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1 Chin J Obstet Gynecol, September 1999, Vol. 34, No. 9 ( CPA) (PCOS), 29 PCOS [16 (CC) (hmg) ], 5 CPA,4 6, CC 12 CC 22,5 (1 hmg,4 CC) hmg6,,8 5,3 ;, 23,( P < ), % %72. 8 % % %21. 8 % (SHBG) 5. 1, %,23. 0 %,36. 2 % % 3 (10. 3 %) CC CC,7 10, 2 (16. 7 %) 1 hmghmg CPA PCOS 46,, CC 3,() Treatment of Polycystic Ovary Syndrome and Related Infertility with Clomiphene Resistance by Compound Cyproterone Acetate TAO Yu, DAI Qing, ZHANG Deyong, et al. Peking Union Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing Abstract Objective To assess the efficacy and safety of compound cyproterone acetate (CPA Co,or Diane235) in the treatment of polycystic ovary syndrome ( PCOS) and to explore its potential role in improving the outcome of ovulation induction in clomiphene (CC) resistant cases. Methods Twenty 2nine proven PCOS patients were enrolled. Seventeen out of them, including 16 who were resistant to CC, had anovulatory infertility. CPA Co was given for 46 cycles. Serum luteinizing hormone(lh), follicle stimulating hormone(fsh), estradiol ( E 2 ), testosterone( T), androstenedione (A), dehydroepiandrosterone (Ds), sex hormone binding globvlin ( SHBG), insulin concentrations, total cholesterol, triglycerides( TG), high density lipoprotein2cholesterol ( HDL2C), low density lipoprotein2 cholesterol ( LDL2C ), apolipoprotein A, apolipoprotein B and transvaginal pelvic ultrasonography were determined before, 23 cycles and 46 cycles after treatment. After stopping the drug, CC or human menopausal gonadotropin were re2administered in 12 patients ( 22 cycles) and 5 cases ( 6 cycles) respectively for induction of ovulation. Results All patients had regular uterine bleeding during CPA Co therapy. Acne improved in 8 cases. Hirsute score didn t decrease significantly. Serum LH, FSH, E 2, A, T, Ds concentrations decreased significantly ( P < ), while SHBG levels increased by 5. 1 times after treatment. Meanwhile, bilateral ovarian volumes shrunk and follicle numbers decreased significantly ( P < ). Serum insulin levels did not change significantly. As to the lipid profile, the most striking change was % increase of HDL2C and % decrease of LDL2C, although TG also increased by % % of patients had mild and transient adverse effects. Serum alanine transaminase increased in 3 cases. After stopping treatment, CC induced 5. 3 % (by cases) or % (by cycles) ovulation rate and 2 pregnancies achieved in 12 CC resistant patients. Conclusion CPA Co has antiandrogenic effects on PCOS patients clinically, biochemically : (,,,, ), B ( )

2 Chin J Obstet Gynecol, September 1999, Vol. 34, No and in ovarian morphology. Pretreatment of CPA Co may play a role in improving the outcome of ovulation induction in CC resistant cases. Key words Polycystic ovary syndrome Infertility, female Cyproterone acetate Clomiphene ( PCOS), [1 ] PCOS,(CC) 30 % [2 ] (hmg) ( FSH) 28 %, (OHSS) 23 % [2 ],, ( CPA) PCOS, PCOS 29, ( ) (2035 ) , 16, [ Ferriman2Gallwey (F2G) > 4 ]16 8 %12 %(3) , 3 26, PCOS [2 ], 3 22 (75. 7 %), 25 (86. 2 %), (89. 7 %) (A) ( T) (Ds) 21 (72. 4 %), ( INS) 8 (27. 6 %) ( PRL) 18 (62. 1 %), (TG) 14 (48. 3 %), (HDL2C) ( ) A ( APOa ) 10 (34. 5 %), B ( APOb) 15 (51. 7 %) ( TC) (ALT) 16,3, 16 CC 4 (39),(BBT),1 hmg 1,, ,,BBT,F2G < 4, (BMI) 1924, A (SHBG) 1. CPA :,16 CC,9,4 5, CPA 1 [(CPA) 2 mg + 35g, 35 ] 21, 5,46 2. : (1),, F2G(2) (LH) FSH Ds INS T( E 2 ) ( ) A( ) SHBG ( ) (4) 46 ALT TC TG HDL2C APOa APOb LDL2 C TC - TG/ (5 - HDL2C) [3 ] 3. CPA : (1) CC :16 (29 ),CC 12 22, mg 5 > 18 mm, hcg IU (2) hmg :5 (6 ), hmg 1,CC 4 1 > 16 mm > 14 mm E 2 > 550 pmol/ L, hcg 35 (3) :2,7 6 3 LH T INS foxpro, SPSS ( statistical package of social science) t

