Antiandrogens, or androgen blockers, first discovered in the 1960s, prevent androgens from expressing their biological effects on responsive tissues.[1] Antiandrogens alter the androgen pathway by blocking the appropriate receptors or affecting androgen production.[2]
Antiandrogens can be prescribed to treat an assortment of androgen-dependent conditions. In men, antiandrogens are most frequently used to treat prostate cancer.[3] In women, antiandrogens are used to decrease levels of male hormones causing symptoms of hyperandrogenism.[4]
Antiandrogens present in the environment have become a topic of concern. Many industrial chemicals, including phthalates and pesticides exhibit antiandrogenic effects in animal experiments.[5][6] Certain plant species have also been found to produce antiandrogens. In animal studies, environmental antiandrogens can harm reproductive organ development in fetuses exposed in utero as well as their offspring.[5]
Contents
- 1 Medical uses
- 2 Mechanism of action
- 3 Environmental exposure
- 3.1 Pesticides and insecticides
- 3.2 Industrial chemicals
- 3.3 Phytochemicals
- 4 Discovery and development
- 5 See also
- 6 References
Medical uses
Antiandrogens are used to treat an array of medical conditions that are dependent on the androgen pathway. Antiandrogens are often prescribed for men with prostate cancer, benign prostatic hyperplasia, hypersexuality, and male contraception, and for trans women undergoing gender reassignment. For women, antiandrogens are often prescribed for severe cases of acne, amenorrhea, seborrhea, hirsutism, androgenic alopecia, hidradenitis suppurativa, and hyperandrogenism.
Men
Antiandrogens in males can result in hyposexuality (diminished sexual desire or libido), reduced activity or function of the accessory male sex organs, and slowed or halted development or reversal of male secondary sex characteristics.[medical citation needed]
Antiandrogens are often indicated to treat severe male sexual disorders, such as hypersexuality (excessive sexual desire) and sexual deviation such as paraphilia (a disorder involving intense recurrent sexual urges), since lowering male hormone levels decreases libido.[medical citation needed] As a part of a program for registered sex offenders recently released from prisons, the offender is sometimes administered antiandrogen drugs to reduce the likelihood of repeat offenses by reducing sexual drive.[medical citation needed] On occasion, antiandrogens are used as a male contraceptive agent.[medical citation needed]
Prostate cancer
Decreasing the body’s response to androgen can have beneficial effects in treating prostate cancer. Prostate cancer is the most commonly diagnosed form of cancer found in men.[3] Some prostate cancer cells require androgens for growth. To counteract cancer cell proliferation, antiandrogens are used for hormone therapy called androgen deprivation therapy. Some antiandrogens suppress androgen production while others inhibit androgens from binding to the cancer cells’ androgen receptors. These two classes of drugs can be prescribed separately or can be used together for a complete/combined androgen blockade. When the body is deprived of androgens, the therapy is termed castration-based therapy as the lack of androgens mimics castration. By competing with circulating androgens for binding sites on prostate cell receptors, antiandrogens promote apoptosis and inhibit prostate cancer growth.[3] Hormone therapy antiandrogen drugs can be prescribed as monotherapy or in addition to radical radiotherapy or prostatectomy.[3] Antiandrogen monotherapy generally causes fewer side effects in males, although it may block androgen less effectively than combined therapies. Monotherapy is often preferred by men as it is less likely than combined therapies to diminish libido or cause tenderness of the breasts, diarrhea, and nausea.[7]
Androgen-deprivation therapy has been shown to cause initial reduction of prostate tumors.[8] However, antiandrogens can cause prostate cancer tumors to become androgen-independent. Androgen independence occurs when cells that are not reliant on androgen proliferate and spread, while cells that require androgen for survival undergo apoptosis. The cells that do not require androgen become the basis of the tumors, and cause recurring tumors a few years after the initial disappearance of the prostate cancer. Once prostate cancer becomes androgen independent, hormone therapy will most likely no longer benefit the individual and a new treatment approach will be needed.[8]
