Complementary and Alternative Medicine for Women
Lisa G Soldat, MD, MS, FAAFP
The material presented here is being made available by the American Academy of Family Physicians for educational purposes only. Please note that medical information is constantly changing; the information contained in this activity was accurate at the time of publication. This material is not intended to represent the only, nor necessarily best, methods or procedures appropriate for the medical situations discussed. Rather, it is intended to present an approach, view, statement, or opinion of the faculty, which may be helpful to others who face similar situations.
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1. Assess patients’ use of herbal or dietary supplements and provide counseling to encourage safe and effective use.
2. Identify the supplements commonly used by your patient population and when to monitor appropriate labs and therapeutic response.
3. Recommend patient-friendly, evidence-based online
resources about the risks and benefits of using supplements for women’s health concerns, including premenstrual
syndrome, altered menses, sleep disorders, hot flashes, anxiety and depression.
Mind-body practices (hypnosis, CBT, relaxation, biofeedback, mediation, aromatherapy)
Whole-system approaches (TCM, reflexology, acupuncture, homeopathy)
Natural products/dietary supplements (herbs, vitamins, minerals, amino acids, and enzymes)
Studies about most CAM modalities can be described as
Heterogeneous . . . “Low quality”… “Insufficient evidence”… “More studies needed”… “No better than placebo”…
“Appears safe” … “no harm if patient wants to take”
What’s the evidence?
Efficacy and safety of most supplements is difficult to establish due to lack of well-designed, randomized, controlled trials
Limited studies looking at interactions between:
Herbs and drugs
Herbs and other micronutrients
Supplements taken together
Dennehy CE. The use of herbs and dietary supplements in gynecology: an evidence-based review. J Midwifery Womens Health. 2006 Nov-Dec;51(6):402-9.
A difference in philosophy
Traditional Chinese Medicine Western Interpretation
Example: Dong quai
Angelica sinensis (root)
Used for 1000’s of years in Chinese medicine
GSM, dysmenorrhea, PMS, menstrual problems, etc
Unclear which part of the plant is pharmacologically active
May be effective only in combination with other herbs
Shown to affect estrogen levels in animals
Insufficient evidence to rate effectiveness
Safety concerns (interactions with other medications and herbs, photosensitization, anticoagulation, and possible carcinogenicity)
Assess patients’ use of herbal or dietary
supplements and provide counseling to encourage safe and effective use.
Ask patients about supplement use
Not all patients disclose unless specifically asked by the provider
Supplements are pharmacologically active
Alerts provider to monitor for adverse effects and drug-supplement interactions
Promotes dialogue about patient’s underlying health concerns
Provide evidence-based information and correct misperceptions, especially if taken in place of prescription medications
Talking points for discussing supplements with patients
Any evidence that it works?
Is it okay to take with prescribed medications?
What’s the right dose?
How much do supplements cost?
Are there any side effects?
How does one pick the best brand?
Who takes supplements?
52% of adults
59% women, 45% men
Use ↑ with age
Older women 71+ are the highest consumers
Highest prevalence in:
Higher education and income
Food secure, non SNAP-eligible and income > 350% of the poverty level
82% were high income and > 71 yo
Private insurance, > 2 health care visits/year, healthy, exercise, nonsmokers
> 1 prescription med in past 30 days Cowan AE, et al. Dietary Supplement Use Differs by Socioeconomic and Health-Related Characteristics among U.S. Adults, NHANES 2011⁻2014. Nutrients. 2018 Aug 17;10(8):1114.
Most common supplements taken by adults
Especially vitamins B-6, B-12, C, D, or K
75% include Vitamin D
Calcium, iron, zinc, magnesium, selenium, or folate
71% contain calcium
26% vitamin D only
22% omega-3 only
Ginkgo biloba, garlic, ginseng, St John’s wort, Echinacea, saw palmetto, evening primrose oil and ginger
Why are supplements taken?
Top 4 reasons (older adults):
1. Improve health (41%) 2. For bone health 3. Maintain health
4. To supplement the diet
Why was a particular product/brand chosen?
