Gynecology_Novak

Gynecology_Novak. False 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. There is no national or state licensure for hypnotherapists. The International Medical and Dental Hypnotherapy Association will certify hypnotherapists if they meet the minimum eligibility requirements and will provide referrals.


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Gynecology_Novak. 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, each 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 60 additional hours of ASCH-approved workshop training and 5 years


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Gynecology_Novak. have extensive experience in using hypnosis within their professional practices. Certification at this level requires a minimum of 60 additional hours of ASCH-approved workshop training and 5 years of independent practice using clinical hypnosis (14).


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Gynecology_Novak. 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.


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Gynecology_Novak. Transcendental meditation (TM) is a simple, natural, effortless procedure 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. Transcendental meditation is useful in the treatment of hypertension. 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.


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Gynecology_Novak. 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. It is included in the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) diagnostic category “religious or spiritual problem.” 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. 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. Acupuncture is a therapeutic intervention that is used in many Asian systems of medicine.


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Gynecology_Novak. Acupuncture is a therapeutic intervention that is used in many Asian systems of medicine. 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 these 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.


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Gynecology_Novak. Given the Western, biomedical model, acupuncture is difficult to comprehend. There is, however, an intriguing and growing 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 (15). Many of the CAM approaches that claim to have an effect and yet seem to be inconsistent with the biomedical model deserve further investigation.


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Gynecology_Novak. 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 as well as nausea and vomiting (16). Other indications that were considered promising and worthy of more research included headache, low-back pain, stroke, addiction, asthma, premenstrual syndrome, osteoarthritis, carpal tunnel syndrome, and tennis elbow. There is an extensive body of animal research supporting the neurophysiologic effects of acupuncture on the endorphin system.


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Gynecology_Novak. Bruising and minor bleeding are the most common complications of acupuncture and occur in about 2% of all needles placed (17). They rarely require treatment other than local pressure to the needle site. The most significant risk of acupuncture is infection, and cases of hepatitis have been documented when needles were reused. 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.


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Gynecology_Novak. Currently there is no national licensure for acupuncture. Educational requirements for state licensure for acupuncture vary. Forty states either license or register acupuncturists as doctors of oriental medicine or acupuncture physicians. About two-thirds of these states grant licenses. To get 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) (18). These schools provide 3-or 4-year training programs in oriental medicine. The National Certification Commission for Acupuncture and Oriental Medicine (NCCAOM) administers a standardized examination to test entry-level capabilities in acupuncture that consists of a comprehensive written examination, point location examination, and demonstration of clean needle technique (11). An acupuncturist must pass this examination and meet


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Gynecology_Novak. in acupuncture that consists 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 US, many states adopted this examination as the basis for licensure. Medical doctors can practice acupuncture. 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 (19).


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Gynecology_Novak. Homeopathy Homeopathic medicine is a CAM 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.


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Gynecology_Novak. Naturopathic Medicine Unlike oriental medicine or homeopathy, naturopathy does not have a long history of traditional use, nor is it based in a comprehensive system. Naturopathy 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.


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Gynecology_Novak. There is no national licensure for naturopathy, and licensure at the state level is inconsistent. Only 15 states have licensing laws, and those laws differ considerably. Seven 4-year naturopathic medical schools are accredited by the Council on Naturopathic Medical Education (20). 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.


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Gynecology_Novak. The Placebo Effect The role of the placebo effect in various CAM approaches needs to be further elucidated with rigorous scientific research. 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 both 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 experience a placebo response. It would be of great value to medicine if the placebo response were better understood and could be activated more reliably in patients. There is no evidence that the placebo response is more active in CAM than in conventional approaches.


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Gynecology_Novak. Quality Control Quality control issues in CAM are very challenging for several reasons. First, the market demand is huge and is far ahead of the health care system’s ability to address issues of regulation, education, or research. Because CAM, by definition, is inclusive of everything that conventional medicine is not, issues of quality control are extremely difficult. The Federation of State Medical Boards developed the “Model Guidelines for the Use of Complementary and Alternative Therapies in Medical Practice,” approved by the House Delegates of the Federation of State Medical Boards of the United States, Inc., as policy in April 2002 (21). The intention of this initiative was to provide guidelines that are clinically responsible, ethically appropriate, and consistent with what state medical boards consider to be within the boundaries of professional practice and accepted standard of care.


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Gynecology_Novak. 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 significant dollars based on false promises or claims. Second, patients can postpone effective therapy or treatment by turning to CAM modalities exclusive of conventional approaches. This time can be significant in the treatment of many patients’ diseases. Factors that should increase suspicion for potential misuse are listed in Table 13.6. The Potential Benefits: Therapeutic Opportunities


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Gynecology_Novak. 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 CAM? The most basic answer is commitment to the best practice of medicine. If patients are using therapies that are potentially dangerous in their action or in their 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. If there are CAM therapies that can benefit patients, the physician should be knowledgeable about them and be willing to discuss them with patients. In addition to this most fundamental of reasons, there are additional therapeutic opportunities offered by CAM, as shown by the following examples: Table 13.6 Factors that Should Increase Suspicion for Potential Misuse 1.


