CHAPTER 24
Complementary and Integrative Health Approaches
KEY POINTS
1 The spectrum of complementary and integrative approaches is broad and includes
methods worthy of integration into our current practice, and ineffective or fraudulent
practices that should be avoided.
2 A complete history should include the patient’s use of complementary and integrative
health approaches (CIH), particularly botanicals and supplements, as these can have
actions ranging from estrogenic to anticoagulant.
3 The U.S. Food and Drug Administration (FDA) does not regulate botanicals and
supplements, so extra steps must be taken to ensure the quality of such products.
4 The management of many women’s health issues can be enhanced by the integration
of selected CIH approaches.
5 Perceived congruency of values related to life and health with CIH providers was
predictive of use of these approaches; dissatisfaction with conventional medicine is
not a predictor of use of CIH.
6 Acupuncture is of benefit in a variety of conditions, including pain, nausea, and
vomiting during pregnancy, and secondary to chemotherapy.
7 Mind–body approaches such as stress reduction, visualization, and hypnosis are
gaining significance as valuable adjuncts in a spectrum of women’s health concerns,
from surgery to fertility.
According to the 2012 National Health Interview Survey (NHIS), complementary
health approaches are used by an estimated 37% of adult women in the United
States (1). [1] Although evidence exists to support many of these approaches,
some approaches are used in the absence of documented benefit and can be
potentially dangerous and fraudulent (2). The primary users of these therapies are
women, who are frequently making decisions regarding treatment options without
the advice of their physicians. Obstetrician–gynecologists are in an excellent
position to help guide patients in their treatment choices, counseling them about
potentially dangerous treatments and supporting their use of potentially beneficial
ones. The most significant challenge is the lack of training that most obstetrician–
gynecologists have in this area; thus, this chapter reviews the domains of CIH as
they apply to the practice of gynecology.
DEFINITIONS
The changing use of terms related to this field is indicative of the evolution of the
1247field itself. Of note, the National Institutes of Health (NIH) Center has changed its
name from the National Center for Complementary and Alternative Medicine to
the National Center for Complementary and Integrative Health (NCCIH). This
name change is consistent with national trends, and represents the growing
integration of these therapies into mainstream health care. The term
complementary health approaches is typically used when referring to health care
approaches that are based in traditions outside of mainstream Western, or
conventional, medicine. If these approaches are used in place of conventional
health care, the term “alternative” is used. Integrative health refers to the
incorporation of complementary approaches into mainstream health care (3).
NCCIH organizes complementary health approaches into two groups: natural
products and mind body practices. Natural products include herbs or botanicals,
vitamins and minerals, and probiotics, often sold as dietary supplements. Mind
and body practices include a wide array of approaches that are offered by a
trained practitioner or teacher. This group includes acupuncture, yoga, tai chi, qi
gong, chiropractic and osteopathic manipulation, meditation, healing touch,
clinical hypnosis, massage therapy, relaxation techniques, and movement
therapies such as Feldenkrais method and Alexander technique. NCCIH
recognizes that some approaches do not fall into either of these categories, such as
traditional healers, Ayurvedic medicine, traditional Chinese medicine,
homeopathy, and naturopathy (3).
[1] The amount of evidence on the use of these approaches varies widely. A
significant number of randomized controlled trials (RCTs), including those with
sufficient quantity and quality to allow meta-analyses in some areas, were done to
assess the efficacy of acupuncture, botanical medicine, nutritional approaches,
manual therapies, and mind–body medicine. Research in the other domains is
much more limited. Many culturally based practices such as shamanism and
curanderismo have virtually no research basis. A growing number of RCTs are
being done in spiritual healing and homeopathy, but these techniques remain
controversial based on a lack of understood biophysical mechanisms to justify
their efficacy.
Integrative medicine is a distinct entity separate from the practice of CIH.
Integrative medicine neither blindly advocates CIH nor rejects conventional
medicine. Integrative medicine is healing oriented and patient centered and adopts
a whole-person approach to the treatment of disease and the maintenance of
health. It draws on the best practices of medicine, regardless of system of origin.
Typically, integrative medicine would include, in addition to conventional
medicine, CIH techniques that may be of benefit, including nutrition,
movement and exercise, mind–body approaches, and spirituality. In 2013, the
American Board of Integrative Medicine (ABOIM) was created. This was a
1248controversial decision, given that the ultimate goal is to have all physicians obtain
competencies in integrative medicine. Because of the growth of this field, it was
felt that there should be a process to acknowledge expertise in integrative
medicine. As the paradigm of conventional medicine broadens to include other
therapeutic modalities that previously were considered “integrative,” and the
system becomes more accepting of health optimization and holistic disease
management, there is likely to be greater integration of these philosophies,
approaches, and providers. The distinction of “complementary health approaches”
may ultimately no longer be useful, nor will integrative medicine. This approach,
which is inclusive of effective philosophies and approaches that can improve the
health and healing of women and men, will simply become the standard for US
health care.
DEMOGRAPHIC DATA
Using data from the 2012 NHIS, it was estimated that 37.2% of adult women used
complementary health approaches (1). A study of gynecologic oncology patients
revealed that 56% were using CIH, and surveys of menopausal women showed
that 80% were using “nonprescriptive therapies” (4). The Study of Women’s
Health Across the Nation (SWAN) found that approximately one-half of women
were actively using herbal, spiritual, or manipulative therapies (4). A study
examining the use of CIH by women suffering from nausea and vomiting during
pregnancy found that 61% reported using CIH therapies, with the most popular
being ginger, vitamin B6, and acupressure (5). A study evaluating the use of CIH
therapies by women with advanced-stage breast cancer revealed that 73% of
patients used CIH, with relaxation or meditation techniques and botanicals being
used most often (6). The reason most often given for the use of CIH was immune
support, followed by the treatment of cancer. A survey in Washington state
exploring use of integrative therapies for menopause revealed that 76% of women
were using integrative approaches, with 43% of these women using stress
reduction techniques, 37% using over-the-counter integrative approaches, 32%
using chiropractic medicine, 30% massage therapy, 23% dietary soy, 10%
acupuncture, 9% naturopathy or homeopathy, and 5% herbalists (7). Of these
women, 89% to 100% found these approaches to be somewhat or very helpful.
Users of hormone therapy (HT) were 50% more likely to use CIH than those who
never used HT. Following the results of the Women’s Health Initiative
indicating the risks associated with HT, interest in the use of CIH for
management of menopausal symptoms increased.
The Attraction
1249After the publication of the first national surveys on the use of complementary
health approaches stunned the mainstream medical community in the early 1990s,
there was much conjecture regarding why so many patients were turning to these
approaches. A national survey published in 1998 was the first to explore this
question, and its findings remain pertinent (8).
[5] Dissatisfaction with conventional medicine was not predictive of use of
complementary health approaches. Patients were using these approaches
because they were seeking greater congruency of values regarding life,
health, and wellness (8). The implication is that people are happy to use
conventional medicine when they have a diseased or injured body part, but when
their goal is to improve their health or manage a chronic condition or lifestyle
issue, they turn to integrative care providers. Establishing a partnership with
patients can help them explore all of the options for maximizing their health is
critical. The Centers for Disease Control and Prevention (CDC) reported that the
majority (55%) of people stated that their reason for using CIH therapies was that
they thought combining these approaches with conventional ones would help
them, and 26% reported they tried these approaches because medical
professionals had recommended them (9).
The Challenge
The demographics and trends associated with CIH use create challenges for
physicians and patients. A huge market demand creates an opportunity for
products and therapies that may be ineffective, dangerous, or fraudulently
marketed. The development of high patient demand preceded the incorporation of
education regarding CIH for medical students, residents, and practicing
physicians. As a result, patients often make decisions regarding their care without
the benefit of medical advice or the coordination of their care by one provider.
The best practice of medicine necessitates the integration of all therapies that can
benefit the patient and the exclusion of those that can cause harm. Integration of
these techniques requires the collaborative, concerted effort of physicians, CIH
providers, and patients.
COMPLEMENTARY AND INTEGRATIVE THERAPIES
The many types of CIH techniques can be organized into two categories as
outlined by the NIH: natural products and mind body practices. Licensing and
certification requirements for practices vary widely from state to state, but most
techniques have a formal structure for training and accreditation (Table 24-1).
1250Natural Products: Botanical Medicine
Botanical or herbal therapies use botanicals singly or in combination for
therapeutic value. A botanical is a plant or plant part that contains chemical
substances that act on the body. Botanical or herbal medicines were studied
extensively in Europe, and large multicenter trials are beginning to provide
more robust evidence in this country.
Botanical medicine is the area of CIH most conceptually accessible to patients.
Botanicals are the source of the active agents in approximately 25% of
prescription drugs and 60% of over-the-counter drugs. [3] In the United States,
these products are often not perceived as active and are regulated as “dietary
supplements” that are not under the direction of the U.S. Food and Drug
Administration (FDA). The most popular botanicals used in the United States are
listed in Table 24-2.
Complications and Risks
[2] Botanical medicines are being used by an increasing number of patients,
and they often do not inform their clinicians of this use. Certain patients are
at risk for drug–botanical interactions or adverse reactions, and patients
should be questioned about them (Tables 24-3 and 24-4). Mega doses of
vitamins and supplements have associated risks and complications.
[3] Because botanicals are regulated as dietary supplements, quality control
is challenging. In 1994, the Dietary Supplement Health and Education Act
(DSHEA) was enacted (10). This act makes it legal to refer to the supplement’s
effect on the body’s structure or function or to a person’s well-being. Products
within the jurisdiction of DSHEA are easily recognized by the following
statement on their labels: “This product is not intended to diagnose, treat, cure, or
prevent any disease.” Because the FDA does not regulate these products, the
potential for lack of standardization of products, and adulteration or mislabeling,
exists.
It is imperative to review literature. There are several databases that are good
resources for clinicians and patients, including the Natural Medicines
Comprehensive Database (http://www.naturaldatabase.com) and the Natural
Standard (http://www.naturalstandard.com). Numerous drug information
databases contain information about natural product interactions, including
UptoDate (Lexi-Comp interactions), MicroMedex (AltMedDex), and others.
Botanicals can cause toxicity in one of three ways: (i) the products can be
adulterated; (ii) the labels can recommend dosages that exceed appropriate
use and cause toxicity even when the product is safe in appropriate dosages;
and (iii) even when they are of good quality and taken in the correct dosage,
these products can interact with other supplements and pharmaceutical
1251agents. The Institute of Medicine recommended the following measures: seed-toshelf quality control, accuracy and comprehensiveness in labeling and other
disclosure, enforcement against inaccurate and misleading claims, research into
consumer use, incentives for privately funded research, and consumer protection
against all potential hazards.
Training and Licensure in Botanical Therapies
There is no national licensure for botanical or herbal medicine, and there is no
national or professional organization that regulates or accredits Western and
Ayurvedic herbal medicine education. In 1996, the National Certification
Commission for Acupuncture and Oriental Medicine (NCCAOM) developed a
national certification written examination, which tests for entry-level capabilities
in oriental herbal medicine. Passage of this examination allows practitioners to
call themselves Diplomates of Chinese Herbology (Dipl CH). The Commission’s
Web site contains a searchable directory of certified practitioners (11).
Naturopathic physicians are typically trained in botanical medicine as a part of
their 4-year curriculum.
CHIROPRACTIC MEDICINE
Chiropractic medicine focuses on the relationship between structure
(primarily the spine) and function, and the way that relationship affects the
preservation and restoration of health. It uses manipulative therapy as an
integral tool. Chiropractors can legally do more than manipulate and align the
spine, including taking a medical history, performing a physical examination, and
ordering lab tests and x-rays to determine a diagnosis. The spectrum of
chiropractors varies in terms of the conditions treated with manipulation.
Although some practitioners limit their practice primarily to musculoskeletal
problems, others claim to offer effective treatment for virtually any medical
condition. They are referred to as doctors, which can be confusing to patients. The
chiropractic profession is growing quickly, with approximately 77,000
chiropractors in the United States (12).
Complications and Risks
Chiropractic adjustment is considered safe when performed by a licensed
professional. Serious complications are very rare, but may include herniated
disk, cauda equina syndrome, or vertebral artery dissection and stroke after
cervical manipulation with a rotatory component.
Table 24-1 Training and Licensure in Complementary and Integrative Medicine
1252Therapy Training Licensure
Botanical
medicine
None standardized Written examination
developed by the National
Certification Commission
for Acupuncture and
Oriental Medicine tests for
entry-level capabilities in
oriental herbal medicine.
