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Chronic Pelvic Pain in Women &Diagnosis and treatment

os endometriosis

Editor(Not Author):kuan-yu,wei

Vehicle source come from~http://www.aafp.org/afp/20080601/1535.html

Data Source: http://www.aafp.org/afp/991015ap/1753.html

Chronic pelvic pain is defined in a variety of ways. A useful clinical definition

of chronic pelvic pain is noncyclic pain that lasts six months or more; is

localized to the pelvis, the anterior abdominal wall at or below the umbilicus,

or the buttocks; and is of sufficient severity to cause functional disability or

require medical care.1 Other definitions do not require that the pain be

noncyclic.
The etiology of chronic pelvic pain in women is poorly understood. Although

a specific diagnosis is not found in the majority of cases, some common

diagnoses include endometriosis, adhesions, irritable bowel syndrome, and

interstitial cystitis.

The initial history and physical examination can narrow the diagnostic

possibilities, guide any subsequent evaluation, and rule out malignancy or

significant systemic disease. If the initial evaluation does not reveal a specific

diagnosis, a limited laboratory and ultrasound evaluation can clarify the

diagnosis, as well as rule out serious disease and reassure the patient.

The evidence supports the use of oral medroxyprogesterone, goserelin,

adhesiolysis for severe adhesions, and a multidisciplinary treatment approach

for patients without a specific diagnosis. Less supporting evidence is available

for oral analgesics, combined oral contraceptive pills, gonadotropin-releasing

hormone agonists, intramuscular medroxyprogesterone, trigger point and

botulinum A toxin injections, neuromodulative therapies, and hysterectomy.

Eti olo gy
The pathophysiology of chronic pelvic pain is not well understood. 4 A

definitive diagnosis is not made for 61 percent of women with chronic pelvic

pain.5 Many patients and physicians incorrectly assume that all chronic pelvic

pain results from a gynecologic source. One study in the United Kingdom

found that diagnoses related to the urinary and gastrointestinal systems were

more common than gynecologic diagnoses.5 Table 1 lists the more commonly

diagnosed conditions that cause chronic pelvic pain.1,6,7 The four most

commonly diagnosed etiologies are endometriosis, adhesions, irritable bowel

syndrome (IBS), and interstitial cystitis.1,5,6,8

Table 1. Selected Differential Diagnoses of Chronic Pelvic Pain by

Organ System

System Differential diagnoses
Gastrointestinal Celiac disease, colitis, colon

cancer, inflammatory bowel

disease, irritable bowel

syndrome

Gynecologic Adhesions, adenomyosis,

adnexal cysts, chronic

endometritis, dysmenorrhea,

endometriosis, gynecologic

malignancies, leiomyomata

pelvic congestion syndrome,

pelvic inflammatory disease

Musculoskeletal Degenerative disk disease,

fibromyalgia, levator ani

syndrome, myofascial pain,

peripartum pelvic pain

syndrome, stress fractures
Psychiatric/ Abdominal epilepsy,

neurologic abdominal migraines,

depression, nerve entrapment,

neurologic dysfunction, sleep

disturbances, somatization

Urologic Bladder malignancy, chronic

urinary tract infection,

interstitial cystitis, radiation

cystitis, urolithiasis

Other Familial Mediterranean fever,

herpes zoster, porphyria

Information from references 1, 6, and 7.
Key Re co mme nd at io ns for Ev ide nc e

Clinical recommendation Evidence rating References

If the initial history and physical C 4, 18

examination do not reveal a specific

diagnosis, the initial diagnostic workup

should include: a complete blood count,

beta human chorionic gonadotropin

levels, erythrocyte sedimentation rate,

vaginal swabs for chlamydia and

gonorrhea, urinalysis with urine culture,

and a transvaginal pelvic ultrasound.

Multidisciplinary treatment (medication, B 4

dietary, psychosocial) can be used to

improve symptoms of chronic pelvic
pain.

Oral medroxyprogesterone acetate B 4

(Provera), 50 mg daily, can be used to

reduce pain in women with chronic

pelvic pain.

