Issue: 45 Page: 35-50
Black Cohosh: A Literature Review
by Steven Foster
HerbalGram. 1999; 45:35-50 American Botanical Council
Black Cohosh: A Literature Review
Sidebar: Asian Species
Black cohosh, Cimicifuga racemosa (L.) Nutt., is a member of the buttercup
family (Ranunculaceae) native to deciduous forests of eastern North America. Its use for gynecological conditions predates European settlement of the New World.
In the 19th century it emerged as an important treatment for several female-related
conditions, championed by Dr. John King, an Eclectic physician. Preparations of the root of this American medicinal plant have been used in European phytotherapy
for the treatment of menopausal symptoms for over 50 years. Clinical experience, coupled with chemical, pharmacological, and controlled clinical studies have confirmed
that black cohosh preparations are a safe and effective alternative for hormone
replacement therapies in the treatment of menopause.
Etymology
The genus name Cimicifuga is derived from the Latin cimex, the generic
name for the bedbug (Cimex lectularius L., Cimicidae) and the Latin fugare,
meaning to drive away. This refers to the fact that some species, including the
European C. europaea Schipcz., the Asian C. foetida L., and
the North American C. elata Nutt., among others, have herbage with a
strong, unpleasant fragrance, hence were used as insect repellents. C. racemosa
leaves do not have a strong fragrance. The common name "bugbane" also
honors folk use as an insect repellent. The plant known today as black cohosh
was known throughout much of its American history as "black snakeroot,"
in the United States Pharmacopoeia (USP)— in the first
edition published in 1820 through the seventh revision of 1890. Thereafter, it
is known in USP as Cimicifuga, Black Cohosh, Black Snakeroot,
and Macrotys, remaining official through the 10th decennial revision (1926), but
dropped from the 11th decennial revision (1936). Other common names by which Cimicifuga
racemosa has been known include rattleweed, rattleroot, snake root, rattle
snakeroot, rattlesnake root, and blacksnake root.2
Botanical Description of Black Cohosh
Black cohosh is an erect, smooth-stemmed perennial growing from four to eight
feet in height. The large, alternate, tri-ternately compound leaves are borne
on short, clasping petioles. The ovate, acute leaflets, two to three inches in
length, are thin, smooth, two or three-lobed with sharp double-serrate margins.
The long, wand-like, white flowers, about an inch in diameter, are borne on a
terminal branching spike-like raceme. The main feature of the flowers is the numerous
showy stamens, consisting of slender filaments with white anthers. Four or five
white, small concave sepals are larger than the nearly inconspicuous, stamen-like
petals. The solitary white pistil is smooth and sessile. The fruit is a dry oval
ribbed follicle splitting along a ventral suture with eight to ten triangular
brown seeds in two rows. In the south, it begins blooming in mid to late June.
Toward the northern part of its range, blooming begins as late as early August.
During the flowering period the conspicuous flowering stalks can be seen from
a distance even in wooded habitats. In rich deciduous woods it is common on hillsides,
generally growing under heavy shade, though in open woods that have been selectively
cut or even clear-cut, it will survive for a year or two in nearly full sun. It
occurs in woodlands from Massachusetts south to South Carolina, west to Arkansas
and Missouri, and north to southern Ontario.3
Botanical History of Black Cohosh
Delving into its botanical history requires little more than paraphrasing John
Uri Lloyd and Curtis Gates Lloyd’s exhaustive treatment of Cimicifuga
in what was to be a monumental series on American medicinal plants, Drugs
and Medicines of North America (Vol. 1, 1884-85). The series was abandoned
after only two volumes were published.
According to Lloyd and Lloyd, the first description of our subject comes in
the Amaltheum Botanicum (1705), the final of six volumes of Leonard Plukenet’s
"Phytographia" series published between 1691 and 1705. Plukenet (1641-1706)
was named Regius Professor of Botany and appointed to oversee the gardens at Hampton
Court in 1689. His "Phytographia" was a catalog of plants which came
into the possession of this medical doctor who followed botanical pursuits to
the neglect of medicine. Black cohosh was crudely figured under the name "Christopheriana
facie, Herba spicata, ex Provincia Floridana."4,5,6
Pre-Linnaean (before ca. 1750) writers classed it under the generic concept of
Actaea (under Tournefort’s designation, Christopheriana)
with descriptors recognizing the plant’s long spike.7 Several
German review works cite R. Morrison (1680) for providing the first description
of the plant as Christopheriana canadensis; however, Morrison is not
listed as a reference by Linnaeus.8
The first modern botanical name is Actaea racemosa L., published in
Species Plantarum (1753). Later, Linnaeus separated the genus Cimicifuga
from Actaea based on characteristics of the fruit (in Actaea a fleshy berry,
in Cimicifuga dry follicles), of the European species C. foetida (L.)
L., but did not move the North American C. racemosa from Actaea to his later concept
of Cimicifuga.
The evolution of the name Cimicifuga racemosa takes some interesting
turns of nomenclatural nuance. The plant was first considered under the genus
Cimicifuga as C. serpentaria (L.) Pursh in Frederick Pursh’s
Flora Americae Septentrionalis (1814).9 Pursh (1774-1820),
as the Lloyds point out, was actually the first to publish the name under the
present concept of the genus; therefore, his designation C. serpentaria,
they state, should have been the correct scientific name for the species. However,
some of Pursh’s designations have since been deemed illegitimate names by
botanical authorities.
Four years later, Thomas Nuttall (1786-1859) again used the old specific name
(racemosa), calling it C. racemosa in his 1818 work, The Genera of
North American Plants. It is interesting to note that Nuttall was Pursh’s
predecessor in the service of Benjamin Smith Barton (1766-1815), botanical patron
and professor of natural history and botany (later, also professor of materia
medica) at the University of Pennsylvania. Nuttall began revising Pursh’s
1814 Flora, but his work evolved into an entirely new botanical treatment
of North American plants, widely praised by his contemporaries. In the same year,
Cimicifuga racemosa was also mentioned by William Paul Crillon Barton
(1786-1856), nephew of B. S. Barton, in his Compendium florae Philadelicae
(vol 2., p. 12), but without acknowledgment of Nuttall having named the plant.
Since Barton mentioned Nuttall’s 1818 Genera, the Lloyds assumed
Nuttall’s work was published first. Thus, botanical luminaries of the day,
such as Augustin Pyramus de Candolle (1778-1841), erroneously attributed authorship
of the name to Barton.10
The name C. racemosa was also published by Stephen Elliot (1771-1830),
a prominent South Carolina citizen and botanist, six years after publication by
Nuttall and Barton. The eminent American botanists John Torrey and Asa Gray, in
their important works on American botany, both credit Elliot as the author of
the name "Cimicifuga racemosa." Hence, the plant is seen designated
as "Cimicifuga racemosa Elliot" (incorrect), "Cimicifuga
racemosa W. Barton" (incorrect), and Cimicifuga racemosa (L.)
