4-Androstene-3,6,17-trione

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4-Androstene-3,6,17-trione
4-Androstene-3,6,17-trione.png
Clinical data
Routes of
administration
By mouth
Legal status
Legal status
Identifiers
  • (10R,13S)-10,13-dimethyl-
    1,7,8,9,10,11,12,13,15,16-decahydro-2H-cyclopenta[alpha]phenanthrene-3,6,17(14H)-trione
CAS Number
ChemSpider
UNII
CompTox Dashboard (EPA)
Chemical and physical data
Formula C19H24O3
Molar mass 300.398 g·mol−1
3D model (JSmol)
  • O=C4\C1=C\C(=O)CC[C@@]1([C@H]3CC[C@@]2(C(=O)CC[C@H]2[C@@H]3C4)C)C
  • InChI=1S/C19H24O3/c1-18-7-5-11(20)9-15(18)16(21)10-12-13-3-4-17(22)19(13,2)8-6-14(12)18/h9,12-14H,3-8,10H2,1-2H3/t12-,13-,14-,18+,19-/m0/s1 Yes check.svgY
  • Key:PJMNEPMSGCRSRC-IEVKOWOJSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

4-Androstene-3,6,17-trione (4-AT; also marketed as 6-OXO or 4-etioallocholen-3,6,17-trione) is a drug or nutritional supplement that may increase the testosterone-estrogen ratio, but has no proven effect on body composition. Its use can be detected in urine. [2] [3]

4-AT is a potent irreversible aromatase inhibitor that inhibits estrogen biosynthesis by permanently binding and inactivating aromatase in adipose and peripheral tissue. [4] [5] [6] Aromatase is responsible for the conversion of testosterone to estradiol. Blocking aromatase causes the body to decrease in levels of estradiol, which then results in increase of LH and consequently, testosterone. Since testosterone has myotropic activity and estradiol does not, elevated testosterone levels increase muscle mass. However, there appear to be no human or animal studies testing the hypothesis that 4-AT will produce an anabolic effect.

4-AT is used by steroid or prohormone users to counteract estrogen level increases caused by aromatization during their steroid cycle. This helps minimize side effects such as gynecomastia but can lead to acne. Also, after a steroid cycle, the compound may be used to shorten the recovery from the testicular suppression that can be the result of the use of steroids.

Baylor University conducted an eight-week study to determine the effects of 300 mg or 600 mg of 4-AT in resistance-trained males. Compared to baseline, free testosterone increased by 90% for 300 mg group and 84% for 600 mg group, respectively. Also dihydrotestosterone and the ratio of free testosterone to estradiol increased significantly. The report concluded that "[t]he results of this study indicate that eight weeks of 6-OXO supplementation had no effect on body composition or clinical safety markers, but incompletely inhibited aromatase activity and significantly increased endogenous DHT levels that were attenuated after a three-week washout period". [7] This study did not utilize a control group and was funded in part by two producers of commercial 4-AT. [7]

In a FDA Warning Letter [ citation needed ] dated July 7, 2006, the U.S. Food and Drug Administration (FDA) argues that marketing of 4-AT violates the Federal Food, Drug, and Cosmetic Act and as such products containing it are adulterated by legal definition.

In 2008, Health Canada issued a warning that 4-AT had a health risk related to blood clotting and recommended all users immediately cease use. [8]

Related Research Articles

<span class="mw-page-title-main">Estrogen</span> Primary female sex hormone

Estrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal activity: estrone (E1), estradiol (E2), and estriol (E3). Estradiol, an estrane, is the most potent and prevalent. Another estrogen called estetrol (E4) is produced only during pregnancy.

<span class="mw-page-title-main">Anastrozole</span> Chemical compound

Anastrozole, sold under the brand name Arimidex among others, is an antiestrogenic medication used in addition to other treatments for breast cancer. Specifically it is used for hormone receptor-positive breast cancer. It has also been used to prevent breast cancer in those at high risk. It is taken by mouth.

An androgen prohormone, or proandrogen, is a prohormone of an anabolic-androgenic steroid (AAS). They can be prohormones of testosterone or of synthetic AAS, for example, nandrolone (19-nortestosterone). Dehydroepiandrosterone (DHEA), DHEA sulfate (DHEA-S), and androstenedione may all be considered proandrogens of testosterone.

<span class="mw-page-title-main">Androstenedione</span> Endogenous weak androgen

Androstenedione, or 4-androstenedione, also known as androst-4-ene-3,17-dione, is an endogenous weak androgen steroid hormone and intermediate in the biosynthesis of estrone and of testosterone from dehydroepiandrosterone (DHEA). It is closely related to androstenediol (androst-5-ene-3β,17β-diol).

