Conjugated estrogens

Not to be confused with Estrogen conjugate or Esterified estrogens.

Conjugated estrogens
Estrone sulfate, the primary active component in conjugated estrogens (constitutes about 50 to 70% of total content)
Equilin sulfate, the second most major active component in conjugated estrogens (constitutes about 20 to 30% of total content)
Combination of
Estrone sulfateEstrogen
Equilin sulfateEstrogen
17α-Dihydro-equilin sulfateEstrogen
Clinical data
Trade namesCenestin, Enjuvia, Premarin, others
Other namesCEs; Conjugated equine estrogens; CEEs; Pregnant mares' urine; Estrogens, conjugated
AHFS/Drugs.comMultum Consumer Information
Routes of
administration		By mouth, topical, vaginal, intravenous injection, intramuscular injection[1][2]
Drug classEstrogen
ATC code
Legal status
Legal status
  • US: WARNING[3]
  • In general: ℞ (Prescription only)
Pharmacokinetic data
BioavailabilityVariable[4]
Protein bindingHigh (to albumin and SHBGTooltip sex hormone-binding globulin)[4][1]
MetabolismLiver[4][1]
Elimination half-lifeEstrone: 26.7 hours
Estrone (BA): 14.8 hours
Equilin: 11.4 hours[5][unreliable medical source?]
ExcretionKidney[4]
Identifiers
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.031.987 Edit this at Wikidata
  (verify)

Conjugated estrogens (CEs), or conjugated equine estrogens (CEEs), sold under the brand name Premarin among others, is an estrogen medication which is used in menopausal hormone therapy and for various other indications.[6][4][1][7] It is a mixture of the sodium salts of estrogen conjugates found in horses, such as estrone sulfate and equilin sulfate.[1][7][6] CEEs are available in the form of both natural preparations manufactured from the urine of pregnant mares and fully synthetic replications of the natural preparations.[8][9] They are formulated both alone and in combination with progestins such as medroxyprogesterone acetate.[6] CEEs are usually taken by mouth, but can also be given by application to the skin or vagina as a cream or by injection into a blood vessel or muscle.[1][2]

Side effects of CEEs include breast tenderness and enlargement, headache, fluid retention, and nausea among others.[4][1] It may increase the risk of endometrial hyperplasia and endometrial cancer in women with an intact uterus if it is not taken together with a progestogen like progesterone.[4][1] The medication may also increase the risk of blood clots, cardiovascular disease, and, when combined with most progestogens, breast cancer.[10] CEEs are estrogens, or agonists of the estrogen receptor, the biological target of estrogens like estradiol.[1][4] Compared to estradiol, certain estrogens in CEEs are more resistant to metabolism, and the medication shows relatively increased effects in certain parts of the body like the liver.[1] This results in an increased risk of blood clots and cardiovascular problems with CEEs relative to estradiol.[1][11]

Premarin, the major brand of CEEs in use, is manufactured by Pfizer and was first marketed in 1941 in Canada and in 1942 in the United States.[7] It is the most commonly used form of estrogen in menopausal hormone therapy in the United States.[12][13] However, it has begun to fall out of favor relative to bioidentical estradiol, which is the most widely used form of estrogen in Europe for menopausal hormone therapy.[13][14][15][16] CEEs are available widely throughout the world.[6] An estrogen preparation very similar to CEEs but differing in source and composition is esterified estrogens.[1] In 2020, it was the 283rd most commonly prescribed medication in the United States, with more than 1 million prescriptions.[17][18]

  1. ^ a b c d e f g h i j k l Kuhl H (August 2005). "Pharmacology of estrogens and progestogens: influence of different routes of administration". Climacteric. 8 (Suppl 1): 3–63. doi:10.1080/13697130500148875. PMID 16112947. S2CID 24616324.
  2. ^ a b "Drugs@FDA: FDA Approved Drug Products". United States Food and Drug Administration. Retrieved 19 February 2018.
  3. ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 October 2023.
  4. ^ a b c d e f g h "PREMARIN- estrogens, conjugated tablet, film coated Wyeth Pharmaceuticals LLC, a subsidiary of Pfizer Inc". labeling.pfizer.com. Retrieved 3 June 2019.
  5. ^ Cite error: The named reference DrugBank was invoked but never defined (see the help page).
  6. ^ a b c d Sweetman SC, ed. (2009). "Sex hormones and their modulators". Martindale: The Complete Drug Reference (36th ed.). London: Pharmaceutical Press. p. 2087. ISBN 978-0-85369-840-1.
  7. ^ a b c Fritz MA, Speroff L (28 March 2012). Clinical Gynecologic Endocrinology and Infertility. Lippincott Williams & Wilkins. pp. 751–3. ISBN 978-1-4511-4847-3.
  8. ^ Moscou K, Snipe K (1 December 2012). Pharmacology for Pharmacy Technicians Pageburst E-Book on VitalSource2: Pharmacology for Pharmacy Technicians Pageburst E-Book on VitalSource. Elsevier Health Sciences. pp. 573–. ISBN 978-0-323-08578-6.
  9. ^ IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, World Health Organization, International Agency for Research on Cancer (2007). Combined Estrogen-progestogen Contraceptives and Combined Estrogen-progestogen Menopausal Therapy. World Health Organization. pp. 378–. ISBN 978-92-832-1291-1.
  10. ^ Pickar JH, Archer DF, Kagan R, Pinkerton JV, Taylor HS (August 2017). "Safety and benefit considerations for menopausal hormone therapy". Expert Opinion on Drug Safety. 16 (8): 941–954. doi:10.1080/14740338.2017.1343298. PMID 28664754. S2CID 24155838.
  11. ^ Scarabin PY (December 2014). "Hormones and venous thromboembolism among postmenopausal women". Climacteric. 17 (Suppl 2): 34–37. doi:10.3109/13697137.2014.956717. PMID 25223916. S2CID 5084606.
  12. ^ Cite error: The named reference pmid24176763 was invoked but never defined (see the help page).
  13. ^ a b Quereda F (2017). "Hormone Therapy (I): Estrogens, Progestogens, and Androgens". Menopause. Springer. pp. 181–196. doi:10.1007/978-3-319-59318-0_11. ISBN 978-3-319-59317-3.
  14. ^ L'Hermite M (August 2017). "Bioidentical menopausal hormone therapy: registered hormones (non-oral estradiol ± progesterone) are optimal". Climacteric. 20 (4): 331–338. doi:10.1080/13697137.2017.1291607. PMID 28301216. S2CID 4771048.
  15. ^ Simon JA (July 2014). "What if the Women's Health Initiative had used transdermal estradiol and oral progesterone instead?". Menopause. 21 (7): 769–783. doi:10.1097/GME.0000000000000169. PMID 24398406. S2CID 30292136.
  16. ^ Holtorf K (January 2009). "The bioidentical hormone debate: are bioidentical hormones (estradiol, estriol, and progesterone) safer or more efficacious than commonly used synthetic versions in hormone replacement therapy?". Postgraduate Medicine. 121 (1): 73–85. doi:10.3810/pgm.2009.01.1949. PMID 19179815. S2CID 2060730.
  17. ^ "The Top 300 of 2020". ClinCalc. Retrieved 7 October 2022.
  18. ^ "Estrogens, Conjugated - Drug Usage Statistics". ClinCalc. Retrieved 7 October 2022.