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Gynecology_Novak. Table 13.6 Factors that Should Increase Suspicion for Potential Misuse 1. Providers or products that make claims that are grandiose and dubious, for example; chiropractors who claim to cure insulin-dependent diabetes or offer alternative approaches to cure 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. Decreased harm of interventions: Chiropractic medicine to treat acute low-back pain and potentially avoid surgery; mind–body approaches to decrease anxiety and need for medical management Treatment of conditions when conventional approaches fail: Treatment of nausea and vomiting of pregnancy with acupuncture, vitamin B6, and ginger


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Gynecology_Novak. Treatment of conditions when conventional approaches fail: Treatment of nausea and vomiting of pregnancy with acupuncture, vitamin B6, and ginger Prevention: Increased intake of isoﬂavones to potentially decrease the risk of breast cancer Improved outcomes: Successful management of menopausal symptoms in patients at risk for breast cancer


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Gynecology_Novak. One of the greatest barriers regarding issues of CAM is a lack of communication. As multiple studies show, most patients do not tell their physicians of their use of CAM. Often, this is the case even when the physicians are receptive to the topic. Given the prevalence of use and the potential for interactions with conventional approaches, it is imperative that questions regarding CAM 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 CAM therapies that patients used in the past or are using presently, particularly anything ingestible. If a patient is seeing a CAM practitioner, it is best to specifically ask if they recommended any supplements or botanicals. Oriental medicine practitioners or


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Gynecology_Novak. particularly anything ingestible. If a patient is seeing a CAM 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.


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Gynecology_Novak. Three factors contribute to an interesting dynamic that often arises when discussing issues of CAM with patients. This is an area in which (i) very few physicians received 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 altogether. The development of CAM therapies and their integration into the treatment plans is a 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 dilemmas. This is a significant step in building a


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Gynecology_Novak. 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 dilemmas. This is a significant step in building a trusting and therapeutic relationship with patients interested in CAM.


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Gynecology_Novak. It is useful to share the following decision tree with patients when making decisions regarding the use of CAM (Fig. 13.1). Step One: Assess Potential Harm Although research regarding CAM approaches is often less than optimal, the potential for any therapy to do harm should be thoroughly evaluated (to the best of available knowledge). It is necessary to evaluate the potential to cause both direct harm and indirect harm. Potential for Direct Harm This should include any evidence regarding potential harm directly from the therapy or potential interactions. When lacking good evidence, assessment of the invasiveness of the therapy is a strong predictor of risk.


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Gynecology_Novak. Potential for Indirect Harm This should include an assessment of potential harm caused by postponing effective treatments, and by financial exploitation. Many CAM 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.


Gynecology_Novak

Gynecology_Novak. 1. Assess potential harm 2. Assess potential benefit What is the potential for direct harm? (from the treatment itself; e.g., toxicity, injury) High What is the potention for indirect harm? (e.g., postponing other treatments, financial exploitation) DO NOT RECOMMEND DO NOT RECOMMEND DO NOT RECOMMEND Are there data on efficacy? Low High Low Yes No Yes No DO NOT RECOMMEND Is there cultural evidence? Is there strong patient belief? 3. Assess the quality of product or provider (e.g., independent product assessment, licensing body, patient experience) 4. Assess the integration with the conventional treatment plan Acceptable Unacceptable Evidence shows no efficacy Evidence shows efficacy Indeterminant DO NOT RECOMMEND No Yes Can the provider be integrated? (e.g., desires collaboration, supports integration of conventional and CAM approaches) No Yes RECOMMEND (informing patient of rationale for recommendation and level of evidence for the approach) Can the approach be integrated? (e.g., no


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Gynecology_Novak. integration of conventional and CAM approaches) No Yes RECOMMEND (informing patient of rationale for recommendation and level of evidence for the approach) Can the approach be integrated? (e.g., no significant interactions or contraindications with conventional treatments)


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Gynecology_Novak. Figure 13.1 Decision Tree for Integrating Complementary and Alternative Medicine Approaches. Scientific Evidence A review of the peer-reviewed literature should certainly be conducted for evidence of the effectiveness of the approach under consideration. 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 chelation, which was in use for a relatively short time and is associated with considerable debate regarding its benefit.


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Gynecology_Novak. 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, both 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 product and accuracy of labeling may be useful.


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Gynecology_Novak. Provider It can be difficult to assess the skill level of CAM 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 CAM 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 treatment plan is important. The same is true for CAM 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.


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Gynecology_Novak. 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 CAM alike, should be assessed for their willingness to integrate their care for the benefit of their patients. If any 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 CAM and willingness to learn about the techniques. At a minimum, physicians should know the basics about which CAM 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 physician and patient alike.


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Gynecology_Novak. some benefit with magnesium, St. John’s wort, and vitamin E. There was no benefit in their review of evening primrose oil. A meta-analysis reviewing the data on supplements for dysmenorrheal concluded there was effectiveness for magnesium, vitamin B1, and vitamin B6, and data for magnesium was promising (23).


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Gynecology_Novak. Calcium Calcium, 900 to 1,200 mg per day in divided doses, has at least some effect on the symptoms of PMS, premenstrual dysphoric disorder, and dysmenorrheal, specifically negative affect (mood swings, depression, tension, anxiety, crying spells), water retention (edema of extremities, breast tenderness, abdominal bloating, headache, fatigue), food cravings (changes in appetite, cravings for sweet or salt), and pain (lower abdominal cramping, generalized aches and pains, low backache) (22). One of the largest studies to date examined the effect of calcium, 1,200 mg per day, and reported a 50% decrease in PMS symptoms (24). In addition, the Women’s Health Study showed that higher intakes of calcium and vitamin D may be associated with a lower risk of developing breast cancer in premenopausal women, particularly with more aggressive breast tumors (25).