Family or friend endorsement
Gahche JJ, Bailey RL, Potischman N, Dwyer JT. Dietary Supplement Use Was Very High among Older Adults in the United States in 2011-2014. J Nutr. 2017;147(10):1968-1976
Know which supplements are typically used by your patients
Follow labs if indicated
Monitor supplements for therapeutic response
Expected response time for any particular supplement
Several weeks before improvement expected
Treatment for 4 weeks before significant improvement in sx
Recommend no longer than one year of use 15
Warfarin: most frequently implicated drug
St. John’s wort: the most drug-herb interactions
Cytochrome P450: most frequent mechanism herb-induced alteration
> 1 possible interactions found in 31%
Serious interactions seem to be uncommon
Loya AM, González-Stuart A, Rivera JO. Prevalence of polypharmacy, polyherbacy, nutritional supplement use and potential product interactions among older adults living on the United States- Mexico border: a descriptive, questionnaire-based study. Drugs Aging. 2009;26(5):423-36.
Your 68 year old patient has been treated for many years with hydrochlorothiazide for hypertension. She mentions in passing that she’s been taking a calcium + vitamin D pill twice a day, along with a daily MVI, for “bone health” and general well-being. What drug- supplement adverse reaction is she at risk for?
A. Metabolic alkalosis B. Metabolic acidosis C. Photosensitivity D. Hypotension
Prescription medications and supplement use in older adults
Number of supplements taken
70% took > 1
54% took 1-2
29% took > 4
73% take > 3 prescription medications
8% taking >3 Rx’s were also taking >1 botanical supplement
Gahche JJ, Bailey RL, Potischman N, Dwyer JT. Dietary Supplement Use Was Very High among Older Adults in the United States in 2011-2014. J Nutr. 2017;147(10):1968-1976
Taking more than the upper tolerable intake level (UL) of which of the following could potentially be harmful in pregnancy?
B. Vitamin A C. Folic acid D. Iodine
E. All of the above
When is it too much of a good thing?
Taking more than recommended on the label
Taking different supplements together that have the same ingredients
Adding to a diet already fortified with same ingredients
Adults > 71 yo: UL was exceeded for folic acid (7%), vit A (3%) and vit B-6 (4%)
Bailey RL, Pac SG, Fulgoni VL, Reidy KC, Catalano PM. Estimation of Total Usual Dietary Intakes of Pregnant Women in the United States. JAMA Netw Open. 2019;2(6):e195967. doi:10.1001/jamanetworkopen.2019.5967
Fortified foods + PNV
33% of pregnant women get too much folic acid
28% of pregnant women get too much iron
36% get too little iron
45% get too little vitamins D, E and magnesium
Gernand AD. The upper level: examining the risk of excess micronutrient intake in pregnancy from antenatal supplements. Ann N Y Acad Sci. 2019 May;1444(1):22-34.
Supplements are marketed as safe, natural and health-promoting . . . .
81% believed premarketing proof of safety should be required
> 50% believe such regulations already existed
72% of patients would still use even if a negative government study exists
Blendon RJ, DesRoches CM, Benson JM, et al. Americans' views on the use and regulation of dietary supplements. Arch Intern Med 2001; 161:805.
. . . . But are they as safe as claimed?
Study of ER visits for supplement-related adverse events
Extrapolated 23,000 ER visits/year
Average age 32 years, women > men
9% hospitalized (16% were > 65 year-olds)
32% due to micronutrients (top 3: MVI, iron, calcium)
66% due to botanicals
25% Weight loss supplements (women > men)
10% Energy/bodybuilding (men > women)
3% each sexual enhancement, cardiovascular, sleep/sedation
Geller AI, et al. Emergency Department Visits for Adverse Events Related to Dietary Supplements. N Engl J Med. 2015 Oct 15;373(16):1531-40.
