MENOPAUSE MANAGEMENTHERMAN MILLER, JR., M.D.

Medical Director: A Woman’s Choice of JacksonvilleMarch 8,2019

Disclosure Statement

§ I do not have a vested interest in or affiliation with any corporate organization offering financial support or grant money for this continuing education program, or any affiliation with an organization whose philosophy could potentially bias my presentation

Introduction§ Hormone Therapy(HT) involves

administration of synthetic estrogen and progestogen to replace a woman’s depleting hormone levels and thus alleviate menopausal symptoms. HT has been linked to various risks. Debates regarding its risk-benefit ratio continues

§ Estrogen-containing products are the most effective approved therapies for managing hot flashes and genitourinary syndrome of menopause(GSM), also for bone protection

Learning Objectives

§ Discuss quality of life challenges and tactics experienced during menopause

§ Review the role of estrogen and symptom management using pharmacotherapy in 2018

§ Discuss lifestyle management and non-hormonal treatment

Learning Objectives

§ Review the methods of hormonal delivery systems in women experiencing menopause

§ Recognize the methods of hormonal delivery systems in women experiencing menopause

Question 1: Which of the following are FDA approved indications for hormone therapy in menopausal women?

A. Treatment of menopausal symptoms

B. Prevention of menopausal osteoporosis

C. Prevention of colorectal cancer and dementia

D. A and BE. All of the above

Answer 1

Answer 2

Answer 3

Answer 4

Answer 5

20% 20% 20%20%20%

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Question 2: Which of the following is TRUE about bioidenticals according to NAMS?

A. Most have not undergone any rigorous clinical testing for safety or efficacy

B. Because of biovavailability and activity, underdosages and overdosages are possible

C. Compounded bioidenticals are recommended in preference to conventional hormone therapy

D. A and BE. All of the above Answ

er 1

Answer 2

Answer 3

Answer 4

Answer 5

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30

Question 3: What has the NAMS, and other organizations indicated for management of vasomotor symptoms in women undergoing menopause?

A. Systematic hormone therapy, oral routes, alone or combined with a progestin

B. Systematic HT, including transdermal routes, alone or combined with a progestin

C. Systematic HT, including oral and transdermal routes, alone or combined with a progestin

D. Compounded bioidentical FDA approved products

Answer 1

Answer 2

Answer 3

Answer 4

Answer 5

20% 20% 20%20%20%

30

Question 4: What is the NAMS, and ACOG statement on discontinuing systemic HT?

A. Therapy should be used only for 5 yrs.

B. Therapy should be stopped at age 65

C. Standardized protocols should be use for tapering or discontinuing HT

D. Therapy should be discontinued after 10 yrs even in symptomatic patients

E. None of the above

Answer 1

Answer 2

Answer 3

Answer 4

Answer 5

20% 20% 20%20%20%

30

Introduction

§ Women in U.S. experience menopause at average age of 51 years

§ Can also result from chemotherapy and oopherectomy

§ In the U.S., approx. 40 million women are at or near menopause

Quality of Life Issues

§ 75% of these women experience symptoms of estrogen withdrawal

§ VMS§ Depression§ Mood Swings§ Insomnia§ Dysfunctional Family and Workplace

relationships

Quality of Life Issues

§ Decreased sex drive§ Urge or Stress Urinary incontinence§ Fatigue§ Lost productivity§ Loss of self-esteem

VASOMOTOR SYMPTOMS

§ Altered Thermoregulation due to decreased Estrogen

§ Increase in heart rate§ Undulations in core body temperature§ Loss of REM sleep-linked to memory loss§ Lethargy and Fatigue from morning to

evening

Vasomotor Symptoms

§ Most common among women during perimenopause and early menopause

§ VMS-reddening of skin(flushing)§ Excessive sweating-confined to upper body

only§ Study of Women`s Health Across the Nation

(SWAN) –race, age, ethnicity, educational attainment, lifestyle, and menopausal status

§ Most symptoms were pre or early peri-menopausal

Vasomotor Symptoms

§ VMS reported by 45.5% AA, 35.4% Hispanics, 31.2% Caucasians respectively.