In one study, the efficacy of reducing prostate cancer cells by castration was compared to combined androgen blockade in which castration is combined with an antiandrogen. Flutamide, nilutamide, bicalutamide, enzalutamide, and apalutamide are non-steroidal, "pure" antiandrogens. Flutamide has several side effects that the newer bicalutamide does not. Used in combination with castration, nilutamide and flutamide were found to have minimal effect on prolonging survival while bicalutamide significantly prolonged life in prostate cancer patients.[9] As a result, since 2007 combined androgen blockade with bicalutamide has been used as an effective, safe, and cost-efficient treatment of prostate cancer.[9]
5α-reductase inhibitors such as finasteride, dutasteride, and alfatradiol are antiandrogenic as they prevent the conversion of testosterone to dihydrotestosterone (DHT).[10] DHT is 3–5 times more potent than testosterone or other androgens (except in skeletal muscle tissue, where testosterone is the main androgen). They are unique because they do not counteract the effects or production of other androgens other than DHT. Dihydrotestosterone is necessary for development of both external male sex organs and the prostate. 5α-reductase inhibitors are most often used to treat benign prostatic hyperplasia since the resulting decrease in dihydrotestosterone inhibits proliferation of prostate cells.[10]
Women
Hyperandrogenism is a condition found in women where ovaries overproduce androgens, which are typically considered male hormones as they are important for the development of male reproductive organs and secondary male characteristics.[4] Antiandrogens can help to counteract androgens that cause skin and hair problems in women. Gonadotropins, pituitary hormones, are involved in ovarian androgen production, and their suppression can result in reduced testosterone production. Antiandrogens can inhibit the release of the gonadotropin luteinizing hormone (LH), suppressing testosterone synthesis in the ovaries.[11] Androgenic alopecia (a type of hair loss and pattern baldness), acne vulgaris, seborrhea, amenorrhea (the absence of menstrual periods), hirsutism (excessive facial and/or body hair in women), and hidradenitis suppurativa can be caused by an excess of androgens.[12][date missing]
Hormonal antiandrogen treatment is given to female patients that suffer from multiple symptoms of hyperandrogenism.[13] Acne is the most common of skin disorders that result from male hormone overproduction. Fewer androgens present in a female’s tissues result in a reduction of oil (sebum) production and bumps (comedone).[12] Antiandrogens are usually combined with topical and oral pharmaceuticals to treat severe acne. In women that suffer from hirsutism due to high testosterone levels, antiandrogens are used to slow hair growth, lighten hair color, and thin the hair. For females with androgenic alopecia, antiandrogens can assist in reducing hair shedding and thinning.[12]
The most common antiandrogens used to treat women with hyperandrogenism are spironolactone and cyproterone acetate. Spironolactone, a steroidal antimineralocorticoid diuretic with additional antiandrogen properties, is used primarily to treat low-renin hypertension, hypokalemia, and Conn's syndrome. Cyproterone acetate is a potent steroidal antiandrogen that is also a potent progestin and antigonadotropin. Oral contraceptives containing progestins have no effect on androgen levels, but may be combined with spironolactone and cyproterone acetate for the purpose of correcting menstrual irregularities.[12]
Antiandrogens are also used to purposefully prevent or counteract masculinization and facilitate feminization in transgender women undergoing hormone replacement therapy.[14]
Mechanism of action
Types
- Androgen receptor (AR) ligands:
- AR antagonists: flutamide, nilutamide, bicalutamide, enzalutamide, apalutamide, cyproterone acetate, megestrol acetate, chlormadinone acetate, spironolactone, canrenone, drospirenone, ketoconazole, topilutamide (fluridil), cimetidine
