Exte Extendin ing Use of Use of Horm Hormone Thera Therapy - - PDF document

9/29/2016 1

Andrew M. Kaunitz MD, FACOG, NCMP

University of Florida Research Foundation Professor and Associate Chairman Department of Obstetrics and Gynecology University of Florida College of Medicine ‐ Jacksonville Director, Menopause & GYN Ultrasound Services UF Southside Women’s Health Specialists

Nams.translational HT 65 plus 9 9 16c

Exte Extendin ing Use of Use of Horm Hormone Thera Therapy Beyond Age Beyond Age 65—Who & 65—Who & When? When?

NAMS 3rd Utian Translational Symposium Andrew M. Kaunitz: Disclosures

• Clinical trial funding to University of Florida

– Bayer, TherapeuticsMD

• Advisory Boards (contraception)

– Allergan, Bayer, Medicines360, Merck, Pfizer

• Consultant (GSM): Shionogi
• Royalties

– UpToDate (contraception, abnormal uterine bleeding)

Extended Use of HT: Overview and Objectives

• Because no RCT data available, providing

guidance to patients regarding use of HT among women age >65 is controversial

– However, clinicians commonly encounter this issue in practice

• Objective: Provide guidance to clinicians

regarding extended duration HT use, based

• n available evidence as well as personal

clinical experience Case: 80‐year old health care provider in good health, BMI 21

• Presented for menopausal management
• Hysterectomy for benign indications 15 years earlier
• In recent years, had been feeling well on oral

estradiol 0.5 mg

• Her former gynecologist, however, discontinued this

medication, and would not discuss alternative treatments

• Off estradiol, frequent and bothersome vasomotor

symptoms reccurred…

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Relevant Issues to Be Reviewed…

• Duration of VMS
• EPT and breast cancer
• Oral vs. transdermal estrogen therapy
• HT and prevention of osteoporosis
• Beers list and insurance coverage of HT
• NAMS 2016 Position Statement

How Long do VMS Persist? (I)

• Penn Ovarian Aging study, population‐based

prospective cohort designed to assess duration of VMS:

– Median duration of bothersome VMS: 10.2 years – Symptoms beginning during perimenopausal transition: > 11.25 years

Freeman EW, et al. Obstet Gynecol 2011.

How Long do VMS Persist? (II)

• Prospective cohort study of women with
• steoporosis:

– Mean age 67 years; mean years since menopause 19 – 11.8% of women reported ‘clinically significant’ hot flushes at baseline; more than half of these symptomatic women continued to report bothersome symptoms 3 years subsequently

Huang AJ, et al. Arch Intern Med 2008.

How Long do VMS Persist? (III)

• A population‐based survey of 85‐year old Swedish women

– 16% of respondents experienced VMS – 10% of respondents were ‘very to moderately distressed’ by their VMS

Vikström J, et al. Climacteric 2013

• Persistent bothersome VMS not unusual in

women > 65 years of age

• In many women, short‐term HT will not be

sufficient to control VMS

9/29/2016 3 Counselling EPT Users regarding Breast Cancer Risks

• Extended use of EPT increases breast cancer

risk

– Benefit: risk profile for extended use EPT less favorable than for ET – Clinicians should periodically review benefit: risk profile of HT with users

NAMS 2016 AM Kaunitz. Menopause June 2014.

Oral vs. Transdermal ET (TDE2)

• Although no RCT data, CVD safety profile of

HT with TDE2 (particularly 0.05 mg or lower dose) appears more favorable than oral HT

• 7 observational studies : lower risk VTE w/TDE2

– One observational study: lower risk CVA

AM Kaunitz. Menopause June 2014. A Bergendal et al.; JA Simon et al. Menopause 2016

TDE2 particularly advisable if baseline CVD risk elevated: – Older age, obesity, hypertension, metabolic syndrome, smoking

Standard dose ET prevents

• steoporosis

– Most estrogen formulations/doses

approved for prevention of osteoporosis

– Standard doses:

• Oral estradiol (E2) 1 mg
• Oral conjugated equine estrogen (CEE)

0.625 mg

• Transdermal (TD) E2 0.05 mg
• NAMS. Menopause 2012.

