???? (premature ovarian failure, POF)

1
??????????????(Study of TCM on Premature
Ovarian Failure)
?? ??????????????? Dr. ling Zhu Department of
Gynecology. the First Affiliated Hospital
Guangzhou University of TCM
Mar/22/2009
New York. USA
2
??????????????

• ???????(2002?-?)
• ???????(2002?-?)
• ???????(2005?)
• ????????(1986?,??)
• ????????(1981?,??)
• ???????(2000?-?)
• ???211????????(2003?-?)
• ???????????????8,?????????(???????????????????
  ?2005????????)

3
??????????????

• ?????????????????????????????????????
• ?????????????????????,??????????????????????
• ????????????????
• ?????????????????,
• ?????????5?6?
• ???????,
• ???????????????

4
????????????Correlated study funds sources of
POF

• ????????(No30400607)(2005.1-2007.12)
• ?????
• National Natural Science Foundation of China
  (No30400607)(2005.1-2007.12)
• ?????????(No403021) (2004.1-2005.12)
• ?????
• Fund by Bureau of TCM , GuangDong province
  (No403021) (2004.1-2005.12)

5
??????

• ?????????40???????,?????(FSH)??????(LH)????(FSHgt40
  IU/L),??????????????
• ?????????0.33,???????2025,??????1020?????
  ?????????POF??????????
• The term premature ovarian failure(POF) describes
  a stop in the normal functioning of the ovaries
  in a woman younger than age 40.  It is also known
  as hypergonadotropic hypogonadism. Amenorrhea is
  a frequent syndrome. The characterstics of the
  patients hormone are high follicle stimulating
  hormone (FSHgt40IU/L) and luteotrophic
  hormone(LH), but low estrogen.
• The disease rate is 0.33, occupy 2025 in
  primary amenorrhea,1020 in secondary
  amenorrhea?

6
?????????study of etiology on POF(1)

• ????? iatrogenic factor
• ???? psychologic factor
• ???? hereditary factor
• ????? immunology factor ??????
• ???? metabolism factor??????
• ????????? environmental factor and affectoi
• ??????????????????????????????POF?
• ??? unknown factor

7
????????? study of etiology on POF(2)

• ???????POF???????????CD8T?????CD4/CD8????,????
  ??????(Plt0.05)?
• Our study indicate the serum CD8T cells with
  POF increase than normal one, the ratio of
  CD4/CD8 decrease.

8
????????? study of etiology on POF(3)

• ???? seven modes of emotions
• ?? six exopathogens
• ???? inherent deficiency
• ??????? surgery, medicines
• ??
• ?? seven modes of emotions(38 ?/122?,?31.15)
• ??????? medicines and diseases(39?/122?,?31. 97)
• ???????????? both seven modes of emotions and
  medicines and diseases(6?/122?,?4.92)
• ???? no cause can be find(39?/122?,?31. 97)
• (???,2008?4?)

9
????????? Pathogenetic characteristic of POF

• ??,????,????
• renal deficiency, insufficiency of qi and blood,
  stagnation of liver-qi and blood stasis

10
????????characteristic of syndrome of POF (1)
?? syndrome ??? Case number ???() percentage ?? syndrome ??? Case number ???() percentage
???? stagnation of liver-QI and renal deficiency 41 33.61 ???? renal deficiency and blood stasis 10 8.20
???? hepatic and renal yin deficiency 22 18.03 ???? stagnation of liver-QI with deficiency of the spleen 9 7.38
(???,2008?4?)
11
????????characteristic of syndrome of POF (2)
?? syndrome ??? Case number ???() percentage ?? syndrome ??? Case number ???() percentage
???? asdthenic splenonephro-yang 19 15.57 ???? carduonephric cisharmony 1 0.82
???? consumption of body-fluid caused by excessive heat 19 15.57 ????splenasthenic fluid-retention 1 0.82
(???,2008?4?)
12
????????characteristic of syndrome of POF (2)

• ?????????
• ??amenorrhea(105?/122?,86.07)
• ????hectic fever and sweating(83?/122?,68.03 )
• ????sexual desire indifference(52?/122?,42.62 )
• ??flustered(47?/122?,38.52 )
• ???insomnia(42?/122?,34.43 )
• ??restlessness(37?/122?,33.03 )
• ????(29?/122?,23.77 )
• ???(22?/122?,18.03 )
• ????(13?/122?,10.66 )
• ????(13?/122?,11.02 )
• (???,2008?4?)

