0 9 Flutamide Flutamide NNP 10 12 in in IN 13 16 the the DT 17 26 treatment treatment NN 27 29 of of IN 30 39 hirsutism hirsutism NN 39 40 : : : 41 50 long-term long-term JJ 51 59 clinical clinical JJ 60 67 effects effect NNS 67 68 , , , 69 78 endocrine endocrine JJ 79 86 changes change NNS 86 87 , , , 88 91 and and CC 92 100 androgen androgen NN 101 109 receptor receptor NN 110 118 behavior behavior NN 118 119 . . . 121 130 OBJECTIVE objective NN 130 131 : : : 132 134 To to TO 135 146 investigate investigate VB 147 150 the the DT 151 160 long-term long-term JJ 161 168 effects effect NNS 169 171 of of IN 172 181 treatment treatment NN 182 186 with with IN 187 190 low low JJ 191 196 doses dose NNS 197 199 of of IN 200 209 flutamide flutamide NN 210 212 on on IN 213 221 clinical clinical JJ 222 225 and and CC 226 234 hormonal hormonal JJ 235 245 parameters parameter NNS 245 246 , , , 247 249 as as RB 250 254 well well RB 255 257 as as IN 258 260 on on IN 261 264 the the DT 265 273 androgen androgen NN 274 282 receptor receptor NN 283 289 status status NN 289 290 , , , 291 293 in in IN 294 301 hirsute hirsute NN 302 307 women woman NNS 307 308 . . . 309 315 DESIGN design NN 315 316 : : : 317 325 Eighteen eighteen CD 326 333 hirsute hirsute NN 334 342 patients patient NNS 343 347 with with IN 348 355 regular regular JJ 356 362 menses mens NNS 363 367 were be VBD 368 375 studied study VBN 376 383 basally basally RB 384 387 and and CC 388 394 during during IN 395 404 treatment treatment NN 405 409 with with IN 410 413 125 125 CD 414 416 mg mg NN 417 426 flutamide flutamide NN 426 427 , , , 428 433 three three CD 434 439 times time NNS 440 443 per per IN 444 447 day day NN 448 451 for for IN 452 454 12 12 CD 455 461 months month NNS 461 462 . . . 463 470 Barrier Barrier NNP 471 473 or or CC 474 486 intrauterine intrauterine JJ 487 500 contraception contraception NN 501 504 was be VBD 505 509 used use VBN 510 516 during during IN 517 520 the the DT 521 526 study study NN 527 529 in in IN 530 538 sexually sexually RB 539 545 active active JJ 546 551 women woman NNS 551 552 . . . 553 559 Safety Safety NNP 560 570 parameters parameter NNS 571 575 were be VBD 576 584 assessed assess VBN 585 595 throughout throughout IN 596 599 the the DT 600 605 study study NN 605 606 . . . 607 616 Hirsutism Hirsutism NNP 616 617 , , , 618 624 graded grade VBN 625 627 by by IN 628 631 the the DT 632 640 modified modify VBN 641 657 Ferriman-Gallwey ferriman-gallwey JJ 658 663 score score NN 663 664 , , , 665 668 and and CC 669 677 hormonal hormonal JJ 678 688 parameters parameter NNS 689 693 were be VBD 694 703 evaluated evaluate VBN 704 711 basally basally RB 712 715 and and CC 716 718 at at IN 719 726 4-month 4-month JJ 727 736 intervals interval NNS 737 743 during during IN 744 753 treatment treatment NN 753 754 . . . 755 777 Gonadotropin-releasing gonadotropin-releasing JJ 778 785 hormone hormone NN 786 789 and and CC 790 794 ACTH acth NN 795 806 stimulation stimulation NN 807 812 tests test NNS 813 817 were be VBD 818 827 performed perform VBN 828 834 before before IN 835 838 and and CC 839 844 after after IN 845 846 3 3 CD 847 849 to to TO 850 851 4 4 CD 852 858 months month NNS 859 861 of of IN 862 869 therapy therapy NN 869 870 . . . 871 873 In in IN 874 882 addition addition NN 882 883 , , , 884 887 the the DT 888 901 concentration concentration NN 902 904 of of IN 905 913 androgen androgen NN 914 923 receptors receptor NNS 924 926 in in IN 927 938 mononuclear mononuclear JJ 939 949 leukocytes leukocyte NNS 950 953 was be VBD 954 962 measured measure VBN 962 963 , , , 964 966 in in IN 967 971 both both CC 972 975 the the DT 976 986 follicular follicular JJ 987 990 and and CC 991 997 luteal luteal JJ 998 1004 phases phase NNS 1005 1007 of of IN 1008 1011 the the DT 1012 1021 menstrual menstrual JJ 1022 1027 cycle cycle NN 1027 1028 , , , 1029 1036 basally basally RB 1037 1040 and and CC 1041 1046 after after IN 1047 1048 4 4 CD 1049 1055 months month NNS 1056 1058 of of IN 1059 1068 flutamide flutamide NN 1069 1078 treatment treatment NN 1078 1079 . . . 