Volume 8, Number 1 | Spring 2013

Kampo Medicine - Current Research
Clinical Experience for Functional Sterility, Complicatedwith Irregular Menstruation and Anovulatory Cycle,
Administrated of Saireito
Takeshi Nakayama
Department of Obstetrics and Gynecology,
Shizuoka Kosei Hospital[Abstract]
Kampo therapy for sterility is often used as single
or adjunctive agent medicated with a western
medicine, for primarily treating the functional
abnormalities such as anovulation. Typically, thechiefpatternsofadministrationaretokishakuyakusan, unkeito, and other agents that
improve blood deficiency. Many researches havebeen reported concerning their efficacy in treatmentof sterility. In recent years, however, many patterns
other than the type of blood deficiency may bepresent due to food satiation and the stress-relateddisease. Thus, newer approaches of Kampo therapy
adapted for the modern age would be necessary forthe treatment of sterility.
Therefore, we tried administrating saireito, aformulation to treat Qi stagnation and fluid
retention, for patients with sterility complicatedwith irregular menstruation or anovulatory cycle. Its
excellent efficacy was demonstrated by assessmentof changes in sex hormonal levels, the recovery rateof menstrual cycle, and the rates of ovulation andpregnancy before and after the oral administration.
Since saireito has ever exerted the alleviating effecton stress in some cases in addition to the improving
effect on ovarian function, it is estimated to be aneffective administration for patients with sterility
accompanied with the menstrual irregularity or the
anovulatory cycle.
Key words: Primary Sterility, Saireito, Irregular
Menstruation, Anovulatory Cycle

6[Introduction]
Saireito is a combination formula made up of
shosaikoto and goreisan for the treatment of
stagnation of liver Qi and fluid disturbance. It is
supposed to have endogenous steroid hormone-likeactions and inhibits platelet aggregation and its
effects for the treatment of gestational edema andhabitual abortion have been confirmed in the field ofobstetrics and gynecology. Recently it has reportedly
shown to be effective for polycystic ovary syndrome
and is therefore expected to be an effective
therapeutic drug for the treatment of abnormal
endocrine metabolism.
In infertility patients, the presence of "Qi" disorder
like Qi depression or Qi stagnation has been pointed
out. Moreover, the metabolic syndrome has developed
into a social problem, so there are not many cases
which blood deficiency is the predominantly major.
Therfore, we tried saireito in patients with functional
sterility complicated by irregularities of menstruation
or ovulation disorders. We examined variations infemale hormone concentrations, menstrual cycle,
variations in ovulation ratio and the occurrence ofpregnancies associated with the internal use ofsaireito to determine whether saireito is an effective
drug for the treatment of infertility.
[Methods]
During the period from January 2008 until December
2011, we prescribed saireito extract granules (Kracie)
8.1 g/bid before the meals after obtaining a sufficient
informed consent for 24 (average age 34.7±4.5 years)out of 89 patients who visited our clinic with thedesire to have children and presented with irregularmenstruation like oligomenorrhea or amenorrhea andwere diagnosed to suffer from ovulation disorders orfunctional sterility. Patients with organic factors likemyoma uteri or the like female factors or else male
factors were excluded. Each individual patientunderwent oriental medical examinations to establish
the disease pattern that were subsequently analyzed,
but prescribed saireito regardless of the pattern. For
this reason the formula may possibly have have been
administered for off-label use. The ethics committeeof our clinic discussed the issue and approved, that in

The Journal of Kampo, Acupuncture and Integrative Medicine (KAIM)

Volume 8, Number 1 | Spring 2013

cases of apparent deviation from the pattern patientsin question were excluded from the study. Bloodexaminations
wereperformed
beforetheadministration, 4 and then 8 weeks later between the
5th to 7th day after onset of the menstruation and thevariations in the measured LH, FSH, LH/FSH,
testosterone values examined. Also, any variations in
the menstrual cycle and the occurrence of ovulations
before and after the administration of saireito wereconfirmed with reference to the basal bodytemperature. Establishment of pregnancies was later
confirmed by the delivery.

