Be a Surgical “Multiplier” in MIGS Inspire Brilliance Through Teamwork

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Scientific Program ChairJubilee Brown, MD

Honorary ChairBarbara S. Levy, MD

PresidentMarie Fidela R. Paraiso, MD

SYLLABUSPANEL SESSION 2:

Menopause Panel: Updates, Emerging Therapies, and Challenging Cases

Professional Education Information

Target Audience This educational activity is developed to meet the needs of surgical gynecologists in practice and in training, as well as other healthcare professionals in the field of gynecology. Accreditation AAGL is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. The AAGL designates this live activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Disclosure of Relevant Financial Relationships As a provider accredited by the Accreditation Council for Continuing Medical Education, AAGL must ensure balance, independence, and objectivity in all CME activities to promote improvements in health care and not proprietary interests of a commercial interest. The provider controls all decisions related to identification of CME needs, determination of educational objectives, selection and presentation of content, selection of all persons and organizations that will be in a position to control the content, selection of educational methods, and evaluation of the activity. Course chairs, planning committee members, presenters, authors, moderators, panel members, and others in a position to control the content of this activity are required to disclose relevant financial relationships with commercial interests related to the subject matter of this educational activity. Learners are able to assess the potential for commercial bias in information when complete disclosure, resolution of conflicts of interest, and acknowledgment of commercial support are provided prior to the activity. Informed learners are the final safeguards in assuring that a CME activity is independent from commercial support. We believe this mechanism contributes to the transparency and accountability of CME. Anti-Harassment Statement AAGL encourages its members to interact with each other for the purposes of professional development and scholarly interchange so that all members may learn, network, and enjoy the company of colleagues in a professional atmosphere. Consequently, it is the policy of the AAGL to provide an environment free from all forms of discrimination, harassment, and retaliation to its members and guests at all regional educational meetings or courses, the annual global congress (i.e. annual meeting), and AAGL-hosted social events (AAGL sponsored activities). Every individual associated with the AAGL has a duty to maintain this environment free of harassment and intimidation. AAGL encourages reporting all perceived incidents of harassment, discrimination, or retaliation. Any individual covered by this policy who believes that he or she has been subjected to such an inappropriate incident has two (2) options for reporting:

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Table of Contents Course Description ........................................................................................................................................ 1 Disclosure ...................................................................................................................................................... 2 Estrogen – More than a Sex Hormone from the Ovary R.J. Turner .................................................................................................................................................... 3 Androgen Therapy in Menopausal Women T.C. Rowe ...................................................................................................................................................... 6 Seeing the Big Picture with the Complicated Patient P. Batur .......................................................................................................................................................... 9 Cultural and Linguistics Competency ......................................................................................................... 12

Panel Session 2: Menopause Panel: Updates, Emerging Therapies, and Challenging Cases

Moderator: Kate A. O’Hanlan Faculty: Pelin Batur, Timothy C. Rowe, Ralph J. Turner

Course Description This session will provide the surgeon with an update on the risks and benefits of hormone therapy for surgical and natural menopause and review the non-hormonal emerging therapies. The role of systemic and vaginal estrogens and of androgen treatments will be reviewed, as well as a discussion of complex case scenarios (i.e. thromboembolism, cancer, severe endometriosis). The session will include an interdisciplinary group of menopause specialists and is intended to promote an informal, open discussion of controversies, differing practice styles and a dialogue on any clinical challenges the audience would like to address.

Course Objectives At the conclusion of this activity, the participant will be able to: 1) Effectively counsel patients deciding about ovary removal and to manage symptomatic menopause, especially in complex medical scenarios.

