Anti-androgen medications are used to treat signs of hyperandrogenism, including skin and hair disorders like acne, seborrhoea, hirsutism, androgenic alopecia and hidradenitis suppurativa. Anti-androgen therapy may bock androgen receptor, reduce adrenal androgen production, reduce ovarian androgen production, reduce pituitary production of prolactin, inhibit 5-alpha reductase or reduce insulin resistance.
Current Anti-Androgen Therapies
Cyproterone acetate is a synthetically derived steroid that acts as a potent anti-androgen. It also possesses progestational properties and can be used to assist conception in subfertile females. Flutamide/nilutamide/bicalutamide are all non-steroidal, pure anti-androgens. Bicalutamide is the newest agent and has the fewest side effects. Finasteride/dutasteride are inhibitors of 5-alpha reductase, an enzyme that prevents the conversion of testosterone into the active form ihydrotestosterone (DHT). They are specific anti-androgens in that they only counteract the effects of testosterone and not other androgens. Spironolactone, a synthetic 17-spironolactone corticosteroid, is commonly used as a competitive aldosterone antagonist and acts as a potassium sparing diuretic. It used to treat low-renin hypertension, hypokalemia, and Conn’s syndrome. It has recognized anti-androgen effects. Ketoconazole is a derivative of imidazole that is used as a broad spectrum antifungal agent. Recognized effects are severe liver damage, but there is also an adrenolytic function. Ketoconazole reduces androgen production in the testes and the adrenal glands. It is a relatively weak anti-androgen, but is used with good effect in patients with Cushing’s syndrome.
Herbal Anti-Androgens
There is an ever-increasing demand for complementary therapies, or those that are perceived as being more natural. The presence of anti-androgenic chemicals in plants, herbs, and foodstuffs provides an alternative to modern synthetic pharmaceuticals. It is also commonly believed that there are fewer adverse effects of such alternative therapies. While this group of treatments may be slow to find favor and may not be used first line, it does at least appear to be more acceptable to patients because of its perceived more natural origins (29). Herbal remedies to block testosterone come in a variety of forms, including capsules, powders, teas and tinctures, or alcohol extracts.
Saw Palmetto (Serenoa repens)
Saw palmetto is a small palm tree native to eastern regions of the United States. Its extract is believed to be a highly effective anti-androgen as it contains phytoesterols. This has been the subject of a great deal of research with regards to the treatment of BPH (19, 20), androgenic alopecia (21), and PCOS (22). In the context of BPH, there have been 2 reasonably sized clinical trials that found that saw palmetto extract use showed no difference in comparison to placebo (23, 24). In meta-analyses, it has been shown to be safe and effective in mild to moderate BPH when compared to finasteride, tamsulosin, and placebo (25, 26).
Saw palmetto is likely safe for most people. Side effects are usually mild. Some people have reported dizziness, headache, nausea, vomiting, constipation, and diarrhea. Saw palmetto is likely unsafe when used during pregnancy or breast-feeding. Saw palmetto might decrease the effects of estrogen in the body, hence taking it along with birth control pills might decrease the effectiveness of birth control pills. It may slow blood clotting and increase the chances of bruising and bleeding. It should be stopped at least 2 weeks before a scheduled surgery. Established dosages for BPH is 160 mg twice daily or 320 mg once daily and for androgenic alopecia is 200 mg twice daily combined with beta-sitosterol 50 mg twice daily.
Reishi mushrooms (Ganoderma lucidum)
Red reishi, commonly known as LingZhi in Chinese, is a mushroom thought to have many health benefits. In a research study exploring the anti-androgenic effects of 20 species of mushrooms, reishi mushrooms had the strongest action in inhibiting testosterone (3). That study found that reishi mushrooms significantly reduced levels of 5-alpha reductase, preventing conversion of testosterone into the more potent DHT. Oral reishi extract is possibly safe for up to one year, but possibly unsafe when taken in a powdered form for more than one month as it might be hepatotoxic. Reishi can also cause other side effects including dryness of the mouth, throat, and nasal area along with itchiness, stomach upset, nosebleeds, dermatitis and bloody stools. There is not enough reliable information about the safety of taking reishi
mushroom if you are pregnant or breast feeding. Reishi mushroom might decrease blood pressure. High doses of reishi mushroom might increase the risk of bleeding in some people with certain bleeding disorders. Anticoagulant / antiplatelet drugs and antihypertensives interact with this medication. Stop using reishi at least 2 weeks before a scheduled surgery.