The occurrence of adverse events related to theinternal use was also investigated. We attempted at
the same time also to make a comparative study
pertaining to Qi, Blood and Water including all
infertility patients, those treated with saireito as wellas the patients in whom pregnancies occurred after
treatment with saireito.
[Results]
The 24 infertility patients presenting with irregularmenstruation were treated with saireito. In 15 ofthese patients a recovery of the menstrual cycle could
be observed (menstrual cycle improvement ratio 63%).
Also, based on the basal body temperature ovulations
were observed in 14 of the patients with anovulatory
cycles and among these ovulation was definitely
established in 9 patients (ovulation ratio 64%).

Table 1: List of patients who became pregnant
Age

BMI

Gravidity

ParityAbortion

Menstrual cycle

Menstrual(before)(after)cycle

OvulatiOvulation

Durationon(after)until(before)PCOS

pregnancy(Cycle)
4

No

Yes

3

Yes

Yes

Yes

2

No

Normal

No

Yes

4

No

Oligomenorrhea

Normal

No

Yes

3

No

0

Oligomenorrhea

Normal

Yes

Yes

6

No

1

3

Oligomenorrhea

Normal

Yes

Yes

7

No

1

1

3

Oligomenorrhea

Normal

No

Yes

2

No

20.7

1

1

1

Oligomenorrhea

Normal

Yes

Yes

6

No

32

18

0

0

0

Oligomenorrhea

Normal

No

Yes

5

Yes

11

34

23.6

0

0

0

Oligomenorrhea

Normal

Yes

Yes

4

No

12

34

19.3

0

0

0

Oligomenorrhea

Oligomenorrhea

Yes

Yes

6

Yes

13

37

17.4

0

0

0

Oligomenorrhea

Oligomenorrhea

No

Yes

12

No

14

40

24.9

0

0

0

Oligomenorrhea

Oligomenorrhea

No

Yes

4

No

15

37

21

2

1

1

Oligomenorrhea

Normal

Yes

Yes

3

No

16

39

39

2

2

0

Oligomenorrhea

Normal

Yes

Yes

7

No

1

33

26.6

1

1

0

Oligomenorrhea

Normal

No

2

28

17.5

1

0

0

Oligomenorrhea

Normal

No

3

34

19.9

0

0

0

Oligomenorrhea

Normal

4

34

20.1

0

0

0

Oligomenorrhea

5

42

28.4

2

1

1

6

33

22.6

0

0

7

40

21.1

5

8

31

21.8

9

24

10

The Journal of Kampo, Acupuncture and Integrative Medicine (KAIM)

Yes

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Volume 8, Number 1 | Spring 2013

Among the 24 infertility patients pregnancies
occurred following treatment with saireito in 16
women (pregnancy rate 67%, see Table 1).
Treatment duration with saireito until establishmentof pregnancies was on the average 4.9±2.5 weeks.
Moreover, while 6 out of the 24 patients werediagnosed with Polycystic Ovary Syndrome (PCOS),
pregnancies occurred in 3 of those patients(pregnancy ratio 50%). A breakdown of the outcomein the 16 women who got pregnant showed ongoing
pregnancies in 14 (87%) women and spontaneousabortion in 2 (13%). The delivery in those women, who
actually gave birth was uneventful for both motherand child, considered to be also due to the fact, thatthe children had simultaneously been medicated andobvious anomalies were not observed.
Regarding fluctuations in the gonadotrophic hormone
levels the LH values before, 4 and 8 weeks
respectively after the administration were 7.1±4.8,
5.5±2.8 and 4.7±1.1 mIU/ml. While the LH
concentration tended to be both before and after theadministration low, significant differences were notobserved. The LH/FSH ratio was 0.88±0.62, 0.62±0.27
and 0.55±0.13 respectively and decreased significantly
before and afer the administration.(P<0.05). No
significant differences were observed in FSH andtestosterone levels (Figure 1).