Passage allows
practitioners to call
themselves Diplomates of
Chinese Herbology (Dipl
CH).
Chiropractic Must complete a 4-year chiropractic
college program of study accredited
by the Council on Chiropractic
Education (CCE)
National
Massage
therapy and
bodywork
There is lack of consistency among
licensure laws; requirements range
from 500–1,000 hours.
Offered at the state level in
46 states.
Hypnotherapy The International Medical
and Dental Hypnotherapy
Association will certify
hypnotherapists if they
meet the minimum
eligibility requirements
and provide referrals.
Clinical
hypnosis
Basic certification requires a
minimum of 40 hours of ASCHapproved workshop training, 20 hours
of individualized training, and a
minimum of 2 years of independent
practice using clinical hypnosis. The
advanced level, called approved
consultant, requires a minimum of 40
additional hours of ASCH-approved
workshop training and 5 years of
independent practice using clinical
American Society of
Clinical Hypnosis (ASCH)
Certification in clinical
hypnosis ensures that the
certified individual is a
bona fide health care
professional who is
licensed in that state to
provide medical, dental, or
psychotherapeutic services.
1253hypnosis.
Meditation
and stress
reduction
None None
Energy
therapies
Given the wide array of energy
therapies, the levels of training vary
tremendously from modality to
modality.
Acupuncture Schools provide 3- or 4-year training
programs in oriental medicine that
consist of about 2,500–3,200 hours.
In most states, the
practitioner must provide
proof that he/she has
attended and graduated
from an accredited school
or from a school that is in
the process of being
accredited by the
Accreditation Commission
for Acupuncture and
Oriental Medicine
(ACAOM).
The right to practice exists
in 46 states and in the
District of Columbia. This
right may be designated by
licensure, certification, or
registration under the state
law.
The National Certification
Commission for Acupuncture and
Oriental Medicine (NCCAOM) tests
entry-level capabilities with a
comprehensive written examination,
point location examination, and clean
needle technique.
An acupuncturist must
pass this examination and
meet continuing education
requirements every 4 years
to retain certification and
licensure.
Medical
doctors can be
certified by
the American
Board of
1254Medical
Acupuncture
by taking a
minimum 300
hours in
training.
Homeopathy Lay homeopaths have no training
standards.
Classical Homeopaths (CCH) are
credential by the Council on
Homeopathic Certification and
requires a minimum of 1,000 hours of
training. Certified Classical
Homeopaths are not licensed as health
care professionals.
Registered homeopathic medical
assistants require 300 hours of
training and MD or DO supervision.
Licensed health care professionals
can also practice homeopathy, and
their training ranges from 200–1,000
hours.
Laws regulating the
practice of homeopathy
vary from state to state.
Naturopathic
medicine
Naturopathic physicians are typically
trained in botanical medicine as a part
of their 4-year curriculum.
Currently only 19 states
have licensing laws, and
licensure efforts are
underway in at least 12
other states. To be eligible
to be licensed/registered as
a naturopathic physician, a
candidate must graduate
from an accredited
naturopathic medical
school and pass national
board examinations.
There are seven 4-year
naturopathic medical
schools accredited by the
Council on Naturopathic
Medical Education in the
United States and Canada.
Table 24-2 Most Used Natural Products
1255Rank/Herb % Change From 2002–2012
1. Fish oil/omega-3 fatty acids 7.8
2. Glucosamine and/or chondroitin 2.6
3. Probiotics/prebiotics 1.6
4. Melatonin 1.3
5. Coenzyme Q10 1.3
6. Echinacea 0.9
7. Cranberry (pills, capsules) 0.8
8. Garlic supplements 0.8
9. Ginseng 0.7
10. Ginkgo biloba .07
From Clarke TC, Black LI, Stussman BJ, et al. Trends in the use of complementary
health approaches among adults: United States, 2002–2012. Natl Health Stat Reports 2015;
(79):1–16.
Training and Licensure
There is a national process for licensure for chiropractic medicine to which all 50
states adhere. Chiropractors must complete a 4-year chiropractic college program
of study accredited by the Council on Chiropractic Education (CCE).
Massage Therapy and Bodywork
Massage therapy involves manipulation of the soft tissues of the body to
normalize those tissues. A wide variety of approaches are available that
include deep tissue massage, Swedish massage, reflexology, Rolfing, and
many others. A number of RCTs documented the value of massage therapy,
particularly in pediatric conditions such as childhood asthma. Some studies show
an increase in dopamine and serotonin, and an increase in natural killer cells and
lymphocytes with regular massage therapy.
1256Massage therapy and bodywork are used by a wide array of people seeking the
benefits of massage, which include physical relaxation, reduced anxiety,
increased circulation, and pain relief. Specific indications for massage include
treatment of acute low-back pain and lymphatic massage for patients with
lymphedema from conditions such as postmastectomy extremity edema. Massage
is used by various practitioners, including physicians, physical therapists,
osteopathic physicians, chiropractors, acupuncturists, nurses, and massage
therapists.
Complications and Risks
Massage should not be used in the presence of bleeding disorders, phlebitis
and thrombophlebitis, edema that is caused by heart or kidney failure, fever
or infections that can be spread by blood or lymph circulation, and leukemia
or lymphoma. Massage should not be performed on or near malignant
tumors and bone metastases; over bruises, unhealed scars, or open wounds;
on or near recent fracture sites; or over joints or other tissues that are
acutely inflamed.
Training and Licensure
There is no national licensure in massage therapy, but 46 states regulate the
profession in some form. There is a lack of consistency among licensure laws,
with requirements ranging from 500 to 1,000 hours. Depending on the state law,
therapists can be referred to as state certified, registered, or licensed (12).
Clinical Hypnosis
Hypnosis involves the induction of trance states and the use of therapeutic
suggestions. Hypnosis has documented value for a variety of psychological
conditions, pain control, and recovery from surgery.
Complications and Risks
There are occasional reports of unanticipated negative effects during and after
hypnosis. The spectrum of reported effects encompassed minor transient
symptoms such as headaches, dizziness, or nausea in experimental situations to
less frequent symptoms of anxiety or panic, unexpected reactions to an
inadvertently given suggestion, and difficulties in awakening from hypnosis.
More serious reactions following hypnosis are attributed to the misapplication of
hypnotic techniques, failure to prepare the participant, and pre-existing
psychopathology or personality factors. There are no known deaths attributed to
the use of hypnosis.
1257False memories of suggested events that did not occur in reality, particularly
when legal and interpersonal battles are involved, can be viewed as an untoward
reaction to psychotherapeutic procedures. In hypnotic and nonhypnotic situations,
leading and suggestive overtures can produce false memories. Because hypnosis
involves direct and indirect suggestions, some of which may be leading in nature,
and because hypnosis can increase confidence of recalled events with little or no
change in the level of accuracy, therapists must be attentive to the problem of
creating false memories.
Training and Licensure
There is no national or state licensure for hypnotherapists. The American Society
of Clinical Hypnosis (ASCH) certification in clinical hypnosis is distinct from
other certification programs in that it ensures that the certified individual is a
health care professional who is licensed in his or her state to provide medical,
dental, or psychotherapeutic services. Certification by ASCH distinguishes the
professional practitioner from the lay hypnotist. There are two levels of
certification; the first is simply called certification, which requires, among other
things, a minimum of 40 hours of ASCH-approved workshop training, 20 hours
of individualized training, and a minimum of 2 years of independent practice
using clinical hypnosis. An advanced level, called approved consultant,
recognizes individuals who obtained advanced training in clinical hypnosis and
who have extensive experience in using hypnosis within their professional
practices. Certification at this level requires a minimum of 40 additional hours of
ASCH-approved workshop training and 5 years of independent practice using
clinical hypnosis (13).
Meditation and Stress Reduction
Meditation is a self-directed practice that can relax the body and calm the
mind. Most meditative techniques came to the West from religious practices in
the East, particularly India, China, and Japan, but it can be found in all cultures of
the world. A National Institutes of Health Consensus Panel in 1996 concluded
that mind–body and behavioral techniques were effective in the treatment of
stress-related conditions and insomnia, and since then evidence for their
effectiveness has continued to grow. Mindfulness-based stress reduction
(MBSR), based on Vipassana meditation from India, is promoted in this country.
This technique is based on the cultivation of mindfulness, an intentional, focused
awareness of nonjudgmental attentiveness to experiences in the present moment.
Vipassana meditation, one of India’s most ancient techniques of meditation, was
taught more than 2,500 years ago as a remedy for universal ills.
1258Table 24-3 Botanicals: Potential for Interactions With Drugs
Drug Class Herb Potential Interactions
Anticoagulants Bilberry Increased risk of bleeding (high dose)
Chamomile Increased risk of bleeding
Coenzyme
Q10
Decreased effectiveness
Danshen Increased risk of bleeding
Dong quai Increased risk of bleeding
Feverfew Increased risk of bleeding
Garlic Increased risk of bleeding
Ginger Increased risk of bleeding
Ginkgo Increased risk of bleeding
Ginseng Increased risk of bleeding
Kava Increased risk of bleeding
St. John’s
wort
Decreased effectiveness
Anticonvulsants Borage Decreased seizure threshold
Comfrey Increased risk of phenobarbital toxicity
Evening
primrose
oil
Decreased seizure threshold
Valerian Increased effects of barbiturates
Antidepressants Ephedra Increased effect of monoamine oxidase inhibitors
Ginseng Increased risk of monoamine oxidase inhibitors
Kava Hypertension
1259St. John’s
wort
Monoamine oxidase inhibitors; increased blood
pressure level
Yohimbine Tricyclics—hypertension; selective serotonin
reuptake inhibitors; increased serotonin levels
Diuretics Aloe Increased risk of hypokalemia
Cascara
sagrada
Increased risk of hypokalemia
Licorice Increased risk of hypokalemia
Senna Increased risk of hypokalemia
Hypoglycemic
agents
Ginseng Risk of hypoglycemia
Stinging
nettle
Potential elevation of blood glucose level
Sedatives Chamomile Increased drowsiness
Kava Increased risk of sedation
Valerian Increased risk of sedation
Data from O’Mathuna DP. Herb-drug interactions. Altern Med Alert 2003;6:37–43.
Transcendental meditation (TM) is a simple method practiced for 15 to 20
minutes in the morning and evening while sitting comfortably with the eyes
closed. During this technique, the individual experiences a unique state of restful
alertness. TM is useful in the treatment of hypertension.
[7] The relaxation response, which can be elicited by any number of
techniques, is a physical state of deep rest that changes the physical and
emotional responses to stress (e.g., decrease in heart rate, blood pressure,
and muscle tension). If practiced regularly, it can have lasting effects when
encountering stress throughout the day.
Table 24-4 Selected Risk Factors for Adverse Reactions or Drug Interactions With
Botanicals
• Bleeding disorders or anticoagulation
• Seizure disorders
1260• Radiation with or without chemotherapy
• Immunosuppression
• Diabetes
• Pregnancy
• Renal insufficiency
• Liver disease
• Heart failure
• Electrolyte imbalances
• Taking sedatives/anxiolytics/central nervous system depressants, oral contraceptives,
diuretics, monoamine oxidase inhibitors, antiretroviral drugs
• Undiagnosed medical conditions
Complications and Risks
Meditation rarely may lead to a “spiritual emergency,” defined as a crisis during
which the process of growth and change becomes chaotic and overwhelming as
individuals enter new realms of spiritual experience. Types of spiritual emergency
include but are not limited to loss or change of faith, existential or spiritual crisis,
experience of unitive consciousness or altered states, psychic openings,
possession, near-death experience, kundalini, shamanic journey, or difficulties
with a meditation practice.
Training and Licensure in Meditation and Stress Reduction
There are many systems of meditation, and there is no nationally recognized
licensing or certification procedure for teachers of meditation. Many mental
health care professionals are trained in a variety of stress reduction techniques.
Energy Therapies
Energy therapies involve the use of energy fields. They are of two categories:
1. Biofield therapies are intended to affect energy fields that purportedly
surround and penetrate the human body. Some forms of energy therapy
attempt to manipulate biofields by applying pressure or manipulating the body
1261by placing the hands in, or through, these fields. Examples include qi gong,
Reiki, and therapeutic touch.
2. Bioelectromagnetic-based therapies involve the unconventional use of
electromagnetic fields, such as pulsed fields, magnetic fields, or alternating
current or direct current fields.
Complications and Risks
Energy-based therapies are the least well researched and the most diverse of all
CIH modalities. It is not possible to address potential complications and risks.
Training and Licensure in Energy-Based Therapies
Given the wide array of therapies that fall under this category, the levels of
training vary tremendously from modality to modality.