Regulation of dietary supplements
Federal Food, Drug and Cosmetics Act
1994 Dietary Supplement Health and Education Act (DSHEA)
Dietary supplements regulated like foods
Lower threshold of evidence for safety compared to drugs
2007: Good Manufacturing Practices (GMP)
Supplement manufacturers must be registered with the FDA to operate
FDA randomly audits manufacturers
Adulterant- and contaminant-free
Manufactured using specific standards for personnel and equipment
DSHEA labeling requirements
Labels must state: “this product is not intended to diagnose, treat, cure or prevent any disease”
Labels allowed to make health claims
“promotes colon health” or “supports brain function”
But not allowed to make specific health claims
Does this label meet DSHEA labeling requirements?
Clinically proven to reduce symptoms of menopause:
Night sweats/hot flashes*
Ideal for women who choose not to take estrogen
Alternative to HRT:
Can replace HRT for menopause symptom relief*
Does this label meet DSHEA labeling requirements?
A. Yes B. No C. Maybe
FDA oversight is limited
Manufacturers not required:
To prove efficacy, safety quality prior to marketing
To report postmarketing adverse events to the FDA
FDA receives reports of < 1% of all serious adverse events
Encourages the public and health care providers to report any suspected cases of significant toxicity to the FDA MedWatch Adverse Event Reporting System
GMP compliance is monitored and certified by third party organizations
Audit and testing of product ingredients and quality
Product safety and efficacy not tested
Does not assure that the product is safe for the condition it treats or appropriate for all patients
US Pharmacopeial Convention (USP)
National Sanitation Foundation (NSF) www.Info.nsf.org/certified/
Not for profit Not for profit For profit
Function Sets the most widely accepted
standards for supplements (and also pharmaceuticals
Audits production sites to ensure GMPs are followed
Tests and rates dietary supplements, vitamins and other health products
U.S. law USP standards are included in
many federal laws
NSF/ANSI 173: Dietary Supplements Manufacturers, brands >100 supplements, 12
Not all of a brand’s products are included
Many (>100) Many (>100)
Sample source Provided by the manufacturer Provided by the manufacturer
Purchased when a manufacturer requests testing
Cost to certify product or verify ingredients
Varies depending on ingredients;
$3000-$15,000 per product plus an additional audit fee of $15,000 and a label fee of 1 cent per bottle
$3000-$5000 per product, plus an audit fee of about
$3000-$5000 per product
Minimum quality criteria
Ingredients match what is on the label
Metals (arsenic, cadmium, chromium, mercury, lead)
Microbiological (yeast, mold, pathogens)
Industrial contaminants (PCBs, etc)
Known adulterants not present
Matches “free from” claims (like gluten)
Example: Heavy metal contamination
Lead in prenatal vitamins
No amount of lead is thought to be safe
FDA: 12.5 mcg/day
CA Prop 65: 0.5 mcg/day
FDA (2008): lead found in all 75 products tested
2016 Canadian study: 26 common PNV tested had 0.1 - 4.0 mcg/day (average 0.535 mcg/d)
Schwalfenberg G, Rodushkin I, Genuis SJ. Heavy metal contamination of prenatal vitamins. Toxicol Rep. 2018;5:390-395. Published 2018 Mar 6.
Recent testing of 3 prenatal vitamins:
#1: Correct amounts, no heavy metals and disintegrated properly
#2: Too little vitamin A, too much iron and iodine, and took 80 min to disintegrate
#3: 17.4% of listed vitamin A and 188% of listed iodine
Vitamin B-12 ranged from 100 to 3500% in different brands
DSHEA: Manufacturers are allowed to have non-GMP certifications
Less expensive than third-party independent testing
Should demonstrate adherence to good manufacturing practices, e.g.:
Precise equipment cleaning to avoid contamination
Documenting ingredient identity and purity
Additional quality testing
Certified Kosher vitamins and mushrooms
NSF Certified Gluten Free Vitamins made with
organic herbs and vegetables
Committed to non- GMO sourcing
“First-Party” seals do not prove safety or efficacy
Not required by FDA
Not based on testing or standards
Can be confusing
Created by manufacturers
To improve perception of high quality
To imitate legitimate third-party seals
May degrade the trust and value of legitimate seals like NSF and USP
Recommend patient-friendly, evidence-based online
resources about the risks and benefits of using supplements for women’s health concerns
Strategies to improve safety
Choose brands that have been independently tested, meet minimum quality criteria and have a seal of approval (verification mark)
“Verified” or “approved” are meaningless labels
This can be difficult and time-consuming for patients
One option: Since 2019, CVS only sells supplements that have had 3rdparty testing
USP, NSF, UL and Eurofins 41
Be skeptical of direct-to-consumer advertising
Promises of a quick fix, for example, "lose 10 pounds in one week.”
