Review Articles
Alternative Medicine and Nephrology
Series Editor: Naomi V. Dahl
Herbs, Menopause, and Dialysis
Beatrix Roemheld-Hamm* and Naomi V. Dahl²
Departments of *Family Medicine and ²Medicine, University of Medicine and Dentistry of New Jersey,
Robert Wood Johnson Medical School, New Brunswick, New Jersey
ABSTRACT
Women with chronic kidney disease (CKD) are at increased
risk for menstrual disorders, early menopause, and osteopor-
osis, and rarely discuss gynecologic and reproductive issues
with their nephrologist. Various complementary and alternat-
ive medicine (CAM) products are of interest to women with
end-stage renal disease (ESRD) who have these disorders.
However, very little is known about the speci®cs of using herbal
medicines in patients on chronic dialysis, resulting in numerous
In the general population, the use of complementary
and alternative treatments increased 380% between 1990
and 1997; among adults who take prescription medica-
tion, 18.4% use at least one herbal product or high-dose
vitamin in addition to their prescriptions. Moreover,
61.5% of users of complementary and alternative
medicine (CAM) therapies do not disclose this use to
their physician (1).
It is no surprise then that in today's health care
environment with its bewildering array of botanical
products, often aggressively marketed to the consumer,
patients with chronic illnesses are particularly interested
in trying to ®nd products that might alleviate some of
their symptoms. This is certainly true for patients with
chronic kidney disease (CKD). As with the general
public, consumers with CKD have been constantly
exposed to information regarding ``natural remedies''
(as botanicals are often called) and often turn to them
in an attempt to alleviate their symptoms with what
they believe are natural and ``safe'' remedies. Women
with CKD are at increased risk for menstrual disorders,
early menopause, and osteoporosis, and rarely discuss
Address correspondence to: Beatrix Roemheld-Hamm, MD,
PhD, Associate Professor of Family Medicine, UMDNJ,
Robert Wood Johnson Medical School, 1 Robert Wood
Johnson Place, New Brunswick, NJ 08901, or e-mail:
hammbr@umdnj.edu.
Seminars in DialysisÐVol 15, No 1 (January±February) 2002
pp. 53±59
53
problems when patients and providers try to ascertain the safety
and ecacy of these products. This article reviews evidence
regarding the safety and ecacy of black cohosh, ginseng,
chastetree, dong quai, evening primrose oil, soy products, and
the so-called natural hormones. Pharmacologic parameters
important to evaluating the quality of botanical products are
discussed, along with recommendations and information
resources.
gynecologic and reproductive issues with their neph-
rologist; few are prescribed hormone replacement
therapy (2±4). Those with symptoms of these disorders
are likely to use botanical and other ``natural''
products, and most have little guidance about the
safety and ecacy of the various botanical products
they might encounter and use. While recently published
opinion-based guidelines may be helpful for healthy
women (5), the CKD patient and her provider
encounter numerous problems when trying to ascertain
the safety and ecacy of these products (6).
As discussed in the previous article of this series,
very little is known about the speci®cs of using herbal
supplements in patients with ESRD undergoing dialy-
sis or after transplantation (7,8). It is almost imposs-
ible to ®nd data regarding the speci®cs of excretion of
botanicals, let alone their dialytic clearance; interac-
tions with other drugs and herbs become more
complex in the renal patient because of the number
of drugs used. The herbs used always have a number
of di€erent chemical compounds; often it is not known
which of these compounds comprise the active ingre-
dients and whether a synergy exists among them.
Moreover, the pharmacologic properties of multiple-
compound substances are inherently dicult to assess
(9). Herb-drug interactions and herb-herb interactions
become more likely in these circumstances. In general,
details regarding the speci®cs of dializability of the
di€erent products are unknown at this point, and
signi®cantly more research is needed to answer
54 Roemheld-Hamm and Dahl
questions of safety and ecacy in this particular
population.
This review article discusses some of the herbs and
supplements most likely used by women with ESRD who
are experiencing symptoms of menopause. A brief case
presentation will be followed by a discussion about black
cohosh, ginseng, chastetree, dong quai, evening primrose
oil, soy products, and the so-called natural hormones.
We will also discuss pharmacologic parameters import-
ant to evaluating the quality of botanical products.
Case Report
A 45-year-old woman with CKD, on hemodialysis, was seen
with complaints of hot ¯ashes, mild vaginal dryness, decreased
libido, and increased irritability with mood swings. All
symptoms had become noticeably worse over the past year.
Her menstrual periods, which had been irregular, ceased
5 months earlier. She uses a diaphragm for contraception.
She is not using any oral or topical hormonal methods and is
interested in a ``natural way'' to deal with the symptoms of
menopause. She has been taking various botanical products on
and o€, without telling any of her health care providers. During
her last visit with her nephrologist, she decided to discuss her
belief that herbs and ``natural'' hormone replacement therapies
are a better choice for her than some of the pharmaceutical
options she has heard about. She has been taking black cohosh,
ginseng, evening primrose oil, soy shakes, dong quai, chaste-
tree, and sees a CAM provider for natural estrogens as well as a
progesterone cream.
Black Cohosh
Black cohosh (Cimicifuga racemosa), also known as
snakeroot, bugbane, and bugwort, is the root of an
herb ®rst used by Native Americans and later intro-
duced to European colonists (10). A German brand of
black cohosh, Remifemin, was introduced in Germany
in the 1950s. Black cohosh, not to be confused with
blue cohosh or white cohosh, is generally used for
perimenopausal and menopausal symptoms (11,12).
Some women also use it for treatment of PMS and
dysmenorrhea (12,13).