1080 1087 RESULTS results NNS 1087 1088 : : : 1089 1098 Flutamide Flutamide NNP 1099 1102 was be VBD 1103 1107 well well RB 1108 1117 tolerated tolerate VBN 1118 1120 in in IN 1121 1124 all all DT 1125 1130 women woman NNS 1130 1131 , , , 1132 1136 with with IN 1137 1140 the the DT 1141 1151 noticeable noticeable JJ 1152 1161 exception exception NN 1162 1164 of of IN 1165 1168 one one CD 1169 1176 patient patient NN 1177 1180 who who WP 1181 1190 presented present VBD 1191 1200 increased increase VBN 1201 1206 serum serum NN 1207 1219 transaminase transaminase NN 1220 1225 after after IN 1226 1227 8 8 CD 1228 1234 months month NNS 1235 1237 of of IN 1238 1245 therapy therapy NN 1245 1246 . . . 1247 1256 Hirsutism Hirsutism NNP 1257 1265 markedly markedly RB 1266 1274 improved improve VBN 1275 1277 in in IN 1278 1281 all all DT 1282 1287 women woman NNS 1288 1294 during during IN 1295 1298 the the DT 1299 1308 treatment treatment NN 1309 1310 ( ( ( 1310 1326 Ferriman-Gallwey ferriman-gallwey JJ 1327 1332 score score NN 1333 1338 after after IN 1339 1340 1 1 CD 1341 1345 year year NN 1345 1346 : : : 1347 1350 4.1 4.1 CD 1351 1354 +/- +/- CC 1355 1358 0.5 0.5 CD 1359 1365 versus versus CC 1366 1370 14.1 14.1 CD 1371 1374 +/- +/- CC 1375 1378 0.9 0.9 CD 1378 1379 ) ) ) 1379 1380 . . . 1381 1382 A a DT 1383 1392 reduction reduction NN 1393 1395 of of IN 1396 1401 serum serum NN 1402 1411 androgens androgen NNS 1412 1415 was be VBD 1416 1421 found find VBN 1421 1422 , , , 1423 1430 whereas whereas IN 1431 1433 no no DT 1434 1440 change change NN 1441 1444 was be VBD 1445 1453 observed observe VBN 1454 1456 in in IN 1457 1463 either either CC 1464 1469 basal basal JJ 1470 1472 or or CC 1473 1488 GnRH-stimulated gnrh-stimulated JJ 1489 1502 gonadotropins gonadotropin NNS 1503 1505 or or CC 1506 1508 in in IN 1509 1512 the the DT 1513 1521 cortisol cortisol NN 1522 1525 and and CC 1526 1528 17 17 CD 1529 1554 alpha-hydroxyprogesterone alpha-hydroxyprogesterone NN 1555 1563 response response NN 1564 1566 to to TO 1567 1571 ACTH ACTH NNP 1571 1572 . . . 1573 1579 Cycles cycle NNS 1580 1588 remained remain VBD 1589 1598 ovulatory ovulatory JJ 1598 1599 . . . 1600 1606 Before before IN 1607 1616 treatment treatment NN 1616 1617 , , , 1618 1621 the the DT 1622 1628 number number NN 1629 1631 of of IN 1632 1640 androgen androgen NN 1641 1650 receptors receptor NNS 1651 1654 was be VBD 1655 1661 higher high JJR 1662 1664 in in IN 1665 1668 the the DT 1669 1675 luteal luteal NN 1676 1680 than than IN 1681 1683 in in IN 1684 1687 the the DT 1688 1698 follicular follicular JJ 1699 1704 phase phase NN 1704 1705 . . . 1706 1710 This this DT 1711 1719 rhythmic rhythmic JJ 1720 1735 differentiation differentiation NN 1736 1747 disappeared disappear VBD 1748 1753 after after IN 1754 1757 the the DT 1758 1766 patients patient NNS 1767 1770 had have VBD 1771 1775 been be VBN 1776 1781 given give VBN 1782 1785 the the DT 1786 1798 antiandrogen antiandrogen NN 1799 1803 drug drug NN 1803 1804 . . . 1805 1816 CONCLUSIONS conclusions NNS 1816 1817 : : : 1818 1827 Flutamide Flutamide NNP 1828 1830 is be VBZ 1831 1840 effective effective JJ 1841 1843 in in IN 1844 1847 the the DT 1848 1857 treatment treatment NN 1858 1860 of of IN 1861 1870 hirsutism hirsutism NN 1871 1874 but but CC 1875 1883 requires require VBZ 1884 1892 constant constant JJ 1893 1905 surveillance surveillance NN 1906 1908 of of IN 1909 1914 liver liver NN 1915 1923 function function NN 1923 1924 . . . 1925 1933 Androgen Androgen NNP 1934 1942 receptor receptor NN 1943 1951 blockade blockade NN 1952 1957 might might MD 1958 1960 be be VB 1961 1972 potentiated potentiate VBN 1973 1975 by by IN 1976 1977 a a DT 1978 1987 reduction reduction NN 1988 1990 of of IN 1991 1996 serum serum NN 1997 2006 androgens androgen NNS 2006 2007 . . . 2008 2017 Flutamide Flutamide NNP 2018 2025 affects affect VBZ 2026 2034 androgen androgen NN 2035 2043 receptor receptor NN 2044 2052 behavior behavior NN 2053 2059 during during IN 2060 2063 the the DT 2064 2073 menstrual menstrual JJ 2074 2079 cycle cycle NN 2079 2080 . . . 2081 2084 The the DT 2085 2092 meaning meaning NN 2093 2095 of of IN 2096 2100 this this DT 2101 2108 finding finding NN 2109 2116 remains remain VBZ 2117 2119 to to TO 2120 2122 be be VB 2123 2133 elucidated elucidate VBN 2134 2135 . . .