- Selective androgen receptor modulators (SARMs) (e.g., andarine, enobosarm (ostarine)) (mixed/partial)
- Androgen synthesis inhibitors
- Enzyme inhibitors
- 5α-reductase inhibitors: finasteride, dutasteride, alfatradiol, saw palmetto extract
- CYP17A1 (17α-hydroxylase, 17,20-lyase) inhibitors: cyproterone acetate, spironolactone, danazol,[citation needed] gestrinone, ketoconazole, abiraterone acetate
- 3β-Hydroxysteroid dehydrogenase inhibitors: danazol,[citation needed] gestrinone, abiraterone acetate
- 17β-Hydroxysteroid dehydrogenase inhibitors: danazol,[citation needed] simvastatin
- CYP11A1 (cholesterol side-chain cleavage enzyme) inhibitors: aminoglutethimide, danazol
- HMG-CoA reductase inhibitors: statins (e.g., atorvastatin, simvastatin)
- Antigonadotropins
- Progestogens: progesterone, cyproterone acetate, medroxyprogesterone acetate, megestrol acetate, chlormadinone acetate, spironolactone, drospirenone, others
- Estrogens: estradiol, ethinyl estradiol, diethylstilbestrol, conjugated equine estrogens, others
- GnRH analogues
- GnRH agonists: buserelin, deslorelin, gonadorelin, goserelin, histrelin, leuprorelin, nafarelin, triptorelin
- GnRH antagonists: abarelix, cetrorelix, degarelix, ganirelix
- Anabolic steroids (e.g., nandrolone, oxandrolone) (mixed/partial)
As can be seen above, some antiandrogens, such as cyproterone acetate, megestrol acetate, spironolactone, and abiraterone acetate, act via multiple mechanisms of action, including both AR antagonism and androgen synthesis inhibition through enzyme inhibition and/or gonadotropin suppression.
Discussion
Antiandrogens are classified as steroidal or non-steroidal. Steroidal antiandrogens counteract androgens and thus also affect secondary sex characteristics. Steroidal antiandrogens directly affect gene expression due to their fat-soluble nature that allows them to diffuse through the plasma membrane’s phospholipid bilayer and prevent the binding of testosterone and dihydrotestosterone (DHT) to the androgen receptor.[15][date missing][publisher missing] Steroidal antiandrogens include cyproterone acetate and spironolactone.
Non-steroidal antiandrogens, or "pure" antiandrogens, such as flutamide, bicalutamide, and enzalutamide, counter androgens and have no steroidal effects. Antiandrogens inhibit circulating androgens by blocking androgen receptors, suppressing androgen synthesis, or acting in both those ways.[13] The most common antiandrogens are androgen receptor (AR) antagonists which act on the target cell level and competitively bind to androgen receptors.[2]
Inhibition of androgen production occurs through a unique mechanism for each antiandrogen. For example, ketoconazole not only competes with androgens such as testosterone and DHT for androgen receptor binding, but also suppresses androgen synthesis by inhibiting cytochrome P450 and 17,20-lyase, which partake in synthesizing and degrading steroids, including the precursors of testosterone. The result is a decrease in the overall testosterone production of the adrenal cortex.[16] Gonadotrophins, which are pituitary hormones capable of altering androgen synthesis, are also affected by antiandrogens. Antiandrogens can suppress gonadotropin secretion by down-regulating gonadotropin-releasing hormone receptors (GnRHR) in the pituitary gland. A decreased amount of GnRHRs results in gonadotropin-releasing hormone (GnRH) not being able to bind sufficiently. GnRH is responsible for the release of the gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH). LH stimulates the Leydig cells of the testes and the theca cells of the ovaries to produce testosterone and indirectly estradiol. Therefore, if GnRH cannot bind, testosterone synthesis is not induced in testes or ovaries.[11][date missing][publisher missing]
Abiraterone acetate is an androgen synthesis inhibitor used in the treatment of prostate cancer which acts by inactivating the enzyme CYP17A1.
Antigonadotropins, including progestins like cyproterone acetate, medroxyprogesterone acetate, and megestrol acetate and GnRH analogues like leuprorelin and cetrorelix, suppress gonadal androgen production by suppressing gonadotropin secretion from the pituitary gland, and hence are antiandrogens that act as androgen synthesis inhibitors.