Goserelin (Zoladex), 3.6 mg subcutaneous B 4

implant, monthly for six months can be

used to reduce pain in women with

chronic pelvic pain.

Adhesiolysis improves pain, but only B 4

when associated with severe adhesions.

Combined oral contraceptive pills C 1, 6

improve cyclic pain.
Nonsteroidal anti-inflammatory drugs C 1, 6

should be used to treat mild to moderate

chronic pelvic pain.

Because the definition of chronic pelvic pain varies, it is difficult to ascertain

its exact prevalence. In the United Kingdom, 3.8 percent of women in the

primary care population report experiencing chronic pelvic pain, defined as

noncyclic pain in the lower abdominal region lasting six months or more and

without a specific disease diagnosis.2 This is similar to the prevalence of

migraine headaches, asthma, and low back pain in the United Kingdom. 2

However, in a 1996 study conducted in the United States, 15 percent of

women indicated they had experienced either constant or intermittent pelvic

pain during the preceding six months, which met the study's criteria for

chronic pelvic pain.3 The same study estimated the cost of outpatient medical

visits associated with chronic pelvic pain to be $880 million per year in the

United States, with 15 percent of women with chronic pelvic pain reporting
lost time from paid work, and 45 percent reporting decreased productivity at

work.3

Eva lu at in g the pa tie nt

 Table 2. Selected Findings on History, Physical Examination, and

Diagnostic Studies

 Finding  Possible significance

 History 

 Hematochezia  Gastrointestinal

malignancy/bleeding

 History of pelvic surgery,  Adhesions
pelvic infections, or use of

intrauterine device

 Nonhormonal pain  Adhesions, interstitial cystitis,

fluctuation irritable bowel syndrome,

musculoskeletal causes

 Pain fluctuates with  Adenomyosis or endometriosis

menstrual cycle

 Perimenopausal or  Endometrial cancer

postmenopausal irregular

vaginal bleeding

 Postcoital bleeding  Cervical cancer or cervicitis (e.g.,

chlamydia or gonorrhea)

 Unexplained weight loss  Systemic illness or malignancy
 Physical examination 

 Lack of uterus mobility on  Endometriosis, pelvic adhesions

bimanual examination

 Nodularity or masses on  Adenomyosis, endometriosis,

abdominal, bimanual hernias, malignancy, tumors

pelvic and/or rectal

examination

 Pain on palpation of outer  Abdominal/pelvic wall source of

back and outer pelvis pain, trigger points

 Point tenderness of  Adhesions, endometriosis, nerve

vagina, vulva, or bladder entrapment, trigger points, vulvar

vestibulitis

 Positive Carnett's sign  Myofascial or abdominal wall cause
of pain

 Diagnostic studies 

 Abnormal urinalysis or  Bladder malignancy, infection

urine culture

 Complete blood count  Infection, systemic illness, or

abnormalities malignancy (elevated/decreased

white blood cell count or anemia)

 Elevated erythrocyte  Infection, malignancy, systemic

sedimentation rate illness

 Positive gonorrhea or  Pelvic inflammatory disease

chlamydia testing

 Transvaginal ultrasound  Adenomyosis,
abnormalities endometriosis/endometrioma,

malignancy

The International Pelvic Pain Society has many helpful resources including

history and physical examination forms (available at

http://www.pelvicpain.org/resources/handpform.aspx), and patient

education materials.

PHY SIC AL EXA MIN ATIO N

The physical examination can identify areas of tenderness and the presence of

masses or other anatomical findings that aid in the diagnosis. However, a lack

of findings during the physical examination does not rule out intra-abdominal

pathology because many patients with a normal examination will have

pathologic findings on subsequent laparoscopy.1
The physical examination should proceed slowly and gently because both the

abdominal and pelvic components of the examination may be painful.

