derived from cholesterol. [12] The indications for this steroid hormone are widely spread, including: treatment of irregular menstrual cycles, prevention of endometrial hyperplasia, and so on.[13] It is also a necessary metabolite in order to produce sex hormones and corticosteroids. [14] Progesterone can also be as a medication such as contraception when combined with estrogen. [15]

Progesterone can also be used to prevent giving birth too soon. In women who are pregnant with a single fetus, asymptomatic in the prenatal stage, and at a high risk of giving pre-term birth spontaneously (going into labor spontaneously before 34 weeks), vaginal progesterone has been found to be effective in preventing spontaneous pre-term birth. Women who are at a high risk of giving pre-term birth spontaneously are those who have a short cervix of less than 25 mm or have previously given pre-term birth spontaneously. Although pre-term births are generally considered to be less than 37 weeks, vaginal progesterone is associated with fewer pre-term births of less than 34 weeks.[16]

The chemical formula of progesterone consists of 12 carbons, 30 hydrogens, and 2 oxygens (C21H30O2). The mechanism of excretion for progesterone is through the hepatic system. The metabolism of progesterone itself is very complex. It can turn into as many as 35 different metabolites when orally ingested. [17] The mechanism of action of progesterone revolves around the steroid being an agonist.[18]

The history of progesterone revolves around two founders, George W. Corner and Willard M. Allen in 1929, who discovered the hormonal action of progesterone.[19] It wasn't until 1934 that pure crystalline progesterone was determined. This was accomplished by Adolf Butenandt in Danzig. [20]

There are various ways that progesterone can effect the body. Progesterone has interactions with hormones such as estrogen. In the presence of estrogen, these two molecules can enhance lobuloalveolar development. The development of this allows for milk production in the breast. [21] Progesterone also has ties to breast cancer. The exact pathiophysiological pathway has not been yet confirmed but it appears to either be an inhibitor or promoter related to breast cancer. The research is currently being conducted to find the specific pathway and cause of the progesterone link to cancer.[22] Progesterone is also linked to skin health. Sex hormones like progesterone have receptors in the skin and typically after menopause, the levels of progesterone decreases. The decreased levels are directly correlates to thinning and wrinkling of skin. This typically results in the physical look of aging due to the decreased amount of collagen produced by the body. [23] There are some treatments that might prove beneficial against this natural aging process. The treatment is called hormone replacement therapy. This treatment consists of estrogen by itself or in combination with progesterone. The administration route for this therapy consists of topical creams, surface lipids, and so on. However, topical creams typically have a better response than surface lipids. Results may vary based on each patient individually, but topical creams have helped reduced wrinkles, skin thickness, skin elasticity, and aging in general more than surface lipids. [24]

Progesterone is available around the world with different types of formulations. It can be in the form of capsules, suppository, topical gel, vaginal rings, tablets, and injection.[25] It can also be provided in combination forms as well especially with estrogen, used as contraception. Pricing for progesterone can vary depending location, insurance coverage, discount coupons, quantity, shortages, manufacturers, brand or generic versions, different pharmacies, and so on. As of currently, 30 capsules of 100 mg of the generic version, Prometrium, from CVS Pharmacy is around $40 without any discounts or insurance applied. The brand version, Progesterone, is around $450 for 30 capsules without any discounts or insurance applied. [26] In comparison, Walgreens offers 30 capsules of 100 mg in the generic version for $51 without insurance or coupons applied. The brand name costs around $431 for 30 capsules of 100 mg.[27] Each pharmacy has different pricing for this medication and it can also vary due to situations as well. For example, a shortage may make the pricing more expensive from the manufacturer. The location can also have an effect on the pricing, such as different countries and locations. Other factors that may influence the pricing may be insurance coverage or lack of insurance coverage. If a certain insurance does not cover the medication, patients may have to pay a higher co-pay or pay out of pocket. For patients that have to pay out of pocket, they may or may not use discount cards from GoodRx, for example. Different medication coupon sites may have different discounts as well. GoodRx, again for example, has GoodRx Gold. This program has a monthly or yearly fee that allows patients to get cheaper discounts on medications.

