bhide bioidentical hormone replacement therapy and evidence based treatment of menopausal symptoms

Compounded Bioidentical Hormone Therapy

Vandana Y. Bhide, MD

Instructor, Division of Hospital Internal MedicineBoard Certified, Internal Medicine, Pediatrics Diplomate, American Board of Integrative and Holistic Medicine (Non-ABMS)

Disclosures• American Medical Seminars-CME lectures (No

pharmaceutical funding)

• Will discuss non-FDA approved compounded estrogen, progesterone, testosterone products, including estriol (investigational new drug)

• Non-FDA approved dietary supplements and botanicals

Objectives• Distinguish the risks and

benefits of bioidentical hormones

• Analyze herbal agents and dietary supplements used for vasomotor and other menopausal symptoms

62 YO asymptomatic female requests “bioidentical” hormones as anti-aging treatment to

A. Conjugated equine estrogen alone to reduce risk of breast cancer

B. Bi-est 3.0 and topical progesterone cream

C. Avoid bioidentical hormones

D. Tri-est and compounded oral micronized progesterone

E. Estradiol patch and micronized progesterone

Audience Response Question 1

promote rejuvenation, longevity, maintain mental alertness, improve bone density. She does not want “synthetic” hormones or patches. She has intact uterus. You advise

52 YO female with peanut allergy requests treatment of vasomotor symptoms and genitourinary syndrome of menopause. You recommend


A. Estradiol patch and conventional oral micronized progesterone

B. Estradiol patch and compounded progesterone cream

C. Estradiol patch and compounded oral micronized progesterone

D. Avoid postmenopausal hormone replacement

E. Soy sauce, yam flavored frozen yogurt, reruns of “Three’s Company”

Bioidentical Hormone Replacement

• Compounds that have the same chemical and molecular structure as hormones that are produced in the human body (National Menopause Society, Endocrine Society)

• Extracted from plantsSanten, RJ et.al. Postmenopausal hormone therapy: an Endocrine Society scientific statement.

J Clin Endocrinol Metab. 2010 Jul; 95(7 Suppl 1):s1-s66.

• Bioidentical hormone therapy recognized by FDA, Endocrine Society as a marketing term

• Not necessarily based on scientific evidenceRosenthal MS. The Wiley Protocol: an analysis of ethical issues. Menopause 2008;15:1014–22.

Compounded Bioidentical Hormone Therapy (CBHT)

• Up to 2.5 million women use CBHT

• In response to concerns about risks of PMHRT in WHI/HERS/PEPI/Million Women studies

• Many women think CBHT safe because “natural”

• Bioidentical does not mean naturalSood, Richa et.al. Counseling Postmenopausal Women about Bioidentical Hormones: Ten Discussion

Points for Practicing Physicians. J Am Board Fam Med 2011;24:202–210.

• Custom compounded by pharmacy health care provider’s prescription

Recommend Against CBHT•North American Menopause Society•American Congress Obstetricians and Gynecologists•American Society Reproductive Medicine•Endocrine Society•American Association of Clinical Endocrinologists•Women's Health Practice and Research Network of the American College of Clinical Pharmacy•U.S. Food and Drug Administration

Human Estrogens• Estrone (E1) -highest concentration in

menopause• Adipose tissue-converts estrone to estradiol• Adrenal hormone androstenedione converted to

estrone

• 17β-estradiol (E2) • Most active biologically• Ovarian follicle/corpus luteum

• Estriol (E3)-16α-hydroxylation of estrone and estradiol

• Placenta• Low levels outside of pregnancy• Not converted to estradiol• Short half life, least potent

Progesterone

• Formed as cholesterol is converted to estrogen and androgens

• Secreted by ovary

• Production stops after menopause

Pattimakiel, Lynn and Thacker, Holly L. Bioidentical hormone therapy: Clarifying the misconceptions. Cleve Clin J Med 2011 Dec;78(12):829-836.

• Before menopause, made in ovary, adrenal cortex

• Peripheral conversion androstenedione and dehydroepiandrosterone (DHEA) to testosterone

• Androgen levels decline over time, unaffected by menopause

Pattimakiel, Lynn and Thacker, Holly L. Bioidentical hormone therapy: Clarifying the misconceptions. Cleve Clin J Med 2011 Dec;78(12):829-836.