Acupuncture and Oriental Medicine
[6] Acupuncture is a therapeutic intervention that is used in many Asian
systems of medicine, with a history extending thousands of years. It has
continued to increase in popularity in the United States, and has a growing
body of evidence supporting its effectiveness. It is based on the theory that there
are energy channels called meridians that run throughout the body, and that
disease results from blockages of this energy. Acupuncture is used as one
approach to release these blockages. It involves stimulating specific anatomic
points in the body along the meridians by puncturing the skin with a very fine
needle (32 gauge or smaller). There are many distinct styles of acupuncture,
which include traditional oriental medicine, Japanese Manaka style, Korean hand
acupuncture, and the Worsley five-element method.
Given the Western, biomedical model, acupuncture is difficult to comprehend.
There is a significant body of research on this technique. In one study involving
stimulation of an acupuncture point located on the lateral aspect of the foot that
corresponds to the visual cortex, magnetic resonance imaging detected activity of
the visual cortex of the brain equivalent to the activity seen when a light is shone
in the eye. No activity was seen when an acupuncture needle was placed 1 cm
away from the designated acupuncture point (14). Many of the CIH approaches
that claim to have an effect and yet seem to be inconsistent with the biomedical
model deserve further investigation.
A 1997 National Institutes of Health Consensus Panel established that
there was convincing evidence for the use of acupuncture in the treatment of
postoperative dental pain, nausea, and vomiting, and promising evidence for
headache, low-back pain, stroke, addiction, asthma, premenstrual syndrome
1262(PMS), osteoarthritis, carpal tunnel syndrome, and tennis elbow. This is not yet
standard practice, and the body of evidence has continued to grow. There is an
extensive body of animal research supporting the neurophysiologic effects of
acupuncture on the endorphin system. The available published literature on
acupuncture in humans is extensive. PubMed searches in 2013 identified almost
20,000 citations with the term “acupuncture” and almost 1,500 RCTs with
“acupuncture” in the title. The Veterans Affairs Evidence-Based Synthesis
Program conducted a systematic review of studies that were published from
January 2005 to March 2013 and provided an overview of the existing literature
on acupuncture, focusing on (1) pain (59 systematic reviews), (2) mental health
(20 systematic reviews), and (3) well-being (44 systematic reviews). The
investigators examined other clinical areas for which at least three reviews and/or
recent large randomized controlled trials (RCTs) exist (48 systematic reviews).
The condition with the greatest evidence of effect was chronic pain (15).
Complications and Risks
Bruising and minor bleeding are the most common complications of acupuncture
and occur in about 2% of all needles placed (16). They rarely require treatment
other than local pressure to the needle site. The most significant risk of
acupuncture is infection. The risk of transmissible infection is eliminated by
onetime use of disposable needles, which is now standard practice in the United
States. Pneumothorax is the second most significant risk of acupuncture. The
needles used are 32 gauge or smaller; therefore, a chest tube usually is not
required for treatment.
Training and Licensure
There are approximately 29,000 licensed acupuncturists in the United States.
There is no national licensure for acupuncture, and the right to practice exists in
46 states and in the District of Columbia. This right may be designated by
licensure, certification, or registration under the state law (12). Educational
requirements for state licensure for acupuncture vary. To become licensed in most
states, the practitioner must provide proof that he or she has attended and
graduated from an accredited school or from a school that is in the process of
being accredited by the Accreditation Commission for Acupuncture and Oriental
Medicine (ACAOM) (17). These schools provide 3- or 4-year training programs
in oriental medicine. The NCCAOM administers a standardized examination to
test entry-level capabilities in acupuncture consisting of a comprehensive written
examination, point location examination, and demonstration of clean needle
technique (11). An acupuncturist must pass this examination and meet continuing
education requirements every 4 years to retain certification and licensure. In the
1263United States, many states adopted this examination as the basis for licensure.
Physician acupuncture practitioners may not be as fully trained in the art as
nonphysician licensed acupuncturists. To be certified by the American Board
of Medical Acupuncture, physicians must take a minimum of 300 hours in
training (18).
Homeopathy
Homeopathic medicine is a CIH alternative medical system based on the work of
the German physician and chemist Samuel Hahnemann approximately 200 years
ago. In homeopathic medicine, there is a belief in “the law of infinitesimals”
and that “like cures like.” Small, highly diluted quantities of medicinal
substances are given to cure symptoms when the same substances given at higher
or more concentrated doses would actually cause those symptoms. The number of
homeopathic practitioners is estimated at 8,500 (12).
Training and Licensure
There are four subgroups of homeopathic practitioners and standards, regulation,
licensure, and educational accreditation vary widely among them. Lay
homeopaths have no training standards. Professional homeopaths can be certified
as a Classical Homeopath (CCH) credentialed by the Council on Homeopathic
Certification. Certification requires a minimum of 1,000 hours of training, and
Certified Classical Homeopaths are not licensed as health care professionals.
Registered homeopathic medical assistants require 300 hours of training and MD
or DO supervision. Licensed health care professionals can practice homeopathy,
and their training ranges from 200 to 1,000 hours. Laws regulating the practice of
homeopathy vary from state to state (12).
Naturopathic Medicine
Naturopathic medicine is a holistic approach to health care that views
disease as a manifestation of alterations in the processes by which the body
naturally heals itself and emphasizes health restoration rather than disease
treatment. Naturopathic physicians employ an array of healing practices,
including diet and clinical nutrition; homeopathy; acupuncture; herbal medicine;
hydrotherapy (the use of water in a range of temperatures and methods of
applications); spinal and soft tissue manipulation; physical therapies involving
electric currents, ultrasonography, and light therapy; therapeutic counseling; and
pharmacology. It is estimated that there are approximately 5,000 naturopathic
physicians practicing in the United States (12).
1264Training and Licensure
There is no national licensure for naturopathy, and licensure at the state level is
inconsistent. Naturopathic medicine is regulated in 19 states, and licensure efforts
are underway in at least 12 other states. To be eligible to be licensed/registered as
a naturopathic physician, a candidate must graduate from an accredited
naturopathic medical school and pass national board examinations. Seven 4-year
naturopathic medical schools are accredited by the Council on Naturopathic
Medical Education in the United States and Canada. This training focuses on
outpatient medicine and does not require a residency. Although the 4-year
programs are rigorous, it is possible to get a naturopathic degree online.
PATIENT CARE ISSUES
The Placebo Effect
There is no evidence that the placebo response is more active in CIH than in
conventional approaches. Just as with conventional medicine, the effects of
certain approaches are more likely than others to be associated with a placebo
response. After exposure to a stimulus believed by the patient and the practitioner
to be an active intervention, the body responds physiologically in an equivalent
manner. Approximately one-third of patients in placebo-controlled trials of
conventional methods experiences a placebo response. It would be of great
value to medicine if the placebo response was better understood and could be
activated more reliably in patients. Clinicians need to understand that the
placebo effect is actually an activated healing response, and the ability to
achieve an equivalent physiologic response to an intervention, without the
risks or costs of an intervention, may be the best possible medicine.
Potential Misuse
In addition to physical risks, patients and physicians alike should be aware of
other areas of potential misuse. Two areas are of particular concern. First, given
that the dollars being spent out of pocket are so significant, there are some
products and some providers whose primary motivation is monetary. Patients can
spend a great deal of money based on false promises or claims. Second, patients
can postpone effective or curative therapy or treatment by turning to CIH
modalities and excluding conventional approaches. This time can negatively
impact the outcome for treatment of many patients’ diseases. Factors that should
increase suspicion for potential misuse are listed in Table 24-5.
Table 24-5 Factors That Should Increase Suspicion for Potential Misuse
12651. Providers or products that make claims that are grandiose and dubious, for
example, approaches that claim to cure insulin-dependent diabetes or offer CIH as
a cure for cancer.
2. Providers or products who foster dependence, for example, therapists who
recommend multiple visits per week or frequent visits for an unlimited period.
3. Providers who recommend products that they sell and from which they profit.
4. Providers or products that support the use of alternative approaches exclusive of
conventional medicine or conventional providers.
The Potential Benefits: Therapeutic Opportunities
Given all of the risks and uncertainties, it is appropriate to ask the question: Why
should physicians educate themselves regarding CIH? The most basic answer is
commitment to the best practice of medicine. [2] If patients are using therapies
that are potentially dangerous in their action or interaction, physicians should be
aware of this possibility and counsel them accordingly. Physicians have a
commitment to offer their patients the best treatment options, regardless of their
system of origin. Physicians should be knowledgeable about CIH therapies that
can benefit patients and be willing and able to discuss them with patients.
[4] In addition to these fundamental reasons, there are therapeutic
opportunities offered by CIH, as shown by the following examples:
Decreased harm of interventions: Chiropractic medicine to treat acute lowback pain and potentially avoid surgery; mind–body approaches to
decrease anxiety and need for medical intervention; integrative approaches
in the treatment of chronic pain and decrease of opioid use
Treatment of conditions when conventional approaches fail: Treatment of
nausea and vomiting during pregnancy with acupuncture, vitamin B6, and
ginger
Prevention: Nutritional approaches to decrease the risk of metabolic and
autoimmune disorders
Improved outcomes: Successful management of menopausal symptoms in
patients at risk for breast cancer; integrative therapies pre- and post-op to
manage pain and nausea
Doctor–Patient Interaction
One of the greatest barriers regarding issues of CIH is a lack of
1266communication. As multiple studies show, most patients do not tell their
physicians about their use of CIH. This can be the case even when the
physicians are receptive to the topic. [2] Given the prevalence of use and the
potential for interactions with conventional approaches, it is imperative that
questions regarding CIH be integrated into the patient history. Many patients
simply do not think of sharing this information with their physicians, so direct and
specific inquiry is necessary. Many practices incorporate this information in a
separate sheet for patients to fill out and for physicians to review and add to the
chart. It is useful to know all CIH therapies that patients used in the past or are
using presently, particularly anything ingestible. If a patient is seeing a CIH
practitioner, it is best to specifically ask if they recommended any supplements or
botanicals. Oriental medicine practitioners or acupuncturists, for example, often
treat with botanical products or herbal teas. Naturopaths and chiropractors often
recommend vitamins and supplements. When patients are asked this history
directly in an atmosphere of respect, they usually are very forthcoming, and the
most significant barrier is broken.
Three factors contribute to an interesting dynamic that often arises when
discussing issues of CIH with patients. This is an area in which (i) most
physicians do not receive formal training, (ii) there is little (albeit increasing)
research in the mainstream medical journals, and (iii) there is a tremendous
amount of information, of variable quality, in the lay press. All of these factors
contribute to a circumstance that often is uncomfortable for physicians. This
discomfort is important to recognize because it can contribute to avoidance of the
topic. The integration of CIH therapies into treatment plans is a relatively new
and evolving area. It is appropriate to begin the conversation with a patient by
explaining that this is new territory in conventional medicine and that you are not
an expert. Most patients have assumed this to be the case, appreciate the honesty,
and value the opportunity to discuss these questions. This is a significant step in
building a trusting and therapeutic relationship with patients interested in CIH.
It is useful to share the following decision tree with patients when making
decisions regarding the use of CIH (Fig. 24-1).
Step One: Assess Potential Harm
Although research regarding CIH approaches is often less than optimal, the
potential for any therapy to do harm should be evaluated (to the best of available
knowledge). It is necessary to evaluate the potential to cause both direct and
indirect harm.
Potential for Direct Harm
This should include any evidence regarding potential harm directly from the
1267therapy or potential interactions. When lacking good evidence, assessment of the
invasiveness of the therapy is a strong predictor of risk.
Potential for Indirect Harm
This should include an assessment of potential harm caused by postponing
effective treatments, and by financial exploitation. Many CIH approaches are
costly, and the patient usually assumes all of the cost. Marketing can prey on
vulnerable patients and result in significant and unnecessary expenditures.
Step Two: Assess Potential Benefits
The potential for any approach to be of benefit should be assessed on several
levels.
Scientific Evidence
A review of the peer-reviewed literature should certainly be conducted for
evidence of the effectiveness of the approach under consideration. There are
numerous excellent textbooks on integrative health (19).
12681269FIGURE 24-1 Decision tree for integrating complementary and integrative medicine
approaches.
Cultural Evidence
Another form of useful information is the historic or cultural use of the approach.
For example, it is valuable to consider whether a therapy has a long history of use
within a given culture. If, on the other hand, the approach has no historic use, this
is important to recognize. Examples include the use of black cohosh for
menopausal symptoms, which was used for centuries with reported safety and
effectiveness, compared with red clover, which has no historic use or track record.
