33 5α Reductase inhibitors

5α-Reductase inhibitors (5-ARIs), also known as dihydrotestosterone (DHT) blockers, are a class of medications with antiandrogenic effects which are used primarily in the treatment of enlarged prostate and scalp hair loss. They are also sometimes used to treat excess hair growth in women and as a component of hormone therapy for transgender women.

Abiraterone acetate, sold under the brand name Zytiga among others, is a medication used to treat prostate cancer. Specifically it is used together with a corticosteroid for metastatic castration-resistant prostate cancer (mCRPC) and metastatic high-risk castration-sensitive prostate cancer (mCSPC). It should either be used following removal of the testicles or along with a gonadotropin-releasing hormone (GnRH) analog. It is taken by mouth.

Δ4-Abiraterone, also known as 17-(3-pyridyl)androsta-4,16-dien-3-one, is a steroidogenesis inhibitor and active metabolite of abiraterone acetate, a drug which is used in the treatment of prostate cancer and is itself a prodrug of abiraterone. D4A is formed from abiraterone by 3β-hydroxysteroid dehydrogenase/Δ5-4 isomerase (3β-HSD). It is said to be a more potent inhibitor of steroidogenesis than abiraterone, and is partially responsible for the activity of abiraterone acetate.

Alfatradiol, also known as 17α-estradiol and sold under the brand names Avicis, Avixis, Ell-Cranell Alpha, and Pantostin, is a weak estrogen and 5α-reductase inhibitor medication which is used topically in the treatment of pattern hair loss in men and women. It is a stereoisomer of the endogenous steroid hormone and estrogen 17β-estradiol.

Azelaic acid is an organic compound with the formula HOOC(CH2)7COOH. This saturated dicarboxylic acid exists as a white powder. It is found in wheat, rye, and barley. It is a precursor to diverse industrial products including polymers and plasticizers, as well as being a component of a number of hair and skin conditioners.

Bexlosteride is a potent and noncompetitive inhibitor of the enzyme 5α-reductase related to finasteride and dutasteride. It is selective for the type I isoform of the enzyme. It advanced to Phase III clinical trials, but development was halted at that stage, and it was never marketed.

Chlormadinone acetate (CMA), sold under the brand names Belara, Gynorelle, Lutéran, and Prostal among others, is a progestin and antiandrogen medication which is used in birth control pills to prevent pregnancy, as a component of menopausal hormone therapy, in the treatment of gynecological disorders, and in the treatment of androgen-dependent conditions like enlarged prostate and prostate cancer in men and acne and hirsutism in women. It is available both at a low dose in combination with an estrogen in birth control pills and, in a few countries like France and Japan, at low, moderate, and high doses alone for various indications. It is taken by mouth.

Cl-4AS-1 is a dual anabolic–androgenic steroid (AAS) and 5α-reductase inhibitor. It is a potent and selective full agonist of the androgen receptor (IC50 = 12 nM) and inhibitor of 5α-reductase types I and II (IC50 = 6 and 10 nM, respectively). Structurally, Cl-4AS-1 is a 4-azasteroid.

Desogestrel, sold under the brand names Cerazette and Mircette among many others, is a progestin medication which is used in birth control pills for women. It is also used in the treatment of menopausal symptoms in women. The medication is available and used alone or in combination with an estrogen. It is taken by mouth.

Dutasteride, sold under the brand name Avodart among others, is a medication primarily used to treat the symptoms of an enlarged prostate. A few months may be required before benefits occur. It is also used for scalp hair loss in men and as a part of hormone therapy in transgender women. It is taken by mouth.

Epitestosterone, or isotestosterone, also known as 17α-testosterone or as androst-4-en-17α-ol-3-one, is an endogenous steroid and an epimer of the androgen sex hormone testosterone. It is a weak competitive antagonist of the androgen receptor (AR) and a potent 5α-reductase inhibitor.

Epristeride, sold under the brand names Aipuliete and Chuanliu, is a medication which is used in the treatment of enlarged prostate in China. It is taken by mouth.

