Flutamide

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Flutamide is a nonsteroidal antiandrogen. It has been administered to transgender women in a number of studies/publications.[1][2][3] It is used for the treatment of hirsutism at dosages ranging from 62.5 mg/day to 500 mg/day and both alone and in combination with oral contraceptives.[4] The overall quality of the evidence for hirsutism is regarded as moderate.[5] Flutamide may be more effective than other antiandrogens like spironolactone, cyproterone acetate, and finasteride for this indication.[5]

Flutamide has a relatively high risk of elevated liver enzymes and hepatotoxicity and has been associated with many cases of severe hepatotoxicity, including deaths.[6][7][8][9][10] The risk is substantially higher than with other nonsteroidal antiandrogens like bicalutamide and nilutamide.[9] Because of its high risk of hepatotoxicity, flutamide has been recommended against for the treatment of androgen-dependent conditions like acne and hirsutism in cisgender women.[7][5][11]

Low or ultra-low doses of flutamide have been reported to lack hepatotoxicity.[12][13][14][15] However, other studies have had very different findings.[16][17][18] In addition, many case reports of severe hepatotoxicity at low or ultra-low doses exist, including deaths.[19][8][20][21]

Studies

Cisgender women

It has been evaluated in the treatment of androgen-dependent conditions like acne, seborrhea, hirsutism, alopecia, and hyperandrogenism (e.g., due to polycystic ovary syndrome) in cisgender women in over 100 clinical studies.[22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65][66][67][68][69][70][71][72][73][74][75][76][77][78][79][80][81][82][83][84][85][86][87][88][89][90][91][92][93][94][95][96][97][98][99][12][100][101][102][13][14][103][104][105][106][107][108][15][109][110][111][112][113][16][114][115][116][117][118][18][119][120]

References

  1. ↑ Giusti, M., Falivene, M. R., Carraro, A., Cuttica, C. M., Valenti, S., & Giordano, G. (1995). The effect of non-steroidal antiandrogen flutamide on luteinizing hormone pulsatile secretion in male-to-female transsexual subjects. Journal of endocrinological investigation, 18(6), 420-426.
  2. ↑ Falivene, M. R., Cuttica, C. M., Valenti, S., & Guido, R. (1995). Androgen receptor blockade with flutamide increases GH secretion in male-to-female transsexuals. Journal of Endocrinological Investigation, 18, 56-56.
  3. ↑ Valenti, S., Fazzuoli, L., & Giusti, M. (2003). Circulating nitric oxide levels increase after anti-androgen treatment in male-to-female transsexuals. Journal of endocrinological investigation, 26(6), 522-526.
  4. ↑ Generali, J. A., & Cada, D. J. (2014). Flutamide: hirsutism in women. Hospital pharmacy, 49(6), 517.
  5. ↑ 5.0 5.1 5.2 Somani, N., & Turvy, D. (2014). Hirsutism: an evidence-based treatment update. American journal of clinical dermatology, 15(3), 247-266.
  6. ↑ Wysowski, D. K., & Fourcroy, J. L. (1996). Flutamide hepatotoxicity. The Journal of urology, 155(1), 209-212.
  7. ↑ 7.0 7.1 Giorgetti, R., di Muzio, M., Giorgetti, A., Girolami, D., Borgia, L., & Tagliabracci, A. (2017). Flutamide-induced hepatotoxicity: ethical and scientific issues. Eur Rev Med Pharmacol Sci, 21(1 Suppl), 69-77.
  8. ↑ 8.0 8.1 Brahm, J., Brahm, M., Segovia, R., Latorre, R., Zapata, R., Poniachik, J., ... & Contreras, L. (2011). Acute and fulminant hepatitis induced by flutamide: case series report and review of the literature. Annals of hepatology, 10(1), 93-98.
  9. ↑ 9.0 9.1 Thole, Z., Manso, G., Salgueiro, E., Revuelta, P., & Hidalgo, A. (2004). Hepatotoxicity induced by antiandrogens: a review of the literature. Urologia internationalis, 73(4), 289-295.
  10. ↑ García, C. M., Andrade, R. J., Lucena, M. I., Sánchez, M. H., Fernandez, M. C., Ferrer, T., ... & Montero, J. L. (2001). Flutamide-induced hepatotoxicity: report of a case series. Revista española de enfermedades digestivas: organo oficial de la Sociedad Española de Patología Digestiva, 93(7), 423-432.
  11. ↑ Schmidt, T. H., & Shinkai, K. (2015). Evidence-based approach to cutaneous hyperandrogenism in women. Journal of the American Academy of Dermatology, 73(4), 672-690.