Another example would be acupuncture, with thousands of years of use,
compared with photobiomodulation, which has been in use for a relatively short
time.
Personal Belief
Another part of the assessment of benefit is to recognize the patient’s belief
system as it pertains to the approach. If the patient has a strong belief in the
approach, and there is no evidence of potential harm, it is often reasonable to
support its use. Activating a healing response or a placebo effect can often be very
therapeutic.
Step Three: Assess the “Delivery System”
When assessing the delivery system, products and providers must be considered.
Product
Assessing the history of the manufacturing company and understanding its
process of quality assurance can be useful. Referral to independent sources for
determining the quality of a product and accuracy of labeling may be useful.
Provider
As with conventional clinicians, it can be difficult to assess the skill level of CIH
providers. Inquiring about the education of a given provider and his or her
licensing status (if there is a licensing body for the field) is an important place to
start. It is useful to talk to other patients who used these services. Finally, one’s
own sense of a provider is extremely important.
Step Four: Assess the Integration
Although the individual CIH therapy may have no evidence of harm and can be of
potential benefit, the way in which it is integrated into the patient’s overall
1270treatment plan is important. The same is true for CIH providers.
Approaches
The therapy or approach should be integrated into the overall treatment plan. For
example, large doses of antioxidant vitamins should not be used in patients
undergoing radiation therapy, as they may counteract the action of the radiation.
Likewise, patients with Down syndrome should not undergo chiropractic
manipulation.
Providers
Perhaps most importantly, the potential for integration of the providers is essential
to assess. If the intention is to offer the patient the best possible care, all
providers, conventional and CIH alike, should be assessed for their willingness to
integrate their care for the benefit of their patients. If any CIH providers are
unsupportive of conventional medicine, it is critical to recognize this and look for
a provider who supports integration of care.
It is useful for each physician to recognize his or her own biases about CIH and
willingness to learn about the techniques. At a minimum, physicians should know
the basics about which CIH approaches may be of benefit to patients and which
may be of harm. Familiarity with resources in the community that are more
focused on these areas can serve the physician and the patient.
SPECIFIC GYNECOLOGIC ISSUES
Menstrual Disorders
Biologically Based Therapies: Supplements and Botanicals
Premenstrual Symptoms
[4] An integrative approach to PMS can be very valuable. Nutritional changes,
exercise, natural products, mind–body approaches, acupuncture, traditional
Chinese medicine, and conventional treatments should be considered.
Calcium
Calcium supplementation, 1,200 to 1,600 mg/day in divided doses, has been
shown to result in a reduction of luteal phase symptoms. In a review published
in the Annals of Pharmacotherapy, it was concluded that calcium
supplementation should be considered a “sound treatment option in women who
experience premenstrual syndrome” (20). Calcium supplements can interfere with
the absorption and effectiveness of iron supplements, thyroid hormones,
1271corticosteroids, and tetracycline and therefore should not be taken at the same
time of day.
Vitamin B6
Vitamin B6 is a water soluble B vitamin that serves as a co-factor in more than
100 enzyme reactions. It has been the subject of many RCTs regarding CIH and
PMS. Evidence suggests some benefit over placebo for the symptoms of
mastalgia, swollen breasts, pain, and depression. Another review of RCTs
indicated that although most of these trials demonstrated some benefit, definite
clinical recommendations could not be made (21). While most controlled studies
on vitamin B6 in the treatment of PMS had limited numbers of patients, which
makes the evidence of positive effects fairly weak, this is a benign therapy in
doses of 100 mg or less and is reasonable to support. It is important to note that
peripheral neuropathies can be seen in doses of 200 mg/day or higher, and
interaction with other medications, specifically anti-Parkinson disease drugs.
Magnesium
Magnesium has less evidence for efficacy in treating the symptoms of PMS than
calcium, although low magnesium levels were reported in women who have
PMS. Two small trials found magnesium in combination with 50 mg of vitamin
B6 was effective in alleviating PMS symptoms (22).
Although more studies are needed to clearly determine effectiveness and which
formulation is most efficacious, the use of magnesium is reasonable to support
clinically and counteracts the constipating effects of calcium. Magnesium can be
taken in 200 to 400 mg/day in divided doses, either cyclically during the luteal
phase or continuously. Side effects from magnesium include abdominal cramping
and diarrhea. Women with renal insufficiency should be cautious, as magnesium
is excreted through the kidneys. Dietary sources of magnesium include green
leafy vegetables, nuts, seeds, whole grains, tofu, and legumes.
Omega-3 Fatty Acids
There are two major types of omega-3 fatty acids: eicosapentaenoic acid (EPA)
and docosahexaenoic acid (DHA). Omega-3 fatty acids act as anti-inflammatory
agents in that they shift arachidonic acid metabolism away from PGF2α and
increase levels of the less inflammatory PGE1. Omega-3 fatty acids are essential
foods, and levels are extremely low in the average diet of individuals in the
United States. They can be increased through dietary means and supplements.
One study looked at essential fatty acids (EFA) and PMS and showed no effect.
There are some positive studies looking at the effectiveness of omega-3 fatty
1272acids in treating mild depression with fish oils. This may be a reasonable
approach to try if one of the patient’s primary symptoms is mood depression (3 g,
divided with meals) (23). Side effects are rare, but occasionally patients will
experience nausea, diarrhea, belching, or an unpleasant taste in the mouth.
Omega-3 fatty acids have an anticoagulant effect and are relatively high in
calories.
Chaste Tree
Chaste Tree (Vitex agnus-castus) is a botanical with a long history of use for
“menstrual disorders.” This botanical is considered one of the primary herbs
for reducing PMS among herbalists, and has support in the literature. Many
small studies have shown promising results, and one larger study examined the
effectiveness of chasteberry on premenstrual dysphoric disorder (PMDD) (24,25).
In this RCT, the active arm received 20 mg of chasteberry daily. Compared with
placebo, the patients receiving chasteberry had a significant improvement in the
combined symptom score (25). A multicenter noninterventional trial examined
the experience and tolerance of chasteberry in 1,634 patients. After use in three
cycles, 93% of women reported a decrease in or cessation of symptoms, and 94%
of patients reported good or very good tolerance to this botanical. Adverse drug
reactions were suspected by physicians in 1.2% of patients, but there were no
serious adverse reactions (26). The primary mechanism of action is not clear, but
Chaste Tree is known to reduce prolactin, increase progesterone, and bind opioid
receptors. In Germany it has been approved for menstrual irregularities, PMS, and
undiagnosed infertility. The typical dose is 20 to 40 mg/day of chaste berry
extract. No significant toxicities were reported when used in appropriate dosages.
St. John’s Wort
St. John’s wort (Hypericum perforatum) is generally recognized as an effective
antidepressant for the treatment of mild to moderate depression, similar to
treatment with standard prescription antidepressants, but the evidence is not
definitive. One open trial of 19 women found that this compound, when used at a
dose of 300 mg/day of a 0.3% hypericin standardized extract, showed a 51%
improvement in mood disturbances in PMS/PMDD (27). This dose is one-third of
that typically used for depression. The most recent RCT showed a “nonsignificant trend for SJW to be superior to placebo.” This trial did not use a
product that contains both active ingredients, namely hypericin and hyperforin
(28). Although adverse reactions occur less frequently than with prescription
antidepressants, care must be exercised with the use of this product. Most
common side effects include gastrointestinal upset, headache, and agitation. Rare
but severe phototoxicity was reported. Because St. John’s wort induces the
1273cytochrome P450 complex, significant drug interactions can occur. Specifically,
reduced levels of birth control pills, theophylline, cyclosporine, and antiretroviral
drugs were reported. Interactions were described with buspirone, statins, calcium
channel blockers, digoxin, and carbamazepine. There are no apparent significant
interactions with Coumadin. The mechanism of action for its efficacy in the
treatment of PMS is not elucidated. There were two isolated reports of pregnancy
occurring in women who were taking oral contraceptives in conjunction with St.
John’s wort. If patients choose to take St. John’s wort, they may want to use a
backup method of birth control or change to a different method.
Ginkgo
Ginkgo (ginkgo biloba) traditionally was used to relieve breast tenderness and
discomfort, improve concentration, and enhance sexual function. Its vascular
effects, particularly with regard to dementia and peripheral vascular disease, were
studied. One large study examined the effectiveness of ginkgo in the treatment of
women with PMS and found that after two cycles with treatment, breast
symptoms were significantly improved in the ginkgo group. The effectiveness in
terms of concentration or libido was not examined (29). In doses ranging from 60
to 240 mg of standardized extract per day, ginkgo showed some clinical efficacy
in the treatment of breast pain, tenderness, and fluid retention. Ginkgo is
promoted as an agent that can increase libido, but the methodology of these
studies was criticized, and further studies are required to better define the
botanical’s role in these areas. Side effects include gastrointestinal upset and
headache. High doses can cause nausea, vomiting, diarrhea, restlessness, or
insomnia. Ginkgo has anticoagulant activity, and care must be taken when used
with anti-inflammatory drugs and with warfarin. The underlying mechanism of
action is believed to be dilation of vessels and increased blood flow.
Other products that are used, but are not recommended, to treat symptoms of
PMS and PMDD are listed in Table 24-6.
Dysmenorrhea
Although dysmenorrhea is managed more effectively than PMS and PMDD with
conventional approaches, treatment still has a failure rate of approximately 20%
to 25%, and many patients seek alternatives. The review concluded that vitamin
B1 is effective in the treatment of dysmenorrhea when taken at 100 mg daily,
although this finding is based on only one large RCT (30). The results further
suggested that magnesium is a promising treatment, but it is unclear what dose or
treatment regimen should be used (30). The addition of fish oils showed
promising results. The concentration of omega-6 fatty acid derived eicosanoids
such as PGE2 is elevated during menstruation in women who experience
1274dysmenorrhea. Dysmenorrhea was associated with low dietary intake of omega-3
fatty acids. Several studies showed supplementation to be effective in the
management of dysmenorrhea (31). Krill omega-3 phospholipids, which contain
phosphatidylcholine with DHA/EPA, outperformed conventional fish oil
DHA/EDP in double-blind studies on PMS and dysmenorrhea (32). Given the
established benefits of omega-3 fatty acids in other conditions, intake of these
compounds can be recommended throughout the menstrual cycle.
Table 24-6 Other Products Often Used to Treat Symptoms of PMS and PMDD (Not
Recommended)
• Tryptophan, an amino acid that is a precursor of serotonin, has been shown in several
trials to improve the symptoms of PMS and PMDD. Impurities in one product made
in Japan have been associated with the development of eosinophilia–myalgia
syndrome (EMS), which can be fatal. It is unclear if all the cases were related to
impurities or if some were related simply to the active ingredients. Until this is
clearly understood, tryptophan should be avoided.
• Dehydroepiandrosterone (DHEA), a hormone secreted by the adrenal glands and
often used for depression, has not been shown to be of benefit in PMS/PMDD.
• Melatonin, a hormone that regulates sleep–wake cycles and often used to prevent jet
lag, has been used for the treatment of PMS. There is no evidence of efficacy, and it
can worsen depression in some patients.
• Black cohosh (Cimicifuga racemosa) has been well studied in the treatment of
menopausal symptoms, but it has not been studied in the treatment of PMS/PMDD.
Although it may prove to be beneficial, data are needed.
• Evening primrose oil is frequently used for PMS, but with the exception of cyclic
mastalgia, research has failed to show benefit beyond placebo.
• Dong quai is an oriental herb often used in combination with other herbs for the
treatment of menstrual disorders and menopausal symptoms. Its effectiveness has not
been researched.
• Kava has been used to treat anxiety and irritability, and several studies have
documented its effectiveness. It has, however, been associated with hepatotoxicity,
even necessitating liver transplant. It is unclear whether this effect was related to
drug or alcohol interactions, contaminants, or the kava itself.
PMS, premenstrual syndrome; PMDD, premenstrual dysphoric disorder.
1275Body-Based Methods
Premenstrual Symptoms
Massage relieves anxiety, sadness, and pain immediately after the therapy,
but it does not reduce symptoms of PMS/PMDD overall.
There is no evidence to support the effectiveness of chiropractic
manipulation in these conditions. One small (N = 25) placebo-controlled
crossover study showed the group receiving chiropractic treatment had a
significant improvement in symptoms, but the group that received placebo first
improved over baseline with the placebo and experienced no further improvement
when they received the active treatment (33).