Use of the words "guaranteed" or "scientific breakthrough.”
Advertising on social media
Products marketed as herbal alternatives to an FDA-approved drug or as having effects similar to prescription drugs.
Popular marketing terms
(not recognized by FDA)
Any substance that may be considered a food or part of a food and provides medicinal or health benefits including the prevention and treatment of disease
Foods with added ingredients that may provide a health benefit beyond the traditional nutrients it contains
Health-protecting compounds from plant sources
Cosmetics with ingredients marketed to provide medicinal or health benefits including the prevention and treatment of disease
Patient (and physician)-friendly, credible online resources
Federal Trade Commission
Additional physician resources
NIH National Center for Complementary and Alternative Medicine https://nccih.nih.gov
Herblist App (free, lists >50 common herbs)
Drugs and Lactation Database
NIH Office of Dietary Supplements (ODS)
Evidence-based, current information for health professionals
List of dietary supplement fact sheets
Overview addressing effectiveness, safety and quality
Dietary supplement label
Physician-patient communication prior to starting a supplement
Government’s role in regulating dietary supplements
Your patient knows the brand of supplement she takes but not the dose or what is in it.
Your EMR does not recognize the brand.
Where can you find more information?
Dietary Supplement Label Database
Full label information as provided by manufacturer
Not verified to be accurate or compliant with FDA regulations
Not an endorsement or guarantee of accuracy by NIH
Finding Valid Information:
Example: Evening Primrose Oil
Several of your patients have told you that they have used evening primrose oil for hot flashes. Their opinions are mixed about whether it is helpful.
What’s your opinion?
Is there evidence that it works?
Is one brand superior to another?
National Center for Complementary and Integrative Health
Two internet subscription databases (there are more)
Institutional and personal subscriptions available
Uses Safety and
Insufficient evidence to
Product testing for quality concerns
Test results: approved or not approved
Description, indications, adverse effects, literature review
What to consider when buying/using any particular product
ConsumerLab: Results of product testing
Product name, serving size, and suggested daily dose
Amount claimed for specific ingredients per label’s daily serving
Test results Cost for daily suggested serving dose on label Other comments Overall results:
APPROVED or NOT APPROVED
Contained label amounts
Did not exceed contamination limits for lead, cadmium and
Product A EPO: 1300 mg
GLA: 110-130 mg Linoleic acid: 850-900 mg Oleic acid: 80-130 mg
APPROVED Yes Yes $0.24 (per 200 mg GLA)
Product B EPO: 130 mg
GLA: 130 mg Linoleic acid: 960 mg Oleic acid: 40 mg
NOT APPROVED Yes: GLA and linoleic acid No: > 110% of oleic acid than claimed
Yes $0.20 (per 200 mg GLA) Organic:
Identify the supplements commonly used by your
patient population and when to monitor appropriate labs and therapeutic response
Dietary supplements marketed for many conditions
Pregnancy and breastfeeding
Hair, skin and nails
Urinary tract infection
Premenstrual Syndrome (mild symptoms)
Most studied, all with low quality evidence
Cognitive behavioral therapy
Calcium (no more than 1200 mg total)
Chasteberry (Vitex agnus castus )
20-40 mg extract daily
Vitamins D, B-6, Evening primrose oil
Likely no better than placebo
Evening primrose oil
St. John’s Wort Hofmeister S, Bodden S. Premenstrual Syndrome and Premenstrual Dysphoric Disorder.