  12. ↑ 12.0 12.1 Ibanez, L., Jaramillo, A., Ferrer, A., & de Zegher, F. (2005). Absence of hepatotoxicity after long-term, low-dose flutamide in hyperandrogenic girls and young women. Human Reproduction, 20(7), 1833-1836.
  13. ↑ 13.0 13.1 Legro, R. S. (2006). Long-term, low-dose flutamide does not cause hepatotoxicity in hyperandrogenic women. Nature Clinical Practice Endocrinology & Metabolism, 2(4), 188-189.
  14. ↑ 14.0 14.1 Calaf, J., Lopez, E., Millet, A., Alcaniz, J., Fortuny, A., Vidal, O., ... & Espinos, J. J. (2007). Long-term efficacy and tolerability of flutamide combined with oral contraception in moderate to severe hirsutism: a 12-month, double-blind, parallel clinical trial. The Journal of Clinical Endocrinology & Metabolism, 92(9), 3446-3452.
  15. ↑ 15.0 15.1 Dikensoy, E., Balat, O., Pence, S., Akcali, C., & Cicek, H. (2009). The risk of hepatotoxicity during long-term and low-dose flutamide treatment in hirsutism. Archives of gynecology and obstetrics, 279(3), 321-327.
  16. ↑ 16.0 16.1 Paradisi, R., Fabbri, R., Porcu, E., Battaglia, C., Seracchioli, R., & Venturoli, S. (2011). Retrospective, observational study on the effects and tolerability of flutamide in a large population of patients with acne and seborrhea over a 15-year period. Gynecological Endocrinology, 27(10), 823-829.
  17. ↑ Bruni, V., Peruzzi, E., Dei, M., Nannini, S., Seravalli, V., Sisti, G., & Fambrini, M. (2012). Hepatotoxicity with low-and ultralow-dose flutamide: a surveillance study on 203 hyperandrogenic young females. Fertility and sterility, 98(4), 1047-1052.
  18. ↑ 18.0 18.1 Castelo-Branco, C., Hernández-Angeles, C., Alvarez-Olivares, L., & Balasch, J. (2016). Long-term satisfaction and tolerability with low-dose flutamide: a 20-year surveillance study on 120 hyperandrogenic women. Gynecological Endocrinology, 32(9), 723-727.
  19. ↑ Castelo-Branco, C., & Del Pino, M. (2009). Hepatotoxicity during low-dose flutamide treatment for hirsutism. Gynecological Endocrinology, 25(7), 419-422.
  20. ↑ Osculati, A., & Castiglioni, C. (2006). Fatal liver complications with flutamide. The Lancet, 367(9517), 1140-1141.
  21. ↑ Amorim, M. D. F. D. D., Amorim, W. P. D. D., Duques, P., Amorim, P. D. D., & Vasconcelos, J. R. D. (2005). Flutamide-induced hepatotoxicity during treatment of acne: a case report. Anais Brasileiros de Dermatologia, 80(4), 381-384.
  22. ↑ Lyons, F., & Shuster, S. (1982). Sex difference in response of the human sebaceous gland to topical flutamide. British Journal of Dermatology, 107(6), 697-699.
  23. ↑ Cusan, L., Dupont, A., Bélanger, A., Tremblay, R. R., Manhes, G., & Labrie, F. (1990). Treatment of hirsutism with the pure antiandrogen flutamide. Journal of the American Academy of Dermatology, 23(3), 462-469.
  24. ↑ Motta, T., Maggi, G., Perra, M., Azzolari, E., Casazza, S., & D'Alberton, A. (1991). Flutamide in the treatment of hirsutism. International Journal of Gynecology & Obstetrics, 36(2), 155-157.
  25. ↑ Marcondes, J. A., Minnani, S. L., Luthold, W. W., Wajchenberg, B. L., Samojlik, E., & Kirschner, M. A. (1992). Treatment of hirsutism in women with flutamide. Fertility and sterility, 57(3), 543-547.
  26. ↑ Fruzzetti, F., De Lorenzo, D., Ricci, C., & Fioretti, P. (1993). Clinical and endocrine effects of flutamide in hyperandrogenic women. Fertility and sterility, 60(5), 806-813.
  27. ↑ Couzinet, B., Pholsena, M., Young, J., & Schaison, G. (1993). The impact of a pure anti‐androgen (flutamide) on LH, FSH, androgens and clinical status in idiopathic hirsutism. Clinical endocrinology, 39(2), 157-162.
