University of Florida Research Foundation Professor and Associate Chairman Department of Obstetrics and Gynecology University of Florida College of Medicine Jacksonville Medical Director and Director of Menopause amp GYN Ultrasound Services ID: 641844
Download Presentation The PPT/PDF document "Andrew M. Kaunitz MD, FACOG, NCMP" is the property of its rightful owner. Permission is granted to download and print the materials on this web site for personal, non-commercial use only, and to display it on your personal computer provided you do not modify the materials and that you retain all copyright notices contained in the materials. By downloading content from our website, you accept the terms of this agreement.
Slide1
Andrew M. Kaunitz MD, FACOG, NCMP
University of Florida Research Foundation Professor and Associate ChairmanDepartment of Obstetrics and GynecologyUniversity of Florida College of Medicine - JacksonvilleMedical Director, and Director of Menopause & GYN Ultrasound ServicesUF Southside Women’s Health Specialists
FOMA.District2.men.ht. 5 21 17
Treatment of Menopausal Symptoms: A 2017 Update for CliniciansSlide2
Learning Objectives: Menopause & Hormone Therapy
Our patients will likely spend more than one third of their lifespan as menopausal women…By remaining up to date, we can help our patients make sound choices regarding HT Identify vasomotor symptoms (VMS) and recommend hormonal / nonhormonal treatmentRecognize risks of HT, with emphasis on breast cancer, venous thromboembolism (VTE), and coronary heart disease (CHD)Slide3
Abbreviations
HT = hormone therapyET = estrogen therapyCE = conjugated equine estrogen,E2=estradiolEPT = combination estrogen-progestin therapy = Women’s Health Initiative (WHI)Slide4
Andrew M. Kaunitz, M.D.
DISCLOSURESClinical Trials (Funding to University of Florida Research Foundation):Bayer
TherapeuticsMD
Advisory Boards
AllerganBayer
MithraPfizerConsultant
Shionogi
Royalties
UpToDate
North American Menopause Society
Menopause
Editorial Board
Board of Trustees
HT Position Statement writing group memberSlide5
Vasomotor Symptoms (VMS)
Can be triggered by warm environments, hot drinks, emotional stressVMS: Most common reason women seek care at time of menopausal transition HD Nelson. Lancet 2008
Spontaneous sensations of warmth, usually felt on chest, neck and face
may be called ‘hot flushes’ or ‘night sweats’
often associated with perspiration, palpitations and anxiety
may impair quality of life
Variable in frequency, duration and severity
usually < 5 minutesSlide6
Prevalence and Timing of VMS
Experienced by > 50% of menopausal womenSubstantial increase in frequency and severity during menopausal transition (perimenopause)For some women, VMS persist 6 months to several years, with ↓ frequency and intensity over timeMean duration bothersome VMS 10.2 years
EW Freeman, et al. Obstet Gynecol 2011
HD Nelson. Lancet 2008Slide7
Treatment of VMS
Treatment appropriate when VMS disrupt daytime activities and/or sleepEstrogen used for many decades used to treat VMS most effective treatment numerous randomized, placebo-controlled trials75% reduction in VMS frequencysignificant reduction in VMS severityOral and transdermal estrogen have similar efficacyProgestin therapy, including DMPA and megestrol
also effective in treating VMS
HD Nelson. JAMA 2004 AH MacLennan, et al. Cochrane Database Syst Rev 2004
HD Nelson. Lancet 2008Slide8
Hormone TherapyClear
VMS: most common indication for HTHT’s efficacy in treating VMS well-establishedControversialOur understanding of HT’s safety…. Slide9
WHI: Women’s H
ealth InitiativeMulticenter, double-blind, placebo-controlled trial of women age 50-79 years at baseline, designed to assess HT’s impact on cardiovascular disease Mean age at screening 63-64 yearsPlanned 10-year trial; stopped early
CEE/MPA v. placebo: N= 16,608 , stopped Summer ’02, mean follow-up 5.2 years
CEE v. placebo: N = 10,739 , stopped Spring ’04, mean follow-up 6.8 years
Largest RCT of menopausal hormone therapy
Writing Group WHI. JAMA 2002
WHI Steering Committee. JAMA 2004Slide10
CVA
WHI EPT Study: Findings at Early Interruption Summer 2002
VTE/PE
MI
Risks
Benefits
Breast Cancer
Fracture
Colon Cancer
Adapted from: Writing Group WHI. JAMA 2002Slide11
WHI ET Initial Findings: Summary as of 2004
ET component of study stopped early after 6.8 years of follow-upET not found to significantly impact risk of breast cancer, CHD, PE, or colorectal cancersignificant reduction in hip fracture riskOverall safety of ET appears greater than EPT2004 findings received less attention than 2002 report
WHI Steering Committee. JAMA 2004Slide12
WHI’s Impact on Use of HT in US Women
Since 2002, use of all HT has decreased substantiallyMain initial conclusion from WHI is that HT not appropriate to prevent coronary heart diseaseNonetheless, following WHI findings in 2002, many clinicians remain reluctant to treat women with bothersome menopausal symptomsMany symptomatic women not treated…
PI Jewett, et al. Obstet Gynecol 2014 J
Shifren and I Schiff. Obstet Gynecol 2010Slide13Slide14
WHI: 13-Year Follow-up: EPT and ET…
JE Manson, et al. October 2, 2013Slide15
Risk of Breast Cancer @13 Years Cumulative f/u in Participants OVERALL (all ages at randomization)
EPT Hazard Ratios (HRs):Significant ↑ risk breast cancer: 1.28ET Hazard Ratios: Significant ↓ risk breast cancer: 0.79
JE Manson, et al. JAMA October 2, 2013 Slide16
EPT and Elevated Risk of Breast Cancer
What does an HR of breast cancer of 1.28 mean?Putting HR of 1.28 in context:<1 additional case per 1,000 EPT users annually (WHI) can be attributed to HTHR with EPT slightly higher than that seen with one daily glass of wine; less than HR with 2 daily glasses (Nurses Health Study)1 in 5 breast cancers occurring in women using EPT can be attributed to HT
JE
JE Manson
, et al.