Am Fam Physician. 2016 Aug 1;94(3):236-40. PMID: 27479626.
Premenstrual Dysphoric Disorder
Cognitive behavioral therapy
Meta-analysis, low quality data: decreased symptoms of anxiety, depression; improved coping skills compared to other interventions
May be a useful adjunct to pharmacologic treatment
Many heterogeneous studies, insufficient evidence
Busse JW, et al. Psychological intervention for premenstrual syndrome: a meta-analysis of randomized controlled trials. Psychother Psychosom. 2009;78(1):6-15.
Low quality evidence
Probably no better than placebo
Evening primrose oil, vitamin E
Soy milk improved symptoms compared to cow’s milk
Ooi SL, Watts S, McClean R, Pak SC. Vitex Agnus-Castus for the Treatment of Cyclic Mastalgia: A Systematic Review and Meta-Analysis. J Womens Health (Larchmt). 2020 Feb;29(2):262-278.
No evidence of benefit or harm for any modality
Very limited evidence of benefit for
Vitamins E, B-1, B-6, D-3, fish oil supplements, ginger, magnesium
Lavender, clary sage and rose traditionally used for dysmenorrhea
Pattanittum P, et al. Dietary supplements for dysmenorrhoea. Cochrane Database of Systematic Reviews 2016, Issue 3. Art. No.: CD002124.
Galactagogues: few studies, insufficient evidence
Banana flower, fennel, fenugreek, ginger, ixbut, levant cotton, moringa, palm dates, pork knuckle, shatavari, silymarin, torbangun leaves or other natural mixtures)
Foong SC, Tan ML, Foong WC, Marasco LA, Ho JJ, Ong JH. Oral galactagogues (natural therapies or drugs) for increasing breast milk production in mothers of non-hospitalised term infants. Cochrane Database Syst Rev.
2020 May 18;5(5):CD011505.
Calcium and vitamin D:
Modest improvement in slowing bone loss in postmenopausal women
No effect on reducing fracture risk
Mixed results of benefit
Weak evidence for many others
Vitamin K, strontium, magnesium, boron, DHEA, black cohosh 63
Soy isoflavones and bone density
Osteoporosis Prevention Using Soy (OPUS) study
50% less effective than risedronate
Higher amounts of isoflavones (120 mg) were needed to maintain and/or increase bone density in postmenopausal women
1-2 years of treatment
Bone density in lower back and hip were not increased
Pawlowski JW, et al. Impact of equol-producing capacity and soy-isoflavone profiles of supplements on bone calcium retention in postmenopausal women: a randomized crossover trial. Am J Clin Nutr. 2015 Sep;102(3):695-703.
Many products, none with studies showing efficacy and safety
Botanical massage oils
“Warming” vaginal lubricants
Proprietary blend (Sage leaf, red raspberry leaf, kudzu root extract, red clover extract, capsicum pepper, licorice root, bayberry fruit, damiana leaf, valerian root, ginger root, black cohosh root)
Likely has both estrogenic and antiestrogenic effects 65
The story of Avlimil
2003 marketed to “boost sex drive, regularize menstruation and relieve menopausal hot flashes”
Advertised that one small study showed benefit for libido
but product studied had different ingredients than the commercial blend product
2006 The FTC charged the manufacturer for making false and unsubstantiated claims
2008 owner convicted for mail fraud
2012 $24 million class action lawsuit
Company went bankrupt, bought by landlord and renamed
Avlimil is still on the market…just for menopause symptoms
CAM used by 50 – 75% of postmenopausal women
89-100% of women find it be somewhat or very helpful
Women with history of breast cancer are 6x more likely to use soy-based products
Placebos reduce symptoms in 25 - 50% of patients
Nedrow A, Miller J, Walker M, Nygren P, Huffman LH, Nelson HD. Complementary and alternative therapies for the management of menopause-related symptoms: a systematic evidence review. Arch Intern Med. 2006 Jul 24;166(14):1453-65.