Palpation of the outer pelvis and back may reveal trigger points that indicate

a myofascial component to the pain. The pelvic examination should begin

with a single-digit, one-handed examination. A moistened cotton swab

should be used to elicit point tenderness in the vulva and vagina. The patient

should be checked for any nodules, masses, or point tenderness along the

bladder or other musculoskeletal structures. Once the single-digit, one-

handed examination is completed, a bimanual examination should be

performed to check again for nodularity, point tenderness, cervical motion

tenderness, or lack of mobility of the uterus.7 A rectal examination may show

rectal or posterior uterine masses, nodularity, or pelvic floor point tenderness.

Testing for Carnett's sign should be performed by placing a finger on the

painful, tender area of the patient's abdomen and having the patient raise

both legs off the table while lying in the supine position (Figure 1). A positive

test occurs when the pain increases during this maneuver and is associated

with a myofascial cause of the pain. This may also indicate that the cause of

the pain is within the abdominal wall (e.g., fibromyalgia or trigger point).

Visceral pain should not worsen during the maneuver.17
Figure 1. Carnett's sign for patients with pelvic pain. The examiner places his

or her finger on the tender area of the patient's abdomen and asks the patient

to raise both legs off the table. An increase in the patient's pain during this

maneuver is considered a positive test.

LA BO RATO RY /SP EC IAL IZED TE STS

If the history and physical examination do not lead to a diagnosis, then cancer

screenings appropriate to the patient's age and associated risk factors should

be performed. It may be appropriate to obtain a serum beta subunit of human
chorionic gonadotropin (ß-hCG) level to rule out pregnancy; a complete blood

count; a urinalysis and urine culture; an erythrocyte sedimentation rate; and

vaginal swabs to test for gonorrhea and chlamydia.18 Transvaginal ultrasound

is also useful during the initial evaluation to investigate any pelvic masses or

nodules found during the physical examination and to reassure the patient if

no significant abnormalities are discovered.4,18

Magnetic resonance imaging and computed tomography should not be used

routinely, but can help assess any abnormalities found on ultrasound.19 Some

urologists use the intravesical potassium sensitivity test to help diagnose

interstitial cystitis.20 Laparoscopy is often used when the diagnosis remains

elusive after the initial workup or to confirm, and possibly treat, suspected

endometriosis, adhesions, or both.7
FIGURE 2. Combined with endometriosis and basic anatomy of retrograde

menstruation.
FIGURE 3. Laparoscopic excision of nodular endometrial lesions overlying

the rectum.

Data Source: http://www.aafp.org/afp/991015ap/1753.html

Tre at men t

Few randomized controlled trials have studied the treatment of chronic pelvic

pain. Because different definitions of chronic pelvic pain were used in some of

these studies, many treatment recommendations are based on expert opinion

or cohort/observational studies.
Treatment should be directed at the underlying cause of the pelvic pain.

Figure 2 shows a suggested algorithm for the evaluation and management of

patients with chronic pelvic pain.1,4,6,18,21-23 In patients for whom a specific

diagnosis is not made, a multidisciplinary approach (i.e., addressing dietary,

social, environmental, and psychological factors in addition to standard

medication therapy) has been shown to improve outcomes over medication

therapy alone.4 Table 3 lists specific details and references regarding the most

common medication treatment options.1,4,6,21,22,24,25

Evaluation and Treatment of Chronic Pelvic Pain in Women
Figure 4. Algorithm for the evaluation and treatment of chronic pelvic pain in

women presenting to primary care. (ß-hCG = beta subunit of human

chorionic gonadotropin; NSAIDs = nonsteroidal anti-inflammatory drugs.)

Information from references 1, 4, 6, 18, and 21 through 23.