<span class="mw-page-title-main">Nandrolone</span> Anabolic steroid

Nandrolone, also known as 19-nortestosterone, is an endogenous androgen which exists in the male body at a ratio of 1:50 compared to testosterone. It is also an anabolic steroid (AAS) which is medically used in the form of esters such as nandrolone decanoate and nandrolone phenylpropionate. Nandrolone esters are used in the treatment of anemias, cachexia, osteoporosis, breast cancer, and for other indications. They are not used by mouth and instead are given by injection into muscle or fat.

<span class="mw-page-title-main">Aromatase inhibitor</span> Class of drugs

Aromatase inhibitors (AIs) are a class of drugs used in the treatment of breast cancer in postmenopausal women and in men, and gynecomastia in men. They may also be used off-label to reduce estrogen conversion when supplementing testosterone exogenously. They may also be used for chemoprevention in women at high risk for breast cancer.

<span class="mw-page-title-main">Metandienone</span> Androgen and anabolic steroid

Metandienone, also known as methandienone or methandrostenolone and sold under the brand name Dianabol (D-Bol) among others, is an androgen and anabolic steroid (AAS) medication which is still quite often used because of its affordability and effectiveness for bulking cycles. It is also used non-medically for physique- and performance-enhancing purposes. It is often taken by mouth.

<span class="mw-page-title-main">Prasterone</span> Medical usage of the prasterone compound

Prasterone, also known as dehydroepiandrosterone (DHEA) and sold under the brand name Intrarosa among others, is a medication as well as over-the-counter dietary supplement which is used to correct DHEA deficiency due to adrenal insufficiency or old age, as a component of menopausal hormone therapy, to treat painful sexual intercourse due to vaginal atrophy, and to prepare the cervix for childbirth, among other uses. It is taken by mouth, by application to the skin, in through the vagina, or by injection into muscle.

<span class="mw-page-title-main">Exemestane</span> Breast cancer medication

Exemestane, sold under the brand name Aromasin among others, is a medication used to treat breast cancer. It is a member of the class of antiestrogens known as aromatase inhibitors. Some breast cancers require estrogen to grow. Those cancers have estrogen receptors (ERs), and are called ER-positive. They may also be called estrogen-responsive, hormonally-responsive, or hormone-receptor-positive. Aromatase is an enzyme that synthesizes estrogen. Aromatase inhibitors block the synthesis of estrogen. This lowers the estrogen level, and slows the growth of cancers.

<span class="mw-page-title-main">Androstenediol</span> Chemical compound

Androstenediol, or 5-androstenediol, also known as androst-5-ene-3β,17β-diol, is an endogenous weak androgen and estrogen steroid hormone and intermediate in the biosynthesis of testosterone from dehydroepiandrosterone (DHEA). It is closely related to androstenedione (androst-4-ene-3,17-dione).

<span class="mw-page-title-main">Trenbolone acetate</span> Chemical compound

Trenbolone acetate, sold under brand names such as Finajet and Finaplix among others, is an androgen and anabolic steroid (AAS) medication which is used in veterinary medicine, specifically to increase the profitability of livestock by promoting muscle growth in cattle. It is given by injection into muscle.

<span class="mw-page-title-main">4-Hydroxytestosterone</span> Chemical compound

4-Hydroxytestosterone (4-OHT), also known as 4,17β-dihydroxyandrost-4-en-3-one, is a synthetic anabolic-androgenic steroid (AAS) and a derivative of testosterone that was never marketed. It was first patented by G.D. Searle & Company in 1955 and is testosterone with a hydroxy group at the four position. 4-OHT has moderate anabolic, mild androgenic, and anti-aromatase properties and is similar to the steroid clostebol (4-chlorotestosterone).

<span class="mw-page-title-main">Adrenosterone</span> Chemical compound

Adrenosterone, also known as Reichstein's substance G , as well as 11-ketoandrostenedione (11-KA4), 11-oxoandrostenedione (11-OXO), and androst-4-ene-3,11,17-trione, is a steroid hormone with an extremely weak androgenic effect, and an intermediate/prohormone of 11-ketotestosterone. It was first isolated in 1936 from the adrenal cortex by Tadeus Reichstein at the Pharmaceutical Institute in the University of Basel. Originally, adrenosterone was called Reichstein's substance G. Adrenosterone occurs in trace amounts in humans as well as most mammals and in larger amounts in fish, where it is a precursor to the primary androgen, 11-ketotestosterone.

<span class="mw-page-title-main">1,4,6-Androstatriene-3,17-dione</span> Chemical compound

1,4,6-Androstatriene-3,17-dione (ATD) is a potent irreversible aromatase inhibitor that inhibits estrogen biosynthesis by permanently binding and inactivating aromatase in adipose and peripheral tissue. It is used to control estrogen synthesis.

<span class="mw-page-title-main">Testolactone</span> Chemical compound

Testolactone is a non-selective, irreversible, steroidal aromatase inhibitor which is used as an antineoplastic drug to treat advanced-stage breast cancer. The drug was discontinued in 2008 and is no longer available for medical use.