  28. ↑ Sir-Petermann, T., Rabenbauer, B., & Wildt, L. (1993). Endocrinology: The effect of flutamide on pulsatile gonadotrophin secretion in hyperandrogenaemic women. Human Reproduction, 8(11), 1807-1812.
  29. ↑ Cusan, L., Dupont, A., Cossette, M., & Labrie, F. (1993). Flutamide in the treatment of female androgenic alopecia. Can J Dermatol, 5, 421-427.
  30. ↑ Tremblay, R. R. (1993). Compromise in the treatment of hirsutism with flutamide. In vivo (Athens, Greece), 7(6A), 549-551.
  31. ↑ Grimaldi, F., Proto, G., & Bertolissi, F. (1993). Flutamide—effects and side effects. Fertility and sterility, 59(4), 937.
  32. ↑ Marugo, M., Bernasconi, D., Meozzi, M., Del Monte, P., Zino, V., Primarolo, P., & Badaracco, B. (1994). The use of flutamide in the management of hirsutism. Journal of endocrinological investigation, 17(3), 195-199.
  33. ↑ Erenus, M., Gürbüz, O., Durmuşoğlu, F., Ergun, T., & Pekin, S. (1993). The efficacy of flutamide in the treatment of hirsutism. Marmara Medical Journal, 6(1).
  34. ↑ Cesur, V., Kamel, N., Uysal, A. R., Erdogan, G., & Baskal, N. (1994). The use of antiandrogen flutamide in the treatment of hirsutism. Endocrine journal, 41(5), 573-577.
  35. ↑ Ciotta, L., Cianci, A., Marletta, E., Pisana, L., & Palumbo, G. (1994). Treatment of hirsutism with flutamide and a low-dosage oral contraceptive in polycystic ovarian disease patients. Fertility and sterility, 62(6), 1129-1135.
  36. ↑ Cusan, L., Dupont, A., Gomez, J. L., Tremblay, R. R., & Labrie, F. (1994). Comparison of flutamide and spironolactone in the treatment of hirsutism: a randomized controlled trial. Fertility and sterility, 61(2), 281-287.
  37. ↑ Erenus, M., Gürbüz, O., Durmuşoğlu, F., Demirçay, Z., & Pekin, S. (1994). Comparison of the efficacy of spironolactone versus flutamide in the treatment of hirsutism. Fertility and sterility, 61(4), 613-616.
  38. ↑ Howe, R. S., Chow, R. P., & Stevens, C. L. (1994). Use of flutamide for self-induced androgen excess. A case report. The Journal of reproductive medicine, 39(10), 838-840.
  39. ↑ Motta, T., Maggi, G., & D’Alberton, A. (1994). Flutamide and hirsutism. Journal of endocrinological investigation, 17(8), 673-673.
  40. ↑ Dodin, S., Faure, N., Cédrin, I., Mechain, C., Turcot‐Lemay, L., Guy, J., & Lemay, A. (1995). Clinical efficacy and safety of low‐dose flutamide alone and combined with an oral contraceptive for the treatment of idiopathic hirsutism. Clinical endocrinology, 43(5), 575-582.
  41. ↑ Moghetti, P., Castello, R., Negri, C., Tosi, F., Magnani, C. M., Fontanarosa, M. C., ... & Muggeo, M. (1995). Flutamide in the treatment of hirsutism: long-term clinical effects, endocrine changes, and androgen receptor behavior. Fertility and sterility, 64(3), 511-517.
  42. ↑ Pucci, E., Genazzani, A. D., Monzani, F., Lippi, F., Angelini, F., Gargani, M., ... & Genazzani, A. R. (1995). Prolonged treatment of hirsutism with flutamide alone in patients affected by polycystic ovary syndrome. Gynecological Endocrinology, 9(3), 221-228.
  43. ↑ Diamanti-Kandarakis, E., Mitrakou, A., Hennes, M. M., Platanissiotis, D., Kaklas, N., Spina, J., ... & Raptis, S. (1995). Insulin sensitivity and antiandrogenic therapy in women with polycystic ovary syndrome. Metabolism, 44(4), 525-531.
  44. ↑ Müderris, İ. İ., Bayram, F., Şahin, Y., Keleştimur, F., Tutuş, A., & Ayata, D. (1996). The efficacy of 250mg/day flutamide in the treatment of patients with hirsutism. Fertility and sterility, 66(2), 220-222.
  45. ↑ Grigoriou, O., Papadias, C., Konidaris, S., Antoniou, G., Kavakitsos, P., & Giannikos, L. (1996). Comparison of flutamide and cyproterone acetate in the treatment of hirsutism: a randomized controlled trial. Gynecological Endocrinology, 10(2), 119-123.