Table 3. Common Medications for Treatment of Chronic Pelvic Pain

Treatment Comment

Combined oral Evidence supports use in patients with dysmenorrhea;21

contraceptives no quality studies show benefit in patients with

chronic pelvic pain

Oral Only medication with evidence showing some benefit

medroxyprogest in most patients with chronic pelvic pain (excluding
erone acetate those with endometriosis, primary dysmenorrhea,

(Provera), 50 mg chronic active pelvic inflammatory disease, and

daily irritable bowel syndrome)4

Depot Studies only show benefit in patients with chronic

medroxyprogest pelvic pain related to endometriosis22

erone (Depo-

Provera), 150

mg IM every

three months

NSAIDs No studies show benefit specifically for treatment of

chronic pelvic pain; recommendation from

expert/consensus opinions only1,6

GnRH agonists Goserelin effective for pelvic congestion and has longer

(i.e., goserelin duration of effect than medroxyprogesterone; monitor

[Zoladex]) patient for bone density loss1,4,6
Levonorgestrel One study supports benefit in patients with chronic

intrauterine pelvic pain related to endometriosis24

system (Mirena) http://www.2womenshealth.com/14-Mirena-Mini-

Pills/Mirena.htm

Danazol Use for six months only; associated with a high

incidence of side effects25

GnRH = gonadotropin-releasing hormone; IM = intramuscularly; NSAIDs

= nonsteroidal anti-inflammatory drugs.

Information from references 1, 4, 6, 21, 22, 24, and 25.

A recent Cochrane analysis of treatments for chronic pelvic pain found that

only the following treatments have shown benefit: oral medroxyprogesterone

acetate (Provera), 50 mg daily; goserelin (Zoladex), an injectable

gonadotropin-releasing hormone (GnRH) agonist; a multidisciplinary

approach; counseling after a negative ultrasound; and lysis of deep
adhesions.4 Lysis of adhesions is only beneficial for more severe cases. This

Cochrane review excluded patients with known endometriosis, IBS, primary

dysmenorrhea, and chronic, active pelvic inflammatory disease, as these

disease populations have slightly different therapeutic options than the larger

population of patients with chronic pelvic pain.4

For pain that appears to be cyclic in nature, hormonal treatments (continuous

or cyclic low-dose oral contraceptive pills, progestins, or GnRH agonists)

should be considered, even if the cause is thought to be IBS, interstitial

cystitis, or pelvic congestion syndrome, because these conditions may also

respond to hormone treatments.1,4,21,22 Specific management of IBS,

endometriosis, and interstitial cystitis has been described elsewhere.13,26,27

Although selective serotonin reuptake inhibitors have not been shown to be

effective for treating chronic pelvic pain,4 they may be used to treat

concomitant depression. Trigger point injections of the abdominal wall for

myofascial causes of chronic pelvic pain have also shown some benefit.28,29
AN ALG ES ICS

Oral analgesics, such as acetaminophen, nonsteroidal anti-inflammatory

drugs (NSAIDs), and opioid analgesics, are commonly used to treat moderate

pain; however, there are no prospective controlled studies that show a

specific benefit in chronic pelvic pain.1 If opioid analgesics are necessary to

control pain, long-acting opioids with scheduled dosing may be used in

conjunction with a treatment plan similar to that used when treating other

chronic, painful conditions.6 Vitamin B1 and oral magnesium have been

shown to benefit patients with dysmenorrhea, but there are no trials that

evaluated their effectiveness for non- menstrual-related pain.30 A recent

randomized, controlled, open-label study showed that gabapentin

(Neurontin), alone or in combination with amitriptyline, provided significant

pain relief in women with chronic pelvic pain.23 Botulinum toxin type

A(Botox) injections into the pelvic floor muscles have also shown benefit.31,32
SUR GIC AL AND NE RV E ST IMU LAT ION
THE RA PI ES

Among surgical therapies, only lysis of severe adhesions has been shown to

benefit patients with chronic pelvic pain.4 Total abdominal hysterectomy

showed some benefit in observational and cohort studies.33,34 Presacral

neurectomy, along with ablative therapy for endometriosis, has shown benefit

in the treatment of dysmenorrhea that is centrally located in the pelvis,35 but

this finding cannot be generalized to chronic pelvic pain.