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Gynecology_Novak. Vitamin B6 Vitamin B6 binds to estrogen and progesterone receptors and was the subject of most of the randomized controlled trials regarding CAM and PMS. Evidence suggests some benefit over placebo for the symptoms of mastalgia, swollen breasts, pain, and depression. Another review of randomized controlled trials indicated that although most of these trials demonstrated some benefit, definite clinical recommendations could not be made (26). 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. Vitamin B6 for the treatment of dysmenorrheal was more effective at reducing pain than both placebo and a combination of magnesium plus vitamin B6 (23). It is important to note that peripheral neuropathies can be seen in doses of 200 mg per day or higher, as well as interaction with other medications,


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Gynecology_Novak. a combination of magnesium plus vitamin B6 (23). It is important to note that peripheral neuropathies can be seen in doses of 200 mg per day or higher, as well as interaction with other medications, specifically anti-Parkinson’s disease drugs.


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Gynecology_Novak. 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. Whereas the evidence is less strong, several studies show a significant decrease in PMS symptoms (27,28). In the three randomized controlled trials, only the study using magnesium pyrrolidone carboxylic acid showed significant effect. One with no effect was limited by only 1 month of supplementation. In research on its effectiveness for dysmenorrheal, magnesium was more effective than placebo for pain relief, and the need for additional medication was less. There was no significant difference in the number of adverse effects experienced (23).


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Gynecology_Novak. Although more studies are needed to clearly determine effectiveness and which formulation is most efficacious, use of magnesium is reasonable to support clinically and counteracts the constipating effects of calcium. Magnesium can be taken in 200 to 400 mg per day divided doses, either cyclically during the luteal phase or continuously.


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Gynecology_Novak. Vitamin E Studies performed in the 1940s suggested that vitamin E might be effective in the treatment of menstrual disorders such as PMS. Recent studies for PMS were mixed. Two randomized controlled trials investigating vitamin E (in d-alpha tocopherol form) showed promising results in the treatment of PMS over placebo (29). A randomized controlled trials studying the effect of vitamin E on dysmenorrhea showed decreases in both severity and duration of pain, as well as blood loss (30). The dosing regimen used was 200 IU twice a day beginning 2 days before the expected menses and continued for the first 3 days of menstruation. It is believed that the mechanism of action of vitamin E is an inhibition of arachidonic acid release with a consequential decrease in prostaglandin formation. Vitamin E with mixed tocopherols at 400 IU per day with meals is considered safe and may be of benefit.


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Gynecology_Novak. Most controlled studies on vitamin B6 in the treatment of PMS have limited numbers of patients; therefore, the evidence of positive effects is fairly weak (31). This is a benign therapy in doses of 100 mg or less. A systematic review of nine trials indicated significant benefit over placebo for the symptoms of mastalgia, swollen breasts, pain, and depression (32). 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 prostaglandin F2α (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 as well as supplements (Table 13.7). One study looked at essential fatty


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Gynecology_Novak. Table 13.7 Omega-3 Content of Foodsa a For general health, individuals should try to consume 7–10 g of omega-3 fatty acids weekly. Data from United States Department of Agriculture. USDA national nutrient database. Beltsville, MD: USDA; 2004. Available online at http://www.nal.usda.gov/fnic/foodcomp/search acids (EFA) and PMS and showed no effect. There are some positive studies looking at the effectiveness of omega-3 fatty acids 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) (33). 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.


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Gynecology_Novak. Chasteberry Chasteberry (Vitex agnus-castus) is a botanical with a long history of use for “menstrual disorders.” Many small studies have shown promising results, and one larger study examined the effectiveness of chasteberry on PMDD (34,35). In this randomized controlled trial, 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 (35). 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 (36). A randomized, single-blind trial comparing Vitex and ﬂuoxetine showed equal symptom reduction at 2 months (58% and 68%, respectively) (37). In


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Gynecology_Novak. but there were no serious adverse reactions (36). A randomized, single-blind trial comparing Vitex and ﬂuoxetine showed equal symptom reduction at 2 months (58% and 68%, respectively) (37). In both arms, there were significantly improved symptoms. Two of the three randomized controlled trials evaluating chasteberry for PMS showed some benefit on symptoms such as irritability, mood swings, anger, breast tenderness, and headaches. In the study with no benefit, the placebo arm was a soy-based product, which may reduce symptoms of PMS. Because chasteberry contains iridoids and ﬂavonoids, the mechanism of action is believed to be stimulation of dopamine D2 receptors, which decrease prolactin levels. In vitro, it inhibits opioid, mu, and kappa receptors. It has no effect on luteinizing hormone or follicle-stimulating hormone levels (38). Vitex restores progesterone levels and in Germany is used to treat menstrual irregularities and undiagnosed infertility. No significant toxicities were


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Gynecology_Novak. or follicle-stimulating hormone levels (38). Vitex restores progesterone levels and in Germany is used to treat menstrual irregularities and undiagnosed infertility. No significant toxicities were reported with Vitex extracts when used in appropriate dosages.


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Gynecology_Novak. St. John’s Wort St. John’s wort (Hypericum perforatum) is recognized as an effective antidepressant for the treatment of mild to moderate depression. One open trial of 19 women found that this compound, when used at a dose of 300 mg per day of a 0.3% hypericin standardized extract, showed a 51% improvement in mood disturbances in PMS/PMDD (39). This dose is one-third of that typically used for depression. The most recent randomized controlled trial 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 (22). 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 cytochrome P450 complex, significant drug interactions can occur.


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Gynecology_Novak. gastrointestinal upset, headache, and agitation. Rare but severe phototoxicity was reported. Because St. John’s wort induces the cytochrome 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.