White Peony (Paeonia lactiflora)
Chinese peony is a widely grown ornamental plant with several hundred selected cultivars. Many of the cultivars have double flowers with the stamens modified into additional petals. White peony has been important in traditional Chinese medicine and has been shown to affect human androgen levels in vitro. In a 1991 study in the American Journal of Chinese Medicine Takeuchi et al described the effects of paeoniflorin, a compound found in white peony that inhibited the production of testosterone and promoted the activity of aromatase, which converts testosterone into estrogen (7). To date, there have been no studies that translate or explore the clinical effects. Peony has been used safely for up to 4 weeks. It can cause stomach upset and dermatitis. Peony is possibly unsafe when taken by mouth during pregnancy and lactation. Some developing research suggests that peony can cause uterine contractions. Peony may increase the risk of bleeding in some people with certain bleeding disorders. Anticoagulant / antiplatelet drugs and phenytoin (it may decrease the amount of phenytoin) interact with this medication. It has to be stopped at least 2 weeks before a scheduled surgery.
Chaste Tree (Vitex agnus-castus)
Chaste tree (or chasteberry) is a native of the Mediterranean region and is traditionally used to correct hormone imbalances. In ancient times, it was believed to be an anaphrodisiac, hence the name chaste tree. Clinical studies have demonstrated effectiveness of medications produced from extract of the plant in the management of premenstrual syndrome (PMS) and cyclical mastalgia (14). The mechanism of action is presumed to be via dopaminergic effects resulting in changes of prolactin secretion from the anterior pituitary. At low doses, it blocks the activation of D2 receptors in the brain by competitive binding, causing a slight increase in prolactin release. In higher concentrations, the binding activity is sufficient to reduce the release of prolactin (15). Reduction in prolactin levels affects FSH and estrogen levels in females and testosterone levels in men. There is as yet no information regarding its efficacy in endocrine disease states such as PCOS, however, one small-scale study has demonstrated this prolactin reducing effect in a group of healthy males, and the implication is that it could be of use in mild hyperprolactinemia (16, 17). One could also theorize that it could be refined for use as a male contraceptive, because testosterone reduction should reduce libido and sperm production. This topic is further explored in a review by Grant & Anawalt (18). Vitex agnus-castus is likely safe for most people when taken by mouth and applied to skin. Uncommon side effects include upset stomach, nausea, itching, rash, headaches, acne, trouble sleeping, and weight gain. Use during pregnancy or breast-feeding is possibly unsafe. It should be avoided in hormone-sensitive condition such as endometriosis; uterine fibroids; or cancer of the breast, uterus, or ovaries, during IVF procedures. It may decrease effectiveness of contraceptive pills. It has dopamine agonist like actions, hence might affect therapy for Parkinson’s disease, Schizophrenia or other psychotic disorders. Crude herb extracts are typically used in doses of 20-240 mg per day up to 1800 mg per day in 2-3 divided doses.
Green Tea (Camellia sinensis)
In addition to supporting the cardiovascular system and somewhat reducing the risk of cancer and type 2 diabetes (8), green tea may also have an important anti-ndrogen effect because it contains epigallocatechins, which inhibit the 5-alpha-reductase conversion of normal testosterone into DHT. As previously noted, this anti-androgen mechanism may help to reduce the risk of BPH, acne, and baldness. As yet, no randomized controlled trials of green tea for these androgen dependent conditions have been conducted. Green tea is likely safe for most adults when consumed in moderate amounts. Green tea extract is possibly safe for most people when taken by mouth or applied to the skin for a short time. In some people, green tea can cause stomach upset and constipation. Green tea extracts have been reported to cause hepatotoxicity in rare cases. Drinking more than five cups per day is possibly unsafe because of the caffeine. These side effects can range from ild to serious and include headache, nervousness, sleep problems, vomiting, diarrhea, irritability, irregular heartbeat, tremor, heartburn, dizziness, ringing in the ears, convulsions, and confusion. Green tea seems to reduce the absorption of iron from food. The fatal dose of caffeine in green tea is estimated to be 10-14 grams (150-200 mg per kilogram). During pregnancy and lactation about 2 cups per day is possibly safe. It may make anemia worse, the caffeine in it may affect nxiety disorders, bleeding disorders, heart conditions, diabetes, irritable bowel syndrome, glaucoma, blood pressure. Some reports have linked it to osteoporosis (caffeine increases amount of urinary calcium excretion) and hepatic diseases. It interacts with stimulant drugs, some quinolone antibiotics, birth control pills, antidepressants, nticoagulants, nicotine, theophylline, verapamil etc. Doses of green tea vary significantly, but usually range between 1-10 cups daily (three cups approximately rovides 240-320 mg of the active ingredients, polyphenols). To make tea, people typically use 1 teaspoon of tea leaves in 8 ounces boiling water.