Several other therapies using the neuromodulation theory of treating pain

have been evaluated in patients with chronic pelvic pain. Uncontrolled

studies of sacral nerve stimulation in women with chronic pelvic pain have

shown some benefit.36,37 Two trials have shown some benefit in using

percutaneous tibial nerve stimulation to treat chronic pelvic pain,38,39 although

there are no large, placebo-controlled studies that confirm these findings.
Re fer ra l

Family physicians should consider referring patients with chronic pelvic pain

for diagnostic procedures (e.g., laparoscopy, colonoscopy, cystoscopy), for

therapeutic options (e.g., surgery or GnRH agonist treatment) that are beyond

their scope of care, or if the underlying diagnosis and best treatment option

are unclear. By performing a thorough initial work-up and knowing the local

subspecialty practice scope and patterns, family physicians should be able to

select the specific test or specialty (e.g., gynecology, urology, gastroenterology

or pain management) in their community that would best provide the

information and care that the patient requires. Because a multidisciplinary

treatment approach will benefit most patients with chronic pelvic pain,4 the

referring family physician should stay engaged in the care of the patient and

coordinate the plan of care with any subspecialists involved.
REFERENCES

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2. Zondervan KT, Yudkin PL, Vessey MP, Dawes MG, Barlow DH, Kennedy SH. Prevalence

and incidence of chronic pelvic pain in primary care: evidence from a national general

practice database. Br J Obstet Gynaecol. 1999;106(11):1149-1155.

3. Mathias SD, Kuppermann M, Liberman RF, Lipschutz RC, Steege JF. Chronic pelvic pain:

prevalence, health-related quality of life, and economic correlates. Obstet Gynecol.

1996;87(3):321-327.

4. Stones RW, Mountfield J. Interventions for treating chronic pelvic pain in women. Cochrane

Database Syst Rev. 2000;(4):CD000387.
5. Zondervan KT, Yudkin PL, Vessey MP, Dawes MG, Barlow DH, Kennedy SH. Patterns of

diagnosis and referral in women consulting for chronic pelvic pain in UK primary care. Br J

Obstet Gynaecol. 1999;106(11):1156-1161.

6. Howard FM. Chronic pelvic pain. Obstet Gynecol. 2003;101(3):594-611.

7. Tu FF, As-Sanie S, Steege JF. Musculoskeletal causes of chronic pelvic pain: a systematic

review of diagnosis: part 1. Obstet Gynecol Surv. 2005;60(6):379-385.

8. Parsons CL, Bullen M, Kahn BS, Stanford EJ, Willems JJ. Gynecologic presentation of

interstitial cystitis as detected by intravesical potassium sensitivity. Obstet Gynecol.

2001;98(1):127-132.

9. Royal College of Obstetricians and Gynaecologists. Guideline No. 41: The initial

management of chronic pelvic pain. London, U.K.:RCOG;2005.

10. Zondervan KT, Yudkin PL, Vessey MP, et al. Chronic pelvic pain in the community-

symptoms, investigations, and diagnoses. Am J Obstet Gynecol. 2001;184(6):1149-1155.
11. Bordman R, Jackson B. Below the belt: approach to chronic pelvic pain. Can Fam

Physician. 2006;52(12):1556-1562.

12. Price J, Farmer G, Harris J, Hope T, Kennedy S, Mayou R. Attitudes of women with

chronic pelvic pain to the gynaecological consultation: a qualitative study. Br J Obstet

Gynaecol. 2006;113(4):446-452.

13. Mounsey AL, Wilgus A, Slawson DC. Diagnosis and management of endometriosis. Am

Fam Physician. 2006; 74(4):594-600.

14. Jamieson DJ, Steege JF. The association of sexual abuse with pelvic pain complaints in a

primary care population. Am J Obstet Gynecol. 1997;177(6):1408-1412.

15. Lentz GM, Bavendam T, Stenchever MA, Miller JL, Smalldridge J. Hormonal manipulation

in women with chronic, cyclic irritable bladder symptoms and pelvic pain. Am J Obstet

Gynecol. 2002;186(6):1268-1271.