Testosterone

Hormone/Steroid Classes

• Class A- Found in nature• Conjugated equine estrogens (sulfate

esters)

• 50% estrone sulfate

• 50% estrogens native only to horses

• Extracted from pregnant mare's urine

Bhavnani, Bhagu R. and Stanczyk, Frank Z., Misconception and Concerns about Bioidentical Hormones Used for Custom-Compounded Hormone Therapy. The Journal of Clinical Endocrinology and Metabolism. Dec 2011. 97 (3).

Hormone/Steroid Classes• Class B-native to the body

• Chemically synthesized from plant sources

• Mexican yam (Dioscorea villosa), soybean• Sterols diosgenin and stigmasterol

• Mexican yam converted to progesterone, dehydroepiandrosterone, androstenedione, testosterone

• Soy converted to estradiol, estrone, estriol, synthetic conjugated estrogens


Hormone/Steroid Classes

• Class B-native to the body

• Humans lack enzymes to convert diosgenin and stigmasterol to estrogens/progestins/androgens

• No hormones are extracted intact from plant source

• Chemical synthesis of 17β estradiol from diosgenin requires at least 15 reactions


Compounded Bioidentical Hormones

• Amount of hormone extracted depends on chemical process/alcohol used for extraction

• Actual amount of hormone may be variable

• All compounded bioidentical hormones are manmade

Non Bioidentical Hormones

• Conjugated equine estrogen (CEE)• Equilin sulfate (mares) • Estrone sulfate• Extracted from urine pregnant mares

• Ethinyl estradiol used in combined oral contraceptives

• Medroxyprogesterone

FDA approved Bioidentical Hormones

• 17β-estradiol• Oral• Transdermal patch

• Transdermal bypasses hepatic metabolism• Results in estrone:estradiol ratio of 1:1• Similar to pre-menopausal levels

• Vaginal ring• Creams and gels

• Progesterone (oral)• Brand name progesterone is micronized in peanut oil Files, Julia A. et.al. Bioidentical Hormone Therapy Mayo Clin Proc. 2011 Jul; 86(7): 673–680.

Advantages of Compounded Hormones

• FDA-approved progesterone micronized in peanut oil.

• Compounded progesterone can eliminate peanut oil• Cellulose or olive oil

• Dosage and component flexibility

• Low-dose formulations

• Possible reduced cost • Separate co-pays for estrogen patch/micronized

progesterone

• Highly individualized prescriptionsCommittee on Gynecologic Practice and the American Society for Reproductive Medicine Practice

Committee, Compounded Bioidentical Menopausal Hormone Therapy. No 532, August 2012 (Reaffirmed 2014). Obstet Gynecol 2012;120:411–5.

Compounded Hormones

• Estrogens • 17β-estradiol, estrone, estriol

• Progesterone • 100-200 mg/day

• Testosterone • 2–10 mg once/day

• Dehydroepiandrosterone (DHEA)

• Pregnenolone

CBHT Delivery

• Troches (lozenges) for buccal administration

• Vaginal suppositories

• Creams, gels, lotions

• Sublingual tablets

• Subdermal implantsACOG Committee on Gynecologic Practice and theAmerican Society for Reproductive Medicine Practice Committee. Number 532, August 2012. (Reaffirmed 2014).

Bi-est Estriol: Estradiol 80%:20% or 90%:10%

• Bi-est 2.0• 1.6 mg estriol and 0.4 mg estradiol

• Bi-est 2.5 • 2.0 mg estriol and 0.5 mg estradiol

• Bi-est 3.0• 2.4 mg estriol and 0.6 mg estradiol

• Absorption of Bi-est not as consistent as estradiol patch

Sood R, Warndahl RA, et al. Bioidentical compounded hormones: A pharmacokinetic evaluation in a randomized clinical trial. Maturitas 2013;74:375.–382.

Tri-est

• Estriol:Estrone:Estradiol

• 80%:10%:10% (8:1:1 ratio)

• 1.25-2.5 mg/day

Davis, Ruth et.al. Risks and Effectiveness of Compounded Bioidentical Hormone Therapy: A Case Series. J of Women’s Health. 23 (8) 2014.

Estrogen Receptors

• α receptor activation responsible for proliferative effects of estrogens

• Ovary, endometrium, breast cancer cells

• β receptor activation balances α-receptor effects

• Endothelial cells, bone, kidney, lung

Files, Julia A. et.al. Bioidentical Hormone Therapy Mayo Clin Proc. 2011 Jul; 86(7): 673–680.