  46. ↑ Moghetti, P. A. O. L. O., Tosi, F. L. A. V. I. A., Castello, R. O. B. E. R. T. O., Magnani, C. M., Negri, C. A. R. L. O., Brun, E., ... & Muggeo, M. I. C. H. E. L. E. (1996). The insulin resistance in women with hyperandrogenism is partially reversed by antiandrogen treatment: evidence that androgens impair insulin action in women. The Journal of Clinical Endocrinology & Metabolism, 81(3), 952-960.
  47. ↑ Müderris, İ. I., Bayram, F., Şahin, Y., & Kelestimur, F. (1997). A comparison between two doses of flutamide (250 mg/d and 500 mg/d) in the treatment of hirsutism. Fertility and sterility, 68(4), 644-647.
  48. ↑ Falsetti, L., Fusco, D. D., Eleftheriou, G., & Rosina, B. (1997). Treatment of hirsutism by finasteride and flutamide in women with polycystic ovary syndrome. Gynecological Endocrinology, 11(4), 251-257.
  49. ↑ Bertelloni, S., Baroncelli, G. I., Sorrentino, M. C., Costa, S., Battini, R., & Saggese, G. (1997). Androgen-receptor blockade does not impair bone mineral density in adolescent females. Calcified tissue international, 61(1), 1-5.
  50. ↑ Zemtsov, A., & Wilson, L. (1997). Successful treatment of hirsutism in HAIR-AN syndrome using flutamide, spironolactone, and birth control therapy. Archives of dermatology, 133(4), 431-433.
  51. ↑ Gwiezdzinski, Z., Urbanowski, S., & Szelemej, R. (1997). 2.5% solution of flutamide (a nonsteroidal antiandrogen) in the topical treatment of acne vulgaris. A double-blind randomized study. Journal of dermatological treatment, 8(2), 75-78.
  52. ↑ Falsetti, L., De Fusco, D., & Rosina, B. (1997). Finasteride and flutamide in the treatment of hirsutism. Minerva ginecologica, 49(10), 463-468.
  53. ↑ Kaya, F., Seçkin, D., & Turanlı, A. Y. (1997). Comparison of the efficacies of cyproterone acetate, spironolactone and flutamide in the treatment of hirsutism. Journal of the European Academy of Dermatology and Venereology, 1001(9), S150.
  54. ↑ De Leo, V., Lanzetta, D., D’Antona, D., la Marca, A., & Morgante, G. (1998). Hormonal effects of flutamide in young women with polycystic ovary syndrome. The Journal of Clinical Endocrinology & Metabolism, 83(1), 99-102.
  55. ↑ Diamanti-Kandarakis, E., Mitrakou, A., Raptis, S., Tolis, G., & Duleba, A. J. (1998). The effect of a pure antiandrogen receptor blocker, flutamide, on the lipid profile in the polycystic ovary syndrome. The Journal of Clinical Endocrinology & Metabolism, 83(8), 2699-2705.
  56. ↑ De Leo, V., La Marca, A., Lanzetta, D., Cariello, P. L., D'antona, D., & Morgante, G. (1998). Effects of flutamide on pituitary and adrenal responsiveness to corticotrophin releasing factor (CRF). Clinical endocrinology, 49(1), 85-89.
  57. ↑ Somani, V. K., Sucharita, V., Sharma, V. K., & Sita, V. N. V. L. (1998). The efficacy of flutamide, an antiandrogen in idiopathic hirsutism. Indian Journal of Dermatology, Venereology, and Leprology, 64(1), 17.
  58. ↑ Müderris, I. I., & Bayram, F. (1999). Clinical efficacy of lower dose flutamide 125 mg/day in the treatment of hirsutism. Journal of endocrinological investigation, 22(3), 165-168.
  59. ↑ Fruzzetti, F., Bersi, C., Parrini, D., Ricci, C., & Genazzani, A. R. (1999). Treatment of hirsutism: comparisons between different antiandrogens with central and peripheral effects. Fertility and sterility, 71(3), 445-451.
  60. ↑ Venturoli, S., Marescalchi, O., Colombo, F. M., Macrelli, S., Ravaioli, B., Bagnoli, A., ... & Flamigni, C. (1999). A prospective randomized trial comparing low dose flutamide, finasteride, ketoconazole, and cyproterone acetate-estrogen regimens in the treatment of hirsutism. The Journal of Clinical Endocrinology & Metabolism, 84(4), 1304-1310.