• ?????????
• ??menorrhea(19?/20?,100)
• ??dreamful sleep(18?/20?,90)
• ????vaginal unsmooth ??(17?/20?,85)
• ????(16?/20?,80)
• ??restlessness(6?/122?,80)
• ????ademosyne(13?/20?,65)
• ??(8?/20?,40)
• ??(7?/20?,35)
• (??????,2004?7?)

13
??????Treatment on POF

• ??????,??????,??????
• differentiation of symptoms and signs
• renal deficiency, insufficiency of qi and blood,
  stagnation of liver-qi and blood stasis
• ?????????,????,??????????????????
• Method of treatment Tonifying kidney and balance
  yin and yang , nourishing qi and blood, disperse
  the depressed liver-energy and promoting blood
  flow

14
????(????),?????(1)invigorate the liver and
kidney, disperse the depressed liver-energy and
promoting blood flow

• ??,?,36?,??,2008?5?10????
• ?????
• Menolipsis more than 6 months.
• ??????????2003???????,????????????,????,????,?????
  ??,??,????,?2005?8????????FSH53.1IU/L,LH37.8
  IU/L,E2140.12 pmol/L,PRL10.3ug/L????????2007?10?
  ???????FSH78.3IU/L,LH56.2 IU/L,E2220.12
  pmol/L?LMP2007?11?2??
• The womans menstruation was regular before 2003.
  Since then her menstruation was irregular
  because of stronger stress and instable emotions.
  After polymenorrhea, oligomenorrhea occurred.
  She went to hospital to check serum hormones.
  Her hormones were FSH53.1IU/L,LH37.8
  IU/L,E2140.12 pmol/L,PRL10.3ug/L?She was
  treated by Progynova(estradiol valerate)?She
  rechecked hormones on Oct. 2007FSH78.3IU/L,LH56
  .2 IU/L,E2220.12 pmol/L?LMPNov-2-2007?

15
????(????),?????(2)invigorate the liver and
kidney, disperse the depressed liver-energy and
promoting blood flow

• ?????????,????,???????????????,???,???
• ??????????,?????,???,???,???,??,???,??,??,???????
  ???
• G1P1
• Thin, insomnia, dreamful sleep ,restlessness, eye
  sockets dim. red tip of tongue with edge
  petechia, thin and whitish fur, small puls.

16
????(????),?????(3)invigorate the liver and
kidney, disperse the depressed liver-energy and
promoting blood flow

• ??????
• Diagnose POF.
• ??????,?????
• differentiation of symptoms and signs yin
  asthenia generating intrinsic heat, congestion of
  the liver.
• ??????(????),?????
• Method of treatment invigorate the liver and
  kidney, disperse the depressed liver-energy and
  promoting blood flow
• ????? Zuogui Pill
• ??ShenDi 15g ???ShanZhuYu 12g ??HuangJing 20g
• ???TuSiZi 15g ???luJiao glue 9g(??melting)
• ???GuiBan glue 9g (??melting)??? NiuXi 15g
• ??YuJin 15g ??CaiHu 10g ??BaiShao 10g
• ???YeJiaoTen 15g ??GanChao 6g

17
????(????),?????(4)invigorate the liver and
kidney, disperse the depressed liver-energy and
promoting blood flow

• 2008?5?24???????,????,?????,????,????????,???????
  ??????,????15g, ??10g??????,???????
• returned visit on May-24-2008
• Less Restlessness , insomnia, dreamful sleep, no
  menstruation,Loose stools. Dark and red tip of
  tongue, thin and whitish fur, small puls. Removed
  ???luJiao glue 9g(??melting), ??HuangJing
  20g,added???HeHuanPi 15g, ??Chuan Xiong 10g in
  order to calm the nerves and disperse the
  depressed liver-energy and promoting blood flow.
• ??ShenDi 15g ???ShanZhuYu 12g ???TuSiZi 15g
• ???GuiBan glue 9g (??melting)??? NiuXi 15g
• ??YuJin 15g ??CaiHu 10g ??BaiShao 10g
  ???YeJiaoTen 15g
• ??GanChao 6g ???HeHuanPi 15g, ??Chuan Xiong
  10g

18
????(????),?????(5)invigorate the liver and
kidney, nourishing qi and blood, disperse the
depressed liver-energy and promoting blood flow