Estrogen Receptors

• Estrone –mostly binds to to estrogen receptor α

• 17β-estradiol -binds to estrogen α and β receptors

• Estriol -weak binding to estrogen receptor α and β

Estriol• Safety of estriol unknown

• Estriol may stimulate breast cancer cellsLippert C, Seeger H, Mueck AO.The effect of endogenous estradiol metabolites on the

proliferation of human breast cancer cells. Life Sci. 2003 Jan 10;72(8):877-83.

• Protection against breast cancer unprovenMcBane, Sarah E. et.al. Use of Compounded Bioidentical Hormone Therapy in Menopausal

Women: An Opinion Statement of the Women's Health Practice and Research Network of the American College of Clinical Pharmacy. 34 (4); 410–423, April 2014.

• Estriol not approved by FDA• FDA: “Pharmacies should not compound drugs

containing estriol unless the prescriber has a valid investigational new drug (IND) application.”

US Department of Health & Human Services, Food and Drug Administration. Transcript of FDA press conference on FDA actions on bio-identical hormones. http://www.fda.gov/downloads/NewsEvents/Newsroom/MediaTranscripts/ucm122174

Estrogen-Testosterone Therapy & Breast Cancer Risk in Natural Menopause

• 2.5 X in current users of estrogen plus testosterone vs women who never used HT

• Significantly higher compared to estrogen-only therapy (P=0.007)

• Slightly more than estrogen and progesterone therapy (P = 0.11)

• HT with testosterone-17.2% increased risk of breast cancer per year of use

Tamimi, RM, et al . Combined Estrogen and Testosterone Use and Risk of Breast Cancer in Postmenopausal Women. Archives of Internal Medicine 2006,166:1483-1489.

Salivary Hormone Levels• Anti-Aging doctors-urine/serum hormone

levels unreliable because measure protein bound, biologically inactive hormone

• Free hormone moves freely into salivary glands and represents ultrafiltrate of serum

• Salivary levels are not reliable Schmidt, Peter. The 2012 Hormone Therapy Position Statement of The North American Menopause Society. Menopause. 2012 Mar; 19(3): 257–271.

• Saliva samples do not remain stable in storage• Interassay test results can be variable• Affected by diet, time of dayHodis HN, Mack WJ. Postmenopausal hormone therapy in clinical

perspective. Menopause 2007; 14:944–957.

• Dose on symptom relief rather than estrogen/ progesterone/testosterone levels

Controversial-Progesterone Transdermal creams and gels• Salivary and capillary levels high but serum levels

remain low

• Do serum or salivary levels represent tissue levels?

• Progesterone cream does not achieve serum levels to prevent endometrial proliferation

Du, J.Y., Sanchez, P., Kim, L., Azen, C.G., Zava, D.T., and Stanczyk, F.Z.Percutaneous progesterone delivery via cream or gel application in postmenopausal women: a randomized cross-over study of progesterone levels in serum whole blood saliva capillary blood. Menopause. 2013; 20: 1107–1226.

Regulation Compounded Hormones

• Dietary Supplement Health and Education Act of 1994 (DSHEA)

• Compounded hormones considered to be supplements

• Dietary supplements are not required to prove safety or efficacy

• Cannot claim treatment or curative properties

• Compounded pharmacies regulated by state boards of pharmacy

Labeling Hormones

• FDA requires Black Box warning on conventional hormones based on WHI concerns

• Compounded preparations are not regulated by FDA and have no official package insert

• Exempt from Black Box warning that hormones may lead to serious injury or death

• Pharmacies are not required to report adverse events

FDA Testing Internet Bioidentical Hormones • 29 compounded drugs from 12 compounding

pharmacies

• 10 products (34%) failed quality test

• 9 products (one of which was progesterone) contained less active ingredient than indicated

U.S. Food and Drug Administration. Report: limited FDA survey of compounded drug products. Silver Spring (MD): FDA; 2009. http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/PharmacyCompounding/ucm155725.htm

Summary Compounded HRT• Not FDA approved

• Treat symptomatic menopausal women

• Use lowest possible dose for shortest durationGoodman NF, Cobin RH, Ginzburg SB, Katz IA, Woode DE. American Association of Clinical

Endocrinologists Medical Guidelines for Clinical Practice for the diagnosis and treatment of menopause: executive summary of recommendations. Endocr Pract 2011;17:1–25.