16. Moore J, Barlow D, Jewell D, Kennedy S. Do gastrointestinal symptoms vary with the

menstrual cycle? Br J Obstet Gynaecol. 1998;105(12):1322-1325.
17. Howard F. Evaluation of chronic pelvic pain in women. In: UpToDate, Rose, BD (Ed),

Waltham, MA: UpToDate, 2007.

18. Gambone JC, Mittman BS, Munro MG, Scialli AR, Winkel CA; Chronic Pelvic

Pain/Endometriosis Working Group. Consensus statement for the management of chronic

pelvic pain and endometriosis: proceedings of an expert-panel consensus process. Fertil

Steril. 2002;78(5):961-972.

19. Cody RF Jr, Ascher SM. Diagnostic value of radiological tests in chronic pelvic pain.

Baillieres Best Pract Res Clin Obstet Gynaecol. 2000;14(3):433-466.

20. Daha LK, Riedl CR, Hohlbrugger G, Knoll M, Engelhardt PF, Pflüger H. Comparative

assessment of maximal bladder capacity, 0.9% NaCl versus 0.2 M Kcl for the diagnosis of

interstitial cystitis: a prospective, controlled study. J Urol. 2003;170(3):807-809.

21. Proctor ML, Roberts H, Farquhar CM. Combined oral contraceptive pill (OCP) as

treatment for primary dysmenorrhea. Cochrane Database Syst Rev. 2001(4):CD002120.
22. Schlaff WD, Carson SA, Luciano A, Ross D, Bergqvist A. Subcutaneous injection of depot

medroxyprogesterone acetate compared with leuprolide acetate in the treatment of

endometriosis-associated pain. Fertil Steril. 2006;85(2):314-325.

23. Sator-Katzenschlager SM, Scharbert G, Kress HG, et al. Chronic pelvic pain treated with

gabapentin and amitriptyline: a randomized, controlled pilot study. Wien Klin Wochenschr.

2005;117(21-22):761-768.

24. Petta CA, Ferriani RA, Abrao MS, et al. Randomized clinical trial of a levonorgestrel-

releasing intrauterine system and a depot GnRH analogue for the treatment of chronic

pelvic pain in women with endometriosis. Hum Reprod. 2005;20(7):1993-1998.

25. Selak V, Farquhar C, Prentice A, Singla A. Danazol for pelvic pain associated with

endometriosis. Cochrane Database Syst Rev. 2001;(4):CD000068.

26. Metts JF. Interstitial cystitis: urgency and frequency syndrome. Am Fam Physician.

2001;64(7):1199-1206.

27. Viera AJ, Hoag S, Shaughnessy J. Management of irritable bowel syndrome. Am Fam

Physician. 2002; 66(10):1867-1874.
28. Ling FW, Slocumb JC. Use of trigger point injections in chronic pelvic pain. Obstet

Gynecol Clin North Am. 1993;20(4):809-815.

29. Langford CF, Udvari Nagy S, Ghoniem GM. Levator ani trigger point injections: an

underutilized treatment for chronic pelvic pain. Neurourol Urodyn. 2007;26(1):59-62.

30. Dennehy CE. The use of herbs and dietary supplements in gynecology: an evidence-

based review. J Midwifery Womens Health. 2006;51(6):402-409.

31. Jarvis SK, Abbott JA, Lenart MB, Steensma A, Vancaillie TG. Pilot study of botulinum toxin

type A in the treatment of chronic pelvic pain associated with spasm of the levator ani

muscles. Aust N Z J Obstet Gynaecol. 2004;44(1):46-50.

32. Abbott JA, Jarvis SK, Lyons SD, Thomson A, Vancaille TG. Botulinum toxin type A for

chronic pain and pelvic floor spasm in women: a randomized controlled trial. Obstet

Gynecol. 2006;108(4):915-923.

33. Hillis SD, Marchbanks PA, Peterson HB. The effectiveness of hysterectomy for chronic

pelvic pain. Obstet Gynecol. 1995;86(6):941-945.
34. Kjerulff KH, Langenberg PW, Rhodes JC, Harvey LA, Guzinski GM, Stolley PD.