Course Outline

4:10 Welcome, Introductions, and Course Overview K.A. O’Hanlan 4:15 Estrogen – More than a Sex Hormone from the Ovary R.J. Turner 4:25 Androgen Therapy in Menopausal Women T.C. Rowe4:35 Seeing the Big Picture with the Complicated Patient P. Batur4:45 Panel Discussion All Faculty 5:10 Adjourn

Page 1

PLANNER DISCLOSURE The following members of AAGL have been involved in the educational planning of this workshop (listed in alphabetical order by last name). Art Arellano, Professional Education Director, AAGL* Linda D. Bradley, Medical Director, AAGL* Erin T. Carey Consultant: MedIQ Mark W. Dassel Contracted Research: Myovant Sciences Erica Dun* Adi Katz* Linda Michels, Executive Director, AAGL* Erinn M. Myers Speakers Bureau: Laborie Medical Technologies, Teleflex Medical Other: Unrestricted educational grant to support NC FPMRS Fellow Cadaver Lab: Boston Scientific Corp. Inc. Amy Park* Grace Phan, Professional Education Specialist, AAGL* Harold Y. Wu* Linda C. Yang Other: Ownership Interest: KLAAS LLC Kate A. O'Hanlan Speakers Bureau: Baxter Other: Course Support: Cardinal Health, Medical Products and Services, CONMED Corporation, CooperSurgical, Ethicon Endo-Surgery, Lexion Medical, Medtronic, Stryker Endoscopy Other: provide pelvic trainers: 3-Dmed Other: provide trocars for course: Applied Medical

SCIENTIFIC PROGRAM COMMITTEE Linda D. Bradley, Medical Director, AAGL* Jubilee Brown* Nichole Mahnert* Shanti Indira Mohling* Fariba Mohtashami Consultant: Hologic Marie Fidela R. Paraiso* Shailesh P. Puntambekar* Matthew T. Siedhoff Consultant: Applied Medical, Caldera Medical, CooperSurgical, Olympus Amanda C. Yunker Consultant: Olympus Linda Michels, Executive Director, AAGL*

FACULTY DISCLOSURE The following have agreed to provide verbal disclosure of their relationships prior to their presentations. They have also agreed to support their presentations and clinical recommendations with the “best available evidence” from medical literature (in alphabetical order by last name). Pelin Batur* Kate A. O'Hanlan Speakers Bureau: Baxter Other: Course Support: Cardinal Health, Medical Products and Services, CONMED Corporation, CooperSurgical, Ethicon Endo-Surgery, Lexion Medical, Medtronic, Stryker Endoscopy Other: provide pelvic trainers: 3-Dmed Other: provide trocars for course: Applied Medical Timothy C. Rowe* Ralph J. Turner Consultant: Health Grades Speakers Bureau: Merck Nexplanon

Content Reviewer has nothing to disclose.

Asterisk (*) denotes no financial relationships to disclose.

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Estrogen – More than a Sex Hormone from the Ovary

Ralph J. Turner, MD, FACOG, NCMP

Zeid Women’s Health CenterTyler, TX, USA

48th Global Congress on MIGS, Vancouver, BC, Canada November 11, 2019

Disclosures

DisclosuresConsultant: Health GradesSpeakers Bureau: Merck Nexplanon

Objectives

• Discuss the role of estrogen as a hormone of homeostasis and a critical regulator of

metabolism in women and men.

• Define the ubiquitous nature of estrogen receptors (ER) throughout woman’s life,

including the Timing Hypothesis, the Critical Window and the Geripause.

• Provide clinical and basic science evidence to manage those patients who

phenotypically prefer the quality of life under life-long euestrogenemia.

A Theory of Euestrogenemia (Open Access) DOI:10.1097/GME.0000000000000895

HISTORIC MILESTONES IN HORMONE THERAPY (HT)

1930 Commerical availability of Estrogen (1940 CEE)

1963 Wilson RA, Wilson TA. …”adequate estrogen puberty to grave”. J Am Geriatric

Soc 1963; 11:347–362. “Healthy forever”; Retrospective studies in 1980’s

1991 Women’s Health Initiative (HT, CaD, Diet Mod) “Metabolically compensated hypo-

estrogenemic women”14; Pts with moderate/ severe VMS excluded from RCT!

1996 Timing Hypothesis- T.B. Clarkson “Estrogen (E) effects on arteries vary with

stage of reproductive life & extent of subclinical atherosclerosis progression.”1

2002 WHI (E+P) prematurely ended; WHI (E alone) goes to 2004.

2002 Dubal /Wise; Estrogen and neuroprotection: from clinical observations to

molecular mechanisms.2 Critical Window

New emphasis on Estrogen and ERs in basic science –a foundation for translational care.