• FDA approved bioidentical estradiol and progesterone available

• Longterm safety estriol unknown

• Avoid progesterone cream and testosterone

• Compounded micronized progesterone for peanut allergic patients

62 YO asymptomatic female requests “bioidentical” hormones as “anti-aging” treatment to

A. Conjugated equine estrogen alone to reduce risk of breast cancer

B. Bi-est 3.0 and topical progesterone cream

C. Avoid bioidentical hormones

D. Tri-est and compounded oral micronized progesterone

E. Estradiol patch and micronized progesterone


promote rejuvenation, longevity, maintain mental alertness, improve bone density. She does not want “synthetic” hormones or patches. She has intact uterus. You advise

52 YO female with peanut allergy requests treatment of vasomotor symptoms and genitourinary syndrome of menopause. You recommend


A. Estradiol patch and conventional oral micronized progesterone

B. Estradiol patch and compounded progesterone cream

C. Estradiol patch and compounded oral micronized progesterone

D. Avoid postmenopausal hormone replacement

E. Soy sauce, yam flavored frozen yogurt, reruns of “Three’s Company”

Vandana Y. Bhide, M.D.

Beyond Hot Flashes:Botanicals for

Menopausal Symptoms

52 YO female with hypertension requests “herbal” non-hormonal approach to menopausal symptoms including vasomotor symptoms, mood changes, anxiety, and insomnia. What evidence based regimen could you suggest?

A. Trial of meditation, Black Cohosh, valerianB. Avoid soy isoflavanes in patient with history of breast cancerC. Inform patient of the risk of hepatotoxicity with kava kavaD. Inform patient of medication interactions with St. John’s WortF. All of the above

1994 Dietary Supplement Health and Education Act (DSHEA)

• Products containing dietary ingredient, including vitamins, minerals, amino acids, animal extracts, probiotics, enzymes, herbs or other botanicals

• Not required to undergo FDA review for safety and effectiveness

• Cannot claim to diagnose, treat, cure or prevent any disease

Difficult to Prove-Efficacy of Botanicals

Mind-Body Therapies Menopausal Symptoms

• 2010 – met-analysis 21 studies

• Meditation, yoga, tai chi

• Reduced frequency and intensity of hot flashes, mood and sleep changes, stress symptoms, muscle/joint pain

Innes KE, Selfe TK, Vishnu A. Mind-Body therapies for menopausal symptoms: a systematic review. Maturitas. 2010;66(2):135–149.

NIH National Center for Complementary and Alternative Medicine. https://nccih.nih.gov/health/menopause/menopausesymptoms?nav=gsa

Vasomotor Symptoms- Potential Serotonergic Botanicals

• Black Cohosh

• Kudzu (vine-legume Pueraria labata)

• Kava Kava-hepatotoxicity

• Dong Quai-increased INR with warfarin

• Licorice-hypokalemia, interacts with spironolactone

Bunchorntavakul, C. and Reddy, K. R. (2013), Review article: herbal and dietary supplement hepatotoxicity. Alimentary Pharmacology & Therapeutics, 37: 3–17.

Vasomotor Symptoms- Potential Phytoestrogens

• Soy

• Red clover

• Kudzu

• Mexican yam

• Chasteberry

• Licorice

• Rhubarb

• Hops

• Phytoestrogens-weak estrogen agonists, partial agonists, or antagonists to endogenous estrogens

• Bind estrogen β receptor• ? Add progesterone for

endometrial protection • Avoid in women with or at

risk for breast, uterine, or ovarian cancer

Hajirahimkhan, Atieh et.al. Botanical Modulation of Menopausal Symptoms: Mechanisms of Action? Planta Med 2013; 79(07): 538-553.

Vasomotor Symptoms- Potential Progesterone-like Herbs

• Red clover

• Chasteberry

• Mexican yam

• Hops

Black Cohosh (Actaea racemosa and Cimicifuga racemosa)- Buttercup family

• Roots and rhizomes (underground stems)

• Extracts are standardized to 26 deoxyactein content (chemicals called saponins)

• Usual dose 20 mg tablet bid

• Vasomotor symptoms-conflicting results

• Rare reports liver damage/failure

• No known drug-drug interactions

Soy (pea plant)

• Soy protein 20-60 gm (34-80 mg isoflavones) daily • Studes mixed results• Modestly decreased frequency and severity of hot

flashes • Moderate strength of evidence improved anxiety

symptoms: 7 trials, n=853Grant MD, Marbella A, Wang AT, Pines E, Hoag J, Bonnell C, Ziegler KM, Aronson N. Menopausal

Symptoms: Comparative Effectiveness Review No. 147. (Prepared by Blue Cross and Blue Shield Association Technology Evaluation Center Evidence-based Practice Center under Contract No.290-2007-10058-I.) AHRQ Publication No. 15-EHC005-EF. Rockville, MD: Agency for Health care Research and Quality; March 2015. www.effectivehealthcare.ahrq.gov/reports/final.cfm.