Black cohosh has been used safely in well-designed
studies lasting up to 6 months (11,14±16). For this
reason, the German Commission E, an expert panel
instituted by a German government agency to evaluate
the safety and ecacy of herbal products, endorsed its
use for no longer than 6 months, although there is no
indication that its use for longer periods is unsafe (13).
No data are currently available on its safety in women
undergoing dialysis (personal communication, manufac-
turer of Remifemin).
In the general population, black cohosh has been
shown to be an e€ective treatment for hot ¯ashes. There
is some evidence it can be as e€ective as estrogen
replacement therapy for some patients. Often signi®cant
improvements in symptoms appear within 4 weeks
(10,11,14,16).
Laboratory evidence of estrogenic activity has been
con¯icting. Whether black cohosh has an estrogen-like
bene®cial e€ect on osteoporosis is uncertain (17,18);
however, it appears that black cohosh is not a
phytoestrogen. Some authors have suggested that black
cohosh can be safely used in women with a history of
breast cancer, citing laboratory evidence that black
cohosh does not stimulate the proliferation of estrogen
receptor (ER)-positive breast cancer cells (10,11,19).
Black cohosh was no better than placebo in treating
hot ¯ashes in women taking tamoxifen for breast
cancer, though a reduction in night sweats was ob-
served (15).
Reported side e€ects are gastrointestinal discomfort,
headache, dizziness, weight gain, feeling of heaviness in
the legs, and cramping (11,12,15,19,20). Black cohosh
does not appear to be mutagenic, teratogenic, or
carcinogenic (10,20), and no interactions with other
medications are known to occur (21).
Many of the studies that have shown black cohosh
to be e€ective used a German product standardized to
contain 1 mg triterpene glycosides, calculated as
27-deoxyacetin per 20 mg tablet (Remifemin). For
patients without medical illnesses, the dosage of
Remifemin is 20±40 mg twice a day. Other products'
dosages vary depending on the extraction process
(20).
There are no studies looking at the safety and
e€ectiveness of black cohosh in women with ESRD.
Patients who insist on taking black cohosh should be
advised to start at a low dose, observe its impact on their
hot ¯ashes, and adjust the dose slowly according to their
symptoms.
Ginseng
The use of ginseng, speci®cally Panax ginseng, one
of the ginseng varieties, has been described for
centuries in Asian medicine. Panax ginseng is used to
improve well-being, especially physical and sexual well-
being, but also mental performance and psychological
functioning. It has been shown to stimulate immune
function, cognitive function, concentration, and work
eciency (10,22,23). The quality of ginseng products is
extremely variable, and this raises concerns regarding
their safety and ecacy. Certain ginseng products have
been found to have contaminants that could poten-
tially a€ect patients with ESRD to an even greater
degree than the general population. A recent study
evaluating 22 ginseng products (Asian, American, and
Siberian ginseng products) found that only 9 products
tested met the criteria for ginseng quality (amount of
ginsenoside content and the absence of pesticides and
heavy metals). Eight products contained unacceptable
levels of various pesticides; two of those products had
pesticide levels more than 20 times the allowed
amount, two products contained unacceptable lead
levels, and seven products had less than the required
concentration of ginsenosides (24).
ESRD patients taking ginseng with tricyclic antide-
pressants such as amitriptyline, antiarrhythmics such as
 HERBS, MENOPAUSE, AND DIALYSIS
amiodarone, or certain b-blockers may be at risk for drug
interactions as there is some evidence that a Panax
ginseng root extract can mildly inhibit cytochrome P-450
2D6 activity. However, it appears to have no e€ect on
CYP3A4 activity (25).
Chastetree (Vitex agnus-castus)
Chastetree or chasteberry is used to treat PMS
(9,13,26), especially premenstrual breast pain (27) and
®brocystic breasts (28). It is also used for di€erent types
of menstrual irregularities (9,10), and for sexual dys-
function, reducing sexual desire (28), as well as histori-
cally for decreased libido (27). Chastetree stimulates
luteinizing hormone (LH) and may decrease follicle
stimulating hormone (FSH) levels as well (22,27,29,30).
Studies have demonstrated a prolactin-inhibiting e€ect
with higher doses of the herb (27,30). In healthy women,
chasteberry has been used safely in studies lasting up to
1.5 years (26,27,31,32).
Side e€ects include nausea, vomiting, dizziness,
headache, tiredness, and dry mouth; in general, side
e€ects are dopaminergic in nature (22,23,28,33,34).
This adverse e€ects pro®le is particularly troublesome
for ESRD patients, who may already experience
these problems. Chasteberry is contraindicated in preg-
nancy (31,32). Interactions may occur with hormone
replacement therapy, oral contraceptives, or other sex
hormones.
The common oral dosage for PMS and other con-
ditions is 20±40 mg of the dried extract per day
(13,26,27,35). Chasteberry ¯uid extract (40 drops/day)
has also been used (27,31,34). No data exist on its safety
in the ESRD patient or its dializability.
Dong Quai
Dong quai (Angelica sinsensis) is used for dysmenor-
rhea, amenorrhea, and menopausal symptoms (32,36).
Dong quai has not been shown to be e€ective for hot
¯ashes (37). Large oral doses can cause photosensitivity
and photodermatitis (28,36). It is unclear whether it is
safe for patients with estrogen-dependent cancers. Dong
quai is not recommended during pregnancy due to its
uterine stimulant and relaxant e€ects (32,36,38). Dong
quai constituents can be carcinogenic, mutagenic, and
photocarcinogenic even without excessive light expo-
sure (28).