  61. ↑ Paoletti, A. M., Cagnacci, A., Orrù, M., Ajossa, S., Guerriero, S., & Melis, G. B. (1999). Treatment with flutamide improves hyperinsulinemia in women with idiopathic hirsutism. Fertility and sterility, 72(3), 448-453.
  62. ↑ Falsetti, L., Gambera, A., Legrenzi, L., Iacobello, C., & Bugari, G. (1999). Comparison of finasteride versus flutamide in the treatment of hirsutism. European journal of endocrinology, 141(4), 361-367.
  63. ↑ Falsetti, L., & Gambera, A. (1999). Comparison of finasteride and flutamide in the treatment of idiopathic hirsutism. Fertility and sterility, 72(1), 41-46.
  64. ↑ Wang, H. S., Wang, T. H., & Soong, Y. K. (1999). Low dose flutamide in the treatment of acne vulgaris in women with or without oligomenorrhea or amenorrhea. Changgeng Yi Xue Za Zhi, 22(3), 423-432.
  65. ↑ Pazos, F., Escobar-Morreale, H. F., Balsa, J., Sancho, J. M., & Varela, C. (1999). Prospective randomized study comparing the long-acting gonadotropin-releasing hormone agonist triptorelin, flutamide, and cyproterone acetate, used in combination with an oral contraceptive, in the treatment of hirsutism. Fertility and sterility, 71(1), 122-128.
  66. ↑ Moghetti, P., Castello, R., Zamberlan, N., Rossini, M., Gatti, D., Negri, C., ... & Adami, S. (1999). Spironolactone, but not flutamide, administration prevents bone loss in hyperandrogenic women treated with gonadotropin-releasing hormone agonist. The Journal of Clinical Endocrinology & Metabolism, 84(4), 1250-1254.
  67. ↑ Yücelten, D., Erenus, M., Gürbüz, O., & Durmuşoğlu, F. (1999). Recurrence rate of hirsutism after 3 different antiandrogen therapies. Journal of the American Academy of Dermatology, 41(1), 64-68.
  68. ↑ Dalton, M. (1999). Flutamide was more effective than finasteride for idiopathic hirsutism. Evidence-based Obstetrics & Gynecology, 1(4), 112.
  69. ↑ BAHCECİ, M., TUZCU, A., DURSUN, M., ERTEM, M., & YÜKSELEN, V. (1999). The Effects of Flutamide on Lipid Profile, Insulin Sensitivity, Hirsutism and Gonadotropins in Women With Polycystic Ovary Syndrome. Turkish Journal of Medical Sciences, 29(6), 677-682.
  70. ↑ Müderris, I. I., Bayram, F., & Güven, M. (2000). A prospective, randomized trial comparing flutamide (250 mg/d) and finasteride (5 mg/d) in the treatment of hirsutism. Fertility and sterility, 73(5), 984-987.
  71. ↑ Moghetti, P., Tosi, F., Tosti, A., Negri, C., Misciali, C., Perrone, F., ... & Castello, R. (2000). Comparison of spironolactone, flutamide, and finasteride efficacy in the treatment of hirsutism: a randomized, double blind, placebo-controlled trial. The Journal of Clinical Endocrinology & Metabolism, 85(1), 89-94.
  72. ↑ Eagleson, C. A., Gingrich, M. B., Pastor, C. L., Arora, T. K., Burt, C. M., Evans, W. S., & Marshall, J. C. (2000). Polycystic ovarian syndrome: evidence that flutamide restores sensitivity of the gonadotropin-releasing hormone pulse generator to inhibition by estradiol and progesterone. The Journal of Clinical Endocrinology & Metabolism, 85(11), 4047-4052.
  73. ↑ Leo, V. D., Fulghesu, A. M., La Marca, A., Morgante, G., Pasqui, L., Talluri, B., ... & Caruso, A. (2000). Hormonal and clinical effects of GnRH agonist alone, or in combination with a combined oral contraceptive or flutamide in women with severe hirsutism. Gynecological endocrinology, 14(6), 411-416.
  74. ↑ Ibanez, L., Potau, N., Marcos, M. V., & de Zegher, F. (2000). Treatment of hirsutism, hyperandrogenism, oligomenorrhea, dyslipidemia, and hyperinsulinism in nonobese, adolescent girls: effect of flutamide. The Journal of Clinical Endocrinology & Metabolism, 85(9), 3251-3255.
  75. ↑ Müderris, I. I., Bayram, F., & Güven, M. (2000). Treatment of hirsutism with lowest-dose flutamide (62.5 mg/day). Gynecological endocrinology, 14(1), 38-41.