• 2005 Simpkins – E gives Healthy Mitochondria which gives neuroprotection.”3

• 2005 Kerber/Turner -- Euestrogenemia -- Why should ubiquitous ERs lie fallow?4

• 2006 Carroll-- “Genome-wide analysis of estrogen receptor binding sites” 3600 ER’s/

Estrogen Signaling Pathways5

• 2007 Suzuki/Wise “Timing of estrogen therapy after ovariectomy dictates the efficacy

of its neuroprotective and anti-inflammatory actions.”6 Critical Window

• 2007 Turner/Kerber –”Geripause”, when restoring E2 doesn’t achieve desired effects.

ERs down-regulated, or signaling pathways are no longer effective7

New emphasis on Estrogen and ERs in basic science –a foundation for translational care.

• 2009 Yao/Brinton “Decline in mitochondrial bioenergetics & shift to ketogenic profilein brain during reproductive senescence.”8 ER’s on mitochondria. 36 ATP from glucose vs 2 ATP from ketones. “Brain fog”

• 2012 Mittelman-Smith --“Role of kisspeptin/neurokinin B/dynorphin (KNDy) neurons in cutaneous vasodilatation and the estrogen modulation of body temperature”9 (VMS) Arcuate nucleus (site for Monoclonal Ab)

• 2012 Spangenburg (Kinesiologist) – In rat model, E reverses lipolytic dysregulation. ‘‘…E encourage physiological mechanisms that prevent chronic disease.’’… ‘‘the critical regulator of metabolism and not another ovarian hormone.” (Theory)

Page 3

New emphasis on Estrogen and ERs in basic science –a foundation for translational care.

● 2013 Sarrel et al -‘‘estrogen avoidance’’ since WHI, in women aged 50 -59 years from 2003 to 2009, resulted estimated 18,601 to 91,610 excess deaths from women who stopped HT or never started HT.12

● 2015 Kerber/Turner - In menopausal transition, transient hypo-estrogenemia at the KNDy neurons is the “canary in the coal mine” for ER dysfunction.12

● 2016 Levine “Menopause accelerates biological aging.”13

● 2017 Turner/Kerber – Theory of Euestrogenemia – a unifying concept Maintaining estrogen concentration to permit >3600 ER’s & Estrogen signaling pathways to function optimally. “Euestrogenemia” 14

Theory of Euestrogenemia (copyrighted; used with permission)

● X-axis –age in years● Y-axis- concentration of estrogen● P = Pregnancy● ANvD = Autonomic Neurovascular

Dysregulation● LD = Lipolytic Dysregulation● Inset – Menopause transition● Dotted line – proposed Euestrogenemia● “Bump” - WHI

New emphasis on Estrogen and ERs in basic science –a foundation for translational care.

● 2018 Miller – “Hot flashes”= VMS = Autonomic Neurovascular Dysregulation. Theory explains 4 types (by onset, duration & severity) 15

● 2018 Papadakis – OsteoLAUS DEXA scans – Women on HT age 47-53 had lower Android Fat Mass, lower Visceral Adipose Tissue & lower BMI. CU< PU & NU; HT treated Lipolytic dysregulation. 16 (Theory)

● 2019 Lundberg/Turner/Kerber – ER-beta (Esr2) modulates metabolism of otoconalproteins in vestibule of inner ear. E treats & reverses (BPPV) Benign Paroxysmal Positional Vertigo in postmenopausal women.17 (Theory)

● 2019 McCoy - Sjögren’s International Collaborative Clinical Alliance (SICCA) “…lower cumulative estrogen exposure appears to augment the clinical expression of disease.“18 (Theory) Less estrogen – Worse Sjögren’s

Hormone therapy/ Eu-estrogenemia14

● Women – just to name a few…● Retinal artery blood flow● Balance – Better sway velocity

performance● Benign Paroxysmal Positional

Vertigo (BPPV)● E2 = MAO Inhibitor● Dentition

● Eu-estrogenemia in men!● Polish study of 501 men with Chronic HF &

reduced LVEF, middle quintile of serum [E2] longest survival

● Osteoporosis – Bioavailable [E2] <11pg/mL

● Prostate cancer survivors on androgen deprivation therapy have more rapid onset of Alzheimer’s Disease. Failure to aromatize T to E2 impacts mitochondrial bio-energetics?

