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Module 14: Clinical & Applied Pharmacology Evidence Guide

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My friend
is taking bl
cohosh...
Talking about
CAMs
for menopause
Abstract: This article discusses the integration of complementary and alternative
medicine therapies as part of the healthcare decision-making dialogue between
nurse practitioners and patients seeking relief of menopause-related symptoms.
By Lorraine Steefel, DNP, RN, CTN-A; Joyce Hyatt, DNP, CNM; and
Gerti Heider, PhD, APRN, GNP, BC
Illustration by Electric Crayon /istock photo (c)
I'm concerned about
hormone therapy.
What about something
"natural"?
ack
I've heard that
acupuncture
works...
A
lthough menopause is a normal part of the aging
process and affects an estimated 50 million wom
en in the United States today, it brings a multitude
of symptoms that vary from mildly uncomfortable to
 severe.1 Some women still use hormone replacement ther
apy (HRT) to counter symptoms even though the Women's
Health Initiative, which raised serious questions about
HRT's long-term safety, infuenced many to discontinue it.
Many women have since sought forms of complementary
and alternative medicine (CAM)-a group of diverse med
ical and healthcare systems, practices, and products that are
not generally considered part of conventional  medicine-to
ease menopause-related symptoms.2
 Menopause and symptoms
Natural menopause is identified as occurring after "12
consecutive months without menstrual periods that are not
associated with a physiologic (lactation) or pathologic
cause."3 According to the National Institutes of Health's
Consensus Statement, Management of Menopause-related
Symptoms, many women who experience the natural,
permanent cessation of periods, usually in their early 50s,
have few or no symptoms and do not need treatment.
Others, especially those with menopause induced by
surgery, chemotherapy, or radiation, are more likely to
experience bothersome or disabling symptoms and need
effective treatment.3
Although some symptoms may be related to aging, there
appears to be a strong link associated with menopause and
specific symptoms: hot flashes, night sweats, and sleep
 diffculties. The Study of Women's Health Across the Nation
(SWAN), a multisite, longitudinal, epidemiologic study of
3,306 U.S. women ages 42 to 52, provides important statis
tical, symptom-related data.4 The study, now in its 11th year,
Keywords: complementary and alternative medicine, menopausal symptoms, menopause
48 The Nurse Practitioner -  Vol. 38, No. 8
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Copyright (c) 2013 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

Page 2
The Study of Women's Health Across the
Nation provides the most comprehensive
data to date on menopausal transition.

is the most comprehensive to date on menopausal transi
tion. The majority of women (78% to 80%) reported hot
fashes and night sweats, especially  during late perimeno
pause (irregular periods) and postmenopause (after 12
months of period cessation); 38% experienced diff culty
sleeping.5,6
Although it is uncertain whether cognitive problems,
urinary incontinence, mood changes, or physical complaints
are due to menopause or to a combina
tion of aging with menopause, women
in the SWAN study reported a decrease
in cognitive performance, characterized
by not being able to learn as well as they
had during premenopause. This was
found to be temporary with learning
rebounding to  premenopausal levels
after menopause.7 About half of midlife women reported
urinary incontinence, with about 11% reporting a new
onset of incontinence each year. These were more likely to
experience psychological distress and persistent negative
mood.8
As to physical complaints, 9% of women in the SWAN
study reported substantial functional limitations (diff culty
climbing stairs, walking a block, bathing, or dressing), while
another 10% reported some degree of functional limitation.9
Aging in general, however, may bring with it chronic ill
nesses that limit abilities.
 CAM therapies for menopause
Approximately 40% of women seek medical advice for
symptom management; however, the use of CAM is rising
among women.10 In 1999, women in the United States spent
more than $600 million for CAM during the menopausal
transition.11 Data from 6 years of follow-up from the SWAN
study show that 80% had used some form of CAM during
the study.12 Menopausal women are among the highest users
of CAM remedies to alleviate their symptoms.13
The National Center for Complementary and Alterna
tive Medicine (NCCAM) categorizes CAM therapies into
14:
f ve groups
-  Botanical therapies: substances found in nature, such as
herbs, foods, and vitamins, to promote health
-  Energy therapies: energy felds to promote health, includ
ing biofeld therapies such as qi gong, Reiki, and Thera
peutic Touch and bioelectromagnetic-based medicine that
uses electromagnetic felds such as electroacupuncture
-  Manual therapies: manipulation and movement of one
or more parts of the body, used in osteopathy, massage,
chiropractic, Feldenkrais Method, and ref exology
-  Mind-body therapies: techniques to help boost the
mind's ability to influence body functions, such as
Talking about CAMs for menopause
biofeedback, deep relaxation, guided imagery, hypno
therapy, meditation, prayer, support groups, and yoga
-  Alternative medical systems: complete systems of theory
and practice, for example, homeopathy, naturopathy,
traditional Chinese medicine (TCM), and Ayurveda.