Nutt. (correct until recently).11 ,12 The Lloyd brothers point out these discrepancies,
but they themselves perpetuate the citation as Cimicifuga racemosa Elliot,
presumably following Asa Gray, the leading American botanical authority of the
time.13
C. S. Rafinesque (1783-1840) correctly observed that C. racemosa did
not conform to Linnaeus’s description of the fruit, and differs in several
technical aspects from all other Cimicifuga species. Therefore, in 1808
he proposed to place it in a separate genus he designated Macrotrys (from
the Greek for "large" and "bunch," referring to the large
raceme of fruit). The name was adopted by few authors, though Amos Eaton (1776-1842),
the first to attempt to popularize American botany, used Rafinesque’s name
Macrotys (misspelled, dropping the second "r"), in his popular
Manual of Botany, published in eight editions from 1817 to 1840. "Macrotys
serpentaria" was used by Eaton in the fourth edition of his Manual,
published in 1824. In the fifth edition (1829), Eaton reverted to using Macrotys
racemosa. In the first volume of his Medical Flora (1828), Rafinesque
again changes the name, this time designating the plant as Botrophis serpentaria.
Rafinesque explains, "I did so ever since 1808, calling it Macrotrys,
which meant long raceme, which name Decandolle has adopted as a subgenus
of Actaea; but this name being delusive, too harsh, and an abbreviation
of Macrobotrys, I have framed a better one meaning Snake raceme:
the raceme or long spike of flowers being mostly crooked, and like a snake."14
All of these nomenclatural shifts are significant when looking up black cohosh
in 19th century American medical literature. In the first half of the 19th century,
physicians of the Eclectic school, like most of the people, relied on Eaton’s
Manual of Botany as the standard botanical text for North American plants.
Therefore, as a drug, black cohosh is known throughout much of the Eclectic medicine
literature, and well into the 20th century, as "macrotys."15
New Taxonomic Twists
Another reason this taxonomic error is relevant in 1999 is because James A.
Compton and colleagues at the University of Reading (Reading, U.K.), after extensive
morphological and DNA sequence studies, have placed the entire genus Cimicifuga
back into Linnaeus’s original generic concept of Actaea. Thus,
as of August 1998, C. racemosa, once again, after a hiatus of 245 years,
is Actaea racemosa L.16 Further work by Compton and colleagues
will require revisiting the entire generic concept of Cimicifuga as it
relates to Actaea not only in North America, but in Asia and Europe as
well.17 ,18 Name changes and distribution as cited by Compton and colleagues
relative to Cimicifuga are summarized in Table 1.
Since it will take another 100 years for the world botanical, herbal and medical
literature to either accept or reject this name change, this paper will continue
to use the now obsolete name "Cimicifuga racemosa" to refer
to the source plant of the herbal medicine known today as "black cohosh."
Table 1: Species Transfers in the Taxonomy of Black Cohosh
Proposed name |
Recent Name |
Synonyms |
Distribution |
Actaea arizonica (S. Watson) J. Compton |
Cimicifuga arizonica S. Watson |
|
Northern and central Arizona |
Actaea bifida (Nakai) J. Compton |
Cimicifuga heracleifolia var. bifida Nakai |
|
S. Korea (Kongwon) |
Actaea biternata (Siebold & Zucc.) Prantl |
Cimicifuga biternata (Siebold & Zucc.) Miq. |
Pityrosperma obtusifolium Siebold & Zucc., Cimicifuga obtusiloba
(Siebold & Zucc.) Miq., C. japonica var. biternata (Siebold
& Zucc.) Maxim. ex Makino, C. japonica var. obtusiloba (Siebold
& Zucc.) Yatabe, etc. |
Japan (Honshu) |
Actaea brachycarpa (P. K. Hsiao) J. Compton |
Cimicifuga brachycarpa P. K. Hsiao |
Cimicifuga lancifoliolata X. F. Pu & M. R. Jia |
China (Henan, Hubei, Shanxi, Sichuan) |
Actaea cimicifuga L. |
Cimicifuga foetida L. |
|
Europe |
Actaea cordifolia DC. |
Cimicifuga rubifolia Kearney |
Cimicifuga cordifolia (DC.) Torr. & A. Gray [non Pursh 1814,
nom. illeg.], Thalictrodes cordifolia (DC.) Kuntze, Cimicifuga racemosa
var. cordifolia (DC.) A. Gray |
Illinois, North Carolina, Pennsylvania, Tennessee, Virginia |
Actaea dahurica (Turcz. ex Fish. & C. A. Mey.) Franch. |
Cimicifuga dahurica (Turcz. ex Fish. & C. A. Mey.) Maxim. |
Actinospora dahurica Turcz. ex Fisch. & C. A. Mey. |
China (Hebei, Heilongjiang, Henan, Nei Monggol, Jilin, Shaanxi, Shanxi), Korea,
Eastern Siberia, Russian Far East |
Actaea elata (Nutt.) Prantl |
Cimicifuga elata Nutt. |
Thalictrodes elata (Nutt.) Kuntze
|
British Columbia, Oregon, Washington |
Actaea europea (Schipcz.) J. Compton |
Cimicifuga europaea Schipcz. |
|
Europe (Northern Austria, Czech Republic, Southern. Germany, Hungary, Poland,
Romania, Russia (Kaliningrad), Slovak Republic, Ukraine |
Actaea frigida (Royle) Prantl |
Cimicifuga frigida Royle |
Cimicifuga foetida var. longibracteata P. K. Hsiao, Cimi-cifuga
foetida var. bifida W. T. Wang & P. K. Hsiao, etc. |
Bhutan, China (Sichuan, Yunnan), India (Uttar Pradesh, Darjeeling), Myanmar,
Sikkim, Tibet |
Actaea heracleifolia (Kom.) J. Compton |
Cimicifuga heracleifolia Kom. |
|
China (Heilongjiang, Nei Monggol, Jilin, Liaoning), North Korea, South Korea,
Russian Far East (Primorsk) |
Actaea japonica Thunb. |
Cimicifuga japonica (Thunb.) Spreng. |
Actaea acerina Prantl, Cimicifuga acerina Tanaka, Pityrosperma
acerinum Siebold & Zucc., etc. |
China (Gansu, Guizhou, Hainan Island, Henan, Hubei, Shanxi, Sichuan, Yunnan),
Japan (Honshu, Kyushu), S. Korea (Cheju-do) |
Actaea kashmiriana (J. Compton & Hedd.) J. Compton |
Cimicifuga kashmiriana J. Compton & Hedd. |
|
India (Kashmir) W. Tibet, and northeast Pakistan |
Actaea lacinata (S. Watson) J. Compton |
Cimicifuga lacinata S. Watson |
|
Oregon, Washington |
Actaea mairei (H. Lév.) J. Compton |
Cimicifuga mairei H. Lév. |
Cimicifuga foetida L. var. foliolosa P. K. Hsiao, etc. |
China (Gansu, Hubei, Shansi, Sichuan, Yunnan), E. Tibet |
Actaea matsumaurae (Nakai) J. Compton & Hedd. |
Cimicifuga foetida var. matsumurae Nakai |
Cimicifuga foetida f. femina Huth, C. foetida var
leiogyna H. Takeda |
Japan (Honshu) |
Actaea podocarpa DC |
Cimicifuga americana Michx. |
Cimicifuga cordifolia Pursh, Cimicifuga podocarpa (DC.)