§ Women with higher Body Mass Index§ Flushes- narrowing of the thermoneutral

zone in the brain§ Neurotransmitters involved in the

serotonergic, histaminergic, noradrenergic, and opiod systems

Role of Estrogen

§ HRT is well established as the most effective treatment

§ Randomized, double-blinded, crossover study published 50 yrs. Ago

§ Substantial reduction in average # of hot flushes/week with conjugated equine estrogen(cee)

§ Lowest dose recommended, use progesterone in intact uterus

Role Of Estrogen

§ Dose related benefit§ Low doses are effective§ Symptom relief is significant at 4 weeks§ Lower doses take up to 8-12 weeks§ Lower doses have fewer side effects

Sexual Dysfunction

§ E2 loss affects skin and impacts vaginal health

§ Reduction of collagen fibers and glycoaminoglycans affect elasticity and thickness

§ Changes in secretions and vascularity causes thinning of skin

§ Hair loss on the head growth of unwanted hair on chin

Sexual Dysfunction

§ 47% of women in one study reported dryness§ 40% experience dyspareunia§ Altered immune changes increasing risk for

infection§ Only 25% of women will seek help

Sleep Disturbances & Depression

§ Studies have shown estrogen improve sleep qualitiy

§ Decrease estrogen causes symptoms of depression reason unknown

§ Mood was improved with estrogen therapy§ Effects were reversed when switching to

placebo

Health Risks associated with Menopause§ Cardiovascular disease-increased

succeptbility§ Osteoporosis-progressive bone loss§ Alzheimer`s-Cache county study risks varied

with duration of drug use, previous use showed decrease risk, no benefit unless current HT was used for longer than 10 yrs.

WOMEN’S HEALTH INITIATIVE

§ WHI study has caused women and health care providers to desperately find therapies perceived to be safer than conventional pharmaceutical estrogens and progestens.

§ Immediately after the study was released, E2 therapy declined, OTC remedies and alternatives increased.

§ These distrusts are suspended by women when entering the health food store or supplement aisle in the local store

WOMEN’S HEALTH INITIATIVE

§ 1991- 27,300 women, 40 centers

§ Conclusion date 2005

§ Stopped EPT 2002 (16,608 women; 5.2yrs)

§ Stopped ET 2004 (10,739 women; 6.8yrs)

§ Mean age 63.3yrs (66% older than 60)

§ Ages 50-59:33%

§ Ages 60-69:45%

§ Ages 70-79:21%

WOMEN”S HEALTH INITIATIVE

§ Prevention of chronic disease in healthy postmenopausal women ages 50-79 (mean age 63)

§ Designed to assess the role of hormone therapy in prevention of cardiovascular, cognitive decline, osteoporitic fractures and other degenerative diseases of aging

§ WHI trails indicate that MPA, when combined with CEE may have adverse health effects

§ Women age 50 to 59 with this combination showed an increase risk of breast cancer, coronary heart disease, and MI

§ Women age 50 to 59 without a uterus had a decreased risk

WOMEN’S HEALTH INITIATIVE

§ Four clinical trials§ Estrogen (cee.0.625) + Progestin (provera)§ Estrogen (cee 0.625)§ Calcium + Vitamin D§ Low fat diet

JAMA,2002:288:321

WOMEN’S health initiative

§ Major outcomes1. Coronary Heart Disease2. Increase incidence of Invasive Breast Cancer

§ Minor Outcomes1. Stroke, colorectal cancer2. Pulmonary embolism3. Endometrial Cancer4. Hip Fracture

WHI: CEE 0.625mg

RR at 6.8yrs Absolute risk/10K women/yr

§ Heart attack 0.91

§ Stroke 1.39

§ Breast cancer 0.77

§ Colon cancer 1.08

§ Hip fracture 0.61 § Blood clots 1.47

§ Death 1.04

§ All cancers

§ -5

§ +12

§ -7

§ +1

§ -6§ +6

§ +3

§ -7

WHI:CEE 0.625mg + 2.5mg MPA

Relative Risk at 5.2 yrsAbsolute Risk /10k women/yr

§ Heart attack 1.29

§ Stroke 1.41

§ Breast cancer 1.24

§ Colon cancer ).63

§ Hip fracture 0.66§ Blood clots 2.11

§ +7

§ +8

§ +9

§ -6

§ -5§ +18

WHI analysis Ages 50-59

§ 7% decrease in CHD with ET or EPT§ (2 fewer cases/10k women/year of use)§ 24% increase in breast cancer with EPT§ (9 more cases/10k women/year of use)§ 20% decrease in breast cancer with ET§ (7 fewer cases/ 10k women/ year of use)§ 30% decrease in total mortality with ET or

EPT (10 fewer deaths/ 10k women/ year of use

WHI: EPT and Breast Cancer

§ Additional 9 cases per 10k users per year§ Risk increases after 3 yrs of use§ Mammographic density increases§ Breast cancers

1. were slightly larger2. more nodal involvement3. more diagnosed at advanced stages

ET and Breast Cancer

§ WHI: seven less cases per 10k women years

§ Nurses Health Study: no risk increase for up to 15 years of taking cee

Progestin effect?