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Gynecology_Novak. 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 (40). 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. In at least one study, ginkgo was effective in the relief of symptoms related to emotional distress (41). 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


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Gynecology_Novak. (41). 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.


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Gynecology_Novak. Other products that are used to treat symptoms of PMS and PMDD but are not recommended are listed in Table 13.8. 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 Table 13.8 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.


Gynecology_Novak

Gynecology_Novak. 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 is 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.


Gynecology_Novak

Gynecology_Novak. 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. Table 13.9 Findings on Alternative Treatments Magnesium Three small trials were included that compared magnesium with placebo. Overall, magnesium was more effective than placebo for pain relief, and the need for additional medication was lessened. There was no significant difference in the number of adverse effects experienced.


Gynecology_Novak

Gynecology_Novak. Vitamin B6 One small trial showed vitamin B6 to be more effective at reducing pain than both placebo and a combination of magnesium and vitamin B6. Vitamin B1 One large trial showed that vitamin B1 was more effective than placebo in reducing pain. Vitamin E One small trial comparing daily vitamin E with ibuprofen taken during menses showed no difference in pain relief. Omega-3 fatty acids One small trial showed fish oil to be more effective than placebo in pain relief. A number of studies have found that the intake of marine origin omega-3 fatty acids (such as salmon and sardines) decrease symptoms of dysmenorrhea. Given the established benefits of omega-3 fatty acids in other conditions such as heart disease, high intake of these compounds can be recommended throughout the cycle. Adapted from Proctor ML, Murphy PA. Herbal and dietary therapies for primary and secondary dysmenorrhea. Cochrane Database Syst Rev 2001;3:CD002124.


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Gynecology_Novak. alternatives. Table 13.9 lists findings by a Cochrane review study on alternative treatments. 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 randomized controlled trial (23). The results further suggested that magnesium is a promising treatment, but it is unclear what dose or treatment regimen should be used (23). The addition of fish oils showed promising results. The concentration of omega-6 fatty acid derived eicosanoids such as PgE2 are elevated during menstruation in women who experience dysmenorrhea. Dysmenorrhea was associated with low dietary intake of omega-3 fatty acids. Several studies showed supplementation to be effective in the management of dysmenorrheal (42). Krill omega-3 phospholipids, which contain phosphatidylcholine with DHA/EDA, outperformed conventional fish oil DHA/EDP in double blind studies on PMS and dysmenorrhea (43). Given the established


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Gynecology_Novak. Krill omega-3 phospholipids, which contain phosphatidylcholine with DHA/EDA, outperformed conventional fish oil DHA/EDP in double blind studies on PMS and dysmenorrhea (43). Given the established benefits of omega-3 fatty acids in other conditions, such as heart disease, high intake of these compounds can be recommended throughout the menstrual cycle.


Gynecology_Novak

Gynecology_Novak. 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 (44).


Gynecology_Novak

Gynecology_Novak. 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 (45). 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 (45).


Gynecology_Novak

Gynecology_Novak. Mind–Body Interventions 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 (46). 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 (47).


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Gynecology_Novak. Oriental medicine and acupuncture were used traditionally for thousands of years for myriad menstrual symptoms, PMS and PMDD among them. The effectiveness in this domain is not well studied. In one small study (n = 35), there was a 78% reduction in PMS symptoms in the acupuncture arm compared to 6% in the placebo arm (48). There were studies showing the effectiveness of acupuncture in the treatment of mild depression and generalized anxiety, although not all results were positive. There was a Cochrane review on the use of Chinese herbal medicine on PMS, and one on dysmenorrheal. In the review on PMS, the efficacy of Chinese herbal preparations, a randomized controlled trial of Jingqianping showed significant reductions in eliminations of symptoms (49).


Gynecology_Novak

Gynecology_Novak. There was one small but methodologically sound trial of acupuncture in the treatment of primary dysmenorrhea. This trial followed 43 women for 1 year and showed significant effectiveness of acupuncture when compared with placebo (91% of women showed improvement, compared with 10% to 36%, 18%, and 10% in the other groups) (23). In a study that randomized 201 patients, acupuncture improved dysmenorrheal and quality of life compared to usual care (50). In addition, there is some preliminary evidence that acupressure can be an effective, cost-free, and safe therapy for menstrual pain and anxiety. The study taught patients to self-administer 20 minutes of acupressure on Sanyinjian (SP6), which is an acupressure point located above the ankle. In a review on Chinese herbal presentations and their effectiveness on dysmenorrhea, 39 randomized controlled trials were included, involving 3,475 women. Chinese herbal medicine resulted in pain relief, and a decrease in overall symptoms and use of


Gynecology_Novak

Gynecology_Novak. effectiveness on dysmenorrhea, 39 randomized controlled trials were included, involving 3,475 women. Chinese herbal medicine resulted in pain relief, and a decrease in overall symptoms and use of additional medications when compared to the use of pharmaceutical drugs. Individualized Chinese formulations resulted in significant improvement when compared to Chinese health products. Chinese herbal medicine produced better pain relief than acupuncture (51). More research is needed, but this is a promising and safe modality, and if a woman is fully informed and interested in pursing these approaches and has access to a qualified provider, it is appropriate to support.


Gynecology_Novak

Gynecology_Novak. 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 (46). 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 (47). Mind–Body Interventions Mind–body approaches are of particular interest in the infertility patient. The treatments for infertility 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).