Spearmint (Mentha spicata [Labiatae])
Spearmint, usually taken in the form of tea, has been thought for many years to have testosterone reducing properties. It is commonly used in Middle Eastern regions as an herbal remedy for hirsutism in females. Its anti-androgenic properties reduce the level of free testosterone in the blood, while leaving total testosterone and DHEAS unaffected, as demonstrated in a study from Turkey by Akdogan and colleagues, in which 21 females with hirsutism (12 with polycystic vary syndrome and 9 with idiopathic hirsutism) drank a cup of herbal tea steeped with M. spicata twice daily for 5 days during the follicular phases of their menstrual cycles. After treatment with the spearmint tea, the patients had significant decreases in free testosterone with increases in luteinizing hormone, follicle-stimulating hormone, and estradiol (9). There were no significant decreases in total testosterone or DHEAS levels. This study was followed by a randomized clinical trial by Grant (10), which showed that drinking spearmint tea twice daily for 30 days (vs. chamomile tea, which was used as a control) significantly reduced plasma levels of gonadotropins and androgens in patients with hirsutism associated with polycystic ovarian syndrome. There was a significant change in patients’ self-reported dermatology-related quality of life indices, but no objective change on the Ferriman-Gallwey scale. It is possible that sustained daily use of spearmint tea could result in further abatement of hirsutism. Avoid using in large amounts of spearmint during pregnancy and lactation. In theory, using large amounts of spearmint tea might worsen kidney and liver disorders.
Licorice (Glycyrrhiza glabra)
Licorice is a flavorful substance that has been used in food and medicinal remedies for thousands of years. It is also known as “sweet root,” licorice root contains a compound that is about 50 times sweeter than sugar. It has been used in both Eastern and Western medicine to treat a variety of illnesses ranging from the common cold to liver disease. Licorice affects the endocrine system because it contains isoflavones (phytoestrogens), which are chemicals found in plants that may mimic the effects of estrogen and relieve menopausal symptoms and menstrual disorders. Licorice may also reduce testosterone levels, which can contribute to hirsutism in women. A small clinical trial published in 2004 by Armanini and colleagues found that licorice root significantly decreases testosterone levels in healthy female volunteers. Women taking daily licorice root experienced a drop in total testosterone levels after 1 month and testosterone levels returned to normal after discontinuation. It is unclear as to whether licorice root affects free testosterone levels (4). The endocrine effect is thought to be due to phytoestrogens and other chemicals found in licorice root, including the steroid glycyrrhizin and glycyrrhetic acid, which also have a weak anti-androgen effect (5, 6). Consuming licorice daily in large doses for more than 4 weeks may cause side effects. In Pregnancy and breast-feeding it is not safe to take oral licorice. It can raise blood pressure, can decrease potassium levels in the blood, can cause water retention hence should be used with caution in heart disease, hypertension, hypertonia, hypokalemia, kidney disease. It should be avoided in hormone-sensitive conditions such as breast cancer, uterine cancer, ovarian cancer, endometriosis, or uterine fibroids. It may cause loss of libido in men and also worsen erectile dysfunction (ED). It could interact with many drugs like digoxin, OCPs, anticoagulants, ethacrynic acid, medications metabolized by the liver, antihypertensive drugs, corticosteroids, diuretics, etc.