Hormone Therapy – Personal preferences

● I don’t chase/order lab values, unless the PCP wants one drawn

● 0.1 mg E2 patch; cut in ½; or 1/3s● Titrate until too much breast

tenderness● Goal – Cut VMS (ANvD) by 66-75%

● NAMS 2017 Statement – “No

general rule for stopping at age

65.”19

● Serum 100 pg/mL [E2] = 0.1mg patch= 2mg pill E2 = 1.25 mg CEE = 10 mcg Ethinyl Estradiol

● DVT/PE risk – no diff Transdermals vs controls. ESTHER20 & E3N21

● Self-titration oral Esterified E-Methyl Testosterone in post BSO pts for androgen deprivation sxs (~ 1 in 6).

Progestogens

● First 12 days of every 3rd month ( 4 times/yr); lowest Progestin dose

● Micronized Progesterone 100 – 200 mg po hs (sleep benefit?)

● Norethindrone 2.5 – 5 mg po (nice progestin profile/well tolerated)

● Medroxyprogesterone acetate (MPA) 10 mg po (inexpensive)

● Continuous progestin for amenorrhea (May neutralize benefits of E)

● Levonorgestrel intrauterine system (IUD) if at risk of endometrial CA

Page 4

Relative Adverse Events (Hodis) 22

● World Health Organization

● Very common ≥ 1/10

● Common ≥ 1/100 to < 1/10

● Uncommon ≥ 1/1000 to <1/100

● Rare ≥ 1/10000 to < 1/1000

E+P Breast Cancer (8 cases)

WHI 2002

● Very rare < 1/10000

● Beta –carotene Tot Mort 25

● Intens DV control CVD Mort 23

● Calcium supp Stroke 36

● Atorvistatin Hem Stroke 19

● Zolendronate Serious Afib 26

● Pravastatin BreastCA Dx 15

References: Estrogen – more than a sex hormone

1) Clarkson TB. NAMS endowed lecture: estrogen effects on arteries vary with stage of reproductive life and extent of subclinical atherosclerosis progression. Menopause 2007;14:373-384

2) Dubal DB, Wise PM. Estrogen and neuroprotection: from clinical observations to molecular mechanisms. Dialogues Clin Neurosci 2002;4:149-161

3) Simpkins JA, Wang J, Wang X, et al. Mitochondria play a central role in estrogen-induced neuroprotection. Curr Drug Targets CNS Neurol Disord 2005;4:69-83

4) Kerber IJ, Turner RJ. Eu-estrogenemia. J Appl Physiol 2005;99:2471-2472.5) Carroll JS, Meyer CA, Song J, et al. Genome-wide analysis of estrogen receptor

binding sites. Nature Genet 2006;38:1289-1297.6) Suzuki S, et al. Timing of estrogen therapy after ovariectomy dictates the efficacy of

its neuroprotective and anti-inflammatory actions. PNAS USA 2007;104:6013-6018.

References: Estrogen – more than a sex hormone

7. Turner RJ, Kerber IJ. Eu-estrogenemia, WHI, timing and the geripause. Int Urogyn J 2008;19:1461-1463

8. Yao J, et al. Decline in mitochondrial bioenergetics and shift to ketogenic profile in brain during reproductive senescence. Biochem Biophys Acta 2010;1800:1121-1126.

9. Mittelman-Smith MA, et al, Role of kisspeptin/ neurokinin B/dynorphin (KNDy) neurons in cutaneous vasodilatation and the… PNAS Sci USA 012;109:19846-19851

10. Spangenberg EE, et al. Metabolic dysfunction under reduced estrogen levels: looking to exercise for prevention. Exerc Sport Sci Rev 2012;40:195-203.