Gynecology_Novak

Gynecology_Novak. In a study of infertility patients, two group psychological interventions were compared with routine care. The two groups who received group support and cognitive behavioral therapy 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 (52). 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 were 41.9%, higher than those who refused (53). In a case control study examining the impact of hypnosis on pregnancy rate in in


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Gynecology_Novak. techniques was 56% and in those who intended to use these approaches were 41.9%, higher than those who refused (53). 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% (54).


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Gynecology_Novak. Mind–body therapies, such as relaxation techniques and hypnosis, are reasonable to recommend to relieve a wide variety of issues that can arise with infertility patients.


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Gynecology_Novak. The use of acupuncture was studied in the treatment of infertility and overall shows promise. Auricular acupuncture was studied as an alternative therapy for female infertility secondary to oligomenorrhea or luteal insufficiency, and the authors concluded it was a valuable therapy (55). 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% (56). In a randomized controlled trial of 225, women undergoing IVF or intracytoplasmic sperm injection (ICSI) with acupuncture had clinical pregnancy rates of 33.6% versus 15.6% in


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Gynecology_Novak. 28% versus 18% (56). In a randomized controlled trial 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% (57). 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% (58).


Gynecology_Novak

Gynecology_Novak. In a randomized controlled trial 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 (59). In a meta-analysis including seven 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 (60). 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 (61). 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 potentially related to modulating neuroendocrinological factors, increases in uterine and ovarian blood ﬂow, modulating cytokines, and reducing stress,


Gynecology_Novak

Gynecology_Novak. the effect of acupuncture is hypothesized to be potentially related to modulating neuroendocrinological 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 both shortly after the last treatment and also 10 to 14 days after the treatments. The skin temperature of the forehead was increased significantly, suggesting a central inhibition of sympathetic activity (62). 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


Gynecology_Novak

Gynecology_Novak. 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 (63). More studies are needed both 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 is reasonable to support if patients are interested.


Gynecology_Novak

Gynecology_Novak. 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 CAM approaches. In a study examining the use of CAM during menopause, a group of 3,302 women were followed across 6 years, and 80% of them used some form of CAM (64). In a study examining women’s treatment choices after discontinuing hormone therapy (HT), 76% of women reported using nonhormonal alternative therapies, and of these 68% found them helpful (65). 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 hormone therapy was equally or more effective for long-term protection of bones and lipid levels (66). It is reasonable to assume


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Gynecology_Novak. or more effective for symptom relief. Many women believed natural hormone therapy was equally or more effective for long-term protection of bones and lipid levels (66). 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.


Gynecology_Novak

Gynecology_Novak. The list of botanicals 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. Since the 1940s, vitamin E has been studied for the treatment of hot ﬂashes. Although some early studies showed promising results, other studies evaluating 200-to 600-IU doses failed to show an effect. There was one small trial with 51 women that showed an effect on hot ﬂashes of 400 IU daily, but it was suggested that up to 1,200 IU may be necessary to have an effect, doses which are too high to recommend. Vitamin E is an anticoagulant, and spontaneous subarachnoid hemorrhages were reported. One study examining vitamin E in menopausal patients with breast cancer found that after 4 weeks of 800 IU daily, the patients in the treatment arm had on average one less hot ﬂash per day. Although this finding was statistically significant, it was not significant clinically (67).


Gynecology_Novak

Gynecology_Novak. Premenstrual Symptoms and Menopause Black cohosh (Cimicifuga racemosa) has traditionally been used for relief of both 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. Additionally, there are no changes in hormone levels in women taking black cohosh. In laboratory studies, black cohosh actually suppresses rather than stimulates breast cells (68). Women taking black cohosh show


Gynecology_Novak

Gynecology_Novak. there are no changes in hormone levels in women taking black cohosh. In laboratory studies, black cohosh actually suppresses rather than stimulates breast cells (68). Women taking black cohosh show significant improvement in menopausal symptoms, anxiety, and vaginal epithelium. It is well tolerated with no side effects noted. When compared with hormone therapy, black cohosh has comparable results, and women show improvements in hot ﬂashes, fatigue, irritability, and vaginal dryness. In a meta-analysis of randomized controlled trials of black cohosh, the authors concluded that there was a trend in reducing vasomotor symptoms. One study of 304 women demonstrated a decrease in the number and intensity of hot ﬂashes, improvement in mood, sleep, sweating, and sexual disorders. In a double-blind, placebo-controlled trial, black cohosh, 40 mg, was compared with conjugated estrogen, 0.6 mg, and placebo (69). The researchers monitored 62 women for 3 months and black cohosh was found to have


Gynecology_Novak

Gynecology_Novak. placebo-controlled trial, black cohosh, 40 mg, was compared with conjugated estrogen, 0.6 mg, and placebo (69). The researchers monitored 62 women for 3 months and black cohosh was found to have effects equal to conjugated estrogen and to be superior to placebo in decreasing climacteric symptoms. Black cohosh had no effect on endometrial thickening as measured by vaginal ultrasonography, unlike conjugated estrogen, which had a significant increase in endometrial thickening. Additionally, both black cohosh and conjugated estrogen increased the vaginal superficial cells. In a trial comparing black cohosh to placebo and to estrogen over 12 months, black cohosh was found to be effective (70). In a large-scale, controlled, observational study of black cohosh alone and black cohosh in combination with St. John’s wort involving 6,141 women, both therapies were effective and well tolerated. For psychological symptoms, the combination was superior to black cohosh alone (71). Although many


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Gynecology_Novak. with St. John’s wort involving 6,141 women, both therapies were effective and well tolerated. For psychological symptoms, the combination was superior to black cohosh alone (71). Although many published studies have design weaknesses and more research is needed, black cohosh appears to be safe and may be efficacious for the treatment of menopausal symptoms. It should be started at 20 to 40 mg twice daily, standardized to 2.5 triterpenes The Commission E recommends 40 to 200 mg (72).


