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Cyproterone acetate

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Cyproterone acetate
Skeletal formula of cyproterone acetate.
Drug class: Steroidal antiandrogen; Progestogen; Progestogen ester; Antigonadotropin
Dosage range: Oral: 25–100 mg/d[1]
Brand names: Androcur, Cyprostat, Siterone, others
PubChem CID: 9880

Cyproterone acetate (CPA; brand name Androcur among others) is a dual steroidal antiandrogen and progestogen.

Mechanism of actionEdit

CPA has potent antigonadotropic effects via activation of the progesterone receptor and is able to reduce testosterone levels by up to 70 to 80% at dosages that are sufficiently high. In addition to its antigonadotropic effects, the drug also directly binds to and blocks the androgen receptor. It is notable that CPA is not a silent antagonist of the AR but rather is a very weak partial agonist. In other words, it acts mostly as an antagonist of the receptor but retains some capacity to activate it, and this can be observed clinically under certain circumstances. CPA also has weak glucocorticoid effects, which contributes to its side effect profile.

Lower doses of CPA (5 to 25 mg/day) are able to markedly suppress testosterone levels similarly to higher doses (25 to 300 mg/day).

Hormone levels with low‑dose oral cyproterone acetate in AMABs
Dosage Sample Hormone levels Notes Ref
10 mg/day CPA 10 young healthy fertile men (21-35 years, mean 27.2 ± 3.2 years) T: -70%, DHT: -50%, LH: -30%, FSH: -40%, PRL: +75%. T: Before: 495 ± 66 ng/dL; after 4 weeks: 154 ± 23 ng/dL; after 12 weeks: 187 ± 38 ng/dL. Has graphs of T levels (also values and graphs for other hormones). Preliminary paper (second one) has good graph with four points (before, 4 weeks, 12 weeks, after). [2][3][4]
0, 5, or 10 mg/day CPA 25 normal healthy males (20-51 years); 7 in 5 mg group (mean 37 ± 10 years), 8 in 10 mg group (mean 32 ± 8 years), 10 in 0 mg group (mean 32 ± 10 years) 5 mg: T: 663 ± 120 ng/dL to 320 ± 160 ng/dL (-52%); 10 mg: T: 692 ± 180 ng/dL to 340 ± 160 ng/dL (-51%); E2: parallel decrease to T; 5 mg: LH: 2.1 ± 0.7 IU/L to 1.4 ± 0.5 IU/L (-33%); 10 mg: LH: 2.3 ± 1.0 IU/L to 1.2 ± 0.5 IU/L (-48%); 5 mg: FSH: 3.1 ± 1.9 IU/L to 1.8 ± 0.9 IU/L (-42%); 10 mg: FSH: 2.7 ± 1.0 IU/L to 1.5 ± 0.7 IU/L (-44%); Has excellent graphs for all hormones. [5]
10 or 20 mg/day CPA 15 normal healthy fertile males (age 25-35 years); 7 in 10 mg group and 8 in 20 mg group "Androgens (mainly T)": -60% for both 10 and 20 mg/day. LH: Inconsistent changes. FSH: Slight decrease. Has graphs of LH, FSH, and androgen levels that shows both dosages. But all androgens lumped together ("mainly testosterone"). Exact values available in the graph only. [6][7]
0, 5, or 10 mg/day CPA 18 healthy males (age 20-40 years); 6 to each group "The level of plasma testosterone decreased, while the levels of FSH and LH remained unaltered." No other details on T levels given on hormone levels. [8]
5 or 10 mg/day CPA 14 healthy males (20-40 years); 7 in each group "The levels of plasma testosterone were decreased in both the groups." No values or graphs for hormone levels provided. [9]
10 mg/day CPA + 75 mg/day mesterolone 3 normal fertile men (32-35 years) No T levels. Overlap with study above. [10]