Dong quai has been shown to inhibit platelet activa-
tion and aggregation (39). Thus concomitant use of
coumadin can increase the risk of bleeding (39,40). Other
drugs that alter coagulation parameters, as well as herbs
that may have e€ects on the coagulation cascade [anise,
arnica, capsicum, celery, chamomile, clove, danshen,
fenugreek, feverfew, garlic, ginger, ginkgo, Panax gin-
seng, horse chestnut, horseradish, licorice, passion¯ower,
red clover, turmeric, wild carrot, and others (22,38) can
theoretically also interact with dong quai.
Dong quai is widely used in Chinese medicine,
predominantly for a variety of gynecologic conditions.
55
It is often blended with other herbs in pills, powders, and
plaster preparations (36).
The use of this herb is of particular concern in patients
undergoing hemodialysis because of its anticoagulant
e€ects. Uremic patients tend to have disordered platelet
adhesion due to impaired activation of GP IIb-IIIa
receptor and abnormal aggregation due to reduced
intraplatelet adenosine diphosphate (ADP) and sero-
tonin levels (41). Bleeding parameters need to be
monitored very closely for those patients who insist on
using dong quai.
Evening Primrose Oil
Evening primrose oil contains c-linoleic acid (GLA)
and linoleic acid. Together with its metabolites, GLA is a
precursor of prostaglandin E1 and E2 and can inhibit
in¯ammatory pathways via the arachadonic acid path-
way (22,42). Bene®cial e€ects have been found in the
treatment of mastalgia (43,44). Using evening primrose
oil for PMS symptoms (45,46) or hot ¯ashes (47) is not
e€ective. It has been used in numerous studies without
reports of signi®cant side e€ects (36,43,45,48). However,
since c-linoleic acid can increase bleeding time (49),
patients with ESRD and their providers need to be aware
of this potential complication. Evening primrose oil is
contraindicated in pregnancy. Side e€ects include indi-
gestion, nausea, soft stools, and headache (22). It is
approved in Canada as a dietary supplement for
increasing essential fatty acid intake (48).
Estriol and Triestrogen
Some alternative medicine practitioners promote
estriol or triestrogen as safer forms of estrogen therapy
than the conjugated estrogens (50). Estriol is a weak,
short-acting estrogen sometimes used as ``natural''
hormone replacement therapy for symptoms like hot
¯ashes or urogenital atrophy. Triestrogen, also called
Tri-Est, is a mixture of estrone, estradiol, and estriol,
typically in 1:1:8 ratio. Its usual oral dose is 2.5±5 mg/
day, either continuously or cyclically for 25 days a
month. Few trials on this therapy have been completed to
date (51±53). So far there is no reasonable scienti®c
evidence showing that estriol has anticancer e€ects or
that it is safer than estradiol or conjugated estrogens in
the general population (50). The safety and ecacy of its
use for patients with ESRD has not been examined.
Natural Progesterones
While oral micronized progesterone (Prometrium) is
U.S. Food and Drug Administration (FDA) approved
and e€ective (in conjunction with estrogen) for hormone
replacement therapy (54,55), topical forms of progester-
one, sold as creams and typically applied to the skin on
the trunk and extremities in a rotating fashion, are not
FDA-approved products. Safety studies of up to 1 year
have been done (56,57). One clinical trial showed that
56 Roemheld-Hamm and Dahl
topical progesterone cream was superior to placebo in
reducing vasomotor symptoms such as hot ¯ashes in
menopausal women (56). However, the actual progester-
one content in the creams may vary (58). No evidence of
any increase in bone density has been shown (56).
DHEA
Recently there has been increasing interest in the
potential role of androgen replacement in perimeno-
pausal and menopausal women (59,60). As the major
adrenal androgen dehydroepiandrosterone (DHEA) and
its active metabolite DHEA sulfate (DHEAS) reach their
peak levels in young women in their 20s and decline
progressively thereafter, DHEA supplementation has
been suggested as a therapeutic option (61,62). DHEA is
available over the counter as a dietary supplement. While
many women may be taking it (often without the
knowledge of their health care provider), it is not
approved for any indication by the FDA, and its use is
not recommended outside of clinical trials (63).
Wild Yam
Wild yam, which is sometimes promoted as ``natural
DHEA'' and is purported to have hormonal activity, will
not be discussed in detail here; it has not been shown to be
e€ective. Although one of the components in the wild
yam, diosgenin, can be converted to steroidal com-
pounds, including DHEA, in the laboratory, this
synthesis does not occur in the human body. Patients
need to be advised that wild yam extract will not increase
their DHEA levels (36,64). It is possible that wild yam
may have some estrogenic activity, but this has not been
adequately investigated (65).
Soy
Soy products are of particular interest to ESRD
patients who are at high risk for bone disease and for
whom conventional hormone replacement therapy
(HRT) can be problematic both in terms of dosing and
of potential untoward e€ects on access thrombosis
(66,67). This is especially true since recent recommenda-
tions have been published advising against hormone
replacement therapy in women with preexisting cardio-
vascular disease, which may well include most patients
with ESRD (68).
The three main categories of phytoestrogens are
lignans, iso¯avones, and coumestans. Soy products are
high in iso¯avones, which are also found in chickpeas
and other legumes. Flaxseed, or linseed, is very high in
lignans, which are also found in whole grains, beans,
vegetables, and fruits. Coumestans do not play a major
role in the human diet (69,70). Soy and ¯ax contain
phytoestrogens, which are widely used to reduce hot
¯ashes (71±75) and other perimenopausal symptoms
(71,75). They have been shown to be helpful in
preventing osteoporosis and cardiovascular disease in
postmenopausal women (72,74,76).