Kaunitz AM. Menopause June 2014.

Lower dose ET also prevents osteoporosis

– Weekly ultra‐low 0.014 mg patch (TDET): serum E2 levels remain in menopausal range; – BMD maintained/enhanced in two year trial of women (mean age 66; intact uterus)

• No data address ultra‐low dose E2 patch’s impact on

fracture risk: no data available

– Proliferative changes more common in E2 group (8.5%) vs. placebo (1.1.%)

Ettinger B, et al. Obstet Gynecol 2004.

• NAMS. Menopause 2016.

Johnson SR, et al. Obstet Gynecol 2005. Kaunitz AM. Menopause June 2014.

In women using ultra‐low dose ET, consider use of progestogen, or periodic endometrial monitoring

9/29/2016 4 NAMS 2016 HT Position Statement

• “Prevention of bone loss and fracture may be an

indication for extended duration in selected women after appropriate counseling about risks and benefits, recognizing rapid bone loss is seen upon discontinuation.”

• NAMS. 2016

Kaunitz AM. Menopause June 2014

When HT is continued solely for the prevention of

• steoporosis, lower than standard doses appropriate

Notice Received From Insurance Company

• “Your patient is at least 65 years old and has evidence for

either an oral or transdermal estrogen containing preparation. These estrogen containing preparations should be avoided in

• lder women due to the risk of thrombosis and cancer. If

your patient fits this clinical profile, and if not already done, consider reassessment of risks/benefits of continuing estrogen.“

American Geriatrics Society Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults: The American Geriatrics Society 2012 Beers Criteria Update Expert Panel 2012 J Am Geriatr Soc 2012; 60 (4): 616‐631.

Beers Criteria for Potentially Inappropriate Medication Use in Older Adults

• In 1991 the late geriatrician Mark Beers catalogued

medications that “… cause adverse drug events in

• lder adults due to their pharmacologic properties

and the physiologic changes of aging.”

• List includes systemic estrogens (oral and

transdermal) with or without progestins

http://www.americangeriatrics.org/files/documents/beers/PrintableBeersPocketCard.pdf

Use of HT to Treat Menopausal Symptoms: ACOG Guidance

“…ACOG recommends against routine discontinuation

• f systemic estrogen at age 65 years. As with younger

women, use of HT and estrogen therapy should be individualized based on each woman’s risk–benefit ratio and clinical presentation.”

• ACOG. Practice Bulletin 141. Obstet Gynecol January, 2014.

9/29/2016 5 NAMS 2016 HT Position Statement

• “The Beers Criteria recommendation to routinely

discontinue systemic HT after age 65 is not supported by data.”

• “Decisions regarding whether or not to continue HT

beyond the age of 60 should be made on an individual basis, after appropriate evaluation and counseling about potential benefits and risks and with ongoing surveillance. “

NAMS 2016

Some clinicians include NAMS statement when responding to insurance notices denying reimbursement for systemic HT in women age 65+ years

Back to the case….

• Patient counselled regarding nonhormonal treatments

as well as oral and transdermal ET – Elected to start estradiol 0.0375 mg patch

• Called 6 weeks later indicating symptom relief incomplete
• Now doing well on 0.05 mg patch

– Recent DXA: normal bone mineral density: spine and hip – Patient expressed concern regarding prior clinicians’ reluctance to Rx HT; she was enthusiastic regarding, and consented to her history being presented at professional meetings

Conclusion: NAMS 2016 HT Position Statement

• “Decisions about duration of HT require

individualization, including consideration of personal preferences, balancing potential

• ngoing benefits and risks, and decisions to

continue HT for preventative and/or quality

• f life purposes.”
• NAMS. 2016. Kaunitz AM. Menopause June 2014.

Shared decision making helps our patients make sound choices