• 2008?6?7???????,???,?????,???,??????????????
• returned visit on June-7-2008
• sleep better. Normal urine and stool. No
  menstruation restlessness, spargosis. Dark red
  tongue, thin and yellow fur, slippery pulse
• ??????,????,????
• Method of treatment promoting qi to activate
  blood,invigorate the kidney and disperse the
  depressed liver-energy.
• ??TaoRen 15g ???YiMuChao 15g ??ChuanXiong 10g
• ??DangGui 10g ??ShenDi 15g ???TuSiZi 15g
• ??? NiuXi 15g ??YuJin 15g ??CaiHu 10g
• ??BaiShao 10g ???YeJiaoTen 15g
• ???HeHuanPi 15g ??GanChao 6g

19
????(????),?????(6)invigorate the liver and
kidney, disperse the depressed liver-energy and
promoting blood flow

• 2008?6?13??????5?,????,???,???,???,
  ????,???????????????????????????????15,????15g,??3
  g????15g????15g????,????,???????????,5??.
• returned visit on June-13-2008 menstruation came
  after taking medicine, but less. Removed???
  NiuXi 15g , ??YuJin 15g, ???YeJiaoTen 15g,
  ???HeHuanPi 15g, add ???LuLuTong 15g,??ShuiZhi
  3g, ???NvZhenZi 15g, ???HanLianChao 15g. Taking
  the medicine, her menstrual blood volume became
  more.
• ??TaoRen 15g ???YiMuChao 15g ??ChuanXiong 10g
• ??DangGui 10g ??ShenDi 15g ???TuSiZi 15g
• ??CaiHu 10g ??BaiShao 10g ??GanChao 6g
• ???LuLuTong 15g,??ShuiZhi 3g,
• ???NvZhenZi 15g. ???HanLianChao 15g

20
????(????),?????(7)invigorate the liver and
kidney, disperse the depressed liver-energy and
promoting blood flow

• ?????????,??40-50????
• 2008?11?30???FSH13.6IU/L,LH10.7 IU/L,E2289.43
  pmol/L?
• up to now, she is taking ZuoGui pill to regulate
  menstruation. Her cycle is 40-50 days.
• She rechecked hormones on 30-Nov-2008
• FSH13.6IU/L,LH10.7 IU/L,E2289.43 pmol/L?

21
????,??????(1)nourishing yin to lessen
fire,tonifying blood and promoting blood
circulation to remove meridian obstruction

• ??,?,39?,2003?8?13????
• ??5??
• 2002?9??????(10-15?)????,????6-7?,????,???????????
  ?,LMP2003?3?19?,???FSH97.27IU/L,LH32.44IU/L,E2
  20 pmol/L,P0.35nmol/L,PRL6.78ug/L??????,??,???
  ?????????
• ??????
• ??????,????
• ??????,??????
• ??15g ???20g ???12g ???15g ??12g
• ???12g ??15g ??20g ??15g ??15g
• ???30g ??15g
• 25/8????????,????????????
• ???20g ??15g ???10g ??20g ??15g ??15g
• ???30g ??10g ??15g ??6g

22
????,??????(2)nourishing yin to lessen
fire,tonifying blood and promoting blood
circulation to remove meridian obstruction

• 17/9 ??LMP8/9-13/9,???,????
• ???20g ??15g ???10g ??15g ??20g ??15g
• ??10g ??15g ???30g ???30g ???10g ??6g
• 13/10 ??LMP13/10-17/10,????,???,????,??2-3?,????
  ,??????????
• ???20g ??15g ???12g ???15g
• ??12g ??15g ??15g ???30g
• ??20g ??15g ??15g

23
????,??????(3)nourishing yin to lessen
fire,tonifying blood and promoting blood
circulation to remove meridian obstruction

• 23/10??LMP13/10-17/10,??,???,????,???,??,??,????
  ???
• ???20g ??15g ???12g ???15g
• ??30g ??15g ??15g ??15g
• ???10g ??15g ??15g ???30g
• 22/11??LMP10/11-13/10,???,???,???,???,???,??????
  ?????
• 12/11???FSH6.66IU/L,LH6.08 IU/L,E2256
  pmol/L,P4.35nmol/L,T0.88nmol/L?
• ???20g ???12g ??15g ???15g
• ??15g ??15g ??15g ??15g
• ???30g ??10g ???15g ??10g

24
????(1)Related study (1)