11. Sarrel PM, et al. The mortality toll of estrogen avoidance: an analysis of excess deaths among hysterectomized women … Am J Public Health 2013;103:1583-1588.

12. Kerber IJ, Turner RJ. Eu-estrogenemia, KNDy neurons, and vasomotor symptoms. JAMA Intern Med 2015;175:1586.

References: Estrogen – more than a sex hormone

13. Levine ME, Lu AT, Chen BH, et al. Menopause accelerates biological aging. PNAS 2016;113:9327-9332.

14. Turner RJ, Kerber IJ. Theory DOI:10.1097/GME.000000000000089515. Miller, VM, Kling JM, Files JA, et al. What's in a name - are menopausal “hot

flashes” a symptom of menopause or a manifestation of neurovascular dysregulation? Menopause: June 2018 - Volume 25 - Issue 6 - p 700–703

16. Papadakis G, Lamy O, Response to Letter to the Editor. "Menopausal Hormone Therapy Is Associated With Reduced and Total Visceral Adiposity: The OsteoLausCohort“. JCEM 103(11) · August 2018. DOI: 10.1210/jc.2018-01681

17. Lundberg YW, Turner RJ, Kerber IL. Estrogen therapy in post-menopausal women with benign paroxysmal positional vertigo: the role of Eu-estrogenemia . Submitted to Menopause July 2019

References: Estrogen – more than a sex hormone

18. McCoy SS, et al. Sjögren's Syndrome is Associated With Reduced Lifetime Sex Hormone Exposure: A Case‐Control Study Arthritis Care and Research. First published: 24 June 2019 https://doi.org/10.1002/acr.24014

19. The 2017 hormone therapy position statement of The North American Menopause Society. Menopause. 24 (7) pp. 728-753. DOI: 10.1097/GME.0000000000000921

20. Canonico M, et al. The ESTHER Study. Circulation. 2007;115:840-845 DOI: 10.1161/CIRCULATIONAHA.106.642280

21. Canonico M, et al. E3N Cohort Study. Arterioscler Thromb Vasc Biol published online Oct 15, 2009; DOI: 10.1161/ATVBAHA.109.196022

22. Hodis HM. Mack WJ. The Timing Hypothesis and Hormone Replacement Therapy: A Paradigm Shift in the Primary Prevention of Coronary Heart Disease in Women. Part 2: Comparative Risks. J Am Geriatr Soc. https://doi.org/10.1111/jgs.12281

Acknowledgments

● Acknowledgments● Irwin J. Kerber, MD, FACOG, FACS, Assistant Professor of OB-Gyn

University of Texas Southwestern Medical School, Dallas Texas, USA “Father of Eu-estrogenemia”. Friend, mentor, colleague

● Yasser F. Zeid, MD FACOG, FICS. FPMRS● Harry Reich, MD – Laparoscopic Hysterectomy 1988

Page 5

Androgen Therapy in Menopausal Women

Timothy Rowe MB BS, FRCSC, FRCOGAssociate Professor

University of British Columbia

Disclosure

I have no financial relationships to disclose.

Objectives

● Describe serum androgen levels in menopausal women

● Describe the indications and options for androgen therapy in women

● Describe the risks and potential benefits of androgen therapy in menopausal women

● Summarize the International Consensus Statement (2019) on Androgen Therapy in Women

yes

Serum levels of DHEA-S, androstenedione and testosterone in women aged 18-75

Arlt W (2006)

Indications for and against androgen therapy:Endocrine Society Clinical Practice Guideline

FOR:● Postmenopausal women with sexual dysfunction due to hypoactive sexual

desire disorder (HSDD)AGAINST:● Infertility● Sexual dysfunction other than HSDD● Cognitive, cardiovascular, metabolic, or bone health● General well-being

“Androgen therapy” refers to treatment with testosterone and not DHEA

Wierman ME et al. (2014)

Diagnosing HSDD

“Patients’ values and preferences should be the main driver for treatment decisions in this context”

Elraiyah T et al. (2014)

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Options for androgen therapy in women

Pharmaceutical:● Vaginal DHEA (Prasterone)Fractional use of testosterone preparations for men (e.g., AndroGel, Testim, Androderm) is NOT advised