Adverse events associated with the internal use
included the occurrence of mild diarrhea, vomiting
and similar symptoms of gastroenteritis in one
patient (4.2%), but these were alleviated bydiscontinuing the medication. Otherwise, including
clinical laboratory tests, no problematic side effects
were observed.
Examination of Qi, Blood and Water during the visitsof the 89 infertility patients showed Qi deficiency in
31 cases (35%), Qi stagnation in 39 (44%), Blooddeficiency in 50 (56%), Blood stagnation in 31 (35%)
and Water stagnation in 26 (29%) patients. Regarding
the 24 patients treated with saireito 9 (38%)
presented with Qi deficiency, 10 (42%) with Qi
stagnation, 13 (54%) Blood deficiency, 10 (42%) Bloodstagnation and 8 (50%) with Water stagnation.
Among the 16 women in whom a pregnancy occurred 6(38%) presented with Qi deficiency, 6 (38%) with Qi
stagnation, 8 (50%) Blood deficiency, 7 (44%) Bloodstagnation and 7 (44%) with Water stagnation (Table 2).
Table 2: Patterns in infertility patients and patientstreated with saireito

All
infertility
patients(89
patients)
Patients
treatedwithsaireito(24
patients)
Patients
treatedwithsaireito inwhomapregnancy
occurred

Figure 1: Fluctuations in hypophyseal hormones
associated with the administration of saireito

8

Qi

Qi

Blood

Blood

Water

deficiency

stagnation

deficiency

stagnation

stagnation

31/89

39/89

50/89

31/89

26/89

(35%)

(44%)

(56%)

(35%)

(29%)

9/24

10/24

13/24

10/24

8/16

(38%)

(42%)

(54%)

(42%)

(50%)

6/16

8/16

8/16

7/16

7/16

(38%)

(50%)

(50%)

(44%)

(44%)

[Discussion]
The factors responsible for female infertility canbroadly be classified into functional and organic
disorders. Disorders of tubal patency, intrauterine
disorders, peritubal adhesion, myoma uteri,endometriosis etc. can be mentioned as organic

The Journal of Kampo, Acupuncture and Integrative Medicine (KAIM)

Volume 8, Number 1 | Spring 2013

anomalies, but the progress in assisted reproductive
technology (ART） and fiberscopic surgery have led toremarkable improvements in therapeutic results1).
While progress in recombinant preparations andgonadotropin therapies allowed to achieve higher
ovulation ratios in cases of functional anomalies, thepregnancy ratio has not markedly changed andconditions like ovarian hyperstimulation syndrome(OHSS) and multiple pregnancies cannot be avoided.
The results of infertility treatment have improved
remarkably, but there are still some infertility
patients whose cause is unknown, and even if theinfertility treatment with ART is performed, there aremany patients who have difficulty getting pregnant
because of infertility2). Among oriental medical
concepts regarding infertility the "kidneys" arethought to control reproduction, so that the condition
is considered to be based on menstrual anomalies due
to "kidney deficiency"2). However, the condition isoften influenced by multiple factors like anemia andchilling correlated to "Blood deficiency", "Bloodstagnation" caused by circulatory insufficiency,
stress-induced mental conditions like "liver
depression and Qi stagnation", "disorders of the
body's fluid metabolism" due to disorders of pelvic
blood flow etc., which often are present in various
combinations (Figure 2). Some reports state, that
abdominal or tongue examinations showed in actual
clinical practice a close correlation of liver depression
and Qi stagnation, "Blood stagnation" and "disordersof the body's fluid metabolism" with infertility, so that
Bupleurum preparations or drugs for overcoming
Blood stagnation are effective2). Regarding the"pattern" of infertility a study conducted in 1989
showed that approximately 65% of the cases
presented with a deficiency pattern, while excess
patterns were reportedly found in less than 10%.
Regarding anomalies of Qi, Blood and Water "Qi
deficiency" was reported found in 32%, "Qistagnation" in 37%, "Blood deficiency" in 61% and"Blood stagnation" in 22% respectively3). For thisreason formulas for the treatment of "Blooddeficiency": Tokishakuyakusan and unkeito were
frequently chosen and there are multiple reports on
their effects in the treatment of infertility4,5).