Mind-body modalities for menopause
Recommended by North American Menopause Society
Limited data acknowledged
A few randomized trials suggested ↓ perception of hot flashes
Modestly effective for insomnia with or without hot flashes
↓ hot flash severity but not frequency
Johnson A, Roberts L, Elkins G. Complementary and Alternative Medicine for Menopause. J Evid Based Integr Med. 2019;24:2515690X19829380.
Biofeedback, MBSR, and relaxation techniques
Limited evidence for stress reduction, improved quality of life with
Insufficient or no evidence:
Exercise, aromatherapy, reflexology, yoga
Popular for hot flashes
Evidence so far suggests no better than sham acupuncture
Both showed improvement at 6 months after treatment
Ee C, Xue C, Chondros P, Myers SP, French SD, Teede H, Pirotta M. Acupuncture for Menopausal Hot Flashes: A Randomized Trial. Ann Intern Med. 2016 Feb 2;164(3):146-54.
Dietary supplements for menopause
Some/mixed evidence of benefit (compared to placebo)
Phytoestrogens, black cohosh, progesterone cream
Not better than placebo
Wild yam, dong quai, maca, pollen extract, evening primrose oil, vitamin E, flaxseed, ginseng
St. John’s wort: (for associated depression)
Drug/herb interactions (warfarin, antidepressants, BCPs, some cancer drugs)
Valerian (for associated insomnia, anxiety depression)
No major safety concerns with short-term use; long-term use unknown
Richest source: soybeans and soy products; also red clover and kudzu
Soy best studied
Common in Asian diets
Most researched form of phytoestrogens
Richest source: flaxseed, unrefined grains, cereal brans and beans
Most common phytoestrogen in Western diets
Limited research, mixed evidence of efficacy
Alfalfa and clover sprouts, split peas, pinto and lima beans 71
Chen et al (2015) Meta-analysis and systematic review
No treatment effect on menopausal symptoms compared to placebo
Decreased frequency of hot flashes compared to placebo
Franco et al (2016) Meta-analysis of clinical trials
Generally suboptimal, heterogeneous evidence
Modest decrease in hot flashes and vaginal dryness but not night sweats
Composite and specific phytoestrogen supplements
Franco OH, Chowdhury R, Troup J, Voortman T, Kunutsor S, Kavousi M, Oliver-Williams C, Muka T. Use of Plant-Based Therapies and Menopausal Symptoms: A Systematic Review and Meta-analysis. JAMA. 2016 Jun 21;315(23):2554-63..
Chen MN, Lin CC, Liu CF. Efficacy of phytoestrogens for menopausal symptoms: a meta-analysis and systematic review. Climacteric. 2015 Apr;18(2):260-9.
Isoflavone forms vary in potency
Glycosidic isoflavones in food
→ converted by gut microflora to metabolically active aglycone isoflavones
→ 1/3 absorbed as free aglycones
→ 2/3 converted by gut microflora to active metabolites and absorbed
→ Genistein (most abundant)
→ Converted by gut microflora to equol (may have highest estrogen-agonist potency)
Not all people can metabolize dietary isoflavones
Only 30-60% of people have the specific gut bacteria to convert
Glycosidic isoflavones into aglycones, or
Aglycones into equol
Equol-containing supplements given to equol nonproducers appears to significantly lower the incidence and/or severity of hot flashes
Daily JW, Ko BS, Ryuk J, Liu M, Zhang W, Park S. Equol Decreases Hot Flashes in Postmenopausal Women: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. J Med Food. 2019 Feb;22(2):127-139.