Women view CAM therapies as natural and having few
or no adverse effects. They are easy to get, and the claim to
address multiple symptoms furthers the attractiveness of
CAM therapies. Although research f ndings that correlate
CAM therapies with menopausal symptom relief are lim
ited and inconsistent, scientif c rigor of CAM studies has
been improving with more randomized, double-blind,
placebo-controlled trials, and women who use these thera
pies for menopause symptoms generally f nd them to be
benef cial.15,16
Given the growing trend toward the use and self- reported
benef ts of CAM, these therapies can be considered "per
sonal patient preferences," which are central to evidence-based
decision making. However, part of devising the CAM-related
patient plan means that nurse practitioners (NPs) need to be
knowledgeable regarding CAM therapies; which patients are
using CAM therapies and what they are using; and advising
patients regarding any treatment's  safety, risks, and effective
ness (see CAM therapies for menopausal symptom relief).17
 CAM therapies
The SWAN study revealed that in a cohort of 2,118 U.S.
women, approximately 53%, used some type of 21 different
CAM therapies. The most frequently used included a nutri
tious meal plan (range 50% to 77%), exercise (range 63%
to 77%), prayer (range 25% to 80%), and vitamins and
supplements (range 42% to 56%).18 Other CAM therapies
women in this study reported taking included the following:
-  Biological therapies: black cohosh, dehydroepiandros
terone (DHEA), dong quai, f axseed/faxseed oil, ginkgo
biloba, ginseng, glucosamine, Mexican yam/ progesterone
cream, methylsulfonylmethane (MSM), S-adenosyl-l
methionine (SAMe), soy supplements (isofavones or red
clover), St. John's wort, and vitamins  formulated for
women
-  Energy therapies: acupuncture and energy healing
-  Mind-body therapies: yoga, Tai Chi, prayer, and self-help
groups.
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Page 3
Talking about CAMs for menopause
CAM therapies for menopausal symptom relief
Category
Therapy
Symptom
Effectiveness
Botanicals
Black cohosh1,2
Hot fl ashes
Inconsistent or
limited
Dong quai1
Hot fl ashes
Ineffective
Flaxseed/
Hot flashes
Inconclusive
fl axseed oil3
Gingko biloba1
Mood and
Effective for
memory
"mental
enhance-
fl exibility"
ment
May improve
memory
Ginseng1,4
Hot fl ashes
Ineffective for hot
fl ashes
Depression
Effective for
reducing depres
sion, fatigue
Wild Mexican
Hot fl ashes
Ineffective
yam/proges-
Night sweats
terone cream5,6
Soy supple-
Hot fl ashes
Confl icting
ments
night sweats
evidence
(isofl avones
or red
Anxiety
clover)3
Depression
May improve
St. John's
Hot fl ashes
Ineffective for hot
wort1,7
fl ashes
Sleep
Effective for
disorder
reducing sleep
problems
Vitamin E1
Hot flashes
Inconclusive
Hops1,8
Hot fl ashes
Effective
Heart
palpitation
Irritability
Insomnia
Sweating
Evening
Hot fl ashes,
Ineffective
primrose oil6
night
sweats
Drug interactions
Estrogen therapy,
anticoagulants, and
antihypertensive agents
Warfarin
Should not be taken at
the same time as any
conventional oral
medications or other
dietary supplements
Increases risk for bleeding
in people taking antico
agulants; can inhibit
platelet aggregation
Interacts with many drugs
No known interactions
with herbs and supple
ments; it is not known if
wild yams interact with
any medications
Anticoagulant/antiplatelet
drugs, herbs and
supplements; herbs with
estrogenic activity
Anticoagulants, antiretro
virals, selective serotonin
reuptake inhibitors,
immunosuppressants, and
chemotherapeutic drugs
May enhance the effects
of anticoagulants and
interfere with the
lipid-reducing effects of
HMG-CoA reductase
inhibitors (statins)
Herbs and supplements
with sedative properties,
alcohol, central nervous
system depressants
Anticoagulant/antiplatelet
drugs, herbs and
supplements,
phenothiazines
Adverse reactions
Gastrointestinal (GI)
symptoms, nausea,
vomiting, or fatigue
GI disturbances,
photosensitivity
Diarrhea
Rare symptoms:
headache, seizure,
dizziness
GI disturbances,
headache, sleep
disturbances
Large doses can
cause nausea,
vomiting, and
diarrhea
GI symptoms, nausea,
vomiting, or fatigue
Nausea, allergic
reaction, dizziness,
headache
GI disturbances,
rashes, fatigue
Contact dermatitis;
may contribute to
depression
Generally consid
ered safe and has
been used in several
studies without
reports of signifi cant
adverse reactions
(Continued)
50 The Nurse Practitioner -  Vol. 38, No. 8
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Page 4
Talking about CAMs for menopause
CAM therapies for menopausal symptom relief (continued)
Category
Therapy
Symptom
Effectiveness
Drug interactions
Adverse reactions
Mind-Body
Yoga9,10
Hot fl ashes
Inconclusive
Not applicable (n/a)
Minimal
Tai chi
Joint pain
Hypnotherapy
Mood swings
Muscle
Memory and
relaxation