Effectiveness of hysterectomy. Obstet Gynecol. 2000;95(3):319-326.

35. Chen FP, Chang SD, Chu KK, Soong YK. Comparison of laparoscopic presacral

neurectomy and laparoscopic uterine nerve ablation for primary dysmenorrhea. J Reprod

Med. 1996;41(7):463-466.

36. Aboseif S, Tamaddon K, Chalfin S, Freedman S, Kaptein J. Sacral neuromodulation as an

effective treatment for refractory pelvic floor dysfunction. Urology. 2002;60(1):52-56.

37. Siegel S, Paszkiewicz E, Kirkpatrick C, Hinkel B, Oleson K. Sacral nerve stimulation in

patients with chronic intractable pelvic pain. J Urol. 2001;166(5):1742-1745.

38. Kim SW, Paick JS, Ku JH. Percutaneous posterior tibial nerve stimulation in patients with

chronic pelvic pain: a preliminary study. Urol Int. 2007;78(1):58-62.

39. van Balken MR, Vandoninck V, Messelink BJ, et al. Percutaneous tibial nerve stimulation

as neuromodulative treatment of chronic pelvic pain. Eur Urol. 2003; 43(2):158-163.
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The Editor:

She received her pharmaceutical college degree from University of China Medical College in

Taiwan.She has been over twelve years experience works at the field of Medicine.
<花絮>
Zolade x (goserelin)

台北榮民總醫院腫瘤科 趙大中醫師

  乳癌是一個與荷爾蒙密切相關的癌症,病患的乳癌細胞若呈現荷爾蒙

接受體陽性反應(包括雌激素接受體或黃體素接受體),就應該考慮接受適

當的荷爾蒙治療。荷爾蒙治療的選擇,在停經前婦女及停經後婦女有些不

同。停經前婦女其雌激素的來源主要是卵巢,而停經後的婦女則因卵巢已

失去製造雌激素的功能,因此轉而由腎上腺分泌出雌激素的先驅物質,進

而在周邊組織轉變為雌激素。因此在停經前婦女,除了使用傳統的抗雌激

素藥物 tamoxifen 外,設法抑制卵巢功能也就成為乳癌荷爾蒙治療另一個重

點。黃體荷爾蒙刺激素類似物(luteinising hormone releasing hormone

analogue),就是能在這方面發揮療效的藥物之類。而其中最為廣泛研究與

使用的即是 Zoladex (goserelin)。

  根據過去的研究,針對停經前早期乳癌病患,在適當的手術、及局部

放射治療後,若能進一步以手術的方式將卵巢去除、或以放射線照射的方
式將卵巢功能摧毀,則可以明確地延長此類病患的無病存活及整體存活率;

換言之,「摧毀卵巢」:使卵巢喪失分泌雌激素的功能,可提高病患痊癒

的機會。但是這二種「摧毀」卵巢的方式都有不少的副作用,包括對卵巢

的損傷是永久而不可逆的,均使病患直接成為停經狀態,而必須提早面對

停經症候群的威脅(如臉部潮紅、陰道乾燥、性交不適等),其他的缺點則

如手術的風險、骨盆放射治療所造成的骨髓造血功能抑制等。另外,乳癌

病患所接受的化學治療也會導致提早停經(如合併

cyclophosphamide、methotrexate、及 fluorouracil (CMF)的化學治療會導致 60%

以上的病患提早停經),這種化學治療所附帶的「卵巢摧毀」也被視為是化

學治療的治療效益之一。而 Zoladex (goserelin)是一種人工合成之黃體荷爾

蒙刺激素(luteinising hormone releasing hormone, LHRH)的類似物。它是由十

個胺基酸所組成,若採口服在腸道即會被分解,無法發揮作用,所以必須

以注射方式使用。皮下注射後,可持續作用達 28 天之久,因此只要每 28

天注射一次即可發揮作用。Zoladex 進入血液後,會作用於腦下垂體細胞,

佔據細胞表面所有的黃體荷爾蒙刺激素接受體,一開始可能會引發短暫的

黃體荷爾蒙大量分泌,之後便因為接受器下降調節(receptor downregulation)