  76. ↑ Negri, C., Tosi, F., Dorizzi, R., Fortunato, A., Spiazzi, G. G., Muggeo, M., ... & Moghetti, P. (2000). Antiandrogen drugs lower serum prostate-specific antigen (PSA) levels in hirsute subjects: evidence that serum PSA is a marker of androgen action in women. The Journal of Clinical Endocrinology & Metabolism, 85(1), 81-84.
  77. ↑ De, L. (2000). V, Fulghesu AM, la MA, Morgante G, Pasqui L, Talluri B, et al. Hormonal and clinical effects of GnRH agonist alone, or in combination with a combined oral contraceptive or flutamide in women with severe hirsutism. Gynecol Endocrinol, 14(6), 411-6.
  78. ↑ Venturoli, S., Bagnoli, A., Colombo, F. M., Ravaioli, B., Vianello, F., & Mancini, F. (2000). The efficacy of a 125 mg/day regimen of flutamide in maintaining the clinical results in hirsute women. International Journal of Gynecology & Obstetrics, 70, C51.
  79. ↑ Venturoli, S., Paradisi, R., Bagnoli, A., Colombo, F. M., Ravaioli, B., Vianello, F., ... & Seracchioli, R. (2001). Low-dose flutamide (125 mg/day) as maintenance therapy in the treatment of hirsutism. Hormone Research in Paediatrics, 56(1-2), 25-31.
  80. ↑ László, F. A., Toth, S., Kocsis, J., Pávó, I., & Szécsi, M. (2001). Testosterone-secreting gonadotropin-responsive adrenal adenoma and its treatment with the antiandrogen flutamide. Journal of endocrinological investigation, 24(8), 622-627.
  81. ↑ Carmina, E., & Lobo, R. A. (2002). A comparison of the relative efficacy of antiandrogens for the treatment of acne in hyperandrogenic women. Clinical endocrinology, 57(2), 231-234.
  82. ↑ Ajossa, S., Guerriero, S., Paoletti, A. M., Orrù, M., & Melis, G. B. (2002). The antiandrogenic effect of flutamide improves uterine perfusion in women with polycystic ovary syndrome. Fertility and sterility, 77(6), 1136-1140.
  83. ↑ Taner, C., İnal, M., Basoglu, Ö., Onoglu, A., Karanfil, C., Tınar, Ş., & İspahi, Ç. (2002). Comparison of the clinical efficacy and safety of flutamide versus flutamide plus an oral contraceptive in the treatment of hirsutism. Gynecologic and obstetric investigation, 54(2), 105-108.
  84. ↑ Ibanez, L., Valls, C., Ferrer, A., Ong, K., Dunger, D. B., & de Zegher, F. (2002). Additive effects of insulin-sensitizing and anti-androgen treatment in young, nonobese women with hyperinsulinism, hyperandrogenism, dyslipidemia, and anovulation. The Journal of Clinical Endocrinology & Metabolism, 87(6), 2870-2874.
  85. ↑ Ibanez, L., & de Zegher, F. (2003). Low‐dose combination of flutamide, metformin and an oral contraceptive for non‐obese, young women with polycystic ovary syndrome. Human Reproduction, 18(1), 57-60.
  86. ↑ Ibanez, L., & de Zegher, F. (2003). Flutamide-metformin therapy to reduce fat mass in hyperinsulinemic ovarian hyperandrogenism: effects in adolescents and in women on third-generation oral contraception. The Journal of Clinical Endocrinology & Metabolism, 88(10), 4720-4724.
  87. ↑ Sahin, I., Serter, R., Karakurt, F., Demirbas, B., Guler, S., Culha, C., ... & Aral, Y. (2003). Leptin levels increase during flutamide therapy in women with polycystic ovary syndrome. Hormone Research in Paediatrics, 60(5), 232-236.
  88. ↑ Ibanez, L., Ong, K., Ferrer, A., Amin, R., Dunger, D., & de Zegher, F. (2003). Low-dose flutamide-metformin therapy reverses insulin resistance and reduces fat mass in nonobese adolescents with ovarian hyperandrogenism. The Journal of Clinical Endocrinology & Metabolism, 88(6), 2600-2606.
  89. ↑ Gambineri, A., Pelusi, C., Genghini, S., Morselli‐Labate, A. M., Cacciari, M., Pagotto, U., & Pasquali, R. (2004). Effect of flutamide and metformin administered alone or in combination in dieting obese women with polycystic ovary syndrome. Clinical endocrinology, 60(2), 241-249.