3 Chin J Obstet Gynecol, September 1999, Vol. 34, No : , ( ) ( gx s, ) (310 ), ( ) (310 ) 16 F2G ( P > 0. 05) 8 23, :, 23 6 LH/ FSH,SHBG ( P < 0. 01), 46 SHBG 5. 1 INS ( P > 0. 05) 1 3. : 23, ( P < 0. 01), ( P < 0. 01) 46, 23 ( P < 0. 05) 2 4. :HDL2C ( + 55 %) LDL2C (- 23 %) ( P < 0. 01), APOb APOa TC ( P > 0. 05) TG ( %) ( P < 0. 05) HDL2C,1 LDL2C,12 TG (41. 4 %) %(17/ 29),39. 9 %(59/ 148) 15 (10. 1 %) 11 (7. 4 %) 6 (4. 1 %), 3 (2. 0 %), 2 (1. 4 %), 1 (0. 7 %),2 > 2 kg ALT 3 (10. 3 %), : (1) CC :12 CC 22, CPA 7 (58. 3 %) 10 (45. 4 %) 7, 19 mm, E 2 ( ) pmol/ L 6 6 hcg BBT, (16. 7 %) (2) hmg: hmg1 hmg 1, 22 mm,, ,3,, 1,OHSS 2. : 4 CC,,, CC 9,,2 7 15,3 1, 1 ; 3,2 1 3,BBT ; 1 PCOS ( gx s) LH ( IU/ L) FSH ( IU/ L) LH/ FSH E 2 (pmol/ L) A T Ds (mol/ L) INS (mu/ L) SHBG , P < , P < PCOS B ( gx s) (cm 3 ) (cm) (cm 3 ) () (cm) :, 3 P < P < 0. 01

4 Chin J Obstet Gynecol, September 1999, Vol. 34, No PCOS (mmol/ L, gx s) Tc TG LDL2C HDL2C APOa (g/ L) :, 3 P < P < APOb (g/ L) LH T INS, ( ) IU/ L ( ) nmol/ L ( ) mu/ L ( P > 0. 05) PCOS 16 CC, (20 %40 %) [2,4,5 ] %,INS %, A T TG LDL2C INS,,INS T TG APOb 15 (88. 7 %),5 (62. 5 %),LH SHBGDs, CC %,INS % PCOS 16 CC 15, CPA,16 CC, 3 3,1 CC 12,CC, CPA 23, CPA CPA HDL2C LDL2C TG,TC APOa APOb, [5 ], CPA PCOS TG CPA PCOS CC hmg, 2, 3 : hmg [8 ] FSH [4 ] [9 ],, CPA PCOS? 5 2 Gerhard [10 ] 10 CPA, 18, 11 (61 %),1 (5 %) Koloszar [9 ] 8 CC + FSH CPA mg/ d 10,17, %(7/ 12), 2 (16. 7 %) 1 CPA, LH, hmg hmg,, CPA [6 ],, 4. 2 [6 ], : (1) LH, FSH/ LH, SHBG, T [5,6 ] LH (2) CPA,PCOS, [5,7 ] 1 [6 ], 1. 4 %, 23,, 1 LH,, (3) T A Ds E 2 LH FSH, T (4) [6 ] SHBG23, (5) SHBG, T [5,6 ], CPA,2 12 (41. 4 %) TG 3 (10. 3 %) ALT, TG 1 Samsioe G, Dahlgrem E, Janson PO. Potential health hazards in PCOS:

5 Chin J Obstet Gynecol, September 1999, Vol. 34, No. 9 risks and implications in nontreated patients. In : Franks S, Neumann F, eds. Polycystic ovary syndrome. Chester : Adis International LTD, ,1996,22 : :. ( ). :, Yong EL, Ng SC, Chan C, et al. Responses of PCOS and related variants to low2dose follicle stimulating hormone. Int Gynecol Obstet, 1997, 57 : Falsetti L, Pasinetti R. Effects of long2term administration of an oral contraceptive containing ethinyl estradiol and cyproterone acetate on lipid metabolismin women with PCOS. Acta Obstet Gynecol Scand, 1995, 74 : Neumann F. Pharmacological aspects of cyproterone acetate. In : Schindler AE, ed. Antiandrogen2estrogen therapy for signs of androgenization. Berlin : New York Walter de Gruyter, Acien P, Mauri M, Gutiervez M, et al. Clinical and hormonal effects of the combination GnRH2a plus oral contraceptive pills containing ethin2 yloestradiol ( EE) and cyproterone acetate (CPA) versus the EE2CPA pill alone on PCOS2related hyperandrogenisms. Hum Reprod, 1997, 12 : Charbonnel B, Krempf M, Blanchard P, et al. Induction of ovulation in PCOS with combination of a luteinzing hormone releasing hormone analog and exogenous gonadotropins. Fertil Steril, 1987, 47 : Koloszar S, Szollosi J, Bartfai G, et al. Ovulation induction with adjuvant antiandrogen treatment in Stein2Leventhal syndrome. Orv Hetil, 1996, 137 : Gerhard I, Matthes J, Runnebaum B. The induction of ovulation with pulsatile GnRH administration in hyperandrogenic woman after down2 regulation with buserelin or suppression with a oral contraceptive. Hum Reprod, 1993, 8 : ( : : ) ( :) 25,2,,,, 20, ,,, B 1,,,,, , 40,,,, 10 (Wernicke) B 1,,, B mg,1 2,200 mg, 5 :,,1 1, 1, Wernicke,,, 3,,B 1 ; ( - ),, B,Wernicke 2,,( - ), Wernicke, ( + + ), B B 1 Wernicke,, Wernicke,,3 B 1,, B 1,,,,, : Wernicke B 1 ;, ( : : ) ( :)