concentration
Meditation
Exercise
Hot fl ashes
Ineffective
n/a
Minimal (if performed
Night sweats
as directed by a
Disturbed
healthcare provider)
sleep
Energy
Acupuncture9
Hot fl ashes
Inconclusive
n/a
Minimal
healing
Manual
Refl exology1
Hot fl ashes
Ineffective
n/a
Minimal
and body-
severity,
based
night sweats,
anxiety, or
depression
Alternative
Homeopathy1
Hot fl ashes
Inconclusive
Although highly diluted
Minimal
medical
and unlikely to cause
systems
harm, some homeopathic
products may contain
substantial amounts of
active ingredients and
could cause adverse
reactions and drug
interactions.6
SOURCES
1. Borrelli F, Ernst E. Alternative and complementary therapies for the menopause. Maturitas. 2010;66(4):333-343.
2. Geller SE, Shulman LP, van Breemen RB, et al. Safety and efficacy of black cohosh and red clover for the management of vasomotor symptoms: a randomized
 controlled trial. Menopause. 2009;16(6):1156-1166.
3. National Institutes of Health, National Center for Complementary and Alternative Medicine (NCCAM). Herbs at a glance. http://nccam.nih.gov/health/
herbsataglance.htm.
4. Natural Standard Database. Ginseng. www.naturalstandard.com.
5. MedlinePlus. Wild yam. 2011. http://www.nlm.nih.gov/medlineplus/druginfo/natural/970.html.
6. Natural Medicine Comprehensive Data Base. Menopause. http://naturaldatabase.therapeuticresearch.com.
7. Al-Akoum M, Maunsell E, Verreault R, Provencher L, Otis H, Dodin S. Effects of Hypericum perforatum (St. John's wort) on hot flashes and quality of life in
perimenopausal women: a randomized pilot trial. Menopause. 2009;16(2):307-314.
8. Erkkola R, Vervarcke S, Vansteelandt S, Rompotti P, De Keukeleire D, Heyerick A. A randomized, double-blind, placebo-controlled, cross-over pilot study on the
use of a standardized hop extract to alleviate menopausal discomforts. Phytomedicine. 2010;17(6):389-396.
9. Innes KE, Selfe TK, Vishnu A. Mind-body therapies for menopausal symptoms: a systematic review. Maturitas. 2010;66(2):135-149.
10. Lee MS, Kim JI, Ha JY, Boddy K, Ernst E. Yoga for menopausal symptoms: a systematic review. Menopause. 2009;16(3):602-608.
According to a recent systematic review, other CAM
therapies commonly used for symptom relief include the
following19:
-  Alternative medical systems: homeopathy
-  Botanical therapies: probiotics and prebiotics, plant
sterols and stanols, fber, herbal products, hops, and eve
ning primrose oil
-  Manual therapies: ref exology.
 Safety and effectiveness
The inconclusive evidence about safety and effectiveness of
CAM therapies make advisement of patients complicated,
and patients may not always tell their healthcare providers
about the use of CAM therapies.20 Avoiding the questions
rather than initiating the dialogue can be dangerous. For
example, not knowing whether a patient took Herba  ephedrae
(herbal ephedrine), an adrenaline-like stiumlant which was
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Page 5
Talking about CAMs for menopause
available on the U.S. market until 2004, could have resulted
in death because of its potentially dangerous effects on the
heart and nervous system.14, 21
When considering CAM therapies, the decision-
making dialogue should include a discussion of expected
versus possible benef ts, risks, possible adverse reactions,
and possible interaction of one treatment regimen with
another.21 Additionally, patients must understand that
"natural" does not mean inherently safe, as it is possible to
have a toxic reaction to "natural" products, especially if
taken in large doses, or potential adverse effects when
taken with certain prescription medications. The use of
the term "natural" can be a marketing tool to be wary of,
especially when related to products not monitored or
approved by the FDA.22
Given the continued increase in CAM use for meno
pause symptoms, women face the decision about using CAM
with limited scientif c research data and minimal profes
sional guidance from conventional healthcare providers or
alternative practitioners. Although it is challenging, health
care professionals are the best qualifed to examine available
scientific information on CAM and provide up-to-date
recommendations to their patients.17
 Hot flash dialogue
When discussing relief of hot fashes with a patient, the NP
can reference the research fndings in systematic reviews and
practice guidelines as found on the National Institute of
Health National Center for Complementary and Alterna
tive Therapy website.14 The conversation could include the
following topics:
-  Symptom: Mrs. X complains of severe hot f ashes and
night sweats since beginning perimenopause 3 months
ago. After ruling out any other possible cause, Mrs. X is
instructed to keep a symptom diary to be used as a base
line and evaluation of subsequent CAM or conventional
therapies interventions.