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Gynecology_Novak. 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. While the longest study in the literature lasted 12 months, there is no indication that longer use is unsafe.


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Gynecology_Novak. Breast Cancer Multiple studies showed that black cohosh has an inhibitory effect on estrogen receptor breast cancer cells. 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, both 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 (73). 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%) (74). Although it is useful to know that black cohosh is not estrogenic, its efficacy in this


Gynecology_Novak

Gynecology_Novak. Severe hot ﬂashes were reduced in the intervention arm (24%) compared with the tamoxifen-alone arm (74%) (74). Although it is useful to know that black cohosh is not estrogenic, its efficacy in this group of patients is not established.


Gynecology_Novak

Gynecology_Novak. 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 used to combat fatigue or to restore “vital force” for performance enhancement.


Gynecology_Novak

Gynecology_Novak. Panax ginseng is a small perennial that grows in northeast Asia. One study of 12 patients examined its effect on menopausal women, both 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 (75).


Gynecology_Novak

Gynecology_Novak. 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 no significant difference in 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 (76). A second study demonstrated improvement in fatigue, insomnia, mood, and depression (70).


Gynecology_Novak

Gynecology_Novak. 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 (68).


Gynecology_Novak

Gynecology_Novak. 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 is characterized by reproductive complications, including infertility. Despite its presumed estrogenic activity, several studies, including two double-blind, placebo-controlled trials, failed to show an effect over placebo in the treatment of menopausal symptoms (77). A number of meta-analyses concluded that overall red clover was not clinically better than placebo for relief of vasomotor symptoms (70). In a trial involving 252 women, two red clover supplements were compared with


Gynecology_Novak

Gynecology_Novak. concluded that overall red clover was not clinically better than placebo for relief of vasomotor symptoms (70). 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) (78). 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 evidence for a biological 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.


Gynecology_Novak

Gynecology_Novak. Red clover has no clear demonstrable effect, it 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 (Angelica sinensis) has a long history of traditional use in menopause and in the treatment of menstrual problems. Traditionally, 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 (79). 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.


Gynecology_Novak

Gynecology_Novak. 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 hormone therapy for the treatment of anxiety showed that the combined use resulted in a significant decrease in anxiety when compared with hormone therapy alone (80).


Gynecology_Novak

Gynecology_Novak. Kava has the potential for significant, albeit rare, side effects. Cases of hepatotoxicity severe enough to require transplant were reported (81). Other side effects include dermatitis, and a movement disorder similar to Parkinson’s 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 The 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.


Gynecology_Novak

Gynecology_Novak. 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. Patients not taking hormone therapy were given 300 mg of St. John’s wort three times daily, and symptoms were evaluated at baseline and at 5, 8, and 12 weeks by both the patients and physicians. At baseline, 80% to 90% of all symptoms were moderate to marked in severity. By 12 weeks, 20% to 30% remained at this level, whereas most patients had only slight symptoms or were symptom free. There was no change in vasomotor symptoms; 80% of patients reported that their sexuality was substantially enhanced.


Gynecology_Novak

Gynecology_Novak. this level, whereas most patients had only slight symptoms or were symptom free. There was no change in vasomotor symptoms; 80% of patients reported that their sexuality was substantially enhanced. Of 106 patients, 4 reported adverse effects. These effects included skin rash with sun exposure, gastrointestinal upset, headache, and fatigue (82). In a randomized trial of 301women using a combination of black cohosh and St. John’s wort, the treatment was superior to placebo for both climacteric and psychological symptoms (83). 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.


Gynecology_Novak

Gynecology_Novak. Chasteberry (Vitex agnes) 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 chasteberry in menopause is not demonstrated. 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 (84). Side effects include gastrointestinal upset and headaches, and drug interactions can occur with estrogens, statins, and calcium channel blockers. Ginkgo has an anticoagulant effect.


Gynecology_Novak

Gynecology_Novak. Phytoestrogens are plant-based compounds that have weak estrogenic activity. They appear to have SERM activity with modest agonist effect at the beta estrogen receptor. Phytoestrogens are categorized as isoﬂavones, coumestans, lignans, or ﬂavonoids. The most promoted of these groups is isoﬂavones, which are genistein, daidzein, or glycitein. Soybeans and soy products are a rich source of isoﬂavones. Several reviews and meta-analyses found mixed results on menopausal symptoms (70,85). 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 randomized controlled trial of 366 women demonstrated endometrial hyperplasia in 3.8% of women who consumed 150 mg per day of isoﬂavones for 5 years versus 0% in the placebo arm (85).