Dysmenorrhea
A Cochrane review of the use of spinal manipulation for primary and
secondary dysmenorrhea concluded that overall there is no evidence to
suggest that spinal manipulation is effective in the treatment of primary or
secondary dysmenorrhea. In four trials, high-velocity, low-amplitude
manipulation was no more effective than sham manipulation, although it was
possibly better than no treatment (34). Three of the smaller trials indicated a
difference in favor of the manipulation; the one trial with sufficient sample size
found no difference. There was no difference in adverse effects between the two
groups (34).
Mind–Body Interventions
[7] Relaxation techniques showed some very promising results for women
with PMS/PMDD. One study examined the effect of the relaxation response for
15 minutes, twice a day, for 3 months, compared with women who read for the
same amount of time, and women who charted their symptoms. Of women in the
relaxation response group, 58% experienced improvement in their symptoms,
compared with 27% for the reading group, and 17% for the charting group (35).
Given that there are many other health benefits to the relaxation response,
with no cost and no risk, it is a good technique to recommend to patients.
Cognitive-behavioral therapy (CBT) and group therapy were of benefit in several
small studies. In one study, CBT was effective in reducing psychological and
somatic symptoms and impairment of functioning when compared to controls. In
two additional studies, the authors found that CBT reduced PMS symptoms
compared to the control group (36).
Oriental Medicine and Acupuncture
Oriental medicine and acupuncture have been used for thousands of years for
1276myriad menstrual symptoms. There is a growing body of evidence supporting the
effectiveness of acupuncture, particularly in the treatment of pain. A Cochrane
review in 2011 found 34 trials on acupuncture or acupressure for dysmenorrhea.
Of the 10 trials that were included, 6 were examining acupuncture and 4 on [6]
acupressure. Meta-analysis of the acupuncture trials (n = 673) showed
significant benefit on dysmenorrhea, headache, nausea, and quality of life
compared to the control arm, NSAIDs, and Chinese herbs. The meta-analysis
on the acupressure studies showed a significant improvement in
dysmenorrhea compared to placebo (37). More research is needed, but this is a
promising and safe modality. If a woman is fully informed and interested in
pursuing these approaches and has access to a qualified provider, it is very
appropriate to support.
Homeopathy
The use of homeopathy in the treatment of PMS and PMDD is not well studied,
and neither is its effectiveness in the treatment of related disorders such as
depression or anxiety. One study did claim positive results but was fairly weak in
design and in showing improvement (36). In one small but well-done study on
individualized homeopathic remedies, 90% of patients had at least 30%
improvement in their symptoms, compared to 37.5% having that degree of
improvement in the placebo arm (36).
Infertility
Mind–Body Interventions
Mind–body approaches are of particular interest in the infertility patient. The
treatments for infertility are stress inducing, and increased stress is associated
with decreased fertility (and increased risk of such things as gestational diabetes,
preterm labor and delivery, and prolonged labor).
In a study of infertility patients, two group psychological interventions were
compared with routine care. The two groups who received group support and
CBT had fertility rates of 54% and 55%, respectively, compared with the control
group, which had a pregnancy rate of 20%. There were large and disparate
dropout rates, which complicate the interpretation of these results (38). In Austria,
physicians are required to prescribe psychotherapeutic therapy for every patient
undergoing assisted reproductive techniques. These approaches include
psychotherapy, hypnotherapy, relaxation, and physical perception exercises. A
review of its success associated with pregnancy rates found that of the 1,156
women, the cumulative pregnancy rate of those who utilized the mind–body
techniques was 56% and in those who intended to use these approaches it was
127741.9%, higher than those who refused (39). In a case control study examining the
impact of hypnosis on pregnancy rate in in vitro fertilization (IVF), the pregnancy
rate in those cycles where hypnosis was used was 53% versus 28% in the
controls, and the implantation rate 30% versus 14% (40).
[7] Mind–body therapies, such as relaxation techniques and hypnosis, are
appropriate to recommend to relieve a wide variety of issues that can arise
with infertility patients, and perhaps improve fertility.
Acupuncture and Oriental Medicine
[6] The use of acupuncture has been studied in the treatment of infertility
and overall shows promise. Auricular acupuncture was studied as a therapy for
female infertility secondary to oligomenorrhea or luteal insufficiency, and the
authors concluded it was a valuable therapy (41). Another study used
electroacupuncture in anovulatory women with polycystic ovarian syndrome and
found that regular ovulation was induced in more than one-third of the women.
After early positive results, there were several recent studies on acupuncture and
IVF. In a study of 228 women examining acupuncture and IVF, while the
difference did not reach statistical significance, the pregnancy rate in the
acupuncture arm was 31% versus 23% in the control arm, and ongoing pregnancy
rates at 18 weeks’ gestation was 28% versus 18% (42). In an RCT of 225, women
undergoing IVF or intracytoplasmic sperm injection (ICSI) with acupuncture had
clinical pregnancy rates of 33.6% versus 15.6% in the control group, and ongoing
pregnancy rates of 28.4% versus 13.8% (43). In a trial of 182 women comparing
usual care versus acupuncture 25 minutes before and after embryo transfer versus
acupuncture before and after transfer and 2 days after the transfer, there was again
a significant increase in pregnancy rates with acupuncture, but no additional
benefit was found in the patients who also received acupuncture 2 days after
transfer. The clinical pregnancy rates in the acupuncture group were 39% versus
26% in the controls, and the ongoing pregnancy rate was 36% versus 22% (44).
In an RCT comparing usual care to usual care plus 25 minutes of a
standard acupuncture treatment pre- and postembryo transfer, the
pregnancy rates were 43% in the intervention arm as opposed to 26% in the
control arm (45). In a meta-analysis including 7 trials and 1,366 women, the
authors concluded that the evidence suggests that embryo transfer done with
acupuncture improved pregnancy rates and live births among women undergoing
IVF (46). At the same time, a meta-analysis including 13 trials and 2,500 women
concluded there was not sufficient evidence to conclude that acupuncture
improves IVF clinical pregnancy rates (47). The acupuncture protocols are
typically designed to promote sedation, uterine relaxation, and increased uterine
blood flow. The basis for the effect of acupuncture is hypothesized to be
1278potentially related to modulating neuroendocrinologic factors, increases in uterine
and ovarian blood flow, modulating cytokines, and reducing stress, anxiety, or
depression. Blood flow impedance in uterine arteries, measured as the pulsatility
index, was considered useful in assessing endometrial receptivity to embryo
transfer. A study was performed assessing the effect of electroacupuncture on the
pulsatility index of infertile women. After treatment twice a week for 4 weeks, the
mean pulsatility index was significantly reduced shortly after the last treatment
and 10 to 14 days after the treatments. The skin temperature of the forehead was
increased significantly, suggesting a central inhibition of sympathetic activity
(48). In a study of women undergoing IVF, the women who received acupuncture
had increased cortisol levels and increased prolactin levels when compared to the
controls, trending toward more normal cycle dynamics (49). A retrospective chart
review of 1,069 IVF cycles (fresh, nondonor) compared individualized traditional
Chinese medicine to acupuncture at the time of embryo transfer, to routine IVF
(50). Live birth rates were found to be 48.3% in the routine group, 50.8% in the
acupuncture at time of transfer group, and 61.3% in the traditional Chinese
medicine group. More studies are needed in the efficacy of acupuncture and
infertility and in the mechanisms of action. Clinically speaking, there is
provocative evidence that acupuncture appears safe in early pregnancy, and if
patients are interested, it is reasonable to support.
Menopause
Before the release of the results of the Women’s Health Initiative, 80% of women
in the United States were using “nonprescriptive therapies” to help manage their
menopausal symptoms, and many of these therapies were CIH approaches. In a
study examining the use of CIH during menopause, a group of 3,302 women were
followed across 6 years, and 80% of them used some form of CIH (51). [4] In a
study examining women’s treatment choices after discontinuing HT, 76% of
women reported using nonhormonal integrative therapies, and of these 68% found
them helpful (52). In a study exploring women’s beliefs about “natural
hormones,” women using compounding pharmacies believed that compared with
standard hormones, natural hormones are safer, cause fewer side effects, and are
equally or more effective for symptom relief. Many women believed natural HT
was equally or more effective for long-term protection of bones and lipid levels
(53). It is reasonable to assume that women are exploring and choosing such
therapies in ever increasing numbers, often without being accurately or fully
informed. This expanded market generates more products and promotion of
alternatives. It is imperative that physicians be informed about these options so
they can help patients make medically sound choices. [4] It creates an opportunity
for clinicians to discuss integrative approaches such as nutrition, stress reduction
1279techniques, exercise and movement, acupuncture and oriental medicine, and
massage.
Natural Products
The list of botanicals and supplements promoted and used for the treatment of
menopausal symptoms is extensive. Following is a review of the products most
commonly used and recommended based on research evidence.
Black Cohosh
Menopause
Black cohosh (Cimicifuga racemosa) has traditionally been used for relief of
PMS and menopause symptoms. It has been used in the Native American
population for centuries and in Germany since 1950. Its most studied form is a
brand called Remifemin, which is standardized to 1 mg of deoxyactein and is
administered in a dose of 40 mg two times daily. Most early studies were
uncontrolled, but later studies were more methodologically sound. Initially, it was
felt that black cohosh decreased luteinizing hormone levels, but it is believed that
it may behave like a selective estrogen receptor modulator (SERM), and act at
serotonin receptors. It does not contain phytoestrogens and does not have an
estrogenic effect on vaginal cytology. There are no changes in hormone levels in
women taking black cohosh. In laboratory studies, black cohosh suppresses rather
than stimulates breast cells (54).
A 2012 Cochrane review included 16 RCTs studying perimenopausal and
menopausal women using black cohosh extract on average 40 mg a day for 23
weeks, compared to placebo, HT, red clover, and fluoxetine (55). The review
cited many issues with methodology, and concluded that the evidence is
insufficient to support the use of black cohosh for menopausal symptoms. They
stated that there is adequate justification for further studies. Traditionally, black
cohosh has been used for depressed mood. The authors of a systematic review
concluded that black cohosh was effective in reducing depression and anxiety
(56). If women are informed of the literature, but would like to do a trial of black
cohosh, it is reasonable to support. It should be started at 20 to 40 mg twice daily,
standardized to 2.5 triterpenes. The Commission E recommends 40 to 200 mg
(57). Patients should be informed that it might take 4 to 8 weeks to feel an effect.
Side effects are rare and include gastrointestinal upset, headache, and dizziness.
There has been a rare association with liver damage reported, and women with
liver disease should avoid black cohosh. While the longest study in the literature
lasted 12 months, there is no indication that longer use is unsafe.
Breast Cancer
1280Multiple studies showed that black cohosh has an inhibitory effect on estrogen
receptor breast cancer cells. In a review of 14 RCTs, the authors concluded that
there was no association between black cohosh and an increased risk of breast
cancer (58). One study showed augmentation of the antiproliferative effects of
tamoxifen. In a study that looked at the effectiveness of black cohosh in reducing
menopausal symptoms for breast cancer patients, the placebo group and the group
receiving black cohosh had a 27% reduction in the number and intensity of hot
flashes. Only sweating was significantly more improved in the black cohosh arm
(59). In another study, 136 breast cancer survivors were randomized either to
tamoxifen alone or tamoxifen plus black cohosh. At 6 months, there were no
significant differences, but at 1 year, 47% of women in the intervention arm
versus none in the control group were free of hot flashes. Severe hot flashes were
reduced in the intervention arm (24%) compared with the tamoxifen-alone arm
(74%) (60). In a prospective observational study, 50 women with breast cancer on
tamoxifen were treated with an isopropanolic extract of black cohosh for 6
months. Using the Menopause Rating Scale (MRS II) women on tamoxifen had a
statistically significant reduction in symptoms, including hot flashes, night
sweats, sleep disturbances, and anxiety. There was no improvement in vaginal
dryness. No significant side effects were noted (61). Given that black cohosh is
not estrogenic, and that promising evidence in women with breast cancer exists, it
is reasonable to support a trial of black cohosh in women who are interested.
Ginseng
Many different botanicals use the name ginseng. The two most common are
Siberian ginseng (Eleuthero) and oriental or Korean ginseng (Panax). Both of
these agents are extracted from the root of their respective plants, and both are
traditionally used to combat fatigue or to restore “vital force” for performance
enhancement.