Etonogestrel is a progestin medication which is used as a means of birth control for women. It is available alone as an implant placed under the skin of the upper arm under the brand names Nexplanon and Implanon and in combination with ethinylestradiol, an estrogen, as a vaginal ring under the brand names NuvaRing and Circlet. Etonogestrel is effective as a means of birth control within 8 hours of insertion.

FCE 28260 is an azasteroidal 5α-reductase inhibitor which was developed for the treatment of benign prostatic hyperplasia and androgenic alopecia (pattern hair loss) in the 1990s but was never marketed. FCE 28260 has been found to inhibit rat and human 5α-reductase with half-maximal inhibitory concentrations (IC50) of 15 and 16 nM, respectively, while finasteride had values of 30 and 52 nM.

Finasteride, sold under the brand names Proscar and Propecia among others, is a medication used to treat hair loss and benign prostatic hyperplasia in men. It can also be used to treat excessive hair growth in women and as a part of hormone therapy for transgender women. It is taken by mouth.

Ganoderic acids are a class of closely related triterpenoids found in Ganoderma mushrooms. For thousands of years, the fruiting bodies of Ganoderma fungi have been used in traditional medicines in East Asia. Consequently, there have been efforts to identify the chemical constituents that may be responsible for the putative pharmacological effects. There are dozens of ganoderic acids that have been isolated and characterized, of which ganoderic acid A and ganoderic acid B are the most well characterized. Some ganoderic acids have been found to possess biological activities including hepatoprotection, anti-tumor effects, and 5-alpha reductase inhibition.

Gestodene, sold under the brand names Femodene and Minulet among others, is a progestin medication which is used in birth control pills for women. It is also used in menopausal hormone therapy. The medication is available almost exclusively in combination with an estrogen. It is taken by mouth.

Gestonorone caproate, also known as gestronol hexanoate or norhydroxyprogesterone caproate and sold under the brand names Depostat and Primostat, is a progestin medication which is used in the treatment of enlarged prostate and cancer of the endometrium. It is given by injection into muscle typically once a week.

Izonsteride is a selective inhibitor of the 5α-reductase, with dual effects on both the type I and type II isoforms of the enzyme. It was under development by Eli Lilly and Company and Fujisawa for the treatment of benign prostatic hyperplasia but was never marketed. Izonsteride may also be useful in the treatment of androgenic alopecia.

Lapisteride is a dual inhibitor of both isoforms of the enzyme 5α-reductase. It was under investigation for the treatment of benign prostatic hyperplasia (BPH) and androgenic alopecia, but was never marketed.

α-Linolenic acid (ALA),, is an n−3, or omega-3, essential fatty acid. ALA is found in many seeds and oils, including flaxseed, walnuts, chia, hemp, and many common vegetable oils.

MK-386, also known as 4,7β-dimethyl-4-aza-5α-cholestan-3-one, is a synthetic, steroidal 5α-reductase inhibitor which was first reported in 1994 and was never marketed. It is a 4-azasteroid and a potent and selective inhibitor of 5α-reductase type I and shows high selectivity for inhibition of human 5α-reductase type I over 5α-reductase type II, with IC50 values of 0.9 nM and 154 nM, respectively. The drug was under investigation for potential treatment of androgen-dependent conditions such as acne and pattern hair loss (androgenic alopecia or baldness), but was discontinued in early clinical trials due to observations of hepatotoxicity such as elevated liver enzymes.

MK-434 is a 5α-reductase inhibitor which was under development in the 1990s by Merck & Co for the treatment of a variety of androgen-dependent conditions including benign prostatic hyperplasia, prostate cancer, pattern hair loss, excessive hair growth, acne, and seborrhea but was never marketed. It acts as a selective inhibitor of 5α-reductase type 2. The drug has been found to decrease circulating dihydrotestosterone levels by a maximum of approximately 50% in men. MK-434 is a synthetic 4-azasteroid and is structurally related to other 5α-reductase inhibitors like finasteride.