§ Would reduction in progestin exposure decrease the risk of breast cancer?

§ Use of progestin IUD?

§ ET with strict monitoring of endometrium with US/EMB?

§ Low dose ET with 14 days of progestin every 3 0r 6 months?

WHI: Hormones and CAD

§ CAD: 5 less (ET), additional 7 (EPT)/ 10k/yr

§ CVA: additional 8(EPT), additional 12 (ET)

§ rates of both diverge 1-2 yrs after randomization

§ Timing of EPT use and CVD risk

§ EPT start time RR CVD

§ <10yrs menopause 0.9

§ >20yrs menopause 1.8

WHI: ET arm

§ Age RR MI/CAD death

§ 50-59 0.61

§ 60-69 0.86

§ 70-79 1.10

Analysis of WHI/NHS data

§ RR: 0.66 for EPT started <10 yrs since menopause

§ RR: 1.86 for EPT started >10 yrs since menopause

Toh S et al., Ann Inter Med 2010;152: 21-217

Timing of HT in NHS and CAD Risk§ Start HT near menopause: RR 0.71§ Start HT > 10 yrs after menopause: RR 0.9§ Most started HT in perimenopause and were

free of known Cad at the start of the study

Grodstein F et al. J Wom Health 2006

WHI: Hormones and Bone Health§ WHI 5 (EPT)-6(ET) fewer cases of hip

fractures per 10,000 users /yr 1

§ 45 (EPT)-56(ET fewer any location fractures per 10,000 users/yr

§ RR 0.6-0.7 (30-40% risk decrease)§ Benefit disappears after short-term hormone

use is discontinued 2

1. (Cauley, JAMA,2003;290:1729)

2.(JAMA. 2013;310(13):1353-1368)

WHI: HT and Diabetes

§ HT reduces the risk of new onset DM§ EPT: 21% risk reduction (15 fewer cases per

10,000 women-year of use)§ ET: 12% risk reduction (14 fewer cases per

10,000 women-year of use)

WHI study population

§ Older: mean age 63 (at least >10 years after menopause

§ Risk factors or established CVD:1. History of MI: 1.6%2. History of angina: 2.8%3. HTN on therapy: 35.7%4. Diabetes: 4.4% 5. Hyperlipidemia on therapy: 12.5%6. History of coronary bypass/PTCA: 1.1%

HT:Relative Risks to patients§ Additional adverse events

1. EPT : 1/500 per year2. ET :1/5,000 per year

§ Lifetime risk of Breast cancer§ Baseline: 10% (now 13% ACS 2016)§ After 5 years of EPT: 13%§ ET does not increase risk over 13 years

More recent data§ Estrogens other than CEE Elite trial

§ Oral estradiol over 5yrs associated with loss

progression of subclinical atherosclerosis

when therapy was initiated within 6years

after menopause but not >10 yrs after

menopause

§ Timing of initiation: KEEPS trial

1.(early vs. late intervention with estradiol N. Eng J Med 2016 Mar 31;374(13);122-31

2.(Am Int Med 2014;161:249-260)

Nonhormones§ Paroxetine mesylate is the first nonhormonal

option approved by the FDA to treat moderate to severe vasomotor symptoms in women who can’t or don’t want to use hormones.