Tips for buying isoflavone supplements
Ideal dosage not known
Amounts/ratios of isoflavones in supplements based on:
Intakes in countries where soy is a staple
The development of clinical endocrine effects in premenopausal women
Total soy isoflavones: 40-70 mg/day; or red clover 40 mg/day
> 15 mg genistein, and/or
> 28 mg daidzein
Soy in food
Food Serving mg isoflavones
Tofu yogurt ½ cup 21
Soy flour 100 g 150-200 mg
Soy protein concentrate 100 g 100 mg
Boiled soybeans ½ cup 56
Soy milk 1 cup 6.2
Soybean curd 3 oz 19
Meatless soy burger 1 patty 4.5
Miso ½ cup 57
Edamame ½ cup 16
Soy oils and soy lecithin are devoid of isoflavones
Soy isoflavones and breast cancer
Risk appears to depend on time of life when used, family history and estrogen receptor status
Asian women have lower incidence of breast cancer
Higher soy consumption early in life
2019 Cohort study, 76,000 French women > 50 yo
Soy isoflavone use overall not associated with risk of breast cancer
If current soy isoflavone use
36% ↑ risk if family history of breast cancer
50% ↓ risk of ER+ breast cancer in premenopausal/recently menopausal women
Touillaud M, et al.. Use of dietary supplements containing soy isoflavones and breast cancer risk among women aged >50 y: a prospective study. Am J Clin Nutr. 2019 Mar 1;109(3):597-605..
(Actaea racemosa or Cimicifuga racemosa)
Used mostly for menopausal symptoms
Historically used as a general “women’s” herb
ACOG (2015) clinical guidelines: “data do not show that” herbal dietary supplements like black cohosh “are efficacious for the treatment of vasomotor symptoms”
2016 systematic review and meta-analysis of RCTs
No reduction in VMS found in various formulations vs placebo
Unknown active ingredient(s) and mechanism of action
Raises estrogen levels? LH? FSH?
Brain-related action, eg, modulation of serotonergic pathways?
Antioxidant, anti-inflammatory, or SERM?
No evidence of
↑ risk of recurrence of ER+ breast cancer
Lack of long-term safety data
Recommend avoiding use in pregnancy, breastfeeding, women at high risk for or currently have breast cancer
Tips for buying black cohosh supplements
Make sure it is not BLUE cohosh
Available products vary considerably in chemical composition
Products often standardized to provide at least 1 mg triterpene glycosides per daily dose
Exception: Remifemin currently standardized to be equivalent to 40 mg black cohosh root/rhizome per daily dose of 2 tablets
Synthesized from chemicals in soy and Mexican yam
aka “bioidentical” or “natural” progesterone
Mexican yam neither contains nor can directly provide progesterone
Humans don’t produce the needed enzyme
Mixed evidence of efficacy for hot flashes
Skin absorption is much lower than therapeutic dose
Does not prevent bone loss or improve bone density
Does not lower the risk of endometrial cancer 81
Tips for buying progesterone cream
Concentration should be about 16-25 mg/gram of cream
20 mg of progesterone from cream applied daily to the skin (vary site daily)
Should be used with physician supervision even though little is absorbed
Caution: Risk of containing manufacturing by-products like androstenedione or other steroids (but not enough to be banned from Olympics)
Nearly 2,000 clinical research studies have been published
Multiple types of interactions with gut microbiota theorized
Affecting GI tract function
Interactions with other microbiota outside GI tract
Most popular probiotics: natural gut-dwelling gram-positive bacteria
Lactobacillus, Bifidobacterium, Streptococcus, Saccharomyces, Bacillus, and Enterococcus
Viability at time of purchase
Ability to colonize the gut
Aponte M, Murru N, Shoukat M. Therapeutic, Prophylactic, and Functional Use of Probiotics:
A Current Perspective. Front Microbiol. 2020 Sep 11;11:562048.
Probiotics for bacterial vaginosis
Used alone or in combination with antibiotics
To prevent recurrence or relapse
More research needed
Oral versus vaginal route, dose, duration
Senok AC, Verstraelen H, Temmerman M, Botta GA. Probiotics for the treatment of bacterial vaginosis. Cochrane Database Syst Rev 2009; :CD006289.
BV: what’s the latest?
Combo treatment probiotics + antibiotics more effective than either alone
Unclear efficacy due to quality and heterogeneity of the trials
Vaginal microbiome transplantation
To reconstitute vaginal flora towards a Lactobacillus-dominated vaginal microbiome
For intractable recurrent BV or UTIs
Li C, Wang et al. Probiotics for the treatment of women with bacterial vaginosis: A systematic review and meta-analysis of randomized clinical trials. Eur J Pharmacol. 2019 Dec 1;864:172660
Lev-Sagie A, et al. Vaginal microbiome transplantation in women with intractable bacterial vaginosis.