Norethisterone, also known as norethindrone and sold under many brand names, is a progestin medication used in birth control pills, menopausal hormone therapy, and for the treatment of gynecological disorders. The medication is available in both low-dose and high-dose formulations and both alone and in combination with an estrogen. It is used by mouth or, as norethisterone enanthate, by injection into muscle.

Oleic acid is a fatty acid that occurs naturally in various animal and vegetable fats and oils. It is an odorless, colorless oil, although commercial samples may be yellowish. In chemical terms, oleic acid is classified as a monounsaturated omega-9 fatty acid, abbreviated with a lipid number of 18:1 cis-9. It has the formula CH3(CH2)7CH=CH(CH2)7COOH. The name derives from the Latin word oleum, which means oil. It is the most common fatty acid in nature. The salts and esters of oleic acid are called oleates.

Oxendolone, sold under the brand names Prostetin and Roxenone, is an antiandrogen and progestin medication which is used in Japan in the treatment of enlarged prostate. However, this use is controversial due to concerns about its clinical efficacy. Oxendolone is not effective by mouth and must be given by injection into muscle.

Progesterone (P4) is an endogenous steroid and progestogen sex hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species. It belongs to a group of steroid hormones called the progestogens, and is the major progestogen in the body. Progesterone has a variety of important functions in the body. It is also a crucial metabolic intermediate in the production of other endogenous steroids, including the sex hormones and the corticosteroids, and plays an important role in brain function as a neurosteroid.

Progesterone (P4) is a medication and naturally occurring steroid hormone. It is a progestogen and is used in combination with estrogens mainly in hormone therapy for menopausal symptoms and low sex hormone levels in women. It is also used in women to support pregnancy and fertility and to treat gynecological disorders. Progesterone can be taken by mouth, in through the vagina, and by injection into muscle or fat, among other routes. A progesterone vaginal ring and progesterone intrauterine device used for birth control also exist in some areas of the world.

β-Sitosterol (beta-sitosterol) is one of several phytosterols with chemical structures similar to that of cholesterol. It is a white, waxy powder with a characteristic odor, and is one of the components of the food additive E499. Phytosterols are hydrophobic and soluble in alcohols.

Spironolactone, sold under the brand name Aldactone among others, is a medication that is primarily used to treat fluid build-up due to heart failure, liver scarring, or kidney disease. It is also used in the treatment of high blood pressure, low blood potassium that does not improve with supplementation, early puberty in boys, acne and excessive hair growth in women, and as a part of transgender hormone therapy in transgender women. Spironolactone is taken by mouth.

TFM-4AS-1 is a dual selective androgen receptor modulator (SARM) and 5α-reductase inhibitor. It is a potent and selective partial agonist (Emax = 55%) of the androgen receptor (IC50 = 30 nM) and inhibitor of 5α-reductase types I and II (IC50 = 2 and 3 nM, respectively). TFM-4AS-1 shows tissue-selective androgenic effects; it promotes the accumulation of bone and muscle mass and has reduced effects in reproductive tissues and sebaceous glands. In addition, it does not promote growth of the prostate gland and it antagonizes the actions of dihydrotestosterone (DHT) in the seminal vesicles. Structurally, TFM-4AS-1 is a 4-azasteroid.

Turosteride (FCE-26,073) is a selective inhibitor of the enzyme 5α-reductase which was under investigation by GlaxoSmithKline for the treatment of benign prostatic hyperplasia (BPH), but was never marketed. Similarly to finasteride, turosteride is selective for the type II isoform of 5α-redcutase, with about 15-fold selectivity for it over type I isoform of the enzyme. In animal studies it has been shown to inhibit prostate size and retard tumor growth. It may also be useful for the treatment of acne and hair loss.

Valoneic acid dilactone is a hydrolysable tannin that can be isolated from the heartwood of Shorea laeviforia and in oaks species like the North American white oak and European red oak.