The FDA has approved labeling soy products for
cholesterol reduction in combination with a low fat, low
cholesterol diet. Bene®cial e€ects on total cholesterol
reduction, low-density lipoprotein (LDL) cholesterol
reduction, and triglyceride reduction have been docu-
mented in postmenopausal women (75,77±79) as well as
well as other populations (78±82); high-density lipopro-
tein (HDL) levels remain una€ected. Patients with
ESRD have not been studied. A meta-analysis of
controlled clinical studies looking at substitution of
animal protein with soy protein found signi®cant
reductions of cholesterol, LDL, and triglycerides: total
cholesterol was lowered by 9.3%, LDL cholesterol by
12.9%, and triglycerides by 10.5%; HDL cholesterol was
una€ected (83). However, a recent trial in healthy
postmenopausal women failed to show improvements
in lipoprotein levels or endothelial function after 8 weeks
of treatment with iso¯avones (80 mg/day) (84).
Soy may also increase bile acid excretion and could
have an up-regulating e€ect on LDL receptors (85,86), as
well as possibly weak antioxidant e€ects (86). There is
also some indication that soy might decrease urine
protein excretion in patients with chronic renal failure
(87±89).
Studies show a reduced frequency and severity of hot
¯ashes in perimenopausal and postmenopausal women
(71±75).
Regarding bone density, there is currently no de®nite
evidence that dietary soy or iso¯avone supplementation
bene®ts bone density in healthy women. One recent
human study showed a modest positive e€ect of
iso¯avones on vertebral (but not femoral) bone density
(77). Animal studies have shown some bene®cial e€ects
of soy on bone density (91±94), but a primate study did
not con®rm the results (95). Long-term human studies
have not been done to determine the e€ects of iso¯avones
on bone density.
In premenopausal women, soy food supplementation
lowers endogenous estrogen levels and may help reduce
the rate of breast cancer occurrence or recurrence. While
there is no convincing evidence that soy food supple-
mentation prevents breast cancer occurrence (or reoc-
currence) in postmenopausal women, it does not appear
to be harmful either (96).
In ESRD patients on dialysis, a recent study showed
that patients who ingested an iso¯avone-rich diet had
high levels of genistein and daidzein; it was found that
these levels remained very high for several days due to
lack of renal excretion. The half-life of both compounds
was estimated to be 10-fold longer in ESRD patients than
in healthy subjects. Genistein and daidzein levels were
also measured before and after dialysis in ®ve patients,
both while on their regular diet and after one dose of a
soy protein isolate drink. In both instances the dialysis
treatment did not a€ect blood iso¯avone levels. It was
also found that one-third of hemodialysis patients eating
a standard American diet without the addition of
iso¯avone-rich products had high blood levels of these
iso¯avones, while the remaining two-thirds had unde-
tectable levels (97).
Phytoestrogens are weak estrogens. The iso¯avones in
soy are less than 1% as potent as endogenous estrogens in
 HERBS, MENOPAUSE, AND DIALYSIS
binding assays. Since phytoestrogens will not be picked
up by conventional blood tests for estrogen levels, special
assays must be done. Food soy products such as tofu,
tempeh (fermented from tofu), miso (fermented bean
paste, used for soups), green soybeans, and soymilk are
all considered safe for the general population (28). Both
soy protein isolates, which contain 90% protein product
prepared from defatted soybeans, and soy protein
concentrates, containing 65% protein, are often used
for soy shakes and have a higher phytoestrogen content
than soy-containing natural foods. They are therefore to
be viewed with much more caution. Since no long-term
safety data exist for food-free phytoestrogens in shakes
or tablets, their use should be discouraged, even in the
general population (70).
Soybeans are rich in calcium, iron, potassium, amino
acids, vitamins, and ®ber (28). Soymilk contains 10 mg
of calcium per serving, whereas calcium-forti®ed soymilk
has 80±500 mg of calcium per serving in the form of
tricalcium phosphate. Calcium absorption from soymilk
is signi®cantly worse than from cow's milk (98). Soy can
cause constipation, bloating, and nausea (71). Patients
with ESRD need to be advised that one cup of dry
roasted soybeans contains 2346 mg of potassium, but
that boiling and draining reduces this to 970 mg (99).
For lowering cholesterol, a typical dose is 20±50 g/day
of soy protein (75,80,81,83,100). For preventing osteo-
porosis, 40 g/day of soy protein containing 2±2.25 mg
iso¯avones/g has been used in clinical studies (77,90). No
recommendations exist to date for dosages for chronic
renal failure patients. For proteinuria, a diet limited to
700±800 mg/kg soy protein/day has been used (88).
Quality Parameters of Botanical Products
As previously discussed, the quality of herbal products
that are purchased by patients varies enormously. How
do patients obtain products that are of high quality and
purity? One parameter that can be helpful when
purchasing botanical products is the use of standardiza-
tion, meaning botanical extracts that are standardized to
one speci®c compound. However, this speci®cation may
not be representative of the plant's pharmacologic
activity; moreover, there is no guarantee that the marker
compound is indeed the active ingredient.
The fact that a product label contains information
about standardization does not, in itself, ensure the
quality of the product. The method of growing, the time
and method of harvesting, the storing of the plants, and
the possible contamination with by-products such as
pesticides are not addressed through the use of stan-
dardized extracts. Other quality standards, such as the
use of botanical markers, might be preferable in the
future and more accurate than standardization. Other
standards that patients should look for include a
certi®cate of analysis, the contents (in milligrams), and
the parts of the herb that are used should be speci®ed
(root, rhizome, bark, leaves, ¯owers, seeds, etc.). E€orts
at self-policing of the botanical industry and changes in
regulations promise an end to the Wild West era in
botanical medicine.