Elliot, etc. |
Georgia, Kentucky, Maryland, N. Carolina, Pennsylvania, South Carolina, Tennessee,
Virginia, W. Virginia |
Actaea purpurea (P. K. Hsiao) J. Compton |
Cimicifuga acerina f. purpurea Hsiao |
Cimicifuga purpurea (P. K. Hsiao) C. W. Park & H. W.Lee, Cimicifuga
acerina f. strigulosa P. K. Hsiao, etc. |
China (Anhui, Gansu, Guizhou, Hebei, Henan, Jiangxi, Shanxi, Shaanxi, Sichuan)
|
Actaea racemosa L. |
Cimicifuga racemosa (L.) Nutt. |
Cimicifuga serpentaria Pursh; Botrophis serpentaria Raf.,
Botrophis actaeoides Fisch. & C. A. Mey; Thalictrodes racemosa
(Kl. Kuntze |
Eastern North America: Alabama, Arkansas, Connecticut, Delaware, Georgia,
Illinois, Indiana, Kentucky, Maryland, Massachusetts, Maine, Missouri, New Jersey,
New York, North Carolina, Ohio, Ontario, Pennsylvania, South Carolina, Tennessee,
Virginia, W. Virginia |
Actaea racemosa var. dissecta (A. Gray) J. Compton |
Cimicifuga racemosa var. dissecta A. Gray |
|
Rare variety, in Delaware, along Brandywine Creek near Rockland; Pennsylvania,
Upper Darby |
Actaea simplex (DC.) Wormsk. ex Prantl |
Cimicifuga foetida var. simplex (DC.) G. Don. |
Cimicifuga simplex (DC.) Wormsk. ex Trucz., C. foetida var.
intermedia Regel, C. dahurica, var. tschonoskii Huth,
C. foetida f. hermaphrodita Huth, C. dahurica var.
candollei Huth, etc. |
Russian Far East (Kamachatka), Japan (Honsu), S. Korea, |
Actaea taiwanensis J. Compton, Hedd. & T. Y. Yang |
(new species), related to the N. American A. laciniata |
|
Taiwan |
Actaea yesoensis (Nakai) J. Compton & Hedd. |
Cimicifuga simplex var. yesoensis Nakai |
C. yesoensis (Nakai) Kudo, Cimicifuga simplex f. villosa
Nakai |
Russian Far East, Sakhalin |
Actaea yunnanensis (P. K. Hsiao) J. Compton |
Cimicifuga yunnanensis Hsiao |
|
China (Gansu, Sichuan, Yunnan), Tibet |
North American Species of Cimicifuga
In North America, six species of Cimicifuga are listed by Kartesz.19
From eastern North America, species include C. americana Michx. [Actaea
podocarpa DC.]; C. racemosa (L.) Nutt. [A. racemosa L.],
and C. rubifolia Kearney [A. cordifolia DC., C. cordifolia
(DC.) Torr. & A. Gray]. American bugbane (C. americana) occurs in
deciduous woodlands on steep slopes in deep shaded rocky soils from southern Pennsylvania
to South Carolina and eastern Tennessee. It differs from C. racemosa
primarily in technical characteristics of the flowers and fruits (C. americana
with 3 ovaries and papery follicles). Appalachian bugbane (C. rubifolia)
is an uncommon cool mountain woodland species, occurring in rich deciduous forests
on north-facing slopes, often near streams from southwest Virginia to North Carolina,
Tennessee, adjacent Kentucky, and southern Illinois. Cimicifuga racemosa,
best known as black cohosh (formerly black snakeroot), is the most common American
species.20
Western North American species include C. arizonica S. Wats. [A.
arizonica (S. Watson) J. Compton]; C. laciniata S. Wats. [A.
laciniata (S. Watson) J. Compton]; and C. elata Nutt. [Actaea
elata (Nutt.) Prantl]. Arizona bugbane, C. arizonica, is a rare
species occurring in deciduous woodlands by streams on north-facing slopes or
in canyon bottoms from Coconino County, Arizona. Tall bugbane, C. elata,
is found primarily on north-facing slopes in mixed or deciduous forest in the
coastal ranges from Lane County, Oregon, to Clallam County, Washington, and British
Columbia. Mount Hood or cut-leaved bugbane, C. laciniata, is a rare species
found in boggy ground or open deciduous woodlands, once known only from Lost Lake
at Mount Hood, but since found in other localities north to Silver Star Mountain
in Washington. The western North American species appear to be absent from the
ethnobotanical literature, probably reflecting their rarity.
Ethnobotany: Use by Indigenous North American Peoples
Early American medical authors ascribe knowledge of the use of black cohosh
to eastern North American indigenous groups. Little reliable ethnobotanical data
establishes clear information on use. The Oklahoma Delaware used black cohosh
combined with elecampane (Inula helenium L., Asteraceae) and stoneroot
(presumably Collinsonia canadensis L., Lamiaceae) as a "tonic."30
Among the Iroquois, whose common names for the plant translate to "horse
smells" and "smells like horse," Herrick records that the root
decoction was used to promote the flow of milk. To treat rheumatism, a decoction
of the root was used as a foot bath (while washing the affected parts). A steam
sweat bath was also used. The leaves were also used as a poultice to treat a baby’s
sore back.31
The Cherokee used alcoholic spirits of the roots for the treatment of rheumatism;
also as a tonic, diuretic, anodyne, emmenagogue and for its slight astringent
activity. The root tea was used to treat colds, cough, consumption, constipation,
fatigue, hives, rheumatism, backache, and to make a baby sleep.32 A combination
of white baneberry root (Actaea pachypoda Ell, Ranunculaceae), black
cohosh, chokecherry (Prunus virginiana L., Rosaceae), and crawling phlox
(Phlox stolonifera Sims, Polemoniaceae) was made into an infusion, then
blown four times onto a feverish patient with chills to help reduce the fever.33
This use is sometimes cited in the literature relative to the use of black cohosh
root for the treatment of fever, though the use is obviously ritualistic rather
than pharmacologic in its basis.