Figure 2: Pathology in modern infertility patients(personal proposal)

Qi deficiency

Qi stagnation

Water
stagnation

Anxiety, insomnia, loss ofappetite

Irritability

Edema, obesity,
anomalies ofdischarge

Blood
deficiency

Dietary
weight loss

StressAnemia, xerosis cutis
Circulatory
insufficiency
Blood Dysmenorrhea,
stag- Circulatory failure
nationDysmenorrhea,
ovulation disorder

Saireito is a combination formula composed ofshosaikoto and goreisan that includes 12 crude drugs
and is designed to alleviate stagnation of liver Qi anddisorders of the body's fluid disturbance. The originaltext in the "Shi yi de xiao fang 世医得効方）(Effective
Formulas from Generations of Physicians " by Wci
Yi‐Lin (危亦林 1277-1347) says "very effective forcuring wind damage, summerheat damage andmalaria" and the formula was mainly used for
conditions associated with inflammation. Asada
Sohaku's text "Futsugo Yakushitsu Hokan" contains
the passage: "This formula is used for people with ashosaikoto pattern to alleviate feelings of distressaccompanied by excessive thirst combined withdiarrhea. It is particularly effective for summerheat
epidemics.", describing the symptoms of theshosaikoto pattern. Main indications are nephrotic
syndrome, chronic nephritis and similar renal
diseases, chronic hepatitis etc. where a mild degree of
edema is observed, heat stroke and the like acuteforms of enteritis, exudative otitis media, habitual
headache as well as a combination with steroid
hormones (to reduce dose or alleviate side effects).
Regarding the mechanism of action it has beenreported to stimulate the hypothalamus – hypophysis– adrenal system, while Glycyrrhizae Radix inhibits
the cholesterol metabolism in the liver and reportedly
increases steroid production6). In the field of obstetrics
and gynecology saireito is used for the gestational

The Journal of Kampo, Acupuncture and Integrative Medicine (KAIM)

9Volume 8, Number 1 | Spring 2013edema associated with habitual abortion, and usedespecially often during pregnancy. Saireito
administered as a treatment of habitual abortion has
been reported to be safe for the fetus even during fetalorgan period7). It is therefore presumed to be one ofsafe therapeutic drugs for patients desiring to havechildren. Recently multiple reports describing cases
in which pregnancies have been established throughtreatment with saireito have been published8,9). We
therefore conducted this study based on theassumption, that saireito is an effective formula forthe treatment of infertility.
When 24 patients complaining of infertility associatedwith menstrual irregularities were treated withsaireito, pregnancies were established in 16 of thesepatients (67%) within a period of 4.9±2.5 weeks. In 9(64%) out of 14 patients in whom anovulatory cycles
were observed, ovulations were confirmed based on
the basal body temperature. In former reports about
Kampo treatment for infertility tokishakuyakusan
led to an ovulation ratio of 44% and a pregnancy ratioof 22%, while Unkeito similarly led to an ovulation
ratio of 50-60% and a pregnancy ratio of 18%10). Thus,
compared to the aforementioned Blood deficiency
improving formulas, saireito achieved even higher
ovulation and pregnancy ratios. Comparing the levelsof the gonadotrophic hormones before and afteradministration showed a decreasing tendency for LH
values and moreover a decrease in the LH/FSH ratio
Saireito
probablystabilizes
the(P<0.05).
gonadotrophic hormone balance, thereby possibly
enabling an effective action at hypophseal hormone
levels. Regarding PCOS the number of cases was few
with only 6 patients, but in 3 (50%) of those apregnancy was established. Thus, establishment ofpregnancies was observed in a comparatively highnumber of cases treated with saireito.
Generally, clomifene citrate or gonadotropin
preparations are used for in the field of infertility
therapy as the therapeutic drug for the treatment ofovulatory disorders. Yet, since they might cause thedevelopment of OHSS besides their other effects,
multiple pregnancies could develop in case of
superovulation. For these reasons the benefits of
Kampo therapy with its fewer side effects is currently