57
When advising patients with CKD, it appears clear
that none of the herbal remedies advertised for the
treatment of menopausal symptoms can be recommen-
ded without hesitation until the scienti®c evidence has
improved. However, a ``don't ask, don't tell'' attitude can
worsen potential adverse outcomes. Patients, such as
the one presented earlier, who use these products, ought
to be advised to avoid using multiple herbs and
supplements. If they want to try a single herbal product,
they should ``start low, go slow''; in other words, the
product should be started at a very low dosage and
adjusted slowly over time according to their symptoms.
Supplement use should be documented in the patient's
chart, as should responses, both negative and positive.
Establishing and maintaining a relationship of trust with
patients and a nonjudgmental attitude will help avoid
adverse outcomes.
Appendix: Information Sources
Books
Schulz V, Hansel R, Tyler VE. Rational Phytotherapy,
A Physicians Guide to Herbal Medicine. Berlin: Springer
Verlag, 1997.
Bisset NG, ed. Herbal Drugs and Phytopharmaceutics.
Stuttgart: CRC Press, 1994.
DeSmet PAGM, Keller K, Hansel R, Chandler RF,
eds. Adverse E€ects of Herbal Drugs. Berlin: Springer
Verlag, 1997.
Jellin JM, ed. Natural Medicines Comprehensive
Database. Stockton, CA: Therapeutic Research Faculty,
2001.
Journals
Herbalgram. American Botanical Council and the
Herb Research Foundation, P.O. Box 201660, Austin,
TX 78720; (800)373-7105.
Quarterly Review of Natural Medicine: Review of
current research on dietary supplements and botanicals.
NPRC, 600 First Ave., Suite 205, Seattle, WA 98104;
(206)623-2520.
Organizations
American Botanical Council, http://www.herbal-
gram.org.
Herb Research Foundation, http://www.herbs.org.
World Health Organization, http://www.who.int/
home-page/.
MedWatch, the FDA Safety Information and Adverse
Event Reporting Program, http://www.fda.gov/med-
watch/.
References
1. Eisenberg DM, Davis RB, Ettner SL, Appel S, Wilkey S, Van Rompay M,
Kessler RC: Trends in alternative medicine use in the United States, 1990±
1997: results of a follow-up national survey. JAMA 280:1569±1575, 1998
2. Holley JL, Schmidt RJ: Hormone replacement therapy in postmenopausal
women with end-stage renal disease: a review of the issues. Semin Dial 14:
146±149, 2001
58 Roemheld-Hamm and Dahl
3. Holley JL, Schmidt RJ, Bender FH, Dumler F, Schi€ M: Gynecologic and
reproductive issues in women on dialysis. Am J Kidney Dis 29:685±690,
1997
4. Stehman-Breen CO, Gillen D, Gipson D: Prescription of hormone re-
placement therapy in postmenopausal women with renal failure. Kidney Int
56:2243±2247, 1999
5. American College of Obstetricians and Gynecologists: Use of botanicals for
management of menopausal symptoms. Clinical practice guidelines for
obstetrician-gynecologists. Available at http://www.acog.org/from_home/
publications/misc/pb028.htm, accessed September 1, 2001
6. Foote J, Cohen B: Medicinal herb use and the renal patient. J Ren Nutr 8:
40±42, 1998
7. Dahl NV: Herbs and supplements in dialysis patients: panacea or poison?
Semin Dial 14:186±192, 2001
8. Geraghty ME: Herbal supplements for renal patients: what do we know?
Nephrol News Issues 14:12±13, 2000
9. Tyler VE: Herbs of Choice. Binghamton, NY: Pharmaceutical Products
Press, 1994
10. Blumenthal M, Busse WR, Goldberg A, Gruenwald J, Hall T, Riggins CW,
Rister RS: The Complete German Commission E Monographs: Therapeutic
Guide to Herbal Medicines, 1st ed. Boston, MA: American Botanical
Council, 1998
11. Liske E: Therapeutic ecacy and safety of Cimicifuga racemosa for gyne-
cologic disorders. Adv Ther 15:45±53, 1998
12. Foster S: Black cohosh (Cimicifuga racemosa): a literature review. Herb-
algram 45:35±49, 1999
13. Blumenthal M, Goldberg A, Brinckmann J (eds). Herbal Medicine Ex-
panded Commission E Monographs. Newton, MA: Integrative Medicine
Communications, 2000
14. Lieberman S: A review of the e€ectiveness of Cimicifuga racemosa (black
cohosh) for the symptoms of menopause. J Womens Health 7:525±529, 1998
15. Jacobson JS, Troxel AB, Evans J, Klaus L, Vahdat L, Kinne D, Lo KM,
Moore A, Rosenman PJ, Kaufman EL, Neugut AI, Grann VR: Ran-
domized trial of black cohosh for the treatment of hot ¯ashes among wo-
men with a history of breast cancer. J Clin Oncol 19:2739±2745, 2001
16. Lehmann-Willenbrock E, Riedel HH: Clinical and endocrinologic
studies of the treatment of ovarian insuciency manifestations follow-
ing hysterectomy with intact adnexa. Zentralbl Gynakol 110:611±618,
1988
17. Einer-Jensen N, Zhao J, Andersen KP, Kristo€ersen K: Cimicifuga and
elbrosia lack oestrogenic e€ects in mice and rats. Maturitas 25:149±153,
1996
18. Kruse SO, Lohning A, Pauli GF, Winterho€ H, Nahrstedt A: Fukiic and
piscidic acid esters from the rhizome of Cimicifuga racemosa and the in vitro
estrogenic activity of fukinolic acid. Planta Med 65:763±764, 1999
19. Gruenwald J: Standardized black cohosh (Cimicifuga) extract clinical
monograph. Q Rev Nat Med 3:117±125, 1998
20. Pepping J: Black cohosh: Cimicifuga racemosa. Am J Health Syst Pharm
56:1400±1402, 1999
21. Jellin JM, Gregory P, Batz F, Hitchens K, Burson S, Shaver K, Palacioz K:
Pharmacist's Letter/Prescriber's Letter Natural Medicines Comprehensive
Database, 3rd ed. Stockton, CA: Therapeutic Research Faculty, 2000
22. Newall CA, Anderson LA, Philpson JD: Herbal Medicine: A Guide for
Healthcare Professionals. London: Pharmaceutical Press, 1996
23. Schulz V, Hansel R, Tyler VE: Rational Phytotherapy: A Physician's Guide
to Herbal Medicine, 3rd ed. Berlin: Springer, 1998
24. Product review: Asian and American ginseng. ConsumerLab.com. Avail-
able at http://www.consumerlab.com/results/ginseng.asp, accessed Sep-
tember 9, 2001
25. Gurley BJ, Gardner SF, Hubbard MA: Clinical assessment of potential
cytochrome P450-mediated herb-drug interactions (poster presentation).