The northeastern Algonquians (cited as Penobscots in Moerman,34 but including
the Montagnais, Penobscot, and Mohegan in Moerman’s cited source, Speck)
used the root of black cohosh as a common remedy for kidney trouble, or "feeling
all played out." Two or three small pieces of the root were infused to make
a quart of tea, drunk in one-cup doses two or three times a day. According to
Speck, "At times they drink a good deal of this, which is rather pleasant
to taste."35
Moerman also cites Micmac use as a diuretic, however, the primary reference
cited, "Herbal Remedies of the Maritime Indians,"36 also cites Speck’s
1917 paper on medicine practices of the Northeastern Algonquians. Since black
cohosh’s distribution reaches only into York County, Maine, the southernmost
county of the state, it is unlikely that it was gathered by either the Penobscot
or the Micmac since the plant is well beyond those tribes’ inhabited range.
If used, black cohosh must have been traded with other groups. Correct identity
of the plant is not assured in the fragmented extant ethnobotanical literature
of the northeastern United States.
When the primary references cited by Moerman are examined, it becomes clear
that the ethnobotanical record of use of black cohosh by indigenous groups within
the plant’s range is extremely limited, if not almost entirely lost.
Some writers add additional fragmented ethnobotanical notes to the literature.
Lloyd and Lloyd quote Elisha Smith’s Botanic Physician published
in 1830, (p. 427, "The Indians cure the ague by sweating with the root."37
Ague is normally defined as fever attack or recurrent chills or shivering.
Benjamin Smith Barton also made cursory observations of use by native groups.
"The Actaea racemosa, or Black-Snake-root, is also a valuable medicine,"
he writes. "It is sometimes called Squaw-root, I suppose from its having
been used as a medicine by our Indians. The root of this plant is considerably
astringent. In a putrid sore throat which prevailed in Jersey, many years ago,
a strong decoction of the roots was used, with great benefit, as a gargle. Our
Indians set a high value on it. A decoction of it cures the itch. In North-Carolina,
it has been found useful, as a drench, in the disease of cattle called the murrain."38
In 1822, Jacob M. Bigelow, eminent professor of materia medica at Harvard University
and an important contributor to early USPs, in his commentary on the first USP
adds to early ethnobotanical notations: "We are told that the Indians made
great use of it in rheumatism; also as an agent ad partum accelerandum."39
However, J. U. Lloyd states that it was included in the 1820 USP as Cimicifuga
serpentaria, but was only included in the secondary list through the first
two revisions, and appeared for the first time on the primary list in the 1840
USP.40
Barton’s notations represent the beginning point in ethnobotanical and
American medical literature on black cohosh. While mentioned earlier by Schoepf
in 1785 and Gronovius in 1762, medicinal uses were scant.41 However, Schoepf does
note the root to be a diuretic and anodyne.42
Medical History
In 1818 William Hand, listing the herb under "Cimicifuga serpentaria,"
wrote, "Black Cohosh, Squaw-weed, Rattle-weed, Bug-bane—Recent
root. In strong infusion, promotes fluid, secretions, and is anodyne in chronic
rheumatism, slow fevers, flatulent colics, and in hysterical affections."43
This work establishes use as a home remedy in early 19th-century America.
Even before its admission to the USP, Cimicifuga seems to
have been well-known both as a home remedy and in medical circles. Most authors
from the time of Benjamin Smith Barton’s notations on the use of the plant
until the time of Rafinesque generally quote Barton. Rafinesque expands the list
of applications, calling it astringent, diuretic, sudorific, anodyne, repellent,
emmenagogue, and subtonic.44 He notes that it is a primary remedy of Indian groups
for rheumatism, but also as a gargle for sore throat. Even Bigelow (1822) largely
paraphrases Rafinesque in enumerating uses. Lloyd later explains that the early
writers from Schoepf (1785) through Rafinesque (1828) added little about the use
of black cohosh that had not already been learned from Indians.,45 The first "new"
use he attributes to Horton Howard who in 1836 related case histories citing the
value of a decoction of the root in the treatment of smallpox.46 Later, in 1872,
Dr. G. H. Norris read a paper before the Alabama State Medical Association reporting
on the value of black cohosh preparations in an epidemic of smallpox in Huntsville,
Alabama.47
Use for various nervous afflictions (chorea), rheumatism, as a potent diaphoretic
in cases of fever, and other wide-ranging uses abounded in early 19th century
medical literature. By the mid-nineteenth century medical writings on the plant
began to focus on use for female conditions. In 1849, the newly formed American
Medical Association, then two years old, began to focus on these uses in their
publications. Frances Porcher begins his description of use: "The root is
used in the debility of females attendant upon uterine disorder, and in its action,
is thought to have a special affinity for this organ."48
As the century progressed, black cohosh became of less interest to physicians
of the allopathic school. By the late 1800s its use was little more than a curious
entry in many publications on materia medica. Flückiger and Hanbury claim
it "has been employed chiefly in rheumatic affections. It is also used in
dropsy, the early stages of phthisis [tuberculosis or wasting away of the lungs],
and in chronic bronchial disease."49
Table 2: Clinical Studies on Black Cohosh
Author, Yr, ref. # |
Patients |
Design |
Efficacy Criteria |
Dose |
Outcomes |
Tolerance |
Stolze, 1982 [68] |
704 female patients
(629 evaluated) |
Open, multicenter study with 131 general
practitioners |
Menopausal complaints divided into neurovegetative symptoms and psychological
disturbances |
40 drops Remifemin, b.i.d. for 12 weeks |
After 4 weeks 80% reported clear improvements in symptoms; complete removal
of symptoms in some patients after 6 to 8 weeks |
7% of patients experienced transitory stomach complaints |
Daiber, 1983 [69] |
36 female patients with menopausal complaints in patients who refused hormone
treatment |
Open study in gynecological practices |
Kupperman Menopausal Index and Clinical Global Impression |
40 drops Remifemin, b.i.d. for 6 to 8 weeks |
Improvement in menopausal symptoms in as little as 4 weeks |
Good |
Vorberg, 1984 [70] |
50 female patients with menopausal complaints for which hormone therapy was
contraindicated |
Open study in gynecological practices |
Kupperman Menopausal Index and Clinical Global Impression and Profile of Mood
States |
40 drops Remifemin, b.i.d. for 12 weeks |
Improvement according to Kupperman scale <15; improved mood states including
decrease in weariness, despondency and increase in motivation and mood state |
Good |
Warnecke, 1985 [71] |
60 female patients with menopause |
Open, controlled comparative study |
Karyopyknotic index, Eosinophilic Index, Modified Menopausal Index, SDS Scale,
HAMA Scale, Clinical Global Impression Scale |
Group 1: 40 drops Remifemin 2X/day
Group 2: Conjugated estrogens, 0.625 mg daily
Group 3: Diazepam, 2 mg daily |
Both Remifemin and conjugated estrogens produced stimulation of vaginal mucosa,
with a clear increase in cytological indices along with no changes in cytological
parameters. All three therapies were comparatively good. |
Excellent tolerance of black cohosh preparation |
Stoll, 1987 [75] |
80 female patients |
Randomized double-blind comparative placebo-controlled study, comparing with
conjugated estrogens per day and placebo |
Kupperman Menopausal Index, Hamilton Anxiety Scale, Maturation of Vaginal
Epithelium |
Group 1: 2 tablets of a black cohosh extract (Remifemin) 40 mg 2x/2x tablets/day
Group 2: 0.625 mg daily of conjugated estrogens.
