• No results found

Complementary and Alternative Medicine for Women


Academic year: 2021

Share "Complementary and Alternative Medicine for Women"


Full text


Complementary and Alternative Medicine for Women

Lisa G Soldat, MD, MS, FAAFP

Activity Disclaimer

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.

The AAFP disclaims any and all liability for injury or other damages resulting to any individual using this material and for all claims that might arise out of the use of the techniques demonstrated therein by such individuals, whether these claims shall be asserted by a physician or any other person.

Physicians may care to check specific details such as drug doses and contraindications, etc., in standard sources prior to clinical application. This material might contain recommendations/guidelines developed by other organizations. Please note that although these guidelines might be included, this does not necessarily imply the endorsement by the AAFP.



Disclosure Statement

It is the policy of the AAFP that all individuals in a position to control content disclose any relationships with commercial interests upon

nomination/invitation of participation. Disclosure documents are reviewed for potential conflicts of interest. If conflicts are identified, they are

resolved prior to confirmation of participation. Only participants who have no conflict of interest or who agree to an identified resolution process prior to their participation were involved in this CME activity.

All individuals in a position to control content for this session have indicated they have no relevant financial relationships to disclose.

Learning Objectives

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.



CAM includes

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.

Botanical supplements:

A difference in philosophy

Traditional Chinese Medicine Western Interpretation

https://c1.staticflickr.com/1/171/419584946_2f37026552_z.jpg?zz=1 https://upload.wikimedia.org/wikipedia/commons/8/87/Chinese_traditional_medicine.jpg



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

39% multivitamins

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

9% botanicals

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

Direct-to-consumer advertising

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

Black cohosh

Treatment for 4 weeks before significant improvement in sx

Recommend no longer than one year of use 15


Drug-supplement interactions

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.

AES Question



Question 1

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



AES Question

Question 2

Taking more than the upper tolerable intake level (UL) of which of the following could potentially be harmful in pregnancy?

A. Iron

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 . . . .

National surveys

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

Proper labeling

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

AES Question



Does this label meet DSHEA labeling requirements?


Clinically proven to reduce symptoms of menopause:

Night sweats/hot flashes*

Occasional sleepiness*

Dry skin*

Mood swings/irritability*

Vaginal dryness*

Naturally estrogen-free:

Ideal for women who choose not to take estrogen

Alternative to HRT:

Can replace HRT for menopause symptom relief*

Question 3

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

https://www.fda.gov/safety/medwatch-fda-safety-information-and-adverse-event- reporting-program/reporting-serious-problems-fda

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/


ConsumerLab www.consumerlab.org

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

Free from:


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

Recommended limits

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.

ConsumerLab testing

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

Functional foods

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

NIH MedLinePlus






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)

Natural Medicines


Institutional and personal subscriptions available


Consumer Lab




Home page

Uses Safety and


Insufficient evidence to


Drug Interactions

Interactions Lab

Natural Medicines




Product testing for quality concerns

Product ingredients

Test results: approved or not approved

Encyclopedia articles

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:


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)

$21.50 (softgels)

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:

$11.80 (softgels)



Identify the supplements commonly used by your

patient population and when to monitor appropriate labs and therapeutic response

Dietary supplements marketed for many conditions



Immune support


Pregnancy and breastfeeding

Hair, skin and nails

Sexual problems




Bacterial vaginosis

Vulvovaginal candidiasis

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

Mixed evidence

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.



Cyclic mastalgia

Low quality evidence


Probably no better than placebo

Evening primrose oil, vitamin E

Insufficient evidence


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

Insufficient evidence:


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.


Good evidence

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

Dietary supplements


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

Insufficient evidence

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


Soy isoflavones

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)

→ Daidzein

→ 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..



Black cohosh

(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

Black cohosh

 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

Liver toxicity

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

Progesterone cream

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

Quality concerns:

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

Lactobacillus strains

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?

2019 meta-analysis:

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

Oral probiotics:

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

Induction phase:

Topical clotrimazole + oral probiotic (Lactobacillus + lactoferrin),

Probiotic continued 8 days beyond antifungal

Maintenance phase:

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





Related documents

During the calibration, the local atomic oxygen number flux density at the sensor position is evaluated based on mass spectrometer data and the measured total mass flow rate within

A sprint kayaking specific deterministic model was used to identify key performance related technique factors using data from 12 international-level kayakers.. There

Given that the beta HPV types are also abundantly present in the skin of the general population, epidemiological studies aiming to evaluate the role of cutaneous HPV infection in

We also consider a class of nonconvex Wiener-Hopf equations and establish the equivalence between the regularized nonconvex variational inequalities and the fixed point problems as

Drones as you know are literally named as Unmanned Aerial Vehicles which are produced by foreign companies, also need systematic and technological

Keywords: interethnic relations, migration, ethnic community, integrative image, interethnic tension, regional level, civil identity, supraethnic image, ethnic barriers,

Method: Jurkat cells were incubated with 30 to 1500 μ g/mL concentrations of 50% ethanolic extract of dry fenugreek seeds and were followed for changes in viability (trypan blue

When authors investigated the diversity of the microbiome in the four major types of breast cancer (endocrine receptor (ER) positive, triple positive, HER2+ positive and triple

The court stated, &#34;We are unable to accept the premise that recovery for inter- ference with the use of land should depend on anything as irrelevant as whether the wing

This study of visitors’ narrative stems from a larger empirical work that aimed at investigating the learning outcomes of the adult members of family groups visiting

The thin-dashed vertical lines (second panel) emphasize the high frequency wave with T=2.5 min. The three thick-dashed vertical lines mark the occurrence times of pressure pulses

• Increasing positive Joule parameter significantly increases nanofluid temperature, reduces nano-particle volume fraction (concentration), accelerates the axial flow, boosts the

Metformin for prevention of hypertensive disorders of pregnancy in women with gestational diabetes or obesity: systematic review and meta-analysis of randomized

Boiling increases fat losses and has significant effect (p&lt;0.05) on the results obtained when compared between unprocessed and processed meat samples, but the rate of fat loss

There is little need to emphasize the key role of com- puters and chemical engineering software (CES) for the petroleum industry and chemical engineering related topics.

A single crystal of the compound was grown by keeping the compound under a cold nitrogen gas stream (Oxford Cryostream 600) at 180 K and slowly moving a small liquid zone, created by

In our present study, we found that the LSD1 expression level as well as tumor size, tumor stage could predict patients’ survival by using the log-rank survival analysis,

2 Joint lexical and syntactic analysis The system by Constant and Nivre (2016) is based on a factorized lexical and syntactic representa- tion, that consists of a graph over

below). The levels of surface contamination were investi- gated using XPS, while SEM was used to characterise the surface topography both before and after cleaning. We found that

It is intended that the module will support critical and analytical analysis of evidence and at the end of the module students will have an understanding of toxicology and

Several factors responsible for the poor clinical outcomes observed in TNBC, including age, race, grade, tumor size, lymph node status, and distant metastasis, have been

Double-stranded, terminal restriction fragments containing one parental and one labeled nascent strand bound to BND-cellulose because of a protein associated with them.