Nat Med. 2019 Oct;25(10):1500-1504.
Probiotics for UTIs
Vagina may serve as a reservoir in transfer of intestinal uropathogens to the intestinal tract
Vaginal probiotics: ↓ UTI recurrence compared to placebo
Lactobacillus group compared to antibiotic group:
Shorter interval/more frequent recurrences
Lower development of antibiotic resistance
Beerepoot MA,et al. Lactobacilli vs antibiotics to prevent urinary tract infections: a randomized, double-blind, noninferiority trial in postmenopausal women. Arch Intern Med. 2012 May 14;172(9):704-12.
Stapleton AE, et al. . Randomized, placebo-controlled phase 2 trial of a Lactobacillus crispatus probiotic given intravaginally for prevention of recurrent urinary tract infection. Clin Infect Dis. 2011 May;52(10):1212-7.
Probiotics for vulvovaginal candidiasis
FPIN Clinical Inquiries (2020)
Short-term cure rates ↑ 14%
One-month relapse rates ↓ 66%
Long term recurrent VVC rates may improve over 3-6 months
2019 RCT: Recurrent VVC, new acute episode
Topical clotrimazole + oral probiotic (Lactobacillus + lactoferrin),
Probiotic continued 8 days beyond antifungal
2 caps/day probiotics x 5 days, then 1 cap/day x 10 days monthly
Conclusion: ↓ symptoms and recurrence rates
Russo R, Superti F, Karadja E, De Seta F. Randomised clinical trial in women with Recurrent Vulvovaginal Candidiasis: Efficacy of probiotics and lactoferrin as maintenance treatment. Mycoses. 2019 Apr;62(4):328-335.
Cranberry for UTIs
In vitro findings not reproduced in vivo
Insufficient evidence for prevention of recurrent simple cystitis
Ineffective for treatment of existing UTI
Optimal dose/duration/formulation not known
Probably no harm other than increased calorie and glucose intake
Jepson RG, Williams G, Craig JC. Cranberries for preventing urinary tract infections. Cochrane Database Syst Rev 2012; 10:CD001321.
July 2020: FDA allowed qualified health claims for certain cranberry juice products and UTIs
Qualified Health Claims (QHCs): scientific evidence supporting a claim is
“limited and inconsistent” but doesn’t meet standards for “significant scientific agreement”.
“Consuming one serving (8 oz) each day of a cranberry juice beverage may help reduce the risk of recurrent urinary tract infection (UTI) in healthy women. FDA has concluded that there is limited
scientific evidence supporting this claim.”
“Consuming 500 mg each day of cranberry dietary supplement may help reduce the risk of recurrent urinary tract infection (UTI) in healthy women. FDA has concluded that there is limited scientific
evidence supporting this claim.”
“Estrogen Dominance” (ED):
a new diagnosis, or a new marketing concept?
Too much estrogen compared to progesterone due to inadequate estrogen elimination and/or too much exogenous estrogens
Hot flashes, night sweats, mood swings, irritability, insomnia, foggy thinking, fatigue, weight gain, decreased libido, PMS, irregular periods, hair loss, bloating, tender lumpy breasts, endometriosis, thyroid nodules, cellulite, infertility, anovulation, estrogenic cancers . . .
Treatment: diet and supplements
DIM (diindolylmethane): Claimed to balance estrogen metabolites
Very limited studies with low quality evidence: alters estrogen urinary metabolite profiles in women and has androgen-antagonistic effects
Best Practice Recommendations
1. Just ask.
2. Educate your patients about the potential for harm from excessive micronutrient intake, considering the total amount from combined diet and supplements.
3. Know when to monitor labs and therapeutic response for the supplements commonly used by your patient population.
4. Educate yourself and your patients about how to access reliable on-line resources to assess the risks and benefits of using supplements.
1. A 2. E 3. B