Group 3: placebo |
After 12 weeks, the black cohosh preparation produced a notable increase in
vaginal epithelium and significant improvements in somatic measures, neurovegetative
and psychological symptoms compared with estrogen and placebo. |
Well-tolerated |
Pethö, 1987 [76] |
70 female patients converting from hormone injection therapy to black cohosh
over six month period |
Open study |
Menopausal Index, Subjective observations reported by patients. Number of
hormone injections needed after initiation of therapy |
2 tablets of a black cohosh extract (Remifemin) 40 mg. 2x2 tablets/day |
82% of patients reported black cohosh preparation good or very good.
56
id not require additional hormone injections. |
No side effects reported over 6 months
|
Lehmann-Willenbrock and Riedel, 1988 [77] |
60 female patients with reduced ovary function following hysterectomy with
at least one ovary intact |
Randomized, comparative study in university gynecological clinic over six
month period |
Kupperman Menopausal index (modified). Serum concentrations of hormones Lh
and FSH |
Group 1: 2 tablets of a black cohosh extract (Remifemin) 2x/day. Group 2:
estriol, 1 mg daily. Group 3: conjugated estrogens, 1.25 mg daily.
Group 4: Estrogen-gestagen combination |
Decline in modified Menopausal Index. Improvement of post-operative ovarian
function complaints; no significant differences between therapies. No differences
in LH and FSH-levels |
No significant side effects reported in black cohosh group |
Düker et al, 1991 [72]
|
110 female patients |
Open, controlled, comparative study in university gynecological clinic over
8 weeks |
Serum concentrations of luteinizing hormone and follicle stimulating hormone
before and after therapy |
Significant LH reduction compared to placebo group. No significant change
in FSH concentrations in either group |
Selective LH suppression in menopausal women, no effect on FSH (unlike estrogen
therapy) |
Well-tolerated |
From: Schaper & Brümmer. Remifemin — Active Substance: Liquid
Cimicifuga Extract. The Herbal Preparation for Gynecology [Product Detail Manual]
1997; 43 pp. Two additional studies in the product brochure are not mentioned
as at the time of this writing. They have not been published in peer review journals.
Development in Eclectic Medicine
Flückiger and Hanbury make an interesting observation: "The American
practitioners called Eclectics prepare with Black Snake-root
in the same manner as they prepare podophyllin [resin from mayapple, Podophyllum
peltatum L., Berberidaceae], an impure resin which they term Cimicifugin
or Macrotyn."50 While the so-called "regular school"
(physicians) showed interest in black cohosh early on, in the second half of the
19th century black cohosh evolved to become one of the mainstays of Eclectic materia
medica, primarily through its promotion by Dr. John King. Since the Eclectics
and their allopathic counterparts were often at philosophical, economic, political,
and legal odds, remedies adopted by the Eclectics were largely ignored by the
regular physicians.
The eminent Eclectic physician, John King (1813-1893), gave it considerable
space in the first edition of The Eclectic Dispensatory of the United States
of America (with R. S. Newton, 1852), as well as in subsequent editions,
written by King or co-authored by John Uri Lloyd, later by Harvey Wickes Felter
and J. U. Lloyd.
King became the main proponent of black cohosh in the Eclectic school, and
spoke of it to his students as his "favorite remedy." He had used it
in his practice since 1832. Offered almost exclusively by Eclectic physicians
under the name "macrotys," black cohosh was a primary remedy in both
acute and chronic cases of rheumatism and in related inflammatory conditions,
pulmonary afflictions, chorea, and neuralgic affections. It served as a remedy,
as King put it, "in abnormal conditions of the principal organs of reproduction
in the female." King stated that he found black cohosh "very efficacious
in maladies of the female reproductive organs, as in chronic ovaritis, endometritis;
menstrual derangements, as amenorrhea, dysmenorrhea and menorrhagia, frigidity,
sterility, threatened abortion, uterine subinvolution and to relieve severe after-pains."
King was not only one of the leading 19th-century physicians in Eclectic medicine,
but specialized in obstetrics and gynecology, serving as Professor of Obstetrics
and Diseases of Women in the Eclectic Medical Institute, Cincinnati, and authored
several works on obstetrics.51
Its use in Eclectic practice is summed up in the Lloyd Brothers
Drug Treatise on Macrotys:52
Specific Medicine Macrotys is the remedy first thought of in rheumatism and
rheumatic neuralgia. It is the remedy for unpleasant sensation in the pregnant
uterus; for false pains, and to aid true ones. It is undoubtedly a partus
preparator whenever the woman is troubled with unpleasant sensations in the
last months of pregnancy. It is also a valuable remedy to correct the wrongs of
menstruation, relieving pain, and looking toward normal functional activity.
Macrotys influences directly the reproductive organs. This influence seems to
be wholly upon the nervous system, relieving irritation, irregular innervation,
and strengthening normal functional activity. For this purpose it is unsurpassed
by any agent of our materia medica, and is very largely used.
It is the most prominent remedy for painful conditions with muscular soreness
and tension.
Chemical Investigations
The first rudimentary chemical studies on the root began in 1827. G. W. Mears
obtained tannin, gallic acid, a resin, gum, starch, bitter substances, and extractive
matter from the rhizome. His attempt to find an alkaloid in the plant failed.53
In the early 20th century Finnemore confirmed phytosterin, isoferulic acid, salicylic
acid, sugars, tannins, and long-chain fatty acids. Separate chemical investigations
by Corsan and Linde in the 1950s and ‘60s resulted in isolation of chemical
components to which biological activity was attributed. These were a number of
triterpene glycosides, including the xylosides acetin, cimicifugoside, and 27-deoxyactein.
An isoflavone, formononetin, has also been reported.54 Isoflavones are ubiquitous
in the legume family (Leguminosae or Fabaceae), but are relatively rare in other
plant families. Recent attempts to validate levels of formononetin and the flavone
kaempferol in isopropyl alcohol and ethanol extracts along with five commercial
preparations of black cohosh failed to identify appreciable levels of the flavonoids.
Depending upon analytical methodology the flavones can be found only in trace
amounts.55 Its presence in Cimifuga rhizome is, however, doubtful and might be
due to unintentional admixture of other, similar-looking drug species.