AAPS annual meeting and exposition, Indianapolis, IN, 2000
26. Schellenberg R: Treatment for the premenstrual syndrome with agnus-
castus fruit extract: prospective, randomised, placebo controlled study.
BMJ 322:134±137, 2001
27. Mills S, Bone K: Principles and Practice of Phytotherapy. London: Chur-
chill Livingstone, 2000
28. The Review of Natural Products. St. Louis: Facts and Comparisons, 2000
29. Brown D: Vitex agnus-castus clinical monograph. Q Rev Nat Med 2:111±
121, 1994
30. Merz PG, Gorkow C, Schrodter A, Rietbrock S, Sieder C, Loew D, Der-
icks-Tan JS, Taubert HD: The e€ects of a special agnus-castus extract
(BP1095E1) on prolactin secretion in healthy male subjects. Exp Clin
Endocrinol Diabetes 104:447±453, 1996
31. McCaleb RS, Leigh E, Morien K: The Encyclopedia of Popular Herbs.
Roseville, CA: Prima Health, 2000
32. McGun M (ed): American Herbal Products Association's Botanocal
Safety Handbook. Boca Raton, FL: CRC Press, 1997
33. Jarry H, Leonhardt S, Gorkow C, Wuttke W: In vitro prolactin but not LH
and FSH release inhibited by compounds in extracts of agnus-castus: direct
evidence for a dopaminergic principle by the dopamine receptor assay. Exp
Clin Endocrinol Diabetes 102:448±454, 1994
34. Wuttke W: Dopaminergic action of extracts of agnus-castus. Forschen
Komplementarmedizen 3:329±330, 1996
35. Bratman S, Kroll D: Natural Health Bible. Rocklin, CA: Prima Publishing,
1999
36. Foster S, Tyler VE: Tyler's Honest Herbal, 4th ed. Binghamton, NY:
Haworth Herbal Press, 1999
37. Hirata JD, Swiersz LM, Zell B, Small R, Ettinger B: Does dong quai have
estrogenic e€ects in postmenopausal women? A double-blind, placebo-
controlled trial. Fertil Steril 68:981±986, 1997
38. Brinker F: Herb Contraindications and Drug Interactions, 2nd ed. Sandy,
OR: Eclectic Medical Publications, 1998
39. Heck AM, DeWitt BA, Lukes AL: Potential interactions between alter-
native therapies and warfarin. Am J Health Syst Pharm 57:1221±1227, 2000
40. Page RL, Lawrence JD: Potentiation of warfarin by dong quai. Pharma-
cotherapy 19:870±876, 1999
41. Noris M, Remuzzi G: Uremic bleeding: closing the circle after 30 years of
controversies? Blood 94:2569±2574, 1999
42. Belch J, Hill A: Evening primrose oil and borage oil in rheumatologic
conditions. Am J Clin Nutr 71:S352±S356, 2000
43. Hardy ML: Herbs of special interest to women. J Am Pharm Assoc 40:
234±242, 2000
44. Pye JK, Mansel RE, Hughes LE: Clinical experience of drug treatments for
mastalgia. Lancet 2:373±377, 1985
45. Khoo SK, Munro C, Battistutta D: Evening primrose oil and treatment of
premenstrual syndrome. Med J Aust 153:189±192, 1990
46. Budeiri D, Li Wan Po A, Dornan JC: Is evening primrose oil of value in the
treatment of premenstrual syndrome? Control Clin Trials 17:60±68, 1996
47. Chenoy R, Hussain S, Tayob Y, O'Brien PM, Moss MY, Morse PF: E€ect
of oral gamolenic acid from evening primrose oil on menopausal ¯ushing.