Panax ginseng, also known as Asian, Chinese, or Korean ginseng, is a small
perennial that grows in northeast Asia and is the most widely used. A systemic
review of the evidence for ginseng, which included 10 RCTs, found positive
evidence for its impact on sexual function, sexual arousal, and total hot flashes
score (62). One study of 12 patients examined its effect on menopausal women,
with and without the symptoms of fatigue, insomnia, and depression. At baseline,
the patients with symptoms had significantly higher anxiety states. The
dehydroepiandrosterone sulfate was one-half that of those in the control group,
and the cortisol/dehydroepiandrosterone sulfate ratio was significantly higher in
the symptomatic patients. After treatment, the Cornell Medical Index and anxiety
state decreased to that of the controls, and the cortisol/dehydroepiandrosterone
sulfate ratio decreased significantly, although not to the level of the control group
1281(63).
In terms of the physiologic symptoms, a randomized, multicenter, double-blind
parallel group study compared a standard ginseng extract with placebo. Quality of
life and physiologic parameters were assessed at baseline and after 16 weeks of
treatment. There was no significant difference in symptom relief and the
physiologic parameters of follicle-stimulating hormone, estradiol, endometrial
thickening, maturity index, or vaginal pH. Patients did experience significant
improvement in depression, sense of well-being, and health (64). A second study
demonstrated improvement in fatigue, insomnia, mood, and depression (65).
There is no evidence to support the use of ginseng for relief of physiologic
symptoms. If patients are suffering from psychological symptoms of
menopause, they may benefit from Panax ginseng. Although its mechanism of
action is not clear, Panax ginseng does not appear to be estrogenic. Use of Panax
ginseng should be avoided with stimulants, and it may cause headaches, breast
pain, diarrhea, or bleeding. The recommended dose is 100 mg of a standardized
extract two times daily for 3 of 4 weeks.
The estrogenic effect of black cohosh, dong quai, ginseng, and licorice root
was evaluated by (i) an examination of the effect on cell proliferation of MCF-7
cells (a human breast cancer cell line), (ii) transient gene expression assay, and
(iii) a bioassay in mice. The authors concluded that dong quai and ginseng
stimulate growth of MCF-7 cells independent of estrogenic activity, and that
black cohosh and licorice root do not have estrogenic activity or stimulate the
breast cell line (54).
Red Clover
Red clover (Trifolium pratense) is a member of the legume family, with brand
names including Promensil and Rimostil. It contains at least four estrogenic
isoflavones and is promoted as a source of phytoestrogens. Red clover is a
medicinal herb with no traditional long-term use in menopause. Its estrogenic
effects were first discovered by observing its effects on sheep. The term Clover
syndrome is used to describe the symptoms frequently seen in sheep that consume
large amounts of red clover. This syndrome in sheep is characterized by
reproductive complications, including infertility. A number of meta-analyses
concluded that overall red clover was not clinically better than placebo for relief
of vasomotor symptoms (65). In a trial involving 252 women, two red clover
supplements were compared with placebo across 12 weeks (Promensil, containing
82-mg isoflavones, and Rimostil, containing 57-mg isoflavones) (66). Although
Promensil did reduce hot flashes more quickly than Rimostil or placebo, all three
groups had the same reduction of hot flashes at the end of 12 weeks. Another
large trial of 205 women had similar results. While this does supply some
1282evidence for a biologic effect of Promensil, neither of the red clover supplements
had a clinically significant effect when compared with placebo. Its effect on the
endometrium must be further delineated. In a trial of 109 women looking at the
effect of red clover extract on depression and anxiety, there was a 75% reduction
for anxiety and 78% reduction on depression scores, compared to 21% reduction
with the placebo (67).
Red clover has unclear demonstrable effects, is believed to be estrogenic, and
its effect on the breast and endometrium is not adequately studied. Coumarins are
present in some clover species.
Dong Quai
Dong quai (Angelica sinensis) has a long history of traditional use in menopause
and in the treatment of menstrual problems. In the oriental system of medicine, it
is used in combination with other botanicals. Several studies of the effectiveness
of dong quai in treating the symptoms of menopause failed to show its
effectiveness (68). No evidence exists to support the use of dong quai as a single
agent in the treatment of menopausal symptoms. The use of dong quai in
combination with other herbs, as is done traditionally, is not well studied. It is
important to note that dong quai contains coumarin derivatives.
Kava
Kava (Piper methysticum) is native to the South Pacific, and one of its traditional
uses is to reduce anxiety. It is often recommended for menopausal symptoms,
particularly irritability, insomnia, and anxiety. Studies showed that 100 to 200
mg, three times daily, standardized to 30% kavalactones, decreases irritability and
insomnia associated with menopause. It often is used in combination with other
components, such as black cohosh and valerian, for the management of
menopausal symptoms. One study that examined the use of kava in addition to
HT for the treatment of anxiety showed that the combined use resulted in a
significant decrease in anxiety when compared with HT alone (69).
Kava has the potential for significant, albeit rare, side effects. Cases of
hepatotoxicity severe enough to require transplant were reported (70). Other side
effects include dermatitis, and a movement disorder similar to Parkinson disease,
but reversible. It was removed from many European markets. The use of kava is
not recommended, but if patients are using this botanical (which is available over
the counter), they should be informed of the risks, and advised to avoid taking
kava in conjunction with other anxiety-reducing agents, with alcohol, or
acetaminophen, and have liver function tests performed periodically.
St. John’s Wort
1283The leaves and the tips of the flowers of the plant St. John’s wort (Hypericum
perforatum) have been used medicinally, primarily as an antidepressant. It is used
for anxiety, and in Germany, it is used to treat menopausal mood swings.
Although its mechanism of action is unclear, St. John’s wort does appear to be
beneficial in relieving mild to moderate depression, with 60% improvement in
mood, energy, and sleep with a dose of 300 mg three times daily. Standardization
is controversial, but it is believed to have at least two active ingredients, namely
hypericin and hyperforin. Most research was done on products standardized to
0.3% hypericin. The first trial to examine its use for menopausal symptoms was
done in 1999. [4] The authors of a meta-analysis published in 2014 concluded
that St. John’s wort extract was significantly more effective in the treatment
of menopausal symptoms than placebo (71). In a randomized trial of 301
women using a combination of black cohosh and St. John’s wort, the treatment
was superior to placebo for both climacteric and psychological symptoms (72).
Given the evidence, and its safety profile, it is very reasonable to support the
use of St. John’s wort either alone, or in combination with herbs such as
black cohosh, for hot flashes, depression, or mood swings. St. John’s wort
induces the cytochrome P450 complex. Specifically, lower levels of oral
contraceptives, theophylline, cyclosporine, and antiretroviral drugs were reported.
Interactions were described with buspirone, statins, calcium channel blockers,
digoxin, and carbamazepine. There are no apparent significant interactions with
Coumadin.
Chaste Tree
Chaste Tree (Vitex agnus-castus) has a long history of uses by civilizations
ranging from Greeks to the monks of medieval times. Among the uses is
treatment of menopausal symptoms. Although its use was recommended for this
indication, the efficacy of Chaste Tree in menopause is not demonstrated.
Ginkgo Biloba
Ginkgo biloba is often promoted for the improvement of libido in menopausal
women. Muira puama plus ginkgo had a significant effect in 65% of the patients
in one study (73). Side effects include gastrointestinal upset and headaches, and
drug interactions can occur with estrogens, statins, and calcium channel blockers.
Ginkgo has an anticoagulant effect.
Phytoestrogens
Phytoestrogens are plant-based compounds that have weak estrogenic activity.
They appear to have SERM activity with modest agonist effect at the β-estrogen
receptor. Phytoestrogens are categorized as isoflavones, coumestans, lignans, or
1284flavonoids. The most promoted of these groups is isoflavones, which are
genistein, daidzein, or glycitein. Soybeans and soy products are a rich source of
isoflavones. A 2012 meta-analysis concluded that isoflavones reduced the
frequency and the severity of hot flashes by 20.6% and 26.2%, respectively.
Supplements containing more than 18.8 mg of genistein were significantly more
effective in reducing hot flashes than supplements at lower levels (74). Women
who want to consume phytoestrogens should do so through food products rather
than supplements, and should aim for 100 mg of isoflavones a day, or 25 g of soy
protein. One RCT of 366 women demonstrated endometrial hyperplasia in 3.8%
of women who consumed 150 mg/day of isoflavones for 5 years versus 0% in the
placebo arm (75).
Mind–Body Interventions
Mind–body therapies for the treatment of menopausal symptoms have been
studied in several domains. [7] In a study of clinical hypnosis in breast cancer
survivors, hot flash scores were decreased by 68%, and anxiety, depression, and
sleep were significantly improved (76). In a study with 187 postmenopausal
women with at least seven hot flashes a day, receiving five weekly hypnosis
sessions and self-hypnosis, the hypnosis group had a reduction of hot flashes
frequency hot flash score, interference, sleep quality, and treatment satisfaction all
improved in the treatment arm of 74%, compared to 17% in the control group
(77). [7] In a study of 110 women with hot flashes randomized to either MBSR or
a waitlist control, MBSR significantly improved hot flashes, quality of life, sleep
quality, anxiety, and perceived stress. The hot flash score continued to improve
after the MBSR intervention (78).
Insomnia, which is another frequent symptom of menopause, is a complex,
multifactorial problem. Optimal treatment is described as incorporating the
following components: stress management, coping strategies, enhancement of
relationships, and lifestyle changes that facilitate sleep (79).
[7] Overall, mind–body techniques are a low- or no-cost, low-risk intervention
that can decrease central nervous system adrenergic tone. There is evidence that
these approaches are associated with improvement of hot flashes and other
menopausal symptoms, and provide general health benefits.
Other Mind and Body Approaches
Oriental medicine was used for more than 2,500 years and includes treatment with
acupuncture, herbs, and movement. Although diagnosis and treatment are highly
individualized, from the perspective of oriental medicine, menopause is often
associated with deficiencies in qi, blood, and jing. Acupuncture is one of the beststudied CIH modalities, and more studies of higher quality are needed regarding
1285its application to the menopausal patient. [6] In a meta-analysis of acupuncture in
menopausal patients published in 2015, 12 studies were included with 869
patients. Acupuncture was found to reduce the frequency and severity of hot
flashes, and improve the psychological, somatic, and urogenital subscale scores
(80). In an RCT of 267 women comparing individualized acupuncture plus selfcare to self-care alone, the frequency and the intensity of hot flashes significantly
decreased in the acupuncture arm. Overall, this group had significant
improvement in vasomotor, sleep, and somatic symptoms (81). In a pilot study
looking at the use of acupuncture in patients being treated with tamoxifen, 15
patients were followed for 6 months (82,94). Patients were evaluated before and
after 1, 3, and 6 months of treatment. There was significant improvement in
anxiety, depression, and somatic and vasomotor symptoms. Libido was not
affected. A study with 45 women with breast cancer found significantly decreased
hot flashes with electroacupuncture (83). This is a promising area for those
patients whose options for treatment of these symptoms are limited.
[4] In the hands of a competent practitioner, acupuncture is a safe CIH
modality. If menopausal patients are interested in exploring this technique as
part of their plan for managing symptoms, it is reasonable to support a trial
of acupuncture with a qualified practitioner. Because many of the herbal
treatments in oriental medicine can be estrogenic, it is best to avoid them if
the patient is taking any form of HT.
“Natural” Hormones
There is a myriad of hormonal options for patients, and many that are touted as
“natural alternatives.” Because many hormonally active compounds are available
over the counter, physician awareness about these issues is essential, especially in
light of the findings of the Women’s Health Initiative and the large number of
women seeking “alternatives.”
Natural Versus Bioidentical Hormones
There is a dominant belief in the culture that natural is “good” and synthetic is
“bad.” A natural product is any product with principal ingredients that are of
animal, mineral, or vegetable origins. Natural products may have no resemblance
to the ingredients in their natural state. For example, conjugated equine estrogens
are natural products. They do not resemble anything natural or native to the
human body. It is useful to make this distinction with patients. Very often patients
requesting “natural hormones” are uncertain about what they are actually
requesting. Most patients, when using this term, are looking for bioidentical
hormones, or hormones that are molecularly identical to the hormones their
ovaries produce.
1286The ovaries produce three types of estrogen: 17β-estradiol, estrone, and estriol.
Premenopausally, the predominant estrogen produced by the ovary is 17β-
estradiol, or E2. It is converted back and forth to estrone, E1, which is made in the
fat and is the predominant estrogen postmenopausally. All of the patches, and
several oral formulations such as Estrace, are E2. When E2 is taken orally, much
of it is converted to E1 in the gut. E1 and E2 essentially are equivalent in their
level of estrogenic activity. Estriol, E3, is the weakest of the three estrogens and is
predominantly made in the placenta during pregnancy. It is not conventionally
prescribed and is available only through compounding pharmacies. Estriol is the
predominant form of estrogen in Tri-est and Bi-est. Estriol, Tri-est, and Bi-est are
frequently used and recommended by the integrative medicine community.
