門 診 處 方 討 論 Bromocriptine用於Polycystic ovary syndrome 報告者 : 陳淑燕

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1 門 診 處 方 討 論 Bromocriptine用於Polycystic ovary syndrome 報告者 : 陳淑燕

2 12/23 Clomiphene 50mg/tab 1# TID x 5 days
1. Polycystic ovaries 2. Irregular menstrual cycle 12/ Clomiphene 50mg/tab # TID x 5 days Metformin 500mg/tab # TID x 21 days Bromocriptine 2.5mg/tab 1# BID x 21 days Topaal # TID x 21 days

3 多囊性卵巢症候群 PCOS  多囊性卵巢的病人通常並沒有真正的排卵，而出現的月  臨床表徵包括月經異常、排卵異常、不孕症、肥胖、多
經是屬於無排卵性的，超音波檢查卵巢會呈現許多小囊 的情形，其實每一個小囊就是一個小的卵泡.  臨床表徵包括月經異常、排卵異常、不孕症、肥胖、多 毛症及痤瘡等.  致病原因至今仍不清楚,所以治療的目標只能針對每個 病患的症狀來處理.

4 多囊性卵巢症候群 PCOS 發現許多PCOS 患者的血中insulin及 prolactin過高，所以使用胰島素激敏劑
（insulin-sensitizing agents）的降血糖藥物 （如：metformin、 troglitazone）及抑制泌乳 素分泌藥物如 bromocriptine等以改善其症 狀 .

5 使用前 Prolactin 35.17

6 使用後 Prolactin 25.64

7 Prolactin 的 作 用  Prolactin的主要生理功能是刺激乳房組織生長， 製造和分泌乳汁 。
典型的症狀包括有動情素低(Hypoestrogenism)、 繼發性無月經 ( Secondary amenorrhea ) 、溢 乳 (Galactorrhea)、多毛症、多囊性卵巢症、不 孕等。

8 Bromocriptine 於 PCOS 治療之機轉
 Bromocriptine is an ergot derivative and a direct-acting Dopamine agonist .  Bromocriptine stimulates hypothalamic dopaminergic receptors resulting in an increase in prolactin inhibitor factor, decreasing secretion of prolactin from the anterior pituitary .

9 Bromocriptine於PCOS治療之臨床證據(1)
In a randomized, double-blind study of 55 patients with polycystic ovary disease, similar improvements in ovulatory function were seen with BROMOCRIPTINE (53%) versus placebo (40%). The patients were given tablets containing BROMOCRIPTINE 2.5 milligrams or placebo starting at one-half tablet 2 times a day and increasing to 1 tablet twice daily if 2 ovulatory cycles had not occurred in 3 months. Treatment continued for at least 6 months. ( Buvat et al, 1986 )

10 The only clear effect of chronic BROMOCRIPTINE
administration was that serum prolactin levels were lowered. Many other changes were identical to those seen in the group treated with placebo, including a decrease in elevated serum LH and androgen levels, restoration of cyclical menstrual function and regular ovulation. ( Buvat et al, 1986 )

11 Bromocriptine於PCOS治療之臨床證據(2)
The combination of Clomiphene 50 to 100 mg (from cycle day 5 to 9), Dexamethasone 0.5 to 1 mg/day and Bromocriptine 2.5 to 5 mg daily was reported effective in the treatment of resistant polycystic ovarian disease in 8 women.  Some patients were also resistant to human menopausal gonadotropin and human chorionic gonadotropin. All patients were anovulatory prior to combination therapy. (Homburg et al, 1988)

12  Decreases in the leutinizing hormone:follicle
stimulating hormone ratio were observed, as well as reductions in prolactin and androgen levels to normal. All 8 patients became pregnant within 5 to 11 treatment cycles and ultimately delivered normal babies.  It is recommended that the combination be considered in resistant cases of polycystic ovarian disease. (Homburg et al, 1988)

13 Bromocriptine應用於PCOS治療之劑量
 The initial recommended dosage is 1.25 to 2.5 mg daily. An additional 2.5 mg may be added as tolerated every 3 to 7 days until an optimal therapeutic response is achieved. Up to 15mg/day.  結論建議劑量: 2.5mg BID ~ TID

14 Bromocriptine應用於PCOS治療之注意事項
 副作用 (包括頭暈，姿態性低血壓和噁心) 常常發 生在治療的早期，可以靠以低劑量起始和持 續 性服用而避免發生。  Bromocriptine對大多數的女性病人可以恢復懷孕能 力，因此，假如不想懷孕的話，避孕措施必須做好。

15 Bromocriptine 於 PCOS 之 結 論
 FDA APPROVAL: Adult, no; pediatric, no  EFFICACY: Adult, possibly effective  DOCUMENTATION: Adult, good Referevence: Micromedex Inc. drug evaluation Monographs

16 Reference 1. Micromedex Inc. drug evaluation Monographs. 2004
2. Homburg R, Ashkenazi J & Goldman J: Resistant cases of polycystic ovarian disease successfully treated with a combination of corticosteroids, clomiphene, and bromocriptine. Int J Fertil 1988; 33: 3. Buvat J, Buvat-Herbaut M, Marcolin G et al: A double blind controlled study of the hormonal and clinical effects of bromocriptine in the polycrystic ovary syndrome. J Clin Endocrinol Metab 1986; 63: 4. Drug information handbook