  90. ↑ Ibanez, L., & de Zegher, F. (2004). Ethinylestradiol-drospirenone, flutamide-metformin, or both for adolescents and women with hyperinsulinemic hyperandrogenism: opposite effects on adipocytokines and body adiposity. The Journal of Clinical Endocrinology & Metabolism, 89(4), 1592-1597.
  91. ↑ Sahin, I., Serter, R., Karakurt, F., Demirbas, B., Culha, C., Taskapan, C., ... & Aral, Y. (2004). Metformin versus flutamide in the treatment of metabolic consequences of non-obese young women with polycystic ovary syndrome: a randomized prospective study. Gynecological endocrinology, 19(3), 115-124.
  92. ↑ Bahceci, M., Bilge, M., Tuzcu, A., Tuzcu, S., & Bahceci, S. (2004). Serum prostate specific antigen levels in women with polycystic ovary syndrome and the effect of flutamide+ desogestrel/ethinyl estradiol combination. Journal of endocrinological investigation, 27(4), 353-356.
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  95. ↑ Ibanez, L., & de Zegher, F. (2004). Flutamide–metformin plus an oral contraceptive (OC) for young women with polycystic ovary syndrome: switch from third-to fourth-generation OC reduces body adiposity. Human Reproduction, 19(8), 1725-1727.
  96. ↑ Devoto, E., & Aravena, L. (2004). Effectiveness of flutamide alone or combined with oral contraceptives in the treatment of hirsutism in women. Revista medica de Chile, 132(7), 845-852.
  97. ↑ Inal, M. M., Yildirim, Y., & Taner, C. E. (2005). Comparison of the clinical efficacy of flutamide and spironolactone plus Diane 35 in the treatment of idiopathic hirsutism: a randomized controlled study. Fertility and sterility, 84(6), 1693-1697.
  98. ↑ Ibanez, L., Jaramillo, A. M., Ferrer, A., & de Zegher, F. (2005). High neutrophil count in girls and women with hyperinsulinaemic hyperandrogenism: normalization with metformin and flutamide overcomes the aggravation by oral contraception. Human Reproduction, 20(9), 2457-2462.
  99. ↑ Ibanez, L., & Zegher, F. D. (2005). Flutamide-metformin plus ethinylestradiol-drospirenone for lipolysis and antiatherogenesis in young women with ovarian hyperandrogenism: the key role of metformin at the start and after more than one year of therapy. The Journal of Clinical Endocrinology & Metabolism, 90(1), 39-43.
  100. ↑ Hero, M., Jänne, O. A., Näntö-Salonen, K., Dunkel, L., & Raivio, T. (2005). Circulating antiandrogenic activity in children with congenital adrenal hyperplasia during peroral flutamide treatment. The Journal of Clinical Endocrinology & Metabolism, 90(9), 5141-5145.
  101. ↑ Evans, J. (2005). Low-Dose Flutamide May Help Treat Female Refractory Acne. Family Practice News, 35(17), 42-42.
  102. ↑ Gambineri, A., Patton, L., Vaccina, A., Cacciari, M., Morselli-Labate, A. M., Cavazza, C., ... & Pasquali, R. (2006). Treatment with flutamide, metformin, and their combination added to a hypocaloric diet in overweight-obese women with polycystic ovary syndrome: a randomized, 12-month, placebo-controlled study. The Journal of Clinical Endocrinology & Metabolism, 91(10), 3970-3980.
  103. ↑ Ibanez, L., López-Bermejo, A., del Rio, L., Enríquez, G., Valls, C., & de Zegher, F. (2007). Combined low-dose pioglitazone, flutamide, and metformin for women with androgen excess. The Journal of Clinical Endocrinology & Metabolism, 92(5), 1710-1714.
  104. ↑ Karakurt, F., Sahin, I., Güler, S., Demirbas, B., Culha, C., Serter, R., ... & Bavbek, N. (2008). Comparison of the clinical efficacy of flutamide and spironolactone plus ethinyloestradiol/cyproterone acetate in the treatment of hirsutism: a randomised controlled study. Advances in therapy, 25(4), 321-328.
  105. ↑ Ibanez, L., López‐Bermejo, A., Díaz, M., Enríquez, G., Valls, C., & De Zegher, F. (2008). Pioglitazone (7· 5 mg/day) added to flutamide–metformin in women with androgen excess: additional increments of visfatin and high molecular weight adiponectin. Clinical endocrinology, 68(2), 317-320.