Gynecology_Novak

Gynecology_Novak. Mind–Body Interventions Mind–body therapies for the treatment of menopausal symptoms were studied in several domains, but the trials are often small and not always high quality. In a small prospective trial of 30 women, applied relaxation was compared to estradiol. The women in the relaxation group had a 76% reduction in hot ﬂashes at 6-month follow-up versus 90% in the estradiol arm, which was reached at 12 weeks (86). In another study by Nedstrand et al., 38 women with breast cancer showed improvement in vasomotor symptoms with both applied relaxation and electro-acupuncture (86). In one randomized controlled trial, symptomatic menopausal patients who had at least five hot ﬂashes per 24 hours were randomized to either the relaxation response, to reading, or to a control group. The relaxation response group had significant reductions in hot ﬂash intensity, tension– anxiety levels, and depression compared with the control group, which had no significant changes (87). In another


Gynecology_Novak

Gynecology_Novak. relaxation response group had significant reductions in hot ﬂash intensity, tension– anxiety levels, and depression compared with the control group, which had no significant changes (87). In another randomized controlled trial of symptomatic menopausal patients, women with frequent hot ﬂashes were randomized to paced respiration, muscle relaxation, and alpha-wave feedback. In the paced respiration group, there was significant reduction in the hot ﬂash frequency, whereas muscle relaxation and biofeedback showed no differences. The proposed mechanism of action is decreased central sympathetic activity (88). In a trial with 76 breast cancer patients, an intervention of counseling and emotional support was associated with an improvement in both menopausal symptoms and sexual function compared to the control arm (89). In a trial of 102 women the effect of acupuncture, applied relaxation, estrogens, and placebo were examined. Both acupuncture and applied relaxation reduced the number of hot


Gynecology_Novak

Gynecology_Novak. to the control arm (89). In a trial of 102 women the effect of acupuncture, applied relaxation, estrogens, and placebo were examined. Both acupuncture and applied relaxation reduced the number of hot ﬂashes significantly better than placebo (90).


Gynecology_Novak

Gynecology_Novak. 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 (91). Overall, mind–body techniques are a low-or no-cost, low-risk intervention that can decrease central nervous system adrenergic tone. They are reported to decrease hot ﬂashes and other menopausal symptoms, and provide general health benefits.


Gynecology_Novak

Gynecology_Novak. 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 best-studied CAM modalities, but more studies of higher quality are needed regarding its application to the menopausal patient. The existing studies on acupuncture and menopausal symptoms are mixed. In a systematic review, which included 11 trials and 763 women, concluded that while some studies showed greater benefit with acupuncture than hormone therapy for reducing vasomotor symptoms, many showed no benefit (92). Another systematic review drew the same conclusions (93). In a randomized controlled trial of 267 women comparing individualized acupuncture plus self-care to self-care alone, both the frequency and the intensity of hot ﬂashes significantly decreased in the


Gynecology_Novak

Gynecology_Novak. In a randomized controlled trial of 267 women comparing individualized acupuncture plus self-care to self-care alone, both 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 (94). One uncontrolled study, which explored the experience of more than 300 women, found that 97% of women reported that acupuncture improved their symptoms, and 51% reported being symptom free (95). In a pilot study looking at the use of acupuncture in patients being treated with tamoxifen, 15 patients were followed for 6 months (96). 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 (97). This is a promising area for those patients


Gynecology_Novak

Gynecology_Novak. symptoms. Libido was not affected. A study with 45 women with breast cancer found significantly decreased hot ﬂashes with electroacupuncture (97). This is a promising area for those patients whose options for treatment of these symptoms are limited.


Gynecology_Novak

Gynecology_Novak. In the hands of a competent practitioner, acupuncture is a safe CAM modality. If menopausal patients are interested in exploring this technique as part of their plan for managing symptoms and understand the lack of comprehensive studies, 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 hormonal therapy. “Natural” Hormones There is increasing confusion around the myriad hormonal options for patients. 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.”


Gynecology_Novak

Gynecology_Novak. 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.


Gynecology_Novak

Gynecology_Novak. The ovaries produce three types of estrogen: 17 beta-estradiol, estrone, and estriol. Premenopausally, the predominant estrogen produced by the ovary is 17-beta 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 alternative medicine community.


Gynecology_Novak

Gynecology_Novak. 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 not bioidentical or 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 13.10. Table 13.10 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.


Gynecology_Novak

Gynecology_Novak. Table 13.10 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.


Gynecology_Novak

Gynecology_Novak. 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.


Gynecology_Novak

Gynecology_Novak. 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 doctors did not clarify that the findings were regarding one specific form of estrogen combined with one specific form of progestin. Progestins 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).


Gynecology_Novak

Gynecology_Novak. Bioidentical Estrogens E2, or 17 beta-estradiol, often is used interchangeably with conjugated equine estrogen. It is effective in relieving vasomotor symptoms, helps maintain bone, and improves the lipid profile. It is most bioidentical when delivered in the form of the patch because its oral form is converted to estrone in the gut. (The patch bypasses the liver and is not as beneficial in its effects on high-density lipoprotein and low-density lipoprotein, but it increases triglycerides to a lesser extent.) No comprehensive long-term data regarding its use are available.


Gynecology_Novak

Gynecology_Novak. Estriol, or E3, the weakest of the estrogens that occurs naturally only in high circulating levels during pregnancy, is very popular in the alternative community. It is often promoted as the ideal estrogen, a natural alternative providing all of the benefits of hormone therapy 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 histiologic evaluation of the endometrium revealed no hyperplasia or atypia. Bone mineral density showed no change (98). 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 medroxyprogesterone acetate, 0.625 mg of conjugated estrogen plus 2.5 mg medroxyprogesterone acetate, 1 μg of 1-alpha hydroxy vitamin D3, and 1.8 g calcium lactate containing 250 mg of elemental


Gynecology_Novak

Gynecology_Novak. mg medroxyprogesterone acetate, 0.625 mg of conjugated estrogen plus 2.5 mg medroxyprogesterone acetate, 1 μg of 1-alpha hydroxy vitamin 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 was decreased or without change in the conjugated estrogen and E3 groups, and was 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


Gynecology_Novak

Gynecology_Novak. 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 decreased 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 (99).