2013
WY Chen, et al. 2011Slide17
Risk of All-cause Mortality @13 Years Cumulative f/uin Participants OVERALL (
all ages at randomization)EPT Hazard Ratios (HRs):All-cause mortality: 0.99 (NS)ET Hazard Ratios: All-cause mortality: 0.99 (NS)
WHI recruited women age 50-79 years…
JE Manson, et al. JAMA October 2, 2013 Slide18
All-cause Mortality Hazard Ratios* at 13 Years Cumulative f/u by Age at Randomization
50-59 yearsET: 0.78EPT: 0.88
JE Manson, et al. JAMA October 2, 2013
* All p-values>0.05; but trend by age is meaningful
60-69 years
ET:
1.02
EPT:
0.99
70-79 yearsET: 1.06EPT:1.04Slide19
Conclusions: WHI EPT+ET Trial-- 13 Years of Follow-Up, and Published Literature Overall
HT Risk: Benefit ratio most favorable when initiated in younger menopausal womenHT appropriate for symptomatic patients in their 50s or within 10 years of menopause onsetOverall, R:B ratio more favorable for ET than EPT
AM
Kaunitz
, JE Manson.
Obstet
Gynecol 2015Slide20
Compounded Bioidentical Hormone Therapy
Use growing in the US, with an estimated 2.5 million current usersUse propelled by celebrity endorsementsMost users not aware that Compounded HT not FDA monitored or approvedSalivary testing often employed by MDs prescribing compounded HTSuch testing does not correlate with serum steroid levels
Compounded Progesterone cream often Rxed
…
JV Pinkerton, N Santoro. Menopause 2015 ; AM Kaunitz, JD Kaunitz. Menopause 2015; M Gass, et al. Menopause 2015Slide21
Compounded Bioidentical Hormone Therapy
National survey: cases of endometrial cancer in women using compounded HT FDA-approved bioidentical HT formulations available:estradiol patches, tablets, vaginal cream/tablets, progesterone in oil
capsules
JV Pinkerton, N Santoro. Menopause 2015 ; AM Kaunitz, JD Kaunitz. Menopause 2015; M Gass, et al. Menopause 2015Slide22
VTE & CVA Risk and Route of ET: 7 Observational Studies
Biologic plausibility (transdermal=no first pass hepatic effect)
PY
Scarabin
, et al. Lancet 2003 M Canonico
, Arterioscler Thromb
Vasc Biol
2010 A Bergendal et al.; JA Simon et al. Menopause 2016
C Renoux, et al. J Thromb Haemost
2010 C Renoux, et al. BMJ 2010 L Laliberté, et al. Menopause 2011 RE Roach, et al. J
Thromb Haemost 2012
Oral
estrogen therapy
: ↑
risk VTE &
CVA
Transdermal
ET:
no
↑
riskSlide23
Oral vs. Transdermal Estrogen
PY Scarabin, et al. Lancet 2003 M Canonico,
Arterioscler Thromb
Vasc
Biol 2010 A Bergendal
et al.; JA Simon et al. Menopause 2016C Renoux
, et al. J Thromb Haemost
2010 C Renoux, et al. BMJ 2010 L
Laliberté, et al. Menopause 2011 RE Roach, et al. J Thromb Haemost
2012No randomized trial data comparing benefits and risks Given consistency and biologic plausibility of observational data, reasonable to conclude transdermal estrogen safer re risk of VTEClinicians and
women should discuss this safety issue when making decisions regarding route of HTTransdermal route particularly appropriate for overweight/obese and other HT users at elevated baseline riskReasonable starting dose 0.05 mg estradiol patch (equivalent to 1.0 mg oral estradiol, or 0.625 mg conjugated equine estrogen)Slide24
Menopausal Hormone
Therapy: A Clinician’s Evidence-based 2017 Perspective
Thank you!
The pendulum is swinging…towards an evidence-based perspective on use of hormone
therapy
Clinicians who remain up to date can help patients make sound choices regarding treatment of menopausal symptoms
Systemic HT: appropriate to initiate for most healthy women with bothersome
VMS
who are <age 60, or within 10 years of menopause onset