BMJ 308:501±503, 1994
48. Leung AY, Foster S: Encyclopedia of Common Natural Ingredients Used
in Food, Drugs and Cosmetics, 2nd ed. New York: John Wiley & Sons,
1996
49. Guivernau M, Meza N, Barja P, Roman O: Clinical and experimental study
on the long-term e€ect of dietary gamma-linoleic acid on plasma lipids,
platelet aggregation, thromboxane formation, and prostacyclin produc-
tion. Prostaglandins Leukot Essent Fatty Acids 51:311±316, 1994
50. Fugh-Berman A: Estriol: a kinder, gentler estrogen? Altern Ther Womens
Health 1:51±52, 1999
51. van Haaften M, Donker GH, Sie-Go DM, Haspels AA, Thijssen JH:
Biochemical and histological e€ects of vaginal estriol and estradiol appli-
cations on the endometrium, myometrium and vagina of postmenopausal
women. Gynecol Endocrinol 11:175±185, 1997
52. Granberg S, Ylostalo P, Wikland M, Karlsson B: Endometrial sono-
graphic and histologic ®ndings in women with and without hormonal
replacement therapy su€ering from postmenopausal bleeding. Maturitas
27:35±40, 1997
53. Tzingounis VA, Aksu MF, Greenblatt RB: Estriol in the management of
the menopause. JAMA 239:1638±1641, 1978
54. Langer RD: Micronized progesterone: a new therapeutic option. Int J Fertil
Womens Med 44:67±73, 1999
55. Greendale GA, Reboussin BA, Hogan P, Barnabei VM, Shumaker S,
Johnson S, Barrett-Connor E: Symptom relief and side e€ects of post-
menopausal hormones: results from the Postmenopausal Estrogen/Prog-
estin Interventions Trial. Obstet Gynecol 92:982±988, 1998
56. Leonetti HB, Longo S, Anasti JN: Transdermal progesterone cream for
vasomotor symptoms and postmenopausal bone loss. Obstet Gynecol
94:225±228, 1999
57. Burry KA, Paton PE, Hermsmeyer K: Percutaneous absorption of prog-
esterone in postmenopausal women treated with transdermal estrogen. Am
J Obstet Gynecol 180:1504±1511, 1999
58. Cooper A, Spencer C, Whitehead MI, Ross D, Barnard GJ, Collins WP:
Systemic absorption of progesterone from Progest cream in postmeno-
pausal women. Lancet 351:1255±1256, 1998
59. Katz S, Morales AJ: Dehydroepiandrosterone (DHEA) and DHEA-sul-
fate (DS) as therapeutic options in menopause. Semin Reprod Endocrinol
16:161±170, 1998
60. Barnhart KT, Freeman E, Grisso JA, Rader DJ, Sammel M, Kapoor S,
Nestler JE: The e€ect of dehydroepiandrosterone supplementation to
symptomatic perimenopausal women on serum endocrine pro®les, lipid
parameters, and health-related quality of life. J Clin Endocrinol Metab 84:
3896±3902, 1999
61. Burger HG, Dudley EC, Cui J, Dennerstein L, Hopper JL: A prospective
longitudinal study of serum testosterone, dehydroepiandrosterone sulfate,
and sex hormone-binding globulin levels through the menopause trans-
ition. J Clin Endocrinol Metab 85:2832±2838, 2000
62. Pepping J: DHEA: dehydroepiandrosterone. Am J Health Syst Pharm
57:2044±2048 2056, 2000
63. Parasrampuria J, Schwartz K, Petesch R: Quality control of dehydroepi-
androsterone dietary supplement products. JAMA 280:1565, 1998
64. Skolnick AA: Scienti®c verdict still out on DHEA. JAMA 276:1365±1367,
1996
65. Eagon PK, Elm MS, Hunter DS, Bergerson J, Ayers HH, Tress NB, Eagon
CL: Medicinal herbs: modulation of estrogen action. Conference pro-
ceedings: Era of Hope Meeting for the Department of Defense Breast
Cancer Research Program, Atlanta, GA, 2000
 HERBS, MENOPAUSE, AND DIALYSIS
66. Lindberg JS, Moe SM: Osteoporosis in end-state renal disease. Semin Dial
19:115±122, 1999
67. Mattix H, Singh AK: Estrogen replacement therapy: implications for
postmenopausal women with end-stage renal disease. Current Opinions in
Nephrology and Hypertension 9:201±214, 2000
68. Mosca L, Collins P, Herrington DM, Mendelsohn ME, Pasternak
RC, Robertson RM, Schenck-Gustafsson K, Smith SC Jr, Taubert KA,
Wenger NK: Hormone replacement therapy and cardiovascular disease:
a statement for healthcare professionals from the American Heart As-
sociation. Circulation 104:499±503, 2001
69. KurzerMS, XuX: Dietary phytoestrogens. Annu RevNutr 17:353±381, 1997
70. Strauss L, Santti R, Saarinen N, Streng T, Joshi S, Makela S: Dietary
phytoestrogens and their role in hormonally dependent disease. Toxicol
Lett 102±103:349±354, 1998
71. Albertazzi P, Pansini F, Bonaccorsi G, Zanotti L, Forini E, De Aloysio D:
The e€ect of dietary soy supplementation on hot ¯ushes. Obstet Gynecol
91:6±11, 1998
72. Brzezinski A, Adlercreutz H, Sheoul R, Rosler A, Shmueli A, Tanos V,
Schenker JK: Short-term e€ects of phytoestrogen-rich diet on postmeno-
pausal women. Menopause 4:89±94, 1997
73. Kurzer M: Hormonal e€ects of soy iso¯avones: studies in premenopausal
and postmenopausal women. J Nutr 130:S660±S661, 2000
74. Tham DM, Gardner CD, Haskell WL: Clinical review 97: potential
health bene®ts of dietary phytoestrogens: a review of the clinical, epi-
demiological, and mechanistic evidence. J Clin Endocrinol Metab
83:2223±2235, 1998
75. Washburn S, Burke GL, Morgan T, Anthony M: E€ect of soy protein
supplementation on serum lipoproteins, blood pressure, and menopausal
symptoms in perimenopausal women. Menopause 6:7±13, 1999
76. Setchell KD: Phytoestrogens: the biochemistry, physiology, and impli-
cations for human health of soy iso¯avones. Am J Clin Nutr 68:S1333±
S1346, 1998
77. Potter SM, Baum JA, Teng H, Stillman RJ, Shay NF, Erdman JW Jr: Soy
protein and iso¯avones: their e€ects on blood lipids and bone density in
postmenopausal women. Am J Clin Nutr 68:1375S±1379S, 1998
78. Crouse JR III, Morgan T, Terry JG, Ellis J, Vitolins M, Burke GL: A
randomized trial comparing the e€ect of casein with that of soy protein
containing varying amounts of iso¯avones on plasma concentrations of
lipids and lipoproteins. Arch Intern Med 159:2070±2076, 1999
79. Sirtori CR, Pazzucconi F, Colombo L, Battistin P, Bondioli A, Deschee-
maeker K: Double-blind study of the addition of high-protein soy milk v.