-  What women use: Concerned about hormone therapy
and wishing to try something "natural," Mrs. X is inter
ested in black cohosh, which is a popular herbal therapy
known as a traditional folk remedy for women's health
problems, such as dysmenorrhea and menopause.19
Although it has been recommended for sleep distur
bances, mood disorders, and hot flashes, most of the
evidence is from open-label trials that are fraught with
problems due to placebo effect.23 In European phyto
therapy, Remifemin (an over-the-counter product in the
United States), is commonly recommended as an effective
alternative to HRT for menopause.24
-  How CAM therapy works: Although mechanism of action
remains unclear, black cohosh contains substances with
selective estrogen receptor modulator (SERM) activity,
thought to bind to the estrogen receptors and reduce
luteinizing hormone levels from the pituitary, which may
be responsible for improving many of the climacteric
complaints.25
-  Dosage: Daily dosage used in studies varied from 16 to
127 mg.26 The black cohosh formulation, Remifemin
(Enzymatic Therapy Inc., Green Bay, Wis.), has a usual
dosage of one 20-mg tablet/twice a day.22 The German
Commission E recommends black cohosh for meno
pausal complaints in dosages of 40 to 200 mg, but use
should not exceed 6 months because a long-term safety
profle has not been established.25
-  Effectiveness: Mixed results: Remifemin showed benef t
for vasomotor symptoms, including hot f ashes, sleep
disorders, sexual disorders, sweating, and is consistent
with older German studies.10 The effectiveness of other
possible herbal products for Mrs. X, such as gingko
biloba, ginseng, St. John's wort, or soy supplements is
compared with fndings on the effectiveness of black
cohosh.
-  Safety: Long-term safety is unknown.26 Black cohosh may
bind estrogen receptors and could cause adverse outcomes
similar to those seen with estrogen, but no studies have
been of adequate size or duration to document safety.27
Lack of adequate long-term safety data, mainly on estro
genic stimulation of the breast or endometrium, precludes
recommending long-term use.28
-  Possible adverse events: It is generally well-tolerated, and
no serious adverse events have been linked to usage.26
Adverse events with black cohosh are rare, mild, and
reversible, and the most common adverse events include
gastrointestinal upsets and rashes.29
-  Drug interactions: Potential for unintended drug-drug
interactions are considered, especially with drugs with
known toxicity to the liver or kidneys.
If black cohosh becomes part of the treatment plan,
follow-up to review the response to treatment is necessary,
usually within 4 to 8 weeks.21
 Educating patients
A growing population of women in the United States are
heading toward the menopausal years and seeking CAM for
symptom relief. Even though studies are limited and incon
sistent, women are reporting relief when using CAM thera
pies.16 As the scientific rigor of CAM therapy studies
improves with more reports of randomized, double-blind,
placebo-controlled trials, NPs must provide the information
to patients during patient interactions by using clinical
trial evidence to explain the effectiveness of CAM therapies
as well as those that show little evidence or have ill effects.30
52 The Nurse Practitioner -  Vol. 38, No. 8
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Page 6
Talking about CAMs for menopause
As CAM therapies become patient preferences, they must
22. Pace DT. Menopause: studying the research. Nurs Pract. 2006;31(8):17-23.
23. Fitzpatrick LA. Menopause and hot fashes: no easy answers to a complex
be addressed in the evidence-based decision-making
problem. Mayo Clin Proc. 2004;79(6):735-737.
dialogue where NPs and patients discuss safety, risks, and
24. McKenna DJ, Jones K, Humphrey S, Hughes K. Black cohosh: eff cacy, safety,
benef ts.31
and use in clinical and preclinical applications. Altern Ther Health Med.
2001;7(3):93-100.
25. Russell L, Hicks GS, Low AK, Shepherd JM, Brown CA et al. Phytoestrogens:
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