Compounded:● Testosterone

Pharmacokinetics of TD testosterone cream

Testosterone in vitamin E and almond oil 10mg/mL; 0.5 or 1.0 mL applied to upper arm and massaged for 30-60 seconds

Fooladi E et al. (2014)

Dyspareunia: placebo vs. vaginal DHEA

Labrie F et al. (2017)

Effect of TD testosterone on sexual satisfaction

Satisfying episodes of sexual activity over 4 weeks in 771 postmenopausal women in five countries

Davis SR et al. (2008)

Risks of androgen therapy

Systemic testosterone:Real risks:● Acne and hirsutism● Irreversible deepening of the voice● Adverse changes in liver function and lipidsTheoretical risks:● Increased risk of cardiovascular disease● Increased risk of breast cancerVaginal DHEA:● Application site discharge

2019 Meta-analysis of testosterone therapy in menopausal women

Effect of testosterone therapy on satisfying sexual events, by menopausal status

Islam RM et al. (2019)

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Global Consensus Position Statement on the Use of Testosterone Therapy for Women

● Androgen deficiency is not diagnosed by a biochemical test● The clinical significance of “free testosterone” is uncertain● The only current indication for initiating a trial of testosterone therapy

in a woman is a diagnosis of HSDD● Compounded testosterone preparations cannot be recommended● Although testosterone therapy has not been found to be associated

with serious adverse events, the safety data are currently quite limited

Davis SR et al. (2019)

References● Davison SL, Bell R, Donath S, et al. Androgen levels in adult females: changes with age, menopause,

and oophorectomy. J Clin Endocrinol Metab 2005;90:3847-53● Wierman ME, Basson R, Davis SR, et al. Androgen therapy in women: an Endocrine Society Clinical

Practice Guideline. J Clin Endocrinol Metab 2006;91:3697-3710

● Wierman ME, Arlt W, Basson R, et al. Androgen therapy in women: a reappraisal. J Clin Endocrinol Metab 2014;99:3489-3510

● Arlt W. Androgen therapy in women. Eur J Endocrinol 2006;154:1-11

● Davis SR, Worsley R. Androgen treatment of postmenopausal women. J Steroid Biochem Mol Biol 2014;142:107-14

● Shifren JL, Davis SR. Androgens in postmenopausal women: a review. Menopause 2017;24:970-9

● Labrie F, Archer DF, Martel C, et al. Combined data of intravaginal prasterone against vulvovaginal atrophy of menopause. Menopause 2017;24:1246-56

● Islam RM, Bell RJ, Green S, et al. Safety and efficacy of testosterone for women: a systematic review and meta-analysis of randomized controlled trial data. Lancet Diabetes Endocrinol 2019; AIP 25 July

References● FSFI Questionnaire, at www.fsfiquestionnaire.com

● Fooladi E, Reuter SE, Bell RJ, et al. Pharmacokinetics of a transdermal testosterone cream in healthy postmenopausal women. Menopause 2014;22:44-9

● Elraiyah T, Sonbol MB, Wang Z, et al. The benefits and harms of systemic testosterone therapy in postmenopausal women with normal adrenal function: a systematic review and meta-analysis. J Clin Endocrinol Metab 2014;99:3543-50

● Davis SR, Moreau M, Kroll R et al. Testosterone for low libido in postmenopausal women not taking estrogen. N Engl J Med 2008;359:2005-17

● Labrie F, Archer DF, Koltun W, et al. Efficacy of intravaginal dehydroepiandrosterone (DHEA) on moderate to severe dyspareunia and vaginal dryness, symptoms of vulvovaginal atrophy, and of the genitourinary syndrome of menopause. Menopause 2016;25:1339-53

● Shifren JL. Testosterone for midlife women: the hormone of desire? NAMS Practice Pearl, at www.menopause.org/docs/default-source/professional/practice-pear-testosterone.pdf

● Davis SR, Baber R, Panay N, et al. Global Consensus Position Statement on the use● of testosterone therapy for women. Climacteric 2019; 22(5):429-34

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Seeing the Big Picture with the Complicated Patient

Pelin Batur, MD, NCMP, CCD

Associate Professor of MedicineSubspecialized Women’s Health, Cleveland Clinic

Deputy Editor, Cleveland Clinic Journal of Medicine

Disclosure

I have no financial relationships to disclose

Objectives

● Review best practices for menopause management in medically complex patients

Decision Points . . .