Gynecology_Novak

Gynecology_Novak. It was 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 (100).


Gynecology_Novak

Gynecology_Novak. Oral estriol appears to provide symptom relief and to stimulate breast and endometrial tissue less than estradiol (101). 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.


Gynecology_Novak

Gynecology_Novak. 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 are significant (i.e., 0.5 mg).


Gynecology_Novak

Gynecology_Novak. Although Tri-est and Bi-est are only 20% E2 or E2 plus E3, the dose of these more potent estrogens are significant (i.e., 0.5 mg). Although a certain combination of E1/E2/E3 may prove to have benefits over other forms of hormone therapy and should be explored, this research does not exist. Estriol Vaginal Cream Estriol vaginal cream was studied in women who had recurrent urinary tract infections. This randomized controlled trial 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 (101). In a randomized controlled trial of 27 women on hormone therapy with urogenital atrophy, the addition of vaginal estriol shortened the latency period for urinary symptoms (102).


Gynecology_Novak

Gynecology_Novak. The effect of vaginal estriol cream on the endometrium was evaluated in a study examining long-term use for urogenital atrophy. Patients were given 0.5 mg of estriol cream vaginally for 21 days, then twice weekly for 12 months. Hysteroscopic and histologic examinations were performed at baseline, 6 months, and 12 months. Complete endometrial atrophy occurred in all patients (N = 23) (103). This pilot study needs to be performed in a larger patient population, but its findings are promising.


Gynecology_Novak

Gynecology_Novak. Bioidentical Progestins The Postmenopausal Estrogen-Progestin Intervention (PEPI) trials provided a multicentered, randomized controlled trial that, among other things, compared conjugated equine estrogen plus medroxyprogesterone acetate with conjugated equine estrogen plus natural or micronized progesterone (104). The trial compared 12 days of 10 mg of medroxyprogesterone acetate 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 medroxyprogesterone acetate. This was the case in several other trials (105,106). Given these data, there is no reason not to prescribe micronized progesterone. The arm of the Women’s Health Initiative that was prematurely discontinued was the conjugated equine estrogen/medroxyprogesterone acetate arm.


Gynecology_Novak

Gynecology_Novak. is no reason not to prescribe micronized progesterone. The arm of the Women’s Health Initiative that was prematurely discontinued was the conjugated equine estrogen/medroxyprogesterone acetate arm. The conjugated equine estrogen– alone arm was continued. The role and the effect of medroxyprogesterone acetate should be closely examined. In ovariectomized rhesus monkeys, E2 plus medroxyprogesterone acetate interfered with ovarian estrogen protection against coronary vasospasm. E2 plus micronized progesterone protected against coronary vasospasm. Given the increased cardiovascular risks in women taking conjugated equine estrogen and medroxyprogesterone acetate, combined with the positive data from PEPI, micronized progesterone is an excellent choice for patients who are taking systemic estrogen who still have a uterus.


Gynecology_Novak

Gynecology_Novak. Table 13.11 Progesterone and Wild Yam Creams Natural progesterone was used as a single agent in the treatment of menopausal symptoms. The typical dose is 100 mg per day. More research is needed to demonstrate efficacy.


Gynecology_Novak

Gynecology_Novak. Natural progesterone was used as a single agent in the treatment of menopausal symptoms. The typical dose is 100 mg per day. More research is needed to demonstrate efficacy. Yam Creams, Progesterone Creams Yam creams and progesterone creams, which are both 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 13.11). 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.


Gynecology_Novak

Gynecology_Novak. 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 as well as 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


Gynecology_Novak

Gynecology_Novak. 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 (107).


Gynecology_Novak

Gynecology_Novak. In terms of progesterone creams, a randomized controlled trial of 223 women with severe menopausal symptoms using progesterone cream found the progesterone arm to be no more effective than placebo (108). In another randomized controlled trial, transdermal progesterone was compared to placebo. One-quarter teaspoon of 20 mg of progesterone was used daily for 12 months. In addition, all patients took a multivitamin plus 1,200 mg of calcium. Outcomes evaluated included dual-energy x-ray absorptiometry (DEXA) results, serum thyroid-stimulating hormone, follicle-stimulating hormone, lipids, chemistry, and symptom diary. The group that received the progesterone cream reported 83% improvement in hot ﬂashes compared with 19% improvement in the placebo group. There was no difference in bone density (109).


Gynecology_Novak

Gynecology_Novak. Given the data currently 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 hormone therapy, and it may prove to have other benefits and risks. Table 13.12 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 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


Gynecology_Novak

Gynecology_Novak. Effect of lifelong hormonal exposure Risks and benefits of hormone therapy when initiated at the age of menopause It’s important to communicate to patients what is known regarding hormone therapy and what is not known. Some of the unknown aspects of hormone therapy are listed in Table 13.12. Given the present state of the 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. Studies showed that most surgical patients use some form of CAM. There are special considerations regarding CAM and the surgical patient. These issues primarily fall into two domains: 1. Supplements that, when used perioperatively, may affect the patient’s course 2. CAM approaches that may be of benefit to the surgical patient


Gynecology_Novak

Gynecology_Novak. 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 five 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 female gender, age 35 to 49 years, higher income, Caucasian race, higher education, and problems with sleep, joints, back, allergies, and addiction (110). 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


Gynecology_Novak

Gynecology_Novak. 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 (111). 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 (112).


Gynecology_Novak

Gynecology_Novak. 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 Prolongation of Anesthetic Agents 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.