Soy Isoflavones-daidzein, genistein, glycitein• Isoflavones bind estrogen receptor (ER) β- act as

selective estrogen receptor modulators (SERMs)

• Daidzein-isoflavone found in soy

• 75% of western women, 50% of Asians do not have intestinal bacteria that convert daidzein into the active metabolite S-(−)equol

• S-Equol, daidzein, genistein extracts may be more beneficial than soy

• Soy intake prior to puberty may be protective of breast cancer

Clarkson TB, Utian WH, Barnes S, et al. for the NAMS Isoflavone Translational Symposium Panel. The role of soyisoflavones in menopausal health: report of The North American Menopause Society/Wulf H. Utian Translational Science Symposium in Chicago, IL. (October, 2010). Menopause 2011; 18: 732–753.

SE5-OH- Soy Isoflavane (Phytoestrogen)• 126 equol non-producing postmenopausal

Japanese women 10mg/day S-(−)equol or placebo for 12 weeks

• Soy germ with a strain of equol-producing Lactococcus bacteria (generally recognized as safe) (GRAS).

• Soy Isoflavane daidzein broken down into S-(−)equol • Only 30% to 50% Western women have lactic acid

secreting bacteria to convert daidzein to equol

• p=0.009 reduction in hot flashes and neck or shoulder muscle stiffness

• Avoid soy/daidzein supplements in breast cancerTakeshi Aso, Shigeto Uchiyama, Yasuhiro Matsumura, Makoto Taguchi, Masahiro Nozaki, Kiyoshi

Takamatsu, Bunpei Ishizuka, Toshiro Kubota, Hideki Mizunuma, and Hiroaki Ohta. Journal of Women's Health. January 2012, 21(1): 92-100.

• Isoflavones require P450-metabolism to form active phytoestrogens daidzein and genistein

• NCCAM RCT-black cohosh vs red clover vs HRT vs placebo

• No better than placebo, not as effective as HRTGeller SE, Shulman LP, van Breemen RB, et al. Safety and efficacy of black cohosh and red clover for the management of vasomotor symptoms: a randomized controlled trial. Menopause. 2009;16(6):1156–1166

• Cochrane Review- no improvement with Promensil (red clover extract) but extracts with high (> 30 mg/d) levels of genistein consistently reduced hot flashes

Lethaby Anne et.al. Phytoestrogens for menopausal vasomotor symptoms. The Cochrane Library. 10 Dec. 2013.

Red clover (Trifolium pretense)-legume

Diascorea alata (Purple Yam)

• 50 Taiwanese menopausal women two sachets Diascorea extracts or placebo X 12 months

• Improvement in all Greene Climacteric Scale symptoms except sexual function

• Most improvement in “insomnia,” “feeling tense or nervous,” “excitable,” “musculoskeletal pain”

Hsu, CC et.al. The assessment of efficacy of Diascorea alata for menopausal symptom treatment in Taiwanese women. Climacteric. 2011 Feb;14(1):132-9.

Grant MD, et.al. Menopausal Symptoms: Comparative Effectiveness Review No. 147. (Prepared by Blue Cross and Blue Shield Association Technology Evaluation Center Evidence-based Practice Center under Contract No.290-2007-10058-I.) AHRQ Publication No. 15-EHC005-EF. Rockville, MD: Agency for Health care Research and Quality; March 2015. www.effectivehealthcare.ahrq.gov/reports/final.cfm.