<span class="mw-page-title-main">1-Testosterone</span> Chemical compound

1-Testosterone, also known as δ1-dihydrotestosterone (δ1-DHT), as well as dihydroboldenone, is a synthetic anabolic–androgenic steroid (AAS) and a 5α-reduced derivative of boldenone (Δ1-testosterone). It differs from testosterone by having a 1(2)-double bond instead of a 4(5)-double bond in its A ring. It was legally sold online in the United States until 2005, when it was reclassified as a Schedule III drug.

<span class="mw-page-title-main">7-Keto-DHEA</span> Chemical compound

7-Ketodehydroepiandrosterone (7-keto-DHEA,7-oxo-DHEA), also known as 7-oxoprasterone, is a prohormone produced by metabolism of the prohormone dehydroepiandrosterone (DHEA).

<span class="mw-page-title-main">Bolandiol</span> Chemical compound

Bolandiol is an anabolic-androgenic steroid (AAS) that was never marketed. However, a dipropionate ester derivative, bolandiol dipropionate, has been marketed. Bolandiol and its dipropionate ester are unique among AASs in that they reportedly also possesses estrogenic and progestogenic activity.

Steroidal aromatase inhibitors are a class of drugs that are mostly used for treating breast cancer in postmenopausal women. High levels of estrogen in breast tissue increases the risk of developing breast cancer and the enzyme aromatase is considered to be a good therapeutic target when treating breast cancer due to it being involved in the final step of estrogen biosynthetic pathway and also its inhibition will not affect production of other steroids. Aromatase Inhibitors are classified into two categories based on their structure, nonsteroidal and steroidal; the latter resemble the structure of androstenedione. Steroidal aromatase inhibitors irreversibly inhibit the enzyme by binding covalently to the binding site of aromatase so the substrate cannot access it.

<span class="mw-page-title-main">Testosterone (medication)</span> Medication and naturally occurring steroid hormone

Testosterone (T) is a medication and naturally occurring steroid hormone. It is used to treat male hypogonadism, gender dysphoria, and certain types of breast cancer. It may also be used to increase athletic ability in the form of doping. It is unclear if the use of testosterone for low levels due to aging is beneficial or harmful. Testosterone can be used as a gel or patch that is applied to the skin, injection into a muscle, tablet that is placed in the cheek, or tablet that is taken by mouth.

References

  1. "The World Anti-Doping Code: The 2012 Prohibited List" (PDF). World Anti-Doping Agency. Archived from the original (PDF) on 2012-05-13. Retrieved 2012-07-17.
  2. Van Thuyne W, Van Eenoo P, Mikulcíková P, Deventer K, Delbeke FT (November 2005). "Detection of androst-4-ene-3,6,17-trione (6-OXO) and its metabolites in urine by gas chromatography-mass spectrometry in relation to doping analysis". Biomedical Chromatography. 19 (9): 689–695. doi:10.1002/bmc.496. PMID   15828056.
  3. Deventer K, Van Eenoo P, Mikulcíková P, Van Thuyne W, Delbeke FT (December 2005). "Quantitative analysis of androst-4-ene-3,6,17-trione and metabolites in human urine after the administration of a food supplement by liquid chromatography/ion trap-mass spectrometry". Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences. 828 (1–2): 21–26. doi:10.1016/j.jchromb.2005.08.024. PMID   16213800.
  4. Numazawa M, Tsuji M, Mutsumi A (September 1987). "Studies on aromatase inhibition with 4-androstene-3,6,17-trione: its 3 beta-reduction and time-dependent irreversible binding to aromatase with human placental microsomes". Journal of Steroid Biochemistry. 28 (3): 337–344. doi:10.1016/0022-4731(87)91028-4. PMID   3657156.
  5. Covey DF, Hood WF (April 1981). "Enzyme-generated intermediates derived from 4-androstene-3,6,17-trione and 1,4,6-androstatriene-3,17-dione cause a time-dependent decrease in human placental aromatase activity". Endocrinology. 108 (4): 1597–1599. doi:10.1210/endo-108-4-1597. PMID   7472286.
  6. Hsueh AJ, Erickson GF (December 1978). "Glucocorticoid inhibition of FSH-induced estrogen production in cultured rat granulosa cells". Steroids. 32 (5): 639–648. doi:10.1016/0039-128X(78)90074-0. PMID   734698. S2CID   23530490.
  7. 1 2 Rohle D, Wilborn C, Taylor L, Mulligan C, Kreider R, Willoughby D (October 2007). "Effects of eight weeks of an alleged aromatase inhibiting nutritional supplement 6-OXO (androst-4-ene-3,6,17-trione) on serum hormone profiles and clinical safety markers in resistance-trained, eugonadal males". Journal of the International Society of Sports Nutrition. 4: 13. doi: 10.1186/1550-2783-4-13 . PMC   2100070 . PMID   17949492.
  8. "Health Canada warns consumers not to use the dietary supplements 6-OXO and 1-AD due to potential serious health risks". Health Canada. June 18, 2008.