cows' milk to the diet of patients with severe hypercholesterolaemia and
resistance to or intolerance of statins. Br J Nutr 82:91±96, 1999
80. Teixeira SR, Potter SM, Weigel R, Hannum S, Erdman JW Jr, Hasler CM:
E€ects of feeding 4 levels of soy protein for 3 and 6 wk on blood lipids and
apolipoproteins in moderately hypercholesterolemic men. Am J Clin Nutr
71: 1077±1084, 2000
81. Wong WW, Smith EO, Stu€ JE, Hachey DL, Heird WC, Pownell HJ:
Cholesterol-lowering e€ect of soy protein in normocholesterolemic and
hypercholesterolemic men. Am J Clin Nutr 68:S1385±S1389, 1998
82. Nilausen K, Meinertz H: Variable lipemic response to dietary soy protein in
healthy, normolipemic men. Am J Clin Nutr 68:S1380±S1384, 1998
83. Anderson JW, Johnstone BM, Cook-Newell ME: Meta-analysis of the ef-
fects of soy protein intake on serum lipids. N Engl J Med 333:276±282, 1995
59
84. Simons LA, von Konigsmark M, Simons J, Celermajer DS: Phytoestrogens
do not in¯uence lipoprotein levels or endothelial function in healthy,
postmenopausal women. Am J Cardiol 85:1297±1301, 2000
85. Lissin LW, Cooke JP: Phytoestrogens and cardiovascular health. J Am Coll
Cardiol 35:1403±1410, 2000
86. Setchell KD, Cassidy A: Dietary iso¯avones: biological e€ects and rele-
vance to human health. J Nutr 129:S758±S767, 1999
87. Soroka N, Silverberg DS, Greemland M, Birk Y, Blum M, Peer G,
Iaina A: Comparison of a vegetable-based (soya) and an animal-based
low-protein diet in predialysis chronic renal failure patients. Nephron
79:173±180, 1998
88. Gentile MG, Fellin G, Cofano F, Delle FA, Manna G, Ciceri R, Petrini C,
Lavarda F, Pozzi F, D'Amico G: Treatment of proteinuric patients with a
vegetarian soy diet and ®sh oil. Clin Nephrol 40:315±320, 1993
89. D'Amico G, Gentile MG: E€ect of dietary manipulation on the lipid
abnormalities and urinary protein loss in nephrotic patients. Miner Elec-
trolyte Metab 18:203±206, 1992
90. Alekel DL, Germain AS, Peterson CT, Hanson KB, Stewart JW,
Toda T: Iso¯avone-rich soy protein isolate attenuates bone loss in the
lumbar spine of perimenopausal women. Am J Clin Nutr 72:844±852,
2000
91. Fanti O: Systematic administration of genistein partially prevents bone loss
in ovariectomized rates in a nonestrogen-like mechanism. Am J Clin Nutr
68(suppl):1517, 1998
92. Arjmandi BH, Alekel L, Hollis BW, Amin D, Stacewicz-Sapuntzakis M,
Guo P, Kukreja SC: Dietary soybean protein prevents bone loss in an
ovariectomized rat model of osteoporosis. J Nutr 126:161±167, 1996
93. Arjmandi BH, Birnbaum R, Goyal NV, Getlinger MJ, Juma S, Alekel L,
Hasler CM, Drum ML, Hollis BW, Kukreja SC: Bone-sparing e€ect of soy
protein in ovarian hormone-de®cient rats is related to its iso¯avone content.
Am J Clin Nutr 68:S1364±S1368, 1998
94. Arjmandi BH, Getlinger MJ, Goyal NV, Alekel L, Hasler CM, Juma S,
Drum ML, Hollis BW, Kukreja SC: Role of soy protein with normal
or reduced iso¯avone content in reversing bone loss induced by
ovarian hormone de®ciency in rats. Am J Clin Nutr 68:S1358±S1363,
1998
95. Lees CJ, Ginn TA: Soy protein isolate diet does not prevent increased
cortical bone turnover in ovariectomized macaques. Calcif Tissue Int
62:557±558, 1998
96. Barnes S: Phytoestrogens and breast cancer. Baillieres Clin Endocrinol
Metab 12:559±579, 1998
97. Fanti P, Sawaya BP, Custer LJ, Franke AA: Serum levels and metabolic
clearance of the iso¯avones genistein and daidzein in hemodialysis patients.
J Am Soc Nephrol 10:864±871, 1999
98. Heaney RP, Dowell MS, Ra€erty K, Bierman J: Bioavailability of the
calcium in forti®ed soy imitation milk, with some observations on method.
Am J Clin Nutr 71:1166±1169, 2000
99. USDA Nutrient Database for Standard Reference, release July 14, 2001.
Soybeans. NDB nos. 11451 and 16111. Available at http://www.
nal.usda.gov/fnic/cgi-bin/nut_search.pl, accessed September 9, 2001
100. Bakhit RM, Klein BP, Essex-Sorlie D, Ham JO, Erdman JW Jr, Potter SM:
Intake of 25 g of soybean protein with or without soybean ®ber alters
plasma lipids in men with elevated cholesterol concentrations. J Nutr
124:213±222, 1994