§ Dose is 7.5mg/day§ Wt. gain, decreased libido, and sleep

disturbance along with risk of bone fracture, suicidality, and abnormal bleeding are side effects

Nonhormones

§ VMS- serotonin, and norepinephrine reuptake inhibitors especially useful in women with depression

§ Insomnia and anorexia are most common side effects

§ Gabapentin, anticonvulsant can reduce vms§ Clonidine, alpha adrenergic mediator useful

in women with breast cancer

Other Treatment Options

§ Bioidentical Hormones/Compounded Therapy – biestrogen & triestrogen

§ No well controlled studies to support safety and efficacy

§ No guidelines for dose adjustments(standardization)

§ Compounding is acceptable choice but mass production and marketing beyond state lines do not meet federal requirements

Bioidentical Hormones§ Bioidenticals are not “natural hormones”

§ WHI-led to increase RXs for compounded hormone treatment, no proven safety or efficacy

§ No studies have compared compounded drugs with commercial drugs

§ NAMS does not recommend custom-compounded drugs over well tested govt. approved products

§ NAMS Menopause 2017

Alternative and Behavioral Therapies§ Many women think they are safe because

they can be purchased OTC§ Long term effects have not been studied§ No evidence that yoga, herb supplements,

acupuncture, clover or others have shown to relieve hot flashes

Complementary and Alternative Medicine§ Most commonly employed CAM remedies are

biologic-based therapies, such as botanical medicine, dietary supplements, and orthomolecular medicine

§ Virtually every culture employs some folk method or botanical remedy for treatment of menopausal symptoms

§ SWAN-soy supplements, glucosamine, flaxseed oil, ginkgo, black cohosh, and ginseng

§ Isoflavones-polyphenolic compounds induce disturbances in estrus cycle in sheep, sheep that graze on red clover and cattle fed whole soy may be rendered sterile

§ Asian women do not suffer symptoms because of high soy diet--=not true

§ SWAN study provides excellent data on ethnic groups and symptoms

§ Studies have failed to demonstrate estrogenic activity in natural soy, as evidenced by no change in vaginal maturation index, FSH, SHBG levels and markers of bone turnover

§ Red Clover-rich in isoflavones-Cochrane Collaborative found no decrease in hot flushes

§ Geller and Studee-clover compared to cee, lack of efficacy in clover

§ Black Cohosh-most popular and best studied, at present insufficient data documenting efficacy for menopausal symptoms

§ 4 arm trial comparing black cohosh, red clover, placebo, and CEE

§ After 12 months, 34%, 57%, 63% and 94% reduction of menopausal symptoms respectively

§ Tice et al compared black cohosh and other botanicals with placebo, no statistically significant improvements with any product tested

§ Between 30 -60 cases of hepatotoxicity have

been reported with black cohosh

§ Dong quia-( angelica polymorpha) no

estrogenic activity in humans

§ Primose-(Oenothera biennis) five randomized

trials all had negative findings

§ Ginseng-(Panax ginseng) no effect on hot

flashes, fsh levels, vaginal maturation index

§ Maca-(lepidium meyenii walp) south

american root veg. also called Peruvian

ginseng-no estrogenic activity but safe as

food product

§ Rhubarb-weak binding affinity for e2 no long term studies available, may offer some relief

§ Soy foods do not appear to be effective§ Botanicals ,no better than placebo but can be

perceived as helpful

NonpharmaceuticalInterventions§ Lifestyle modifications- healthy eating,

exercise, smoking cessation§ Paced breathing has been shown to be

helpful§ Weak evidence supporting aerobic exercise,

yoga, or relaxation as Rx for flushes§ Acupuncture no controlled studies§ Regular exercise is encourged for other

health related reasons

UPDATES ON MENOPAUSE§ Lower risk of VTE with trans-dermals vs oral

HT§ WHI cee-mpa clarified the most statistically

prominent risk assoc. with combination HT§ Higher incidence of VTE in women allocated

to cee-mpa

§ BMJ, Jan 9 2019-review of 80,000 women age40-79 developed VTE compared with 390,000 who did not develop VTE

§ HRT overall has increase risk of VTE over not taking HRT

§ Study showed 58% increase risk of VTE with orals with wide variation in them

§ No increase in women using transdermals when compared to women using no HRT

§ Bazedoxifene is an estrogen against in bone and an antagonist in the endometrium

§ BZA 20mg plus CEE0.45mg/daily is approved for mod to severe vasomotor symptoms and prevention of osteoporosis

§ Main adverse effect is increased risk of VT

§ No increase risk of breast ca has been shown so far

§ This is a progestin free regimen

§ Indications in women with uterus1. Treatment of moderate to severe 2. Vasomotor symptoms associated with

menopause

§ Prevention of postmenopausal osteoporosis§ Bazedoxifene alone (no cee) in women with

postmenopausal osteoporosis shows reduction in vertebral, not hip fractures

( Silverman j Bone Miner Res 2008 and 2012)