Antiandrogens may not bind to or block membrane androgen receptors, which are distinct from the classical nuclear AR.[17][18][19]
Environmental exposure
Exposure to antiandrogens can occur unintentionally due to natural or anthropogenic compounds in the environment. Environmental compounds affecting the endocrine system, termed endocrine disruptors, that antagonistically affect androgen receptors and androgen production can negatively affect animals that come in contact with the compounds as well as their future generations.[5] Certain pesticides and insecticides as well as industrial chemicals possess antiandrogen properties. Some species of plants produce phytochemicals with antiandrogenic effects. Exposure to these environmental antiandrogens has resulted in adverse effects on animals that allude to human health risks.[medical citation needed]
Pesticides and insecticides
Exposure to pesticides with antiandrogen properties has been found to negatively affect laboratory animals. Androgens are important in fetal development as well as in pubertal development. Exposure during critical periods of development can cause reproductive malformations in males while exposure after birth and before puberty can delay puberty.[5]
Animal studies with vinclozolin, procymidone, linuron, and the DDT metabolite dichlorodiphenyldichloroethylene (p.p’-DDE) have shown irregular reproductive development due to their function as androgen receptor antagonists that inhibit androgen-activated gene expression.[5][20] Even with low doses of antiandrogenic pesticides, developmental effects such as reduced anogenital distance and induction of areolas were seen in male rats.[5]
Animal studies show that deformities result in offspring exposed to antiandrogens.[5] Male mice can display malformations that resemble the reproductive organs of females as in the case of exposure to vinclozolin or proymidone. Exposure to vinclozolin or procymidone in utero feminized male offspring, as seen in abnormalities of anogenital distance, small or absent sex accessory glands, hypospadias, undescended testes, retained nipples, cleft phallus, and presence of a vaginal pouch. Male mice exposed before puberty to vinclozolin experienced delayed pubertal development visualized by delayed onset of androgen-dependent preputial separation.[5]
Ketoconazole is an imidazole derivative is used as a broad-spectrum antifungal agent effective against a variety of fungal infections. Although ketoconazole is a relatively weak antiandrogen, high doses side-effects lead to reduced levels of androgens from both the testicles and adrenal glands.[5]
Industrial chemicals
Industrial chemicals with antiandrogenic effects are ubiquitous in the environment. Consumer products such as toys and cosmetics may contain phthalates or parabens, which disrupt androgen synthesis.[5][6]
Phthalates are mainly found as softeners in plastics, but also perfumes, nail varnish and other cosmetics. Fetuses that are exposed to a mixture of phthalates in utero may show signs of disrupted reproductive development.[6][21] When Di-n-butyl phthalate (DBP), diisobutyl phthalate (DiBP), benzyl butyl phthalate (BBP), Bis(2-ethylhexyl) phthalate (DEHP) and di-n-pentyl phthalate (DPP) were combined, reductions in both testosterone synthesis and gene expression of steroidogenic pathway proteins were seen. The results in male rats were undescended testes and abnormal development of reproductive tissues.[6]
Parabens are used as preservatives and/or antimicrobial agents and commonly found in food, soap, detergent, toothpaste, disinfectant, cosmetic and pharmaceutical products. Paraben esters, such as butylparaben, have been found to mimic androgen antagonist activity. Antiandrogenic endocrine disruption has been shown in aquatic species, but the mechanism is unknown. Researchers believe parabens have the ability to bind to human androgen receptors but it still remains unclear.[21]
Bisphenols such as bisphenol A are both antiandrogens and estrogens.
Phytochemicals
Antiandrogens can also occur naturally in plants.
The best known plant-derived antiandrogen is 3,3'-diindolylmethane[22][23] found in cruciferous vegetables, which are members of the cabbage family.
The compound N-butylbenzene-sulfonamide (NBBS) isolated from the bark of Prunus africana, the Subsaharan red stinkwood tree, is a specific androgen antagonist and has been used as alternative medicine in benign prostatic hyperplasia.[24][25]
Licorice, or Glycyrrhiza glabra native to southern Europe, India, and parts of Asia has shown antiandrogen activity in male rats.[26]
Discovery and development
Main article: Discovery and development of antiandrogens
See also
- Antiestrogen
- Antiprogestin
References
- ^ "Medical Dictionary: Anti-androgen".