● Menopausal? ● Uterus? ● Indications for HT?

(VMS, GU, Bone, QOL (ie mood/skin/hair/sleep)

● If HT is the woman under 65 or within 10 years of menopause?

● If using HT oral or transdermal? Cycled or continuous?● If postmenopausal and no HT, then check GU and bone!

HT, hormone therapy; VMS, vitamins, minerals, and supplements; GU, genitourinary; QOL, quality of life

What is in our tool kit?

● Non-prescription approaches● Prescription, non-hormonal options● Hormonal options

○ Contraceptives■ progestin-only vs combined hormonal contraception

○ Post-menopause HT ■ ET or EPT■ Oral, transdermal, intravaginal, injection

○ “Bioidentical” hormone therapy (BHT)● Vaginal only● SERMs (ERAAs)

Domains to Evaluate in Postmenopause

me

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Hormone Therapy Risks vs Benefits

In Favor● Symptomatic● Younger● Osteopenic● Healthy lifestyle● Failed

alternatives

Consider Alternatives● >10 yr

postmenopause● Few symptoms● Multiple VTE risk

factors● High breast cancer

risk

WHI, women ages 50-59:Events per 10,000 Women per Year

Manson JE, et al. JAMA. 2013;310:1353-1368.

Cochrane Meta-analysis: All-cause Mortality From RCTs of HT

Boardman HMP, et al. Cochrane Database of Systemic Reviews. 2015;Issue 3:CD002229.

Change in Female Mortality Rates in the US

Kindig DA, et al. Health Affairs. 2013;32:451

Change in Male Mortality Rates From 1992–96 to 2002–06 in US Counties

Change in Female Mortality Rates From 1992–96 to 2002–06 in US Counties

Complex patients: Cardiovascular disease

Complex patients: Breast cancer and vaginal estrogenBreast cancer● Low dose: Serum E2 within PM range (<20 pg/ml)

○ 7.5 mcg ring, 4 & 10 mcg inserts● Moderate dose: Serum E2 >20 pg/ml, intermittently

○ 25 mcg tablets○ CEE cream 0.3 mg (1/2 gram), twice weekly

■ Contains multiple estrogenic compounds● High dose: E2 can reach premenopausal levels1

○ ≥ 0.625 mg CEE cream (1 gm)○ ≥ 50 mcg E2 cream (0.1 mg/gm=100mcg/gm)

■ FDA approved dose: 1-2 gm, 1-3 times weekly■ ACOG suggested dose: 1/2 gm, twice weekly2

1. Climacteric 2015;18:1212. Obstet Gynecol 2016;127(3):e93.

Page 10

Complex patients: Breast cancer and vaginal DHEABreast cancer● Vaginal DHEA

○ Helps in multiple domains of FSD○ Minimal to no absorption, systemic levels in lower postmenopausal range1-3

○ No studies directly compare with vaginal estrogen

● FDA-approved vaginal DHEA 6.5 mg (0.5%)○ Includes warning about use in breast cancer○ Compounded up to 13 mg (1.0%) does not affect serum estrogens or androgens1

● Studied in breast cancer survivors4-5

○ AI users: E2 levels in same as plain moisturizer○ Not on AI: E2 ↑ with treatment (lowest range <5)

1. J Steroid Biochem Mol Biol 2013;138:359-367 2. Menopause 2009;16:897-906.3. Menopause 2015;22(9):950. 4. Support Care Cancer 2018;26:643-650. 5.Support Care Cancer 26(4):1335-1343.