See also

References

  1. ^ a b c "Estrone". Drugs.com. Archived from the original on 2018-06-21. Retrieved 2019-04-12.
  2. ^ a b c "Progesterone". Drugs.com. Retrieved 2019-04-12.
  3. ^ a b c "Synergon label" (PDF).
  4. ^ a b Sweetman SC, ed. (2009). "Sex hormones and their modulators". Martindale: The Complete Drug Reference (36th ed.). London: Pharmaceutical Press. pp. 2101, 2127. ISBN 978-0-85369-840-1. Estrone [...] Progesterone [...] Multi-ingredient: [...] Fr.: Synergon [...] Turk.: Synergon
  5. ^ a b c Addo VN, Tagoe-Darko ED (June 2009). "Knowledge, practices, and attitudes regarding emergency contraception among students at a university in Ghana". International Journal of Gynaecology and Obstetrics. 105 (3): 206–209. doi:10.1016/j.ijgo.2009.01.008. PMID 19232600. S2CID 22216977. Synergon, a combination of progesterone and oestrone in an injectable form, is marketed to induce withdrawal bleeding in women with nongravid amenorrhea; however, it can be used as an arbortifacient [11].
  6. ^ a b c d Kongnyuy EJ, Ngassa P, Fomulu N, Wiysonge CS, Kouam L, Doh AS (July 2007). "A survey of knowledge, attitudes and practice of emergency contraception among university students in Cameroon". BMC Emergency Medicine. 7: 7. doi:10.1186/1471-227X-7-7. PMC 1933435. PMID 17634106. Synergon is dedicated product made up of a combination of progesterone and oestrone in an injectable form. It is used to induce withdrawal bleeding in cases of non-gravid amenorrhoea. In Cameroon, synergon is widely used among students as an abortifacient and is usually administered clandestinely by nurses when a woman presents with amenorrhoea. Such an attitude stemmed from the fact that this product induces withdrawal bleeding, so that some cases of amenorrhoea falsely believed to be due pregnancy are resolved by one or a few intramuscular injections of Synergon. We are not aware of similar findings reported from other countries. Synergon is not produced by the manufacturer as an abortifacient; how it came to be associated with abortion in Cameroon is not known. It is also not known whether it actually induces abortion or it only induces withdrawal bleeding in women with non-gravid amenorrhoea.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  7. ^ Romero R, Nicolaides KH, Conde-Agudelo A, O'Brien JM, Cetingoz E, Da Fonseca E, et al. (September 2016). "Vaginal progesterone decreases preterm birth ≤ 34 weeks of gestation in women with a singleton pregnancy and a short cervix: an updated meta-analysis including data from the OPPTIMUM study". Ultrasound in Obstetrics & Gynecology. 48 (3): 308–317. doi:10.1002/uog.15953. PMC 5053235. PMID 27444208.
  8. ^ a b Baxerres C, Boko I, Konkobo A, Ouattara F, Guillaume A (February 2018). "Abortion in two francophone African countries: a study of whether women have begun to use misoprostol in Benin and Burkina Faso". Contraception. 97 (2): 130–136. doi:10.1016/j.contraception.2017.10.011. PMID 29104024. It is not hard to find [abortion] services in Cotonou [Benin]. [...] The most commonly used method was [manual vacuum aspiration], followed by curettage, and more rarely a Synergon® (progesterone + estrone) injection, a product indicated in the symptomatic treatment of non-gravid amenorrhea.8
  9. ^ McDonnell K (1986). Adverse Effects: Women and the Pharmaceutical Industry. International Organization of Consumers Unions, Regional Office for Asia and the Pacific. p. 15. ISBN 978-967-9973-17-4. Synergon. 10 mg progesterone. 1 mg folliculine [estrone].