Black Cohosh (Actaea racemosa)
Black cohosh (Actaea racemosa) is a plant of the buttercup family. Extracts from these plants are thought to possess analgesic, sedative, and anti-inflammatory properties. Black cohosh preparations (tinctures or tablets of dried materials) are used to treat symptoms associated with menopause, such as hot flashes, although the efficacy has been questioned (11). The inhibitory effects of black cohosh extracts (Cimicifuga syn. Actaea racemosa L.) on the proliferation of human breast ancer cells has been reported recently (12), and Hostsanka. et al (13) have examined the plant’s effects on prostate cancer, another androgen hormone-dependent, pidemiologically important tumor. In that study, the inhibitory effect of an isopropanolic extract of black cohosh (iCR) on cell growth in androgen-sensitive LNCaP and androgen-insensitive PC-3 and DU 145 prostate cancer cells was investigated. The authors found that regardless of hormone sensitivity, the growth of prostate cancer cells was significantly and dose- dependently down regulated by iCR. At a concentration between 37.1 and 62.7 μg/ml, iCR caused 50% cell growth inhibition in all cell lines after 72h. Increases in the levels of the apoptosis-related M30 antigen of approximately 1.8-, 5.9-, and 5.3-fold over untreated controls were observed in black cohosh- treated PC-3, DU 145, and LNCaP cells, respectively, with the induction of apoptosis being dose- and time-dependent. Black cohosh extract was therefore shown to kill both androgen-responsive and non- responsive human prostate cancer cells by induction of apoptosis and activation of caspases. This finding suggested that the cells’ hormone responsive status was not a major determinant of the response to the iCR, and indicated that the extract may represent a novel therapeutic approach for the treatment of prostate cancer. Black cohosh can cause some mild side effects such as stomach upset, cramping, headache, rash, a feeling of heaviness, vaginal spotting or bleeding, and weight gain. It is possibly unsafe when used during pregnancy or breast-feeding. There is some concern that black cohosh might worsen existing breast cancer. It should be avoided in hormone-sensitive conditions (like endometriosis, fibroids, ovarian cancer, uterine cancer, and others) and liver diseases. It might also increase the risk of blood clots in people with preexisting conditions like Protein S deficiency. It may interact with drugs like atorvastatin , cisplatin , medications metabolized by the liver, blood thinners, OCPs, etc.
References
1. Grant P. Polycystic ovary syndrome. Available
from:http://www.yourhormones.info/endocrine_conditions/polycystic_ovary_syndrome.aspx.
2. Lee OD. Think androgen deficiency. Am J Mens Health. 2011;5(5):377. doi: 10.1177/1557988311416633.[PubMed] [Cross Ref]
3. Fujita R, Liu J, Shimizu K, Konishi F, Noda K, Kumamoto S, et al. Anti-androgenic activities of Ganoderma lucidum. J Ethnopharmacol. 2005;102(1):107–12. doi: 10.1016/j.jep.2005.05.041. [PubMed] [Cross Ref]
4. Armanini D, Bonanni G, Palermo M. Reduction of serum testosterone in men by licorice. N Engl J Med.1999;341(15):1158. doi: 10.1056/NEJM199910073411515. [PubMed] [Cross Ref]
5. Somjen D, Knoll E, Vaya J, Stern N, Tamir S. Estrogen-like activity of licorice root constituents: glabridin and glabrene, in vascular tissues in vitro and in vivo. J Steroid Biochem Mol Biol. 2004;91(3):147–55. doi:10.1016/j.jsbmb.2004.04.003. [PubMed] [Cross Ref]
6. Tamir S, Eizenberg M, Somjen D, Izrael S, Vaya J. Estrogen-like activity of glabrene and other constituents isolated from licorice root. J Steroid Biochem Mol Biol. 2001;78(3):291–8. [PubMed]
7. Takeuchi T, Nishii O, Okamura T, Yaginuma T. Effect of paeoniflorin, glycyrrhizin and glycyrrhetic acid on ovarian androgen production. Am J Chin Med. 991;19(1):73–8. [PubMed]
8. Grant P, Dworakowska D. Tea and Diabetes: the laboratory and the real world. In: Preedy V, editor. Tea in Health & Disease Prevention. 1st ed. Elsevier Academic Press; 2012.
9. Akdogan M, Tamer MN, Cure E, Cure MC, Koroglu BK, Delibas N. Effect of spearmint (Mentha spicata Labiatae) teas on androgen levels in women with hirsutism. Phytother Res. 2007;21(5):444–7. doi: 10.1002/ptr.2074. [PubMed] [Cross Ref]
10. Grant P. Spearmint herbal tea has significant anti-androgen effects in polycystic ovarian syndrome. A randomized controlled trial. Phytother Res. 2010;24(2):186–8. doi: 10.1002/ptr.2900. [PubMed] [Cross Ref]
11. Newton KM, Reed SD, LaCroix AZ, Grothaus LC, Ehrlich K, Guiltinan J. Treatment of vasomotor symptoms of menopause with black cohosh, multibotanicals, soy, hormone therapy, or placebo: a randomized trial.Ann Intern Med. 2006;145(12):869–79. [PubMed]
12. Fang ZZ, Nian Y, Li W, Wu JJ, Ge GB, Dong PP, et al. Cycloartane triterpenoids from Cimicifuga yunnanensis induce apoptosis of breast cancer cells (MCF7) via p53-dependent mitochondrial signaling pathway.Phytother Res. 2011;25(1):17–24. doi:10.1002/ptr.3222. [PubMed] [Cross Ref]
13. Hostanska K, Nisslein T, Freudenstein J, Reichling J, Saller R. Apoptosis of human prostate androgen-dependent and – independent carcinoma cells induced by an isopropanolic extract of black cohosh involves degradation of cytokeratin (CK) 18. Anticancer Res. 2005;25(1A):139–47. [PubMed]
14. Daniele C, Thompson Coon J, Pittler MH, Ernst E. Vitex agnus castus: a systematic review of adverse events.Drug Saf. 2005;28(4):319–32. [PubMed]
15. Webster DE, He Y, Chen SN, Pauli GF, Farnsworth NR, Wang ZJ. Opioidergic mechanisms underlying the actions of Vitex agnus-castus L. Biochem Pharmacol. 2011;81(1):170–7. doi: 10.1016/j.bcp.2010.09.013.[PMC free article] [PubMed] [Cross Ref]
16. Azadbakht M, Baheddini A, Shorideh S, Naser Zadeh A. Effect of vitex agnus-castus l. leaf and fruit flavonoidal extracts on serum prolactin concentration. J Med Plants. 2005;4(16):56–61.