• ????????????????30?
• ?????15g,???15g,???10g,???15g,???15g,???20g,???
  10g,???10g,??6g,???15g,??15g,??10g?
• ????,????,????,???30g,??15g
• ????,????,????15g,???15g
• ????,?????,????15g,???15g,??15g?
• 3???1????1????, ??15?,??13?,??2?,????93.33?
• 30 patients with secondary amenorrhea were
  treated by Zuogui pill. One course of treatment
  every 3 months.15 patients were recovery after
  One course of treatment,13 cases were improved
  and 2 ones useless. Its total effective rate is
  93.33 . (???,2008)

25
????(2)Related study (2)

• ??? POF??????????????,???FSH??,E2??,AoAb??,???????
  ???-9(growth and differentiation
  factor-9,GDF-9)mRNA???????,???????????????????POF?
  ????FSH??,????E2??,??AoAb??,??????GDF-9
  mRNA?????,?????????????,??????????????
• Ovarian interstitial of the immune POF(growth and
  differentiation factor-9,GDF-9) mice occurred
  lymphocytes infiltration. The positive cell
  number of GDF-9 mRNA of oocytes decreased. The
  growing follicles and mature follicles decreased
  obviously. ZuoGui Pill could normal the increase
  of FSH and the decrease of E2,inhibit the produce
  of AoAb, rise the positive cell number of GDF-9
  mRNA of oocytes, increase the number of growing
  follicles and mature follicles, release the
  damages of ovarian inflammation. It can treat
  immune premature ovarian failure.

26
????(3)Related study (3)

• ???POF??????????FasL???????, Bcl-2????,Bax????,???
  ????????,????????????????,?????????,??????,???????
  ????,??????,?????????????FasL????,??????????,?????
  ????
• The expression of Fas protein in great folliculus
  and small ones decreased obviously in POF mice.
  The expression of FasL protein in small
  folliculus and stroma increased obviously in
  model mice. The expression of Fas protein in
  great folliculus and small ones increased
  obviously in the mice of different dosage ZGP.
  The expression of Fas protein increased in stroma
  but the expression of FasL protein decreased in
  small folliculus in the mice of low dosage ZGP.
  The expression of Fas protein in stroma also
  increased obviously in the mice of high dosage
  ZGP. The differences were significant compared
  with the model mice.

27
????(????),??????Warming the kidney and spleen,
disperse the depressed liver-energy(, tonifying
and promoting blood flow

• ??,30?,??,2003?4?18????
• ????1??,??2????1?????50??????,????????,???????????
  ???,?????2????,?????2?17?,?2?1??1????????,??,????,
  ????,??,???,???????,????
• ????FSH47. 7IU/L,LH23. 14IU/L,PRL5.
  8p,g/L,E2 230pmoL/L, P3.879nmoL/L, T1.
  09nmoL/L?
• ???????
• ??????,????,????.
• ??????,???????
• ??30g,????????20g,????????????????1Og,????????????
  ??15g?
• ??????4??,???????,??????????,???????
• ??FSH 22. 87IU/L, LH 9.10IU/L, E2
  399pmoL/L,????2?,??????,??,4-5??????BBT????

28
???????????42?????42 patients with secondary
amenorrhea were treated by Erxian soup

• ???????????????????????????????15g,??30g?
• ??3??1???,????3?????????(FSH?E2?LH?)??????
• ??14?,??19?,??9?,?????78.5?E2?FSH?LH???????,?????
  ?,???????(Plt0.05)?????????????77,???????(Plt0.05)
  (????,2008?)
• One course of treatment every 3 months.14
  patients were recovery after treatment,19cases
  were improved and 2 useless. Its total effective
  rate is 78.5 .

29
???????????42?????42 patients with secondary
amenorrhea were treated by Erxian soup

• ??
• ???????????????,
• ???????????????,
• ??????????,
• ????????????????,
• ????????,
• ?????????????????,
• ????????????????,
• ???????????,
• ??????????????

30
????Related study

• ???? ????
• the study at now indicate
• ?? ?????????,??????????
• There is curculigoside in curculiginis rhizoma,
  which can increase the immune ability .
• ???(???)????????,?????????????,???????????
• Epimedium has the function like estrogen. This
  weight ovaries and uterum. Promoting the secrete
  of testosterone

31
????Related study

• ????????E???????????????
• There is vitamin E in morinda root , which
  promotes the functions of ovaries and antidotal.
• ?????????????E?????,???????????
• angelica root can excite uterum and normal low
  vitamin E.
• ????????,??????????????????,???????????????,??????
  ???????,??????????????????????????????
• Lithospermi radix normal the secretion of Gn.