- ^ a b Mowszowicz I (1989). "Antiandrogens. Mechanisms and paradoxical effects". Ann. Endocrinol. (Paris) 50 (3): 50(3):189–99. PMID 2530930.
- ^ a b c d Gillatt D (2006). "Antiandrogen treatments in locally advanced prostate cancer: are they all the same?". J Cancer Res Clin Oncol 1: S17–26. doi:10.1007/s00432-006-0133-5. PMID 16845534.
- ^ a b "Medical Dictionary: Hyperandrogenism".
- ^ a b c d e f g h i j Gray LE, Ostby J, Furr J, Wolf CJ, Lambright C, Parks L, Veeramachaneni DN, Wilson V, Price M, Hotchkiss A, Orlando E, Guillette L (2001). "Effects of environmental antiandrogens on reproductive development in experimental animals". Human Reproduction Update 2 (3): 248–64. doi:10.1093/humupd/7.3.248. PMID 11392371.
- ^ a b c d Rider CV, Furr JR, Wilson VS, Gray LE Jr (Apr 2010). "Cumulative effects of in utero administration of mixtures of reproductive toxicants that disrupt common target tissues via diverse mechanisms of toxicity". International Journal of Andrology 33 (2): 443–62. doi:10.1111/j.1365-2605.2009.01049.x. PMC 2874988. PMID 20487044.
- ^ Kolvenbag GJ, Iversen P, Newling DW (August 2001). "Antiandrogen monotherapy: a new form of treatment for patients with prostate cancer". Urology 58 (2 Suppl 1): 16–23. doi:10.1016/s0090-4295(01)01237-7. PMID 11502439.
- ^ a b Massard, C (June 2011). "Targeting Continued Androgen Receptor Signaling in Prostate Cancer". Clinical Cancer Research 17 (12): 3876–883. doi:10.1158/1078-0432.ccr-10-2815.
- ^ a b Akaza H (Jan 2011). "Combined androgen blockade for prostate cancer: review of efficacy, safety, and cost-effectiveness". Cancer Science 102 (1): 51–6. doi:10.1111/j.1349-7006.2010.01774.x. PMID 21091846.
- ^ a b Flores E, Bratoeff E, Cabeza M, Ramirez E, Quiroz A, Heuze I. (May 2003). "Steroid 5alpha-reductase inhibitors". Mini-Reviews in Medicinal Chemistry 3 (3): 225–37. doi:10.2174/1389557033488196. PMID 12570838.
- ^ a b "Gonadotropin". Retrieved 9 December 2011.
- ^ a b c d Dr. Amanda Oakley. "Hormonal treatment".
- ^ a b Zouboulis CC, Rabe T (March 2010). "Hormonal antiandrogens in acne treatment". Journal of the German Society of Dermatology 8 (Suppl 1): S60–74. doi:10.1111/j.1610-0387.2009.07171.x. PMID 20482693.
- ^ "Antiandrogen Drugs".
- ^ "Steroidal Antiandrogens". Health and Prostate. Retrieved 9 December 2011.
- ^ Witjes FJ, Debruyne FM, Fernandez del Moral P, Geboers AD (May 1989). "Ketoconazole high dose in management of hormonally pretreated patients with progressive metastatic prostate cancer. Dutch South-Eastern Urological Cooperative Group". Urology 33 (5): 411–5. doi:10.1016/0090-4295(89)90037-X. PMID 2652864.
- ^ Bennett NC, Gardiner RA, Hooper JD, Johnson DW, Gobe GC (2010). "Molecular cell biology of androgen receptor signalling". Int. J. Biochem. Cell Biol. 42 (6): 813–27. doi:10.1016/j.biocel.2009.11.013. PMID 19931639.
- ^ Wang C, Liu Y, Cao JM (2014). "G protein-coupled receptors: extranuclear mediators for the non-genomic actions of steroids". Int J Mol Sci 15 (9): 15412–25. doi:10.3390/ijms150915412. PMC 4200746. PMID 25257522.