10 or 25 mg/day CPA 4 healthy men (aged 29-37 years); 3 in 10 mg group, 1 in 25 mg group "The hormone levels studied showed moderate changes in general. FSH was reduced more or less in all cases, whereas LH was insignificantly affected. Testosterone was slightly reduced in contrast to the oestrogen levels which were more significantly lowered." Has weird graphs for 10 mg group. No exact values or percent decreases (but can get from graphs). [11]
20 mg/day CPA 10 healthy males (aged 26-55 years) T: -73% (71-75%): 482 ng/dL (410-560 ng/dL) -> 130 ng/dL (110-162 ng/dL). Also has many other hormones. "Administration of CPA suppressed significantly the levels of hLH (mean suppression: 39%; [34-45%]), hFSH (66%; [47-78%]), T ~73% [71-75%]), DHT (51% [47-55%]), 17-OH-P (59%) and A (30%} in all subjects. [...] The levels of sulphurylated T (34%) and DHT (35%) were also suppressed." Has exact values and graphs. "Finally, judged from the present data and those reported by Moltz etal. (8), it seems reasonable to predict that in subjects receiving daily doses of 10-20 mg of CPA, the plasma levels of T will be consistently at, or below, 5.0 nmol/l [144 ng/dL]." [12]
5 or 10 mg/day CPA 7 fertile men; 4 in each group T: -~40%. Has unwieldy graphs for T, LH, and FSH. Can get exact values from graphs. [13]
30 mg/day CPA 5 normal males Has poor graphs of T. 5 mg/day after in one case; not as good as 30 mg/day CPA in suppressing spermatogenesis or T, which was quite effective. From another source: "Cyproterone acetate has also been tested in man at much smaller doses. Investigations by PETRY et al. (20,21,25) were reported in 1970 and 1972 for 5 normal males given 30 mg CPA per day for 7-15 weeks. There was a severe depression of spermatogenesis but no reduction in libido or disturbed potency. In 4 of the 5 cases seminal plasma volume and fructose concentration decreased. Plasma testosterone levels were significantly lowered. In one patient who had progressed to azoospermia, reduction of the dose to 5 mg/day failed to prevent the return of the ejaculate and the sperm to normal."[6] [14][15][16][17]
10 or 20 mg/day CPA 30 healthy males (age 21-38 years). T: -70%; LH: -35%: "similar observations for FSH". No full text; only abstract. No exact values or graphs. [18]
12.5 or 25 mg/day CPA + 100 mg/week i.m. TE 10 normal males (age 19-42 years); 5 in each group T suppression couldn't be determined because of TE, but LH and FSH dropped to castrate levels (<1 IU/L) in both cases. Has excellent graphs. [19]
12.5 mg/day CPA + 160 mg/day oral TU 8 healthy men (age 25-42 years) T suppression couldn't be determined because of TU, but LH and FSH were measured and dropped to low levels (<1 IU/L) in both cases. Has excellent graphs. [20]
0, 2, or 20 mg/day CPA + 1000 mg/6-8 weeks i.m. TU 24 healthy men, 8 in each group T suppression couldn't be determined because of TU, but LH and FSH were measured and dropped to low levels (<1 IU/L) in both cases. Has excellent graphs for T, LH, FSH, E2, and PRL. Has table of values. [21]
25 or 50 mg/day CPA + moderate-dose oral or transdermal E2 68 transgender females T: -93-94% for both 25 and 50 mg/day. Retrospective. Has graph and tables. [22]