32
??(1) acupuncture and moxibustion

• ????????????????
• ??5-?4 ???
• ?????????? ???????
• ?????????
• ???????????????
• ????,??????,?????20???????????,????????????510??
  ?
• ??20??1?????5 7????1??,6??????
• ??84?POF???????90.4?
• main pointGuanyuan,Zhongji, Dahe,uterus,Shenshu,
  
• hepatic and renal yin deficiency add Sanyinjiao,
  Yinlingquan, Ganshu(Liver Shu), Yinxi, Fuliu.
  Taixi
• asdthenic splenonephro-yang add Pishu, Mingmen,
  Diji
• reinforcing method. Keeping 20 minutes. Every 20
  is a course of treatment. Take a rest for 5-7days
  between two course of treatment. Not exceed 6
  course of treatment.(????,1998?)

33
??(2-1) acupuncture and moxibustion

• ??
• A??????????????????????????????
• B?????????????????
• ?????? ???
• ?????????????????????,???????,?????30min,??10min?
  ?1?,????????,??1??
• ???????????????????,
• ????????????????,
• ?????????,
• ????????????,
• ??????????????
• main point
• Acupoints AGuanyuan,Guilai, uterus,Zhongji,
  Sanyinjiao, Zhusanli, Taichong, Taixi
• Acupoints BGeshu, Ganshu(Liver Shu), Pishu,
  Shenshu, Guanyuanshu ,
• Above two acupoints can be used alternately

34
??(2-2)

• ??3???1??, 2?????,???????1??
• ??60????????13?(??????,????,??FSH?LH?E2??)??14?(
  ??????,????,??FSH?LH?E2????),??3?(??????,????,??FS
  H?LH?E2?????),?????90?
• (????,2008?)

35
??(3)

• ?????????????32?,??8?,??9?,??10?,??5?,?????86.50
  ?
• ?????????????30g,????????20g,????????????????????
  ???????????12g
• Moxibustion points, which is temperature
  sensitive , combined with Guishen Pill treat 32
  patients with POF, 8 patients were recovery after
  treatment,19 cases were improved and 5 useless.
  Its total effective rate is 86.5 .
• (????,2007?)
• ?????POF?? LH ????, ? E2 ?????????????????????????
  ?????????????????
• (???,2008?)

36
???? Treatment of west medicine

• ??????(hormone replacement therapy, HRT)
• ???? ovary transplantation
• ???? ovum donation

37
???????Are there ways to prevent premature
ovarian failure?

• 1???????,??????(????????)?????
• Monitoring ovarian fuctions, it is important
  early discovery and early treatment. (ovarian
  reserve hypofunction)
• 2????????????,???,???????????,???????
• good health life style.
• Stopping smoking and drinking.
• Exercise.
• Adjust food and drink.
• Keeping delighted mental. Learn self-adjustment.

38
??(Summary)

• ?????????????,????,????
• ??????,?????????(????,????),????(??????,????????,
  ????????,????,???),??????????(????)?
• renal deficiency, insufficiency of qi and blood,
  stagnation of liver-qi and blood stasis
• early discovery and early treatment
• invigorate the kidney,treat both spirit and
  body, Notice long-term complication(osteoporosis)

39
??(SUMMARY)
??
THANK YOU

• ????,?????????,????,?????,????,????,????,??????,?
  ?????,???????,????,???????,?????????
• ????,????????,?????????,?????,???????,???????
  ??????,???????,????????????,????,?????,?????????
  (????)

40
???? hereditary factor

• ??POF????????????4-31 ,??????????1,????????POF?
  ???????????,??????X???????????,????????
• The disease rate with family history of POF is
  431, more than normal crowd with 1.
• ???????2?????????????(FSHR)?????3???????????(forkh
  ead transcriptional factor 2, FOXL2)?????,???????
  ??????,?????????????,????POF????????,?????????????
  ??
• FMR 1 (fragile X mental retardation 1, FMR
  1)??????POF??????
• follicle stimulating hormone receptor (FSHR)
  gene mutation forkhead transcriptional factor
  2(FOXL2) gene mutation, fragile X mental
  retardation 1(FMR 1) gene premutation.

41
????? iatrogenic factor

• ????chemotherapy
• ??radiotherapy
• ??operation
• ??????immunosuppressive therapy(??????????????????
  ?????)
• ??????uterine arterial embolism(??????????????????
  ?)?

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