- ^ Lang F, Alevizopoulos K, Stournaras C (2013). "Targeting membrane androgen receptors in tumors". Expert Opin. Ther. Targets 17 (8): 951–63. doi:10.1517/14728222.2013.806491. PMID 23746222.
- ^ Curtis LR (Mar 2001). "Organophosphate antagonism of the androgen receptor". Toxicological Sciences 60 (1): 1–2. doi:10.1093/toxsci/60.1.1. PMID 11222865.
- ^ a b Darbre PD, Harvey PW (Jul 2008). "Paraben esters: review of recent studies of endocrine toxicity, absorption, esterase and human exposure, and discussion of potential human health risks". Journal of Applied Toxicology 28 (5): 561–78. doi:10.1002/jat.1358. PMID 18484575.
- ^ Yang, Sarah (12 May 2003). "Chemical in Broccoli Blocks Growth of Prostate Cancer Cells, New Study Shows". Retrieved 8 April 2015.
- ^ "Plant-derived 3,3'-Diindolylmethane is a strong androgen antagonist in human prostate cancer cells". 6 June 2003. Retrieved 8 April 2015.
- ^ Papaioannou M, Schleich S, Roell D, Schubert U, Tanner T, Claessens F, Matusch R, Baniahmad A (December 2010). "NBBS isolated from Pygeum africanum bark exhibits androgen antagonistic activity, inhibits AR nuclear translocation and prostate cancer cell growth". Invest New Drugs 28 (6): 729–43. doi:10.1007/s10637-009-9304-y. PMID 19771394.
- ^ Schleich S, Papaioannou M, Baniahmad A, Matusch R (July 2006). "Extracts from Pygeum africanum and other ethnobotanical species with antiandrogenic activity". Planta Med. 72 (9): 807–13. doi:10.1055/s-2006-946638. PMID 16783690.
- ^ Zamansoltani F, Nassiri-Asl M, Sarookhani MR, Jahani-Hashemi H, Zangivand AA (August 2009). "Antiandrogenic activities of Glycyrrhiza glabra in male rats". Int. J. Androl. 32 (4): 417–22. doi:10.1111/j.1365-2605.2009.00944.x. PMID 19515171.
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Androgens and antiandrogens
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| Androgens |
| Agonists |
- Anabolic steroids (see here instead)
- Androgenic progestins (e.g., norethisterone, levonorgestrel, medroxyprogesterone acetate)
- Androstanolone
- Androstenediol
- Androstenedione
- DHEA
- DHEA sulfate
- Dihydrotestosterone
- Fluoxymesterone
- Mesterolone
- Methyltestosterone
- Testosterone#
- Testosterone acetate
- Testosterone capropate
- Testosterone cypionate
- Testosterone decanoate
- Testosterone enanthate
- Testosterone isocaproate
- Testosterone phenylpropionate
- Testosterone propionate
- Testosterone undecanoate
- Tibolone
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| SARMs |
- AC-262,356§
- Andarine§
- BMS-564,929§
- Enobosarm (ostarine)§
- LGD-2226§
- LGD-3303§
- S-23§
- S-40503§
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| Antiandrogens |
| Antagonists |
- Abiraterone acetate
- Apalutamide†
- Bicalutamide
- Canrenoic acid
- Canrenone
- Chlormadinone acetate
- Cimetidine
- Cyproterone acetate
- Drospirenone
- Enzalutamide
- EPI-001§
- Flutamide
- Galeterone†
- Ketoconazole
- Megestrol acetate
- Nilutamide
- Nomegestrol acetate
- ODM-201†
- Potassium canrenoate
- Spironolactone
- Topilutamide (fluridil)
- Valproic acid
- VT-464†
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| Enzyme inhibitors |
| 5α-Reductase |
- Alfatradiol
- Chlormadinone acetate
- Dutasteride
- Finasteride
- Saw palmetto extract
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| CYP17A1 |
- Abiraterone acetate
- Cyproterone acetate
- Danazol
- Galeterone†
- Gestrinone
- Ketoconazole
- Orteronel†
- Spironolactone
- VT-464†
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| Others |
- Abiraterone acetate
- Aminoglutethimide
- Cyproterone acetate
- Danazol
- Gestrinone