  10. ^ "Synergon Indications". Generic Drugs. ndrugs.com.
  11. ^ Endokrinologie. Johann Ambrosius Barth Verlag. 1952. Synergon. Progesterone + Follikulin [Estrone]. Amp. Lab. Hépat.
  12. ^ King, Tekoa L.; Brucker, Mary C. (2010-01-04). Pharmacology for Women's Health. Jones & Bartlett Publishers. ISBN 978-1-4496-5800-7.
  13. ^ Sitruk-Ware, R.; El-Etr, M. (August 2013). "Progesterone and related progestins: potential new health benefits". Climacteric. 16 (sup1): 69–78. doi:10.3109/13697137.2013.802556. ISSN 1369-7137.
  14. ^ Baulieu, Etienne-Emile; Schumacher, Michael (2000-10-01). "Progesterone as a neuroactive neurosteroid, with special reference to the effect of progesterone on myelination". Steroids. Progestins, Progesterone Receptor Modulators, and Progesterone Antagonists. 65 (10): 605–612. doi:10.1016/S0039-128X(00)00173-2. ISSN 0039-128X.
  15. ^ Prior, Jerilynn C (2019-04-01). "Progesterone Is Important for Transgender Women's Therapy—Applying Evidence for the Benefits of Progesterone in Ciswomen". The Journal of Clinical Endocrinology & Metabolism. 104 (4): 1181–1186. doi:10.1210/jc.2018-01777. ISSN 0021-972X.
  16. ^ Care, Angharad; Nevitt, Sarah J; Medley, Nancy; Donegan, Sarah; Good, Laura; Hampson, Lynn; Tudur Smith, Catrin; Alfirevic, Zarko (2022). "Interventions to prevent spontaneous preterm birth in women with singleton pregnancy who are at high risk: systematic review and network meta-analysis". BMJ: e064547. doi:10.1136/bmj-2021-064547. ISSN 1756-1833. PMC 8845039. PMID 35168930.{{cite journal}}: CS1 maint: PMC format (link)
  17. ^ PubChem. "Progesterone". pubchem.ncbi.nlm.nih.gov. Retrieved 2023-07-29.
  18. ^ Taraborrelli, Stefania (November 2015). "Physiology, production and action of progesterone". Acta Obstetricia et Gynecologica Scandinavica. 94: 8–16. doi:10.1111/aogs.12771.
  19. ^ Josimovich, J. B. (2013-11-09). Gynecologic Endocrinology. Springer Science & Business Media. ISBN 978-1-4613-2157-6.
  20. ^ Piosik, Romuald (July 2003). "Adolf Butenandt und sein Wirken an der Technischen Hochschule Danzig". CHEMKON. 10 (3): 135–138. doi:10.1002/ckon.200390038.
  21. ^ Blackburn, Susan (2012-04-30). Maternal, Fetal, & Neonatal Physiology - E-Book: Maternal, Fetal, & Neonatal Physiology - E-Book. Elsevier Health Sciences. ISBN 978-0-323-29296-2.
  22. ^ Kuhl, H.; Schneider, H. P. G. (August 2013). "Progesterone – promoter or inhibitor of breast cancer". Climacteric. 16 (sup1): 54–68. doi:10.3109/13697137.2013.768806. ISSN 1369-7137.
  23. ^ Raine-Fenning, Nicholas J.; Brincat, Mark P.; Muscat-Baron, Yves (2003-06-01). "Skin Aging and Menopause". American Journal of Clinical Dermatology. 4 (6): 371–378. doi:10.2165/00128071-200304060-00001. ISSN 1179-1888.
  24. ^ Holzer, G.; Riegler, E.; Hönigsmann, H.; Farokhnia, S.; Schmidt, B. (2005-08-05). "Effects and side-effects of 2% progesterone cream on the skin of peri- and postmenopausal women: results from a double-blind, vehicle-controlled, randomized study: Effects of progesterone cream on the skin". British Journal of Dermatology. 153 (3): 626–634. doi:10.1111/j.1365-2133.2005.06685.x.
  25. ^ "Progesterone (International database)". Drugs.com. Retrieved 2023-07-27.
  26. ^ "Progesterone Prices, Coupons & Savings Tips - GoodRx". www.goodrx.com. Retrieved 2023-07-28.
  27. ^ "Progesterone Prices, Coupons & Savings Tips - GoodRx". www.goodrx.com. Retrieved 2023-07-30.
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