Migraine aura is more common in high estrogen environments, rare with menses

MRM is associated with the late luteal phase decline in estrogen

Aura

Migraine

X

X

Complex patients: Migraine with aura

Calhoun A, Batur P. CCJM 2017; 84(8):631-638Faubion S, Batur P, Calhoun A. Mayo Clinic Proc 2018; 93(5):639-645

Complex patients: Primary Ovarian Insufficiency

● Scant evidence of bone benefit with hormonal contraception

○ Prefer postmenopausal hormone therapy or

○ Medical optimization if secondary amenorrhea

● Patient’s pregnancy goals impact treatment

○ IUD + postmenopausal HT or

○ Cyclic postmenopausal HT

Additional Resources:

● NAMS. Menopause. 2012;19:257-271● ACOG. Obstet Gynecol. 2014;123(1):202-16. ● Endocrine Society. J Clin Endocrinol Metab. 2015;100(11):3975-4011.● International Menopause Society. Climacteric. 2013;16(3):316-337. ● Lipold D, Batur P, Kagan R. Cleve Clin J Med. 2016;83(8):605-612.● McNamara M, Batur P, DeSapri KT. Ann Intern Med. 2015; 162(3):ITC1-15.

Key take aways:

● Remember mortality reduction with HT (and other benefits)!● After breast cancer safer vaginal options are:

○ Estrogen: 4-10 mcg inserts or 7.5mcg ring ○ DHEA: Vaginal 0.5%

● In migraine, use continuous lower estrogen doses● Low estrogen doses ok after menopause, but for bone benefit in POI

aim for serum E2 >50

Help patient weigh risk vs benefits

Page 11

CULTURAL AND LINGUISTIC COMPETENCY Governor Arnold Schwarzenegger signed into law AB 1195 (eff. 7/1/06) requiring local CME providers, such as

the AAGL, to assist in enhancing the cultural and linguistic competency of California’s physicians

(researchers and doctors without patient contact are exempt). This mandate follows the federal Civil Rights Act of 1964, Executive Order 13166 (2000) and the Dymally-Alatorre Bilingual Services Act (1973), all of which

recognize, as confirmed by the US Census Bureau, that substantial numbers of patients possess limited English proficiency (LEP).

California Business & Professions Code §2190.1(c)(3) requires a review and explanation of the laws

identified above so as to fulfill AAGL’s obligations pursuant to California law. Additional guidance is provided by the Institute for Medical Quality at http://www.imq.org

Title VI of the Civil Rights Act of 1964 prohibits recipients of federal financial assistance from

discriminating against or otherwise excluding individuals on the basis of race, color, or national origin in any of their activities. In 1974, the US Supreme Court recognized LEP individuals as potential victims of national

origin discrimination. In all situations, federal agencies are required to assess the number or proportion of LEP individuals in the eligible service population, the frequency with which they come into contact with the

program, the importance of the services, and the resources available to the recipient, including the mix of oral

and written language services. Additional details may be found in the Department of Justice Policy Guidance Document: Enforcement of Title VI of the Civil Rights Act of 1964 http://www.usdoj.gov/crt/cor/pubs.htm.

Executive Order 13166,”Improving Access to Services for Persons with Limited English

Proficiency”, signed by the President on August 11, 2000 http://www.usdoj.gov/crt/cor/13166.htm was the genesis of the Guidance Document mentioned above. The Executive Order requires all federal agencies,

including those which provide federal financial assistance, to examine the services they provide, identify any

need for services to LEP individuals, and develop and implement a system to provide those services so LEP persons can have meaningful access.

Dymally-Alatorre Bilingual Services Act (California Government Code §7290 et seq.) requires every

California state agency which either provides information to, or has contact with, the public to provide bilingual

interpreters as well as translated materials explaining those services whenever the local agency serves LEP members of a group whose numbers exceed 5% of the general population.

~

If you add staff to assist with LEP patients, confirm their translation skills, not just their language skills.

A 2007 Northern California study from Sutter Health confirmed that being bilingual does not guarantee competence as a medical interpreter. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2078538.

US Population

Language Spoken at Home

English

Spanish

AsianOther

Indo-Euro

California

Language Spoken at Home

Spanish

English

OtherAsian

Indo-Euro

19.7% of the US Population speaks a language other than English at home In California, this number is 42.5%

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