European Experience: 1743-1980
Like other American medicinal plants such as Echinacea (Echinacea
spp., Asteraceae) and saw palmetto (Serenoa repens (W. Bartram) Small,
Arecaceae), black cohosh was introduced into Germany in the late 19th century,
following Eclectic acclaim of its therapeutic value. The first person in Europe
to recommend use of Cimicifuga was Colden, who suggested use to stimulate uterine
contractions as early as 1743, apparently inspiring Linnaeus to add the plant
to his Materia Medica in 1749.57, 58 In the early 20th century it became
primarily a homeopathic remedy, then as phytotherapy evolved as a separate aspect
of medical practice in the 1930s, black cohosh became a legitimate therapeutic
agent, supported by pharmacological and clinical research.
In 1944, Gizycki provided the first modern pharmacological evidence in animal
experiments related to estrogen-like effects. Much of the literature until the
end of the 1950s was clinical reports on experience in using black cohosh preparations.
Empirical clinical data tended to emphasize the use of black cohosh for overweight
patients with delayed menstruation, functional nervous conditions, neuralgia with
myalgia and arthralgia, premenopausal patients with endocrine imbalances, or premenstrual
patients with depression. It was found to be particularly useful in general practice
in rural areas where gynecologists were not available.59
By the late 1950s, black cohosh preparations were in wide use by clinicians
in Germany. A debate played out in the scientific literature in the first half
of the 20th century, dominated by clinical case reports (empirical knowledge)
and rather crude animal studies (pharmacological proof), prompted an experimental
pharmacological direction to proving or disproving empirical observations. In
1959 J. Földes conducted a series of experiments to assess the estrogenic
action of an alcoholic extract of black cohosh root (Remifemin) in mice in response
to this debate.
Dose-dependent induction of estrus (with increased uterus weight) was observed
in several test groups of animals. Ovariectomized rats in three groups received
doses of 0.1 ml b.i.d. [two times daily] (six animals); 0.2 ml b.i.d. (six animals)
and 0.3 ml b.i.d. (nine animals) for three days. The first group at the lowest
dose showed no change. In the second group (0.2 ml b.i.d.), estrus was induced
in only two of six animals. In the third group at the highest dose, estrus was
induced in eight out of nine animals. In another experiment 12 three-week-old
female mice were given 0.2 ml of a black cohosh extract (Remifemin) for four days.
Increased uterine weight of the test animals was interpreted to support the concept
of an estrogenic effect for the herb. In another experiment, 40 female rats were
given the extract for two weeks to determine if any histological changes of the
ovaries were induced. No changes were seen compared with controls. Since a sedative
effect was reported for black cohosh, 60 mice were given Remifemin and 20mg/kg
of amphetamine. If a sedative effect could be shown, the black cohosh should theoretically
protect against the effect of amphetamine. No positive results were shown. Twenty
rats were given 0.3 ml of the black cohosh extract for a week, and, on the eighth
day, injected with a thyroid marker to examine any changes in suppressing thyroid
function. No differences were observed between controls and the test group. Another
experiment with six rats did not find any change in thyroid hormone mobilization.60
While the animal experiment on sedative effects failed to produce sedation,
a sedative effect was observed in women enrolled in a follow-up study. The preparation
was given to 41 pre-menopausal and perimenopausal women, who received placebo
before treatment (run-in period) followed by one tablet t.i.d. [three times daily]
of a black cohosh extract (Remifemin). Thirty-one women in the treatment group
experienced a marked reduction in symptoms (hot flashes, headache, nervousness).
While receiving placebo, 37 complained of no improvement. The author concluded
after these early animal experiments followed by a poorly controlled clinical
study, that the preparation had a favorable effect on pre-menopausal and perimenopausal
symptoms, with an emphasis on sedative action. Gastric symptoms were experienced
in three of 41 patients. No other side effects were observed. He believed that
the experiments showed a hormone-like activity.
Other authors of the same period, however, did not believe that black cohosh
had a hormonal effect. Stiehler, based on clinical observation in 53 patients,
rather than controlled experiments, concluded that black cohosh intervenes in
(without interfering with) hormonal mechanisms, producing a normalizing effect
without overriding pituitary control. His experience found black cohosh strikingly
successful for premenopausal and menopausal dysfunction, and juvenile menstrual
irregularities with a shortened follicular phase. However, he believed it was
not indicated for menstrual disorders in general. Of particular note in this clinical
observation, once again, is a mild mood-enhancing activity.61
A paper delivered at the Karlsruhe Therapy Congress in 1956 further catapulted
the herb to prominence in the treatment of menopause. Practitioners were concerned
with finding an alternative to hormone-replacement therapy, which by that time
was showing unwanted side effects in a large number of patients. Practitioners
also recognized the value of black cohosh preparations as a concomitant or alternative
therapy to hormone replacement treatment or the use of potent sedative in cases
of female conditions relative to the onset of puberty, menstrual difficulties,
and menopause symptoms. One thread that continues throughout clinical reports
of this period is a positive effect on mood swings, depressive disorders and psychological
instability sometimes associated with hormonal imbalances. Stefan particularly
recommended black cohosh for juvenile menstrual disorders accompanied by psychological
disorders. In his experience, normal menstruation, interrupted by stress and transition
because of job stress or adjustment to new surroundings, was achieved after administration
for about eight weeks. He concluded that it is particularly valuable in a clinical
context from pre-puberty to menopause, because it combined a mild sedative action
with a hormone-like effect, without being habit-forming, inducing increased bleeding,
or producing other untoward side effects even with long-term administration.62
By 1960, 1,256 case reports in 11 published studies by gynecologists, general
practitioners, internists, and neurologists had evaluated the use of a black cohosh
preparation (Remifemin) for the treatment of menopausal symptoms with positive
benefits, and a marked lack of adverse effects, particularly unphysiological bleeding,
then considered a major limitation of hormone therapy. The largest review (517
patients, by A. Brücker), reports that a dose of 20-30 drops of a liquid
preparation or one tablet t.i.d., taken over a relatively long period of time
(at least eight weeks), produced benefits in 79 percent of women treated. Like
other authors, he suggested that the liquid preparation should be retained in
the mouth as long as possible, and that the tablets should be sucked on rather
than swallowed. Psychological benefits (mood enhancement) were also emphasized.63
Langfritz reported success in using Remifemin in treating juvenile hormone
disorders of young women suffering from dysmenorrhea, oligomenorrhea, premenstrual
syndrome, and other conditions. All patients were observed to have uterine or
ovarian hypoplasia, complaints of cold feet, and underdeveloped breasts. In the
treatment of 73 patients over a four-year period, he concluded that the preparation
helped to normalize juvenile menstrual disorders and relieve or eliminate neurovegetative
symptoms associated with hormonal disorders, without side effects. Langfritz regarded
the treatment not as a hormone substitute, but rather a modifier of autonomic-hormonal
processes (after pathological causes are ruled out).64
By 1962, at least 14 clinical studies or reports involving over 1,500 patients
were published on the use of a black cohosh extract. While most studies were not
rigorously controlled by modern standards, results consistently revealed the preparation
was effective in premenopausal and menopausal symptoms such as a reduction in
hot flashes, improvement of "depressive moods," and improvement of neurovegetative
symptoms and various dysfunctions during menopause. A 1964 clinical report adds
treatment for premenstrual syndrome, then emerging as a recognized and treatable
indication, to the list of potential applications for black cohosh. In reviewing
135 cases of premenstrual syndrome, neurologist E. Schildge administered a black
cohosh extract (Remifemin) at an average dose of 20 drops three times per day
over a period of three to six months. Improvement in general well-being and a
relaxant sedative effect in mood swings and mild depression were observed. No
side effects were reported.65
Studies of the 1980s and 1990s
A number of studies, both pharmacological and clinical, published in the 1980s
and ’90s have shed further light on mechanisms of action, mode of administration,
and efficacy. These studies serve to confirm safety and efficacy and further elucidate
mechanisms of action for the long-standing clinical experience of use of black
cohosh preparations for menopause and postoperative gynecological dysfunction.