Conjugated equine estrogens are composed of more than 10 different molecules
extracted from the urine of pregnant mares. This is a natural product but is neither
bioidentical nor native. In addition to animal conjugated equine estrogen, a
synthetic version, such as Cenestin, is available.
It is difficult to draw conclusions regarding options for the use of these
hormones. The reasons for this are listed in Table 24-7.
Table 24-7 Reasons for Difficulty in Drawing Conclusions Regarding Use of
Hormones
Drawing conclusions regarding options for the use of these hormones is challenging for
a variety of reasons:
1. It is essential to reinforce to patients that all hormones are not created equal.
Different hormones have different effects. For example, estriol is often promoted
as a hormone that does everything that conjugated equine estrogen does but with
none of the risks. Given that it is a significantly weaker estrogen than conjugated
equine estrogen, this is dubious and is not based in scientific evidence.
2. Native or bioidentical hormones are rarely included in research protocols.
The Women’s Health Initiative studied only conjugated equine estrogen
(Premarin) and MPA (Provera). The Postmenopausal Estrogen–Progestin
Intervention (PEPI) used only conjugated equine estrogen, but did compare it with
micronized progesterone (and showed micronized progesterone to be as effective
as medroxyprogesterone acetate at protecting the endometrium and better than
medroxyprogesterone acetate at protecting the lipid benefits of estrogen).
3. All forms of hormone therapy frequently are clumped together as one entity.
The distinctions between the types of hormones studied are rarely made in the
media and often not clear even in the medical literature. The coverage of the
Women’s Health Initiative is a perfect example, as the media generalized its
findings to hormone therapy, and even most information released by and for
1287doctors did not clarify that the findings were regarding one specific form of
estrogen combined with one specific form of progestin.
Bioidentical Hormones
Progestogens
Bioidentical progesterone is available either through compounding pharmacies or
through retail pharmacies as micronized progesterone, natural progesterone, or
progesterone USP (brand name Prometrium). Medroxyprogesterone acetate
(MPA) is a nonbioidentical progestin (i.e., its molecular structure is foreign to the
body).
Bioidentical Estrogens
E2, or 17β-estradiol, often is used interchangeably with conjugated equine
estrogen. It is most bioidentical when delivered in the form of the patch because
its oral form is converted to estrone in the gut. No comprehensive long-term data
regarding its use are available.
Estriol, or E3, the weakest of the estrogens that occurs naturally only in high
circulating levels during pregnancy, is popular in the integrative community. It is
often promoted as the ideal estrogen, a natural alternative providing all of the
benefits of HT with none of the risks. This assumption is not supported by the
literature, as the research on estriol is limited. In one study examining the use of
estriol over 12 months, 53 women were given 2 mg daily. They reported good
symptom relief and satisfaction, and histologic evaluation of the endometrium
revealed no hyperplasia or atypia. Bone mineral density showed no change (84).
In another study examining the effect of estriol, 64 women were followed for 24
months. There were four treatment arms: 2.0 mg E3 plus 2.5 mg MPA, 0.625 mg
of conjugated estrogen plus 2.5 mg MPA, 1 μg of 1α-hydroxyvitamin D3, and 1.8
g calcium lactate containing 250 mg of elemental calcium. Outcome measures
were taken at baseline, 6, 12, 18, and 24 months, and included the following
assessments: bone mineral density at third lumbar vertebrae, serum levels of
osteocalcin, total alkaline phosphatase, and urinary ratios of calcium/creatinine
and hydroxyproline/creatinine. The findings revealed decreased bone mineral
density in the vitamin D and calcium groups and no decrease in the conjugated
estrogen and E3 groups. Osteocalcin and alkaline phosphate were decreased or
without change in the conjugated estrogen and E3 groups, and were increased in
the vitamin D3 and calcium groups. Urinary calcium/creatinine ratios were
decreased with E3 and conjugated estrogen, and there was no decrease with the
use of vitamin D3 and calcium. Urinary hydroxyproline/creatinine ratios were
1288decreased in the conjugated estrogen group, unchanged in the E3 and vitamin D3
groups, and increased in the calcium group. Uterine bleeding was significantly
less in the E3 group compared with the conjugated estrogen group, with 2.4 days
compared with 13 days per person. In conclusion, the study supported the finding
that a bone-preserving effect occurred with E3 when compared with conjugated
estrogen (85).
It has been proposed that estriol might have anticarcinogenic activity. Unlike
estradiol, estriol is not carcinogenic in rodent models, reduces uterine growth,
and enhances phagocytic activity. After one or more pregnancy, estriol excretion
significantly increases in comparison with nulliparous women. This may or may
not be linked to the increased risk of breast and ovarian cancer in nulliparous
women. In a study following over 84,000 Finnish women, oral and transdermal
estradiol was associated with a slightly increased risk of breast cancer (2 to 3
additional cases per 1,000 women across 10 years), while oral estriol and vaginal
estrogens were not associated with an increased risk (86).
Oral estriol appears to provide symptom relief and stimulate breast and
endometrial tissue less than estradiol. It may prove to have mildly beneficial
effects on bone. It appears to exert estrogenic effects on the endometrium and to
have no effect or mild effects on lipids. No clinical interventional trials exist on
the effect of oral estriol use on the breast.
Tri-est and Bi-est
Tri-est and Bi-est are formulations in which the predominant estrogen is estriol.
The typical formulations contain 80% estriol. Typically Tri-est contains 2 mg of
estriol, 0.25 mg of estradiol, and 0.25 mg of estrone, and Bi-est contains 2 mg of
estriol and 0.5 mg of estradiol. It should be noted that these names refer only to
the types of estrogen used, and the specific amounts of each can vary. These
particular formulations are often marketed as the most “natural” form of estrogen
therapy because they contain either two or all three forms of naturally occurring
estrogens. The following factors should be noted:
Tri-est and Bi-est are not formulated in naturally occurring ratios or
quantities.
Although Tri-est and Bi-est are only 20% E2 or E2 plus E3, the dose of
these more potent estrogens is significant (i.e., 0.5 mg).
Although a certain combination of E1/E2/E3 may prove to have benefits
over other forms of HT and should be explored, this research does not
exist.
1289Estriol Vaginal Cream
Vaginal estriol looks promising for local effects with very low estrogen exposure.
In a prospective, double-blind, placebo-controlled study of 167 postmenopausal
women with vaginal atrophy, vaginal dryness and the Global Symptom Score
were significantly improved with 0.005% estriol vaginal gel (87). Estriol vaginal
cream was studied in women who had recurrent urinary tract infections. This RCT
compared vaginal estriol cream with placebo for 8 months of treatment and
showed a significant reduction in urinary tract infections (0.5 vs. 5.9 per patient
year). In the treatment arm, there was a reduction in vaginal pH from 5.5 to 3.8
compared with no decline in the placebo group (88). In an RCT of 27 women on
HT with urogenital atrophy, the addition of vaginal estriol shortened the latency
period for urinary symptoms (89). In a study of postmenopausal women with
urogenital symptoms, 88 were enrolled in this prospective, randomized, placebocontrolled study. The treatment group received intravaginal estriol ovules: 1 ovule
(1 mg) once daily for 2 weeks and then 2 ovules once weekly for a total of 6
months as maintenance therapy, compared to placebo vaginal suppositories. After
therapy, the symptoms and signs of urogenital atrophy significantly improved in
the treatment group in comparison with the control group. Significant colposcopic
improvements were seen in the treatment arm, and there were statistically
significant increases in mean maximum urethral pressure, in mean urethral
closure pressure, and in the abdominal pressure transmission ratio to the proximal
urethra. In addition, 68% of the treated participants reported subjective
improvement in their incontinence, versus 16% in the placebo group (90).
A typical prescription for vaginal estriol cream is 1 mg estriol per gram; insert
1 gram of cream daily for 2 weeks, then twice a week for maintenance.
Bioidentical Progestins
The Postmenopausal Estrogen–Progestin Intervention (PEPI) trials provided a
multicentered RCT that, among other things, compared conjugated equine
estrogen plus MPA with conjugated equine estrogen plus natural or micronized
progesterone (91). The trial compared 12 days of 10 mg of MPA with 200 mg of
micronized progesterone. The micronized progesterone provided equal protection
of the endometrium and was better at protecting the beneficial effects of the
conjugated equine estrogen on the lipid profile. Patients reported that micronized
progesterone had significantly fewer side effects than MPA. This was the case in
several other trials (92,93). Given these data, there is good evidence to prescribe
micronized progesterone. The arm of the Women’s Health Initiative that was
prematurely discontinued was the conjugated equine estrogen/MPA arm. The
conjugated equine estrogen–alone arm was continued. The role and the effect of
MPA should be closely examined. In ovariectomized rhesus monkeys, E2 plus
1290MPA interfered with ovarian estrogen protection against coronary vasospasm. E2
plus micronized progesterone protected against coronary vasospasm. There
continues to be increasing evidence that progesterone improves cardiovascular
function, and that maintaining a baseline of progesterone may be an effective
preventive cardiac measure (94). Given the increased cardiovascular risks in
women taking conjugated equine estrogen and MPA, combined with the positive
data from PEPI, micronized progesterone is an excellent choice for patients who
are taking systemic estrogen and who still have a uterus.
Another area of consideration with bioidentical progesterone is the risk of
breast cancer. While conjugated equine estrogen/MPA leads to an increase in
the risk of breast cancer after approximately 4 years of use, it is not clear if
the same risk is present with micronized progesterone. There are four
observational studies that show a mitigation of that risk when micronized
progesterone is used (95).
Natural progesterone was used as a single agent in the treatment of menopausal
symptoms. The typical dose is 100 mg/day. More research is needed to
demonstrate efficacy.
Yam Creams, Progesterone Creams
Yam creams and progesterone creams, which are sold over the counter, are
distinctly different products. Yam creams should, by definition, not contain
progesterone, but rather should contain phytoprogesterones, plant products that
are progesterone like (Table 24-8). Progesterone creams, by contrast, should
contain progesterone. Part of the challenge is that there is a large media presence
asserting that progesterone creams can solve all that ails menopausal women.
These creams are not regulated by the FDA. Their content is highly variable,
ranging from 700 mg progesterone per ounce to less than 2 mg per ounce in
products whose names imply that they are progesterone creams, not yam creams.
The absorption of these products is highly variable.
Table 24-8 Progesterone and Wild Yam Creams
400–700 mg progesterone per ounce Pro-Gest
Bio Balance
Progonol
OstaDerm
2–15 mg progesterone per ounce PhytoGest
1291Pro-Dermex
Endocreme
Yamcon
Wild Yam Extract
PMS Formula
Menopause Formula
Femarone-Nutri-Gest
Less than 2 mg progesterone per ounce Wild Yam Cream
Progesterone-HP
Wild yam creams (which refer to the genus name Dioscorea villosa, rather than
the fact that they are grown in the wild) are applied topically. They contain
steroidal saponins, including diosgenin, and claim to affect estrogen
steroidogenesis. Although these are interesting products, studies of their safety
and efficacy are needed. In one double-blind, placebo-controlled crossover study,
after a 4-week baseline period, patients received 3 months of active treatment and
3 months of placebo. Symptom diaries were maintained at baseline and then for 1
week of each month. Blood and salivary hormone levels and serum lipids were
assessed at baseline, 3 months, and 6 months. At 3 months, there were no
significant side effects and no change in levels of blood pressure, weight, lipid
levels, follicle-stimulating hormone, glucose, estradiol, or progesterone. In terms
of symptom relief, the placebo and yam cream had a minor effect on the number
and severity of flashes. Wild yam creams appear to be free of side effects, and
they appear to have little effect on menopausal symptoms (96).
Table 24-9 Unknown Aspects of Hormone Therapy
• Risks and benefits of bioidentical hormone therapy (i.e., how the results of the
Women’s Health Initiative translate to bioidentical hormones)
• Role of medroxyprogesterone acetate in increasing certain risks
• Long-term risks and benefits of estriol
• Effects of different doses of hormones
1292• Correlation of circulating hormone levels to different doses, and the correlation of
different hormone levels to risks and benefits
• Effect of lifelong hormonal exposure
• Risks and benefits of hormone therapy when initiated at the age of menopause
In terms of progesterone creams, an RCT of 223 women with severe
menopausal symptoms using progesterone cream found the progesterone arm to
be no more effective than placebo (97). Given the data available, progesterone
or yam creams should not be considered adequate to protect the uterus in a
woman taking systemic estrogen. Progesterone cream may be useful for
symptom relief in women not taking systemic HT, and it may prove to have
other benefits and risks.