的機制,使腦下垂體細胞幾乎不再分泌黃體荷爾蒙刺激素;卵巢在缺乏黃
體荷爾蒙刺激素的刺激下,便也不再分泌雌激素;故接受皮下注射 Zoladex

的婦女,等於處在停經後的狀態,如同卵巢切除手術或放射線照射般的效

果,然而病患不必冒手術的風險,且可能的副作用較低。最重要的是,對

乳癌手術後、接受輔助性荷爾蒙治療的停經前年輕婦女而言,治療後仍恢

復受孕能力,並享受完整女性的生活。

  在治療效果上,根據最近的研究結果發現,對早期腋下淋巴結陽性、

而且荷爾蒙接受體為陽性之停經前女性乳癌病患,在手術後接受每 28 天

3.6 毫克的 Zoladex 皮下注射 2 年,或是每 28 天接受一次輔助性化學治療

(處方為 cyclosphosphamide、methotrexate、fluorouracil,簡稱 CMF)共 6 次,

在平均超過 6 年的追?後發現,其預防復發的效果是相似的;但接受

Zoladex 的病患不必忍受化學治療的副作用,包括噁心/嘔吐、掉髮、感染

等問題;值得注意的是,接受 Zoladex 的病患在二年治療期間,幾乎 100%

達到停經狀態,但在治療期結束後,月經多能恢復(約 80%,之後這婦女也

會隨著自然接近停經年齡而停經);但在接受化學治療組的婦女,約 60%也

會在治療期間停經,但治療後則多半無法恢復。另外,對荷爾蒙接受體陰

性的病患而言,六次 CMF 的輔助性化學治療在預防復發的效果上會優於
Zoladex。在另一個合併 Zoladex 與 tamoxifen 的臨床研究上,此種「比較完

全」的荷爾蒙阻斷治療比化學治療(CMF 處方)在停經前荷爾蒙接受體陽性

的早期乳癌病患上,更能有效延長無病存活期(換言之,更能預防復發),

而且整體存活率也有更好的趨勢。但也有研究發現,同樣對於荷爾蒙接受

體陽性、腋下淋巴結陽性的早期乳癌病史而言,在輔助性化學治療

cyclophos -phamide、doxorubicin、fluorouracil,簡稱 CAF 的處方後,接受

Zoladex 合併 tamoxifen 5 年無病存活率的比較上,優於單獨使用 Zoladex。

總之,Zoladex 合併 tamoxifen 使用,效果較佳,也優於只使用輔助性化學

治療 CMF;而輔助性化學治療 CAF 處方再合併輔助性荷爾蒙阻斷治療

Zoladex 加上 tamoxifen 使用,可能是腋下淋巴結陽性且荷爾蒙接受體陽性

之停經前早期乳癌病患最好的治療選擇。

  對轉移性、晚期的停經前乳癌病患而言,若其轉移部位為短期內不危

及生命的軟組織(如淋巴結、皮膚)或骨骼,而非肺臟、肝臟等重要維生器

官,則 Zoladex 同樣也可作為相當有效的第一線治療藥物,其療效至少和

卵巢切除相似;單獨使用 Zoladex 於這類病患,其反應率即可達三至四成,

另有約三成的病患可維持穩定而不惡化,而合併使用 tamoxifen 效果更佳;
在反應持續時間、疾病無惡化時間上,甚至可能優於化學治療,而且毒性

也較化學治療為輕。若用於 tamoxifen 無效後之第二線荷爾蒙治療,反應率

也有約二成。

  總而言之,Zoladex 對停經前、荷爾蒙接受體陽性的乳癌病患,不論是

當作局部治療後的輔助性治療,或是轉移性、病患的緩解性治療,都是相

當有效的藥物,而且副作用少,使用方便,的確是乳癌病友們的一大福音。

登錄日:92 年 1 月 1 日