Clinically, the treatment is used to improve symptoms such as hot flashes, depression,
and sleep disturbance. Virtually no significant new studies on pharmacology and
clinical use of black cohosh extracts appeared in the 1970s. However, results
of clinical reports from the 1950s and 1960s provided collective data on 1,738
patients (20 percent of whom also received additional hormone therapy) in clinical
and general practice for treatment of menopausal complaints.
In 1982, a retrospective, open, multi-center study involving 704 patients (mean
age 51 years) by 131 general practitioners and gynecologists evaluated how a black
cohosh preparation (Remifemin) improved menopausal complaints. The patients received
40 drops of Remifemin liquid two times per day, and were evaluated after four,
six, and eight weeks of treatment. Results were evaluated subjectively by patients
and objectively by physicians’ diagnoses. Data on 629 patients was available.
In 80 percent of cases, favorable results were attained after six to eight weeks
of treatment. Therapeutic success included relief of neurovegetative complaints
such as hot flashes (86.6 percent improvement, with 43.3 percent experiencing
no hot flashes and 43.3 percent improved), sweating (88.5 percent improvement,
with 49.9 percent experiencing no profuse perspiration and 38.6 percent improved),
headache (91.9 percent improvement with 45.7 percent experiencing complete relief,
36.2 percent improved), vertigo (86.8 percent improvement, with 51.6 percent experiencing
complete relief, 35.2 percent improved), heart palpitation (90.4 percent improvement,
with 54.6 percent experiencing complete relief, 35.8 percent improved) and tinnitus
(92.9 percent improvement, 54.8 percent experiencing complete relief, 38.1 percent
improved). Complete removal of evaluated symptoms was achieved in an average of
over 49 percent, with an additional average of 37.8 percent experiencing improvement
(but not complete relief) of symptoms. Improvement of psychiatric symptoms included
nervousness and irritability (85.6 percent improvement) sleep disturbances (76.8
percent) , and related depressive moods (82.5 percent improvement). Two hundred
and four patients had previously been treated with hormone therapy. Physicians
observed that the black cohosh treatment had advantages over hormone treatment
in 72 percent of cases. In some cases of hormone-treated patients, black cohosh
had no effect, highlighting the need for each patient to be evaluated individually
for treatment. In 93 percent, no side effects were reported. Transient stomach
upset was reported by seven percent of patients, but did not result in discontinuing
treatment. The authoress, H. Stolze, concluded that the black cohosh preparation
was safe and effective as a hormone-free therapeutic treatment for menopause.
Its great advantage in general practice was that it could be administered over
a long period of time without serious risk of side effects.66 A 1983 open study
involving 36 women (45 to 62 years old) with menopausal complaints, most of whom
had refused hormone therapy, was evaluated according to the Kupperman and Clinical
Global Impression scales. They received 40 drops of Remifemin twice a day for
12 weeks. Rates of success similar to those reported by H. Stolze were achieved.67
In 1984 Vorberg reported on the results of an open study in gynecological practices
on 50 patients with menopausal complaints for which hormone therapy was contraindicated.
Forty drops of a black cohosh preparation (Remifemin) were given two times per
day for six to eight weeks. Efficacy was measured by Kupperman Menopausal Index,
Clinical Global Impression and Profile of Mood States. Improvement according to
the Kupperman scale was greater than 15 percent; improved mood states including
decrease in weariness, amelioration of despondency, and increase in motivation
were also reported.68
In 1985 Warnecke published results of an open, controlled, comparative study
in 60 female patients with menopause. The 12-week study compared a black cohosh
preparation, a hormone, and a psychopharmaceutical drug in treating ‘neurovegative,
psychological, and somatic disturbances in menopause. Divided into three groups,
patients received either Remifemin (40 drops b.i.d.), estrogens (0.625 mg daily),
or Diazepam (2 mg daily). Efficacy was measured according to several criteria,
including the Kupperman Menopausal Index, Clinical Global Impression and Profile
of Mood States. Both Remifemin and conjugated estrogens produced stimulation of
vaginal mucosa, with a clear increase in cytological indices. All three therapies
were comparatively good. Tolerance of the black cohosh preparation was deemed
to be excellent. Given the fact that the black cohosh extract performed as well
as the hormone therapy for neurovegetative symptoms and the psychopharmaceutical
for depressive moods, and its lack of side effects, it was considered an excellent
first choice medication for mild to moderate menopausal symptoms.69
In a 1985 pharmacological study by Jarry and Harnischfeger, the authors conducted
experiments to measure levels of serum concentrations of pituitary hormones using
an animal model corresponding to inducing pituitary hormone levels typical of
those measured during menopause in women. After a three-day period, there was
a significant and selective reduction in luteinizing hormone (LH), while serum
concentrations of follicle-stimulating hormone (FSH) and prolactin were unaffected.
Occurences of and increases in hot flashes have been linked to spikes in LH release,
and serve as a parameter by which the endocrinological activity of black cohosh
can be measured. A glycoside fraction of an extract was concentrated by dichloromethane
and believed to be responsible for the effect. The active principle contained
in the lipophilic fraction, believed to be triterpene glycosides, showed definite
endocrinological effects in the animal model, selectively reducing LH serum concentrations,
while not affecting FSH and prolactin release. This study seemed to confirm previous
speculation in both pharmacological and clinical literature of an endocrine-like
efficacy of the root extract.70
Jarry, Harnischfeger, and Düker sought to further characterize the mechanism
of action and the active constituents. They demonstrated endocrine activity of
the rhizome in the in vitro system of the estrogen receptor assay and the in vivo
model of the ovariectomized rat. They identified at least three principles in
a methanol extract that are believed to compete with the hormone estradiol for
binding sites on specific receptor proteins. Three fractions were found that:
(1) do not bind to estrogen receptors but suppress the release of LH; (2) bind
to estrogen receptors and suppress the release of LH; and 3) bind to estrogen
receptors but do not suppress LH. One was identified as the isoflavone, formononetin.