10

reconsidered. Some reports point out, that in modern
society the pathology of infertility patients suggests a
strong psychosomatic correlation, which bestows
great importance on healing "Qi" anomalies with the
Kampo therapy11). In particular "liver depression and
Qi stagnation" and "disorders of the body's fluid
metabolism" are frequently observed pattern in
infertility patients, so that saireito, designed to healstress or obesity seems to the indicated for the"pattern" of modern infertility patients. In practice
Murata's report in 1989 found that 32% of thepatterns were "Qi deficiency", 37% "Qi stagnation",
61% "Blood deficiency" and 22% "Blood stagnation"3),while the current study revealed 35% of the patterns
to be "Qi deficiency", 44% "Qi stagnation", 56% "Blooddeficiency" and 35% "Blood stagnation", indicatingthat the portion of "Qi stagnation" and "Bloodstagnation" has increased as compared with former
reports, which in turn is possibly correlated to thelarger number of established pregnancies throughtreatment with saireito. Moreover, the effectivenessof saireito for the treatment of PCOS has recently also
been confirmed12,13). PCOS is an endocrine disorderassociated with irregularities of menstruation or
polycystic ovaries, hyperandrogenemia or increased
secretion of LH. The pathology suggests, based on thepresence of obesity or insulin resistance, a correlation
with the metabolic syndrome14). This may lead toovulatory disorders and thus frequently be correlated
to the pathology of infertility, so that saireito
presumably is beneficial for infertility patients
suffering from complication with PCOS.
It is well known that tokishakuyakusan or unkeito
are used as Kampo therapy for infertility and theiruse is by now general practice. In recent years thenature of the infertility "pattern" is possibly changing,so that for infertility patients in whom these formulas
do not lead to the establishment of pregnancies, atherapy based on Kampo diagnosis is adopted when it
seems to be necessary to choose a more suitable
formula. Verification of the effectiveness of saireito stillneeds further study, but for modern infertility patientsand complicating menstruation irregularities orovulatory disorders saireito can be considered to be one
effective formula.

The Journal of Kampo, Acupuncture and Integrative Medicine (KAIM)

Volume 8, Number 1 | Spring 2013

[Conclusions]
The internal use of Saireito for the treatment ofinfertility complicated by menstruation irregularities
or ovulatory disorders has led in many patients to anormalization of the menstrual cycle or theestablishment of pregnancies. Apart from improving
ovarial function, saireito also alleviates the stressassociated with infertility treatment and is therefore
considered a possibly effective formula for thetreatment of infertility.

10. Toshiyuki Yasui: Practical lectures to learn
Kampo therapy from experts; menstrualirregularities,
femaleinfertility.
ClinicalObstetrics and Gynecology; 2008; 62: 1061-1066
11. Takashi Kano: Infertility as a psychosomatic
disorder in medical care. Psychosomatic
medicine; 2009; 49: 1171-1176
12. Atsushi Sakai: Investigations of the usefulness ofSaireito for the treatment of polycystic ovary
syndrome. Clinical Obstetrics and Gynecology;
2000; 54: 1330-1333[References]
1. Satoshi Hayakawa: Usefulness of Kampo
therapy for the treatment of infertility．Journalof Clinical and Experimental Medicine; 2003;
204: 1011-1014
2. Naohisa Ushiroyama: The role of Kampo therapy
in the treatment of infertility. Obstetrical and
Gynecological Therapy; 2001; 83: 45-50
3. Takaaki Murata: Introduction into Kampo
therapy in obstetrics and gynecology; Kampo andinfertility. Obstetrical and Gynecological
Therapy; 1989; 58: 693-702
4. Toshihiro
Aono:
Effectivenessof
tokishakuyakusan for the treatment of infertility.
Progress in the research into Kampo therapy inthe field of obstetrics and gynecology; 1995; 12:52-57
5. Masao Igarashi: Effects of unkeito andtokishakuyakusan for the treatment ofinfertility; in particular ovulatory disorders andluteal insufficiency．Kampo Igaku 1985;9:85-88
6. Izumi Iwai: Influence of saireito on the
hypothalamus – hypophysis – adrenal system inrats. Hormones and Clinic; 1992; 40: 745-748
7. Masanori Iwaki: Safety of saireito in thetreatment of infertility. Prog Med 1999; 19: 19691971
8. Tsuyoshi Nakayama: Therapeutic possibilities ofsaireito in the treatment of infertility. Prog Med
2010; 30: 14-15
9. Four cases in which a combination therapy withsaireito led to pregnancies: Toshitake Moriyama.
Medicine and Pharmacology; 2011; 66: 123-128

13. Machi Okamoto: Effects of saireito on theovarian function of patients with polycystic
ovary syndrome. Reprod Med Biol 2010; 9:
191-195
14. Rotterdam

ESHRE/ASRM-Sponsored

PCOS

Consensus Workshop Group: Revised 2003
consensus on diagnostic criteria and long-term
healthrisks

relatedtopolycystic

ovary

syndrome. Fertil Steril 2004; 81: 19-25.

The Journal of Kampo, Acupuncture and Integrative Medicine (KAIM)

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