17. Merz PG, Gorkow C, Schrodter A, Rietbrock S, Sieder C, Loew D, et al. The effects of a special Agnus castus extract (BP1095E1) on prolactin secretion in healthy male subjects. Exp Clin Endocrinol Diabetes.1996;104(6):447–53. doi: 10.1055/s-0029-1211483. [PubMed] [Cross Ref]
18. Grant NN, Anawalt BD. Male hormonal contraception: an update on research progress. Treat Endocrinol.2002;1(4):217–27. [PubMed]
19. Boyle P, Robertson C, Lowe F, Roehrborn C. Updated meta-analysis of clinical trials of Serenoa repens extract in the treatment of symptomatic benign prostatic hyperplasia. BJU Int. 2004;93(6):751–6. doi: 10.1111/j.1464-410X.2003.04735.x. [PubMed] [Cross Ref]
20. Wilt T, Ishani A, Mac Donald R. Serenoa repens for benign prostatic hyperplasia. Cochrane Database SystRev. 2002;(3):CD001423 doi:10.1002/14651858.CD001423. [PubMed] [Cross Ref]
21. Murugusundram S. Serenoa Repens: Does It have Any Role in the Management of Androgenetic Alopecia? J Cutan Aesthet Surg. 2009;2(1):31–2. doi: 10.4103/0974-2077.53097. [PMC free article] [PubMed] [Cross Ref]
22. Liepa GU, Sengupta A, Karsies D. Polycystic ovary syndrome (PCOS) and other androgen excess-related conditions: can changes in dietary intake make a difference? Nutr Clin Pract. 2008;23(1):63–71. [PubMed]
23. Bent S, Kane C, Shinohara K, Neuhaus J, Hudes ES, Goldberg H, et al. Saw palmetto for benign prostatic hyperplasia. N Engl J Med. 2006;354(6):557–66. doi:10.1056/NEJMoa053085. [PubMed] [Cross Ref]
24. Dedhia RC, McVary KT. Phytotherapy for lower urinary tract symptoms secondary to benign prostatic hyperplasia. J Urol. 2008;179(6):2119–25. doi: 10.1016/j.juro.2008.01.094. [PubMed] [Cross Ref]
25. Geavlete P, Multescu R, Geavlete B. Serenoa repens extract in the treatment of benign prostatic hyperplasia.Ther Adv Urol. 2011;3(4):193–8. doi: 10.1177/1756287211418725. [PMC free article] [PubMed] [Cross Ref]
26. Sosnowska J, Balslev H. American palm ethnomedicine: a meta-analysis. J Ethnobiol Ethnomed. 2009;5:43. doi:
10.1186/1746-4269-5-43. [PMC free article] [PubMed] [Cross Ref]
27. Tacklind J, MacDonald R, Rutks I, Wilt TJ. Serenoa repens for benign prostatic hyperplasia. Cochrane Database Syst Rev. 2009;(2):CD001423 doi: 10.1002/14651858.CD001423.pub2. [PMC free article][PubMed] [Cross Ref]
28. Grant P, Ramasamy S. The Pituitary Gland & Erectile Dysfunction. In: Grant P, editor. Erectile Dysfunction: Causes, Risk Factors & Management. Nova Publishers; 2012.
29. Magin PJ, Adams J, Heading GS, Pond DC, Smith W. Complementary and alternative medicine therapies in acne, psoriasis, and atopic eczema: results of a qualitative study of patients’ experiences and perceptions. J Altern Complement Med. 2006;12(5):451–7. doi: 10.1089/acm.2006.12.451. [PubMed] [Cross Ref]