  106. ↑ Pizzo, A., Borrielli, I., Mastroeni, M. T., Fattori, A., Dugo, C., Dugo, N., & Dinatale, A. (2008). Low-dose flutamide in the treatment of hyperandrogenism in adolescents. Minerva pediatrica, 60(6), 1357-1366.
  107. ↑ Dungan, J. S. (2008). Long-Term Efficacy and Tolerability of Flutamide Combined with Oral Contraception in Moderate to Severe Hirsutism: A 12-Month, Double-Blind, Parallel Clinical Trial Calaf J, for the Spanish Working Group for Hirsutism (Hosp de la Santa Creu i Sant Pau, Barcelona; et al) J Clin Endocrinol Metab 92: 3446-3452, 2007. Year Book of Obstetrics, Gynecology and Women's Health, 2008, 142-144.
  108. ↑ Unluhizarci, K., Ozel, D., Tanriverdi, F., Karaca, Z., & Kelestimur, F. (2009). A comparison between finasteride, flutamide, and finasteride plus flutamide combination in the treatment of hirsutism. Journal of endocrinological investigation, 32(1), 37-40.
  109. ↑ Castelo-Branco, C., Moyano, D., Gómez, O., & Balasch, J. (2009). Long-term safety and tolerability of flutamide for the treatment of hirsutism. Fertility and sterility, 91(4), 1183-1188.
  110. ↑ Ibanez, L., López‐Bermejo, A., Díaz, M., Enríquez, G., Del Río, L., & De Zegher, F. (2009). Low‐dose pioglitazone and low‐dose flutamide added to metformin and oestro‐progestagens for hyperinsulinaemic women with androgen excess: add‐on benefits disclosed by a randomized double‐placebo study over 24 months. Clinical endocrinology, 71(3), 351-357.
  111. ↑ Ibanez, L., Lopez-Bermejo, A., Díaz, M., Enríquez, G., Del Río, L., & De Zegher, F. (2010). Low-dose pioglitazone, flutamide, metformin plus an estro-progestagen for non-obese young women with polycystic ovary syndrome: increasing efficacy and persistent safety over 30 months. Gynecological Endocrinology, 26(12), 869-873.
  112. ↑ Esmaeilzadeh, S., Ghorbani, L., Sharbatdaran, M., Bijani, A., & Sajadi, P. (2010). Comparison of flutamide and metformin in overweight-obese women with polycystic ovary syndrome following a hypocaloric dieting.
  113. ↑ de Zegher, F., & Ibanez, L. (2011). Flutamide for androgen excess: low dose is best. Journal of pediatric and adolescent gynecology, 24(2), e43-e44.
  114. ↑ Paradisi, R., Porcu, E., Fabbri, R., Seracchioli, R., Battaglia, C., & Venturoli, S. (2011). Prospective cohort study on the effects and tolerability of flutamide in patients with female pattern hair loss. Annals of Pharmacotherapy, 45(4), 469-475.
  115. ↑ Adalatkhah, H., Pourfarzi, F., & Sadeghi-Bazargani, H. (2011). Flutamide versus a cyproterone acetate-ethinyl estradiol combination in moderate acne: a pilot randomized clinical trial. Clinical, cosmetic and investigational dermatology, 4, 117.
  116. ↑ Ibanez, L., Diaz, M., Sebastiani, G., Sánchez-Infantes, D., Salvador, C., Lopez-Bermejo, A., & de Zegher, F. (2011). Treatment of androgen excess in adolescent girls: ethinylestradiol-cyproteroneacetate versus low-dose pioglitazone-flutamide-metformin. The Journal of Clinical Endocrinology & Metabolism, 96(11), 3361-3366.
  117. ↑ Yazdabadi, A., & Sinclair, R. (2011). Treatment of female pattern hair loss with the androgen receptor antagonist flutamide. Australasian Journal of Dermatology, 52(2), 132-134.
  118. ↑ Amiri, M., Golsorkhtabaramiri, M., Esmaeilzadeh, S., Ghofrani, F., Bijani, A., Ghorbani, L., & Delavar, M. A. (2014). Effect of metformin and flutamide on anthropometric indices and laboratory tests in obese/overweight PCOS women under hypocaloric diet. Journal of reproduction & infertility, 15(4), 205.
  119. ↑ Chiriac, A., Foia, L., Urma, A., Pinteala, T., & Chiriac, A. E. (2016). Flutamide treatment in severe acne in women-still controversial.
  120. ↑ Fulghesu, A. M., Melis, F., Murru, G., Canu, E., & Melis, G. B. (2017). Very low dose of flutamide in the treatment of hyperandrogenism. Gynecological Endocrinology, 1-5.
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