- Ketoconazole
- Mitotane
- Trilostane
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| Antigonadotropins |
- Anabolic steroids (e.g., nandrolone, oxandrolone)
- Estrogens (e.g., estradiol)
- GnRH agonists (e.g., leuprorelin)
- GnRH antagonists (e.g., cetrorelix)
- Progestogens (incl. allylestrenol, chlormadinone acetate, cyproterone acetate, delmadinone acetate, dydrogesterone, medroxyprogesterone acetate, megestrol acetate, nomegestrol acetate, norethisterone acetate, progesterone, spironolactone)
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- #WHO-EM
- ‡Withdrawn from market
- Clinical trials:
- †Phase III
- §Never to phase III
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Androgenics
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Receptor
(ligands) |
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AR
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Agonists
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Mixed (SARMs)
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- AC-262,356
- Andarine
- BMS-564,929
- Enobosarm (ostarine)
- LGD-2226
- LGD-3303
- LGD-4033
- RAD140
- S-23
- S-40503
- TFM-4AS-1
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Antagonists
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- 3α-Hydroxytibolone
- 3β-Hydroxytibolone
- Abiraterone
- Abiraterone acetate
- Apalutamide
- AZD-3514
- Bisphenols (e.g., BADGE, BFDGE, bisphenol A, bisphenol F, bisphenol S)
- Benorterone
- Bicalutamide
- BMS-641,988
- BOMT
- Canrenoic acid
- Canrenone
- Chlormadinone acetate
- Cimetidine
- Cioteronel
- Clometerone
- Cyproterone
- Cyproterone acetate
- Delanterone
- DDT (via metabolite p,p’-DDE)
- Dieldrin
- Dienogest
- Drospirenone
- Endosulfan
- Enzalutamide
- EPI-001
- Epitestosterone
- Fenarimol
- Flutamide
- Galeterone
- Guggulsterone
- Hydroxyflutamide
- Inocoterone
- Ketoconazole
- Lavender oil
- Linuron
- Megestrol acetate
- Mespirenone
- Methiocarb
- Metogest
- Mifepristone
- Nilutamide
- Nomegestrol
- Nordinone
- Norgestimate
- ODM-201
- ONC1-13B
- ORM-15341
- Osaterone
- Oxendolone
- PF-998425
- Potassium canrenoate
- Prochloraz
- Procymidone
- R-2956
- Rosterolone
- RU-58642
- RU-58841
- Spironolactone
- Topilutamide (fluridil)
- Topterone
- Valproic acid
- Vinclozolin
- VT-464
- Zanoterone
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| Enzyme |
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Modulators
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- See here instead (modulators of 20,22-desmolase, 17α-hydroxylase/17,20-lyase, 3β-HSD, 17β-HSD, 5α-reductase, and aromatase).
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| Others |
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Precursors/prohormones
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- Cholesterol
- 22R-Hydroxycholesterol
- 20α,22R-Dihydroxycholesterol
- Pregnenolone
- Pregnenolone sulfate
- 17-Hydroxypregnenolone
- Progesterone
- 17-Hydroxyprogesterone
- 11-Deoxycortisol (cortodoxone)
- DHEA
- DHEA sulfate
- Δ5-Androstenediol
- Δ4-Androstenedione
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Indirect
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- Antigonadotropins (e.g., estrogens, progestogens, prolactin)
- GnRH agonists (e,g, GnRH, leuprorelin)
- GnRH antagonists (e.g., cetrorelix)
- Gonadotropins (e.g., FSH, hCG, LH)
- Kisspeptin
- Plasma proteins (ABP, albumin, SHBG)
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See also: Estrogenics • Glucocorticoids • Mineralocorticoids • Progestogenics
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