St. John’s Wort

• Effective short term treatment mild to moderate depression

• Interacts with multiple medications via P450 system in liver

• 301 German menopausal women vs placebo X 16 wks

• St. John's wort and black cohosh combination effective for hot flashes and psychological symptoms

Uebelhack, Ralf et. al. Black Cohosh and St. John’s Wort for Climacteric Complaints: A Randomized Trial. Obstetrics & Gynecology. Feb. 2006. 107 (2) 247-255

French Maritime Pine (Pinus pinaster)

• Polyphenols (antioxidants found in vegetables)

• 155 menopausal Taiwanese women

• 100 mg Pycnogenol or placebo BID X 6 months

• Women’s Health Questionnaire (somatic, depressed, vasomotor, memory, attractiveness, anxiety, sexual, sleep, menstrual problems)

• Superior to placebo p<0.01 to p<0.001 for each

• HDL increased/LDL decreased significantlyYang, Han-Ming et.al. A randomised, double-blind, placebo-controlled trial on the effect of Pycnogenol on

the climacteric syndrome in peri-menopausal women. Acta Obstetricia et Gynecologica. 2007; 86: 978-985)

Grant MD, Marbella A, Wang AT, Pines E, Hoag J, Bonnell C, Ziegler KM, Aronson N. Menopausal Symptoms: Comparative Effectiveness Review No. 147. (Prepared by Blue Cross and Blue Shield Association Technology Evaluation Center Evidence-based Practice Center under Contract No.290-2007-10058-I.) AHRQ Publication No. 15-EHC005-EF. Rockville, MD: Agency for Health care Research and Quality; March 2015. www.effectivehealthcare.ahrq.gov/reports/final.cfm.

Proprietary combination of evening primrose oil, damiana, ginseng, royal jelly (Lady 4)

• 120 Egyptian women

• Menopause Rating Scale II (MRS-II)

• 86.7% vs 56.7% “much or very much improved” vs placebo p < 0.001

Yakoot, M, Salem A, Omar AM. Effectiveness of a herbal formula in women with menopausal syndrome. Forsch Komplementmed. 2011;18(5):264-8. Epub 2011 Oct 10.

Natural Medicines Comprehensive Database. http://naturaldatabase.therapeuticresearch.com/ nd/Search.aspx?cs=MAYO&s=ND&pt=9&Product=menopause&btnSearch.x=6&btnSearch.y=9

• Avoid if highly bee allergic

Standardized extracts of black cohosh, dong quai, milk thistle, red clover, American ginseng, chaste-tree berry

• 50 Israeli women peri/menopausal

• Phyto-Female or placebo X 3 months

• 47% vs 19% placebo-eliminated hot flashes

• 73% decrease in hot flashes, 69% reduction of night sweats, improved sleep quality

• No liver test or estradiol/FSH level changes

• No change transvaginal ultrasoundRotem C, Kaplan B. Phyto-Female Complex for the relief of hot flushes, night sweats and quality of sleep:

randomized, controlled, double-blind pilot study. Gynecol Endocrinol 2007;23:117-22.

Vitamin E 400 IU daily vs placebo

• 51 Iranian women placebo X 4 wks, Vitamin E X 4 wks

• Decrease in # (5) and severity of hot flashes p < 0.0001

Ziaei S.,Kazemnejad A. ,Zareai M. The Effect of Vitamin E on Hot Flashes in Menopausal Women. Gynecol Obstet Invest 2007;64:204–207.

Grant MD, Marbella A, Wang AT, Pines E, Hoag J, Bonnell C, Ziegler KM, Aronson N. Menopausal Symptoms: Comparative Effectiveness Review No. 147. (Prepared by Blue Cross and Blue Shield Association Technology Evaluation Center Evidence-based Practice Center under Contract No.290-2007-10058-I.) AHRQ Publication No.15-EHC005-EF. Rockville, MD: Agency for Health care Research and Quality; March 2015. www.effectivehealthcare.ahrq.gov/reports/final.cfm.

Ethyl-eicosapentainoic Omega 3 fatty Acids and Vasomotor symptoms

• E-EPA = 45; placebo = 46

• Average number hot flashes/day 2.8

• EPA:decreased by 1.58/day

• Placebo: decreased 0.5

• p=0.04

• No change QOL Lucas M, Asselin G, Merette C, et al. Effects of ethyl-eicosapentaenoic acid omega-3

fatty acid supplementation on hot flashes and quality of life among middle-aged women: a double-blind, placebo-controlled, randomized clinical trial. Menopause 2009;16:357-66.

Valerian (Valeriana officinalis)

• ? GABA inhibitorYurchesen,M. et.al. Evid Based Complement Alternat

Med. 2015.

• Extracted from root/rhizomes

• Randomized, triple-blind, controlled trial

• 100 postmenopausal women in Iran

• Pittsburgh Sleep Quality Index

• 530 mg concentrated valerian extract or placebo twice daily X 4 weeks.