Side effectsEdit

It can cause side effects such as adverse mental health effects like depression, anxiety, fatigue, and suicidal thoughts, elevated liver enzymes, and vitamin B12 deficiency. In addition, rarely, it can cause liver damage and failure, excessively high prolactin levels, meningiomas, and blood clots.

ReferencesEdit

  1. Endocrine_Society_Guidelines#Hormone Regimens
  2. Moltz L, Römmler A, Post K, Schwartz U, Hammerstein J (April 1980). "Medium dose cyproterone acetate (CPA): effects on hormone secretion and on spermatogenesis in men". Contraception. 21 (4): 393–413. doi:10.1016/S0010-7824(80)80017-5. PMID 6771095.
  3. L. Moltz et al (1978). "252. Cyproterone acetate (CPA)-a potential male contraceptive: further studies on the interactions with endocrine parameters". Journal of Steroid Biochemistry. 9 (9): 865. doi:10.1016/0022-4731(78)90952-4. ISSN 00224731.
  4. L. Moltz et al (1978). "Effects of Cyproterone Acetate (CPA) on Pituitary Gonadotrophin Release and on Androgen Secretion Before and After LH-RH Double Stimulation Tests in Men". International Journal of Andrology. 1 (s2b): 713–719. doi:10.1111/j.1365-2605.1978.tb00518.x. ISSN 0105-6263.
  5. Wang C, Yeung KK (March 1980). "Use of low-dosage oral cyproterone acetate as a male contraceptive". Contraception. 21 (3): 245–72. doi:10.1016/0010-7824(80)90005-0. PMID 6771091.
  6. 6.0 6.1 Koch UJ, Lorenz F, Danehl K, Ericsson R, Hasan SH, Keyserlingk DV, Lübke K, Mehring M, Römmler A, Schwartz U, Hammerstein J (August 1976). "Continuous oral low-dosage cyproterone acetate for fertility regulation in the male? A trend analysis in 15 volunteers". Contraception. 14 (2): 117–35. doi:10.1016/0010-7824(76)90081-0. PMID 949890.
  7. U. J. Koch et al (1975). "Über die Verwendbarkeit von Cyproteronacetat zur Fertilitätshemmung beim Mann. Morphologische Veränderungen und Einflüsse auf die Spermienmotilität". Archiv für Gynäkologie. 219 (1-4): 581–582. doi:10.1007/BF00669258. ISSN 0003-9128.
  8. Roy S, Chatterjee S, Prasad MR, Poddar AK, Pandey DC (October 1976). "Effects of cyproterone acetate on reproductive functions in normal human males". Contraception. 14 (4): 403–20. doi:10.1016/S0010-7824(76)80055-8. PMID 975826.
  9. Roy S, Chatterjee S (July 1979). "Studies with cyproterone acetate for male contraception". J. Steroid Biochem.. 11 (1B): 675–80. doi:10.1016/B978-0-08-023796-1.50099-2. PMID 491632.
  10. Roy S, Chatterjee S (July 1979). "The role of antiandrogenic action in cyproterone acetate-induced morphologic and biochemical changes in human semen". Fertil. Steril.. 32 (1): 93–5. doi:10.1016/S0015-0282(16)44122-1. PMID 456634.
  11. Fredricsson B, Carlström K (1981). "Effects of low doses of cyproterone acetate on sperm morphology and some other parameters of reproduction in normal men". Andrologia. 13 (4): 369–75. doi:10.1111/j.1439-0272.1981.tb00067.x. PMID 6456681.
  12. de la Torre B, Norén S, Hedman M, Diczfalusy E (October 1979). "Effect of cyproterone acetate (CPA) on gonadal and adrenal function in men". Contraception. 20 (4): 377–96. doi:10.1016/S0010-7824(79)80048-7. PMID 228907.
  13. Føgh M, Corker CS, Hunter WM, McLean H, Philip J, Schou G, Skakkebaek NE (July 1979). "The effects of low doses of cyproterone acetate on some functions of the reproductive system in normal men". Acta Endocrinol.. 91 (3): 545–52. doi:10.1530/acta.0.0910545. PMID 474042.
  14. Petry, R., Rausch-Stroomann, J. G., Mauss, J., Senge, T., Ai, M., & Berthold, K. (1970). Investigations on the mode of action of the antiandrogens cyproterone and cyproterone acetate in man. Med. Welt, 21, 1336.
  15. Petry, R., Rausch-Stroomann, J. G., Berthold, K., Mauss, J., Senge, M., & Vermeulen, A. (1970). Untersuchungen zum Wirkungsmechanismus der Antiandrogene Cyproteron und Cyproteronacetat beim Menschen (Gonadotropin-, Plasmatestosteron-und morphologische Keimdrüsenuntersuchungen). Verh. dtsch. Ges. inn. Med., 76, 873.
  16. R. Petry et al (1970). "Über den Einfluß von Cyproteronacetat, Norethisteronönanthat und Gestonoroncapronat auf die Hypophysen-Gonadenachse beim Mann". {{{journal}}}. {{{volume}}} ({{{issue}}}): 428–430. doi:10.1007/978-3-642-80591-2_118.
  17. Petry R, Mauss J, Rausch-Stroomann JG, Vermeulen A (September 1972). "Reversible inhibition of spermatogenesis in men". Horm. Metab. Res.. 4 (5): 386–8. doi:10.1055/s-0028-1094040. PMID 4645935.
  18. https://www.popline.org/node/391485
  19. Meriggiola MC, Bremner WJ, Costantino A, Di Cintio G, Flamigni C (May 1998). "Low dose of cyproterone acetate and testosterone enanthate for contraception in men". Hum. Reprod.. 13 (5): 1225–9. doi:10.1093/humrep/13.5.1225. PMID 9647551.
  20. Meriggiola MC, Bremner WJ, Costantino A, Pavani A, Capelli M, Flamigni C (November 1997). "An oral regimen of cyproterone acetate and testosterone undecanoate for spermatogenic suppression in men". Fertil. Steril.. 68 (5): 844–50. doi:10.1016/S0015-0282(97)00363-4. PMID 9389813.
  21. Meriggiola MC, Costantino A, Cerpolini S, Bremner WJ, Huebler D, Morselli-Labate AM, Kirsch B, Bertaccini A, Pelusi C, Pelusi G (December 2003). "Testosterone undecanoate maintains spermatogenic suppression induced by cyproterone acetate plus testosterone undecanoate in normal men". J. Clin. Endocrinol. Metab.. 88 (12): 5818–26. doi:10.1210/jc.2003-030574. PMID 14671175.
  22. Raymond Fung et al (2017). "Is a lower dose of cyproterone acetate as effective at testosterone suppression in transgender women as higher doses?". International Journal of Transgenderism. 18 (2): 123–128. doi:10.1080/15532739.2017.1290566. ISSN 1553-2739.