Counseling Patients
It’s important to communicate to patients what is known regarding HT and what
is not known. Some of the unknown aspects of HT are listed in Table 24-9.
Given the present state of medical knowledge, the need to individualize
treatment plans in menopausal women cannot be overemphasized. It is essential
to clarify patient goals, and individual health risks, history of hormonal exposure
(both length and time), family history, and personal preferences. For women
desiring systemic hormone replacement, the bioidentical choice of
transdermal estradiol and micronized progesterone is preferred.
SURGERY AND COMPLEMENTARY AND INTEGRATIVE
MEDICINE
Studies showed that most surgical patients use some form of CIH. There are
special considerations regarding CIH and the surgical patient. These issues
primarily fall into two domains:
1. Supplements that, when used perioperatively, may affect the patient’s course
2. CIH approaches that may be of benefit to the surgical patient
When examining what patients are using that may affect their surgical course,
the greatest concern and awareness needs to be in the domain of biologically
based therapies. A survey of 2,560 surgical patients in 5 California hospitals
revealed that 68% of patients were using botanicals, 44% of them did not consult
their physician, 56% did not inform their anesthesiologists, and 47% did not stop
them before their surgery. Variables that were associated with use included
1293female gender, age 35 to 49 years, higher income, Caucasian race, higher
education, and problems with sleep, joints, back, allergies, and addiction (98). A
survey based in a tertiary care center examined the use of botanicals and vitamins
in patients preoperatively (N = 3,106). Of the patients studied, 22% were using
botanicals and 51% were using vitamins. The typical users were women in the
age range of 40 to 60 years. The most commonly used compounds were
echinacea, ginkgo biloba, St. John’s wort, garlic, and ginseng (99). In another
study based in a university medical center that surveyed patients undergoing
outpatient surgery, 64% of patients were using supplements, 90% of them were
using vitamins, 43% were using garlic extracts, 32% ginkgo biloba, 30% St.
John’s wort, 18% ma-huang, 12% echinacea, and others were using aloe, cascara,
and licorice (100).
Effects on Surgery
Many of the most commonly used substances have effects of which surgeons and
anesthesiologists should be aware. Botanicals used with anesthesia can lead to the
following complications:
Prolongation of anesthetic agents
Coagulations disorders
Cardiovascular effects
Electrolyte disturbances
Hepatotoxicity
Endocrine effects
The American Society of Anesthesiologists does not have an official guideline,
but it recommends that all natural products be discontinued 2 to 3 weeks before
elective surgery.
Prolongation of Anesthetic Agents
Valerian, kava, ginseng, and St. John’s wort are among the more commonly used
botanicals that may prolong the effects of anesthetic agents. Valerian has sedative
effects that are believed to be mediated by benzodiazepine and γ-aminobutyric
acid (GABA) receptors. For patients who use valerian on a daily basis, it is
suggested that it be tapered off over the weeks preceding the surgery. Kava is
mediated by GABA receptors and potentiates the sedative effects of anesthetics.
The general recommendation is to discontinue its use 24 hours before surgery. St.
John’s wort induces cytochrome P450 enzymes (cyclosporin, indinavir, and
warfarin). It modulates the GABA receptor and inhibits the reuptake of serotonin,
dopamine, and noradrenaline. The recommendation is to discontinue it 5 days
1294preoperatively.
Coagulation Effects
Some of the more commonly used supplements and botanicals that are
reported to have anticoagulative properties include fish oil, ginseng (Asian
and American), ginkgo, garlic, vitamin E, ginger, feverfew, dong quai, saw
palmetto, and chondroitin. Coenzyme Q10, fish oil, and flax seed can have
this effect.
Cardiovascular Effects
Licorice root contains glycyrrhizic acid, which has an aldosterone-like effect
and can result in hypertension, hyperkalemia, and edema. Glycyrrhizic acid
is used in manufactured foods as a sweetener. Ma-huang (ephedra) is
associated with arrhythmias and hypertension, and ginseng is associated with
hypertension. Fish oil, coenzyme Q10, and garlic are associated with
hypotension. There were case reports of reversible episodes of hypertension
and palpitations with glucosamine. Occasional occurrences of hypertension,
tachycardia, and other cardiac complaints of unknown causality were
reported with saw palmetto.
Electrolyte Disturbances
Licorice root was associated with hypernatremia and hypokalemia.
Goldenseal can reduce the effect of antihypertensives. Saw palmetto, ginseng,
and green tea can cause electrolyte disturbances.
Hepatotoxicity and Endocrine Effects
The following botanicals are associated with hepatotoxicity: kava, red yeast rice
(which contains the ingredient in lovastatin), chaparral, valerian, and echinacea.
In terms of endocrinologic effects, both chromium and ginseng can cause
hypoglycemia. Table 24-10 highlights some of the more commonly used
botanicals and vitamins and their possible effects in the surgical patient.
Table 24-10 Commonly Used Botanicals and Vitamins and Their Possible Effects in
the Surgical Patient
Substance Potential Negative Effects
Chaparral Hepatotoxicity
1295Chondroitin Anticoagulative properties
Chromium Hypoglycemia
Coenzyme
Q10
Hypotension; cardiac effects; anticoagulative properties
Dong quai Anticoagulative properties
Echinacea Hepatotoxicity
Feverfew Anticoagulative properties
Fish oil Anticoagulative properties; hypotension
Garlic Anticoagulative properties
Ginger Anticoagulative properties
Ginkgo Anticoagulative properties
Ginseng Anticoagulative properties
Hypertension
Hypoglycemia
Glucosamine Hypoglycemia
Goldenseal Can reduce effect of antihypertensives
Green tea Anticoagulative properties; cardiac effects
Flax seed Anticoagulative properties
Kava Potentiates the sedative effects of anesthetics Hepatotoxicity
Licorice root Hypertension
Hyperkalemia
Hypokalemia
Hypernatremia
Edema
Ma-huang
(ephedra)
Arrhythmias Hypertension
Red yeast rice Hepatotoxicity
Saw palmetto Anticoagulative properties; cardiac effects; electrolyte disturbances
1296St. John’s
wort
Prolongation of anesthetic effects Inhibits reuptake of serotonin,
dopamine, and noradrenaline
Valerian Prolongation of anesthetic effects Hepatotoxicity
Vitamin E Anticoagulative properties
Complementary and Integrative Medicine Approaches That May Benefit the
Surgical Patient
[4] The two domains in which there is the most research and the most promise
with regard to surgical patients are mind–body-based therapies and oriental
medicine and acupuncture.
Oriental Medicine and Acupuncture
A review of the use of acupuncture as the sole source of anesthesia for patients
undergoing cesarean delivery in China reviewed 12 years of experience with
success rates of 92% to 99%. Blood pressure, heart rate, and respiratory rate
remained stable throughout the surgery, which is a significant advantage over
pharmaceutical anesthesia (101). Although it is unlikely that acupuncture will
readily be used as the only source of anesthesia in this country, it demonstrates
the effectiveness of this approach and encourages its consideration as an adjunct.
In one RCT in patients undergoing upper- and lower-abdominal (gastrointestinal)
surgery, acupuncture was given 2.5 cm lateral to the spine before induction.
Postoperatively, patients who received the acupuncture had decreased
postoperative pain, nausea and vomiting, analgesic requirement, and
sympathoadrenal responses. Supplemental morphine use dropped by 50%, and
postoperative nausea was reduced by 30%. Cortisol and epinephrine levels were
reduced 30% to 50% during the recovery phase and the first postoperative day
(102). Several studies specifically looking at nausea and vomiting in women
undergoing gynecologic surgeries showed benefit in both acupuncture and
acupressure (103–105).
In Germany, auricular electrically stimulated anesthesia is frequently used.
Review of one RCT in patients anesthetized with desflurane with and without
auricular acupuncture revealed significantly reduced anesthetic requirement (the
amount of anesthesia required to prevent purposeful movements) (106).
Acupuncture warrants further investigation as an adjunct to anesthesia in
gynecologic patients. Even simple adjuncts, such as the use of acupressure bands
or electroacupressure bands, are reasonable to support as they are safe and
showed some efficacy in decreasing nausea and vomiting postoperatively.
1297Mind–Body Interventions
[7] Mental preparation for surgery results in psychological, physiologic, and
economic benefit. Higher levels of anxiety are associated with a greater risk
of complications, depression, and increased need for anesthesia, decreased
immune function, and a longer time to heal. Many different physiologic
aspects are affected, including decreased chemotaxis and phagocytosis and
decreased inflammatory factors such as cytokines. One study examining wound
healing took healthy dental students and made a standardized scalpel incision in
the palate at two times: one right before examinations and one during summer
vacation. The incisions in these healthy students took 3 days (40%) longer to heal
during times of stress versus times of decreased stress (107). The power of the
spoken word was explored as long ago as 1964, when a study randomized patients
to a preoperative visit characterized by sympathetic, caring, and informative
communication versus an interchange characterized by cursory remarks. The
patients receiving the sympathetic preoperative visit required half the pain
medicines and had a two-and-a-half-day decreased hospital stay (108).
A meta-analysis of mind–body interventions and surgery included 191 studies
and more than 8,600 patients. The use of mind–body approaches, including
such interventions as hypnosis, imagery, and relaxation, was associated with
reduced blood loss, decreased pain, decreased medication use, increased
return of bowel function, decreased psychological stress, and decreased
hospital stay by 1.5 days. In an RCT of 220 women undergoing excisional breast
biopsy or lumpectomy, a 15-minute presurgical hypnosis intervention was
compared to attention control. In the intervention arm, women required
significantly less propofol and lidocaine, and had less pain, nausea, fatigue and
emotional upset. In addition, the institution incurred significantly less cost (109).
In a study of 241 patients undergoing invasive medical procedures randomized to
standard care versus structured attention versus self-hypnosis, the hypnosis had
the most pronounced effects on pain and anxiety and improved hemodynamic
stability (110).
In a study of ambulatory surgery patients receiving spinal anesthesia, patients
who were randomized to listening to soothing music had decreased sedative
requirements during the surgery and in the perioperative period (111). In a study
of women undergoing hysterectomy, patients received standardized anesthesia
and were randomized to music during surgery, music plus positive suggestions, or
the sounds of the operating room. On the day of surgery, both the music group
and the music-plus-suggestion groups received significantly less rescue
anesthesia. On postoperative day 1, the patients who had heard music during
surgery had more effective analgesia and early mobilization. At the time of
discharge, both intervention groups had less fatigue. There was no change in
1298nausea and vomiting, bowel function, or length of stay (112). In another study
with patients undergoing abdominal hysterectomy, patients were randomized to
listen intraoperatively to one of four tapes: positive suggestions regarding pain, or
nausea and vomiting, or both, or white noise. The positive suggestions had no
beneficial effects in reducing nausea and vomiting or the consumption of
analgesics or antiemetics (113).
Although the studies and interventions in mind–body approaches in the
surgical patient are varied, these interventions are low cost and low risk and
may offer very real benefits for the patient, and a greater sense of
empowerment.
CONCLUSION
Physicians are driven by a desire and commitment to provide the best possible
care, with a responsibility to inform patients of all therapies that can be of benefit,
regardless of their system of origin. In practice this is challenging, because there
are many unanswered questions in the use of complementary and integrative
approaches, and there are often not established standards of care. Each physician,
with his or her patient, needs to form his or her own opinions regarding the
appropriate integration of CIH therapies for that patient. Many patients will want
conclusive evidence of any therapy before using it. Others, assured of the relative
safety of a therapy, may require less conclusive evidence. Illustrating this
dilemma, in a systematic review of randomized trials regarding CIH approaches
to PMS, the authors concluded that “despite some positive findings, the evidence
was not compelling for any of these therapies, with most trials suffering from
various methodological limitations. On the basis of current evidence, no
complementary or integrative therapy can be recommended as a treatment for
premenstrual syndrome” (114). Although this concept is appealing in its
simplicity, it may not be in the best interest of patients. It is important to be
consistent in requiring evidence, using the same levels of evidence for
incorporating approaches from CIH as from conventional interventions. As with
many clinical decisions that must be made with incomplete data, many factors
must be considered. The potential risks and benefits must be weighed carefully,
using primum non nocere as the guide.
As more research is done and as medical schools and residency programs
continue to incorporate education about these approaches, the gap between
patients’ desires and standard practices will decrease as appropriate therapies are
seamlessly incorporated, and ineffective and fraudulent ones are discarded
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