• 30% valerian group vs 4% placebo group with sleep quality improvement (P < 0.001).

S. Taavoni et.al., Menopause 2011 Sept; 18(9): 951-5.

Valerian

• Cytochrome P450 3A4• Lovastatin,

itraconazole, fexofenadine

• Avoid with alcohol, benzodiazepines, anesthesia (stop 2 wks)

• 400-900 mg valerian extract up to 2 hours before bedtime for 28 days

Kava Kava-Helped Anxiety but not Hot Flashes

• GABA, dopamine D2, benzodiazepine, opioid (µ and δ), serotonin, histamine (H1 and H2) receptor binding activity

• Hepatotoxicity

• Stems/leaves may be more toxic than roots

• Solvent used for extraction may contribute to toxicity

Yurcheshen M, Seehuus M, Pigeon W. Updates on Nutraceutical Sleep Therapeutics and Investigational Research. Evidence-based Complementary and Alternative Medicine :  eCAM. 2015;2015:105256. doi:10.1155/2015/105256.

Kava Kava (Piper methysticum)

• Meta-analysis Cochrane Review

• 700 patients in 12 randomized, controlled studies

• “The data available…suggest that kava is relatively safe for short-term treatment (1 to 24 weeks)…”

Pittler M. H., Ernst E. Kava extract versus placebo for treating anxiety. Cochrane Database of Systematic Reviews. 2003 (Republished 2010 including additional studies).

Dehydroepiandrosterone (DHEA)

• 12 weeks intravaginal DHEA daily vs placebo

• Vaginal suppository 0.25% (3.25 mg) or 0.50% (6.5 mg) DHEA

• Helped vaginal atrophy, burning, itching, libido, dyspareunia

• Must be converted to estrogen to be effective

• No increase in serum estradiol levels

• Dietary Supplement in USArcher, David. Dehydroepiandrosterone intra vaginal administration for the management of postmenopausal vulvovaginal atrophy. Journal Steroid Biochemistry and Molecular Biology. 145. Jan 2015,139–143

Labrie F, Archer D, Bouchard C, et al. Intravaginal dehydroepiandrosterone (Prasterone), a highly effective efficient treatment of dyspareunia. Climacteric. 2011;14(2):282–288.

Homeopathic Vaginal Gel for GSM

• 186 women received daily oral isoflavones and Lactobacillus sporogenes

• 103 women also used vaginal gel containing isoflavones

• Calendula officinalis extract 1X• Lactobacillus sporogenes• Lactic acid

• Vaginal dryness, itching, burning, erythema, dyspareunia significantly reduced with gel

• Calendula-drowsiness when taken with benzodiazepines, phenobarbital, or zolpidem

Tedeschi, Christina et.al. Comparison of vaginal gel isoflavones versus no topical treatment in vaginal dystrophy: results of a preliminary prospective study. Gyn Endo 2012. 28 (8).

Skin

• Argan oil (oral or topical)

• 30 patients, 30 controls (dietary olive oil)

• Dietary or topical argan oil improved skin elasticity in postmenopausal women

Boucetta, KQ et.al. The effect of dietary and/or cosmetic argan oil on postmenopausal skin elasticity. Clin Interv Aging. 2015 Jan 30;10:339-49.

©2010 MFMER | slide-63

Weight Loss Agents-No Benefit Proven Saper, Robert B. et.al. Common Dietary Supplements for Weight Loss American Family Physician. 2004. 70 (9); 1731-8.

• Apple cider vinegar

• Acai Berries (Avoid prior to MRI)

• Cascara

• Chitosan

• Chromium

• Conjugated linoleic acid

• Dandelion

• Ephedra (Withdrawn)

• Ginseng

• Glucomannan• Green tea• Guar gum• Guggul• Hydroxycitric acid• Laminaria• L-carnitine• Licorice• Psyllium• Pyruvate• Spirulina• St. John’s Wort• Vitamin B5

52 YO female with hypertension requests “herbal” non-hormonal approach to menopausal symptoms including vasomotor symptoms, mood changes, anxiety, and insomnia. What evidence based regimen could you suggest?

A. Trial of meditation, Black Cohosh, valerianB. Avoid soy isoflavanes in patient with history of breast cancerC. Discuss risk of hepatotoxicity with kava kavaD. Discuss medication interactions with St. John’s WortF. All of the above

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bhide bioidentical hormone replacement therapy and evidence based treatment of menopausal symptoms

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