The compound, while binding to estrogen-receptive cells, failed to demonstrate
an LH-suppressant effect. This led them to speculate that other active principles
in the methanol extract have a synergistic effect leading to a LH-suppressant
effect.71 A recent study55 cited by Gruenwald failed to confirm the occurrence
of formononetin in black cohosh or its preparations.72
In 1987, Stoll published the results of a double-blind study comparing the
effects of conjugated estrogens, a black cohosh extract, and placebo. Eighty volunteers
were admitted: 30 received 0.625 mg of an estrogen preparation per day; 30 received
8 mg of black cohosh extract per day (Remifemin), while 20 patients received placebo.
Three parameters were measured. Neurovegetative symptoms (using the Kupperman
Menopausal Index) such as hot flashes, profuse perspiration, headache, vertigo,
heart palpitation, and tinnitus, and the Hamilton anxiety scale (measuring nervousness,
irritability, sleep disturbances, and depressive moods) were evaluated at four-week
intervals. Proliferation status of vaginal epithelium was measured at the beginning
of the study and after 12 weeks of treatment. Treatment was continued for three
months. All three parameters were significantly improved in the black cohosh group
compared with placebo. Estrogen therapy proved to be delivered at too low a dose
for reliable comparative results. The lowest possible dose had been chosen to
limit known side effects of estrogen therapy. The black cohosh preparation was
well-tolerated and produced significant improvement in the measured criteria.
The author concluded that black cohosh not only produced safe and efficacious
results, but was suitable as a treatment of choice in menopausal symptoms.73
In 1987 Pethö reported the results of an open study in 60 female patients
converting from hormone injection therapy to black cohosh over a six -month period.
Two tablets of a black cohosh extract (Remifemin) 40 mg b.i.d. were administered.
Efficacy was measured according to the Kupperman Menopausal Index and subjective
observations reported by patients. The number of hormone injections needed after
initiation of therapy was also a criterion of efficacy. Eighty-two percent of
patients reported the black cohosh preparation as good or very good and 58 percent
did not require additional hormone injections. No side effects were reported over
the six-month period.74
A 1988 German clinical study by Lehmann-Willenbrock and Riedel compared treatment
with the hormone estriol, conjugated estrogens, estrogen-gestagen sequential therapy,
and an extract of black cohosh in 60 women under 40 years of age all of whom had
at least one ovary removed, and still complained of climacteric symptoms. Patients
were randomized into four groups. At intervals of four, eight, 12 and 24 weeks,
LH and serum-FSH levels were measured. A modified Kupperman Scale (measuring psychological,
neurovegetative, and trophic [pertaining to nutrition] symptoms of menopausal
symptoms) was also used for assessment. Among the ovarian deficiency symptoms
scored in this system are hot flashes, sweating, sleep disturbances, depressive
moods, and other related symptoms. Treatment with the black cohosh extract (Remifemin)
was found to be comparable to successful treatment with the three conventional
drug preparations tested. LH and FSH-levels did not change in any group during
treatment. The authors concluded that in cases where conventional hormone therapy
is contraindicated, the plant extract is the therapy of choice.75
In 1991, Düker et al. obtained three types of endocrinologically
active fractions from a commercial isopropanolic extract of black cohosh rhizome
(Remifemin). The study confirmed an LH secretion inhibitory effect in both ovariectomized
rats and in menopausal woman. In the clinical phase involving 110 menopausal women,
for a two-month period, 55 received two 2 mg tablets of Remifemin (8 mg per day),
while the other 55 women received placebo. They demonstrated for the first time
that the extract selectively suppresses LH secretion in menopausal women, and
further confirms an estrogen-like effect of the alcoholic fractions of the root
of the plant. This controlled study confirms long-standing clinical experience
in use of the preparation in the treatment of menopausal-related symptoms for
women who either refuse to take steroid hormone replacement therapy or when such
treatment is contraindicated.76
Although a number of studies, including Düker et al., 1991, have
described the action of black cohosh as "estrogen-like," a clear mechanism
of action has not been described. Therefore, estrogen-like effects have been proposed
based on LH-lowering effects and the assumption that the steroid hormone-like
chemical structures of the triterpene glycosides resulted in interfering with
receptors in the hypothalamus and pituitary gland.77 However, a recent
animal study failed to show estrogenic effects, with no indications of uterotropic
or vaginotropic activity, leading to the conclusion that decreases in LH levels
are caused by interference with neurotransmitters, rather than an estrogenic effect.78
A recent double-blind randomized clinical study by Liske and colleagues looked
at the effects of two different dosages of an isopropanolic black cohosh extract
(Remifemin) in 152 patients with climacterica complaints. The dosages were 40
mg vs 127 mg of the preparation per day for six months. According to the authors
the two dosage regimes showed similar results in efficacy and safety. Hormone
levels of LH, FSH, SHBG. prolactin and estradiol were not influenced by the product.
Vaginal cytology (degree of proliferation) was also not influenced. According
to the authors the study clearly demonstrated that the product had a non-hormone
(non-estrogenic) effect. This study serves to settle the former controversy on
whether or not black cohosh produced an estrogenic effect. 79
Safety and Toxicity
In a 1995 review, Beuscher cited older review works that reported large (unspecified)
doses of black cohosh result in dizziness, nausea, severe headaches, stiffness,
and trembling limbs. However, these symptoms can be traced to literature on 19th-century
homeopathic provings of the herb. In this context, irrelevant to dosage in conventional
phytotherapy, these "provings" result from administration of ultramolecular
doses over a period of time to develop symptoms by which to match disease conditions.
Studies on mutagenicity, and carcinogenicity have proved negative. A study on
long-term administration (six months) in rats failed to show chronic toxicity
at about 90 times the human dose equivalent. Occasional stomach pain or intestinal
discomfort has been reported. These findings concur with over 60 years of safe
clinical experience, particularly in Germany.79 Occasional gastric discomfort
is listed as a potential side effect. Duration is limited to six months (presumably
because of lack of long-term toxicity studies of longer duration).80
Concerns have arisen over the previously described "estrogen-like"
activity in estrogen-receptor-positive patients with mammary carcinomas. However,
recent studies have clarified the situation. Unlike estrogen, a marked inhibition
of the proliferation rate of breast carcinoma cells is reported for a black cohosh
extract (Remifemin). Nesselhut (1993) first confirmed non-proliferation rates
of breast carcinoma cells.82
Results of a recent study on the "influence of an isopropanolic aqueous
extract of Cimicifugae racemosae rhizoma on the proliferation of MCF-7
cells" was presented by J. Freudenstein and C. Bodinet at the 23rd International
Symposium o
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