§

Bazedoxifene§ Adverse side effects (5%)

1. Muscle spasms

2. Nausea

3. Diarrhea

4. Dyspepsia

5. Dizziness

6. Neck pain

7. Abdominal pain

8. Oropharyngeal pain

§ Massive British Million Women`s Study indicated oral HT increased risk of stroke

§ Transdermal estradiol of 0.5mg or less did not

§ 2012, two observational studies from UK and Holland provided additional data confirming safety of transdermal HT with respect to thrombosis

§ 1,058,259 women, RR 1.42 oral vs RR0.82 transdermals

§ Netherland investigators identified 1,082 cases of VTE among women older than 50 years of age using cee-mpa had 4X risk of VTE

§ VTE assoc. with transdermals was almost identical to risk of non users

§ There are now 6 observational studies that agree that transdermal HT is safer then oral HT with respect to VTE

§ 2013- Ospemifene (osphena) orally administrated tissue- selective estrogen agonist/antagonist was approved by the FDA for treatment of dyspareunia caused by vulvar and vaginal atrophy in menopausal women

§ Reduces pain with intercourse, increases vaginal mucosal maturation and vaginal PH

§ Contraindicated with history of MI or VTE and may increase hot-flashes compared to vaginal HT

Ospemifene

§ Contraindications:1. Abnormal genital bleeding2. Estrogen dependent cancer3. DVT, Pulmonary embolism (history)4. History of stroke5. MI

§ Unopposed HT and cee-mpa have different effects on the breast

§ CEE found to be assoc. with lower incidence of invasive breast cancer than placebo (0.27% vs 0.35%) mean follow up 11.8 yrs.

§ This should reassure women on cee that risk on breast cancer is not increased

Kronos Early Estrogen Prevention Study (KEEPS)§ Studied effects of oral vs transdermal HT§ Favorable effects of HT were relief of

menopausal symptoms, improved sleep, quality of life, easing of dyspareunia and preservation of BMD

§ Libido was improved with transdermals§ Orals improved mood, depressive symptoms,

anxiety, tension and cognitive function

§ Neither form increased BP§ First pass thru liver, orals increased LDL and

reduced HDL, orals increased triglycerides, and C-reactive protein

§ Transdermals lipids generally unchanged, glucose tolerance improved, insulin resistance declined.

§ Mood, depression, anxiety, and tension did not improve with transdermals

§ Orals improved memory and cognitive function

§ Transdermals reduced insulin resistance, enhanced libido-related domains of sexual function

§ Many findings are preliminary and require confirmation in other studies the evidence is not conclusive

Effects of Early Menopause

§ 1977 Swedish cohort confirmed ill effects of

early menopause

§ 390 women age 48 at enrollment underwent

BMD

§ Early menopause <47 late >47

§ Early osteoporosis 56% early menopause

compared to 30% late menopause

§ Incidence of fracture per person 1,000yrs,

19.4 early vs 11.6 late

§ Current understanding of efficacy of HT in

lowering risk of osteoporotic fractures in

menopausal women and reduction of CAD and

overall mortality in women in their 50’s or within

first 10 yrs. Of menopause it is important to

advise women who under go early menopause to

use HT unless specific contraindications exist.

§ When HT is initiated within 10 yrs. Of

menopause, risk of CAD is reduced (WHI)

§ E alone or E + P does not increase risk of CAD

§ Continuous E + P was associated with a 76%

reduction of endometrial cancer after 3-5 yrs.

Transdermal Estradiol

§ Transdermal estrogen is highly effective§ Provides benefits at lesser risk§ Estradiol is dosed into the microcirculation§ Effective doses are closer approx. of

endogenous estradiol secretion§ Supraphysiologic production of

hepatoproteins and steroid metabolites are minimized ,if not eliminated

Transdermal V.S. Oral Estradiol§ Coagulation Factors: oral increases hepatic

production, transdermal has little or no effect§ Lipids: oral increase, transdermal decrease§ C-Reactive Protein: oral produce a two fold

rise, no effect from transdermals

Transdermals§ UK study looked at 80,000 women (40-79)

who developed VTE, compared with 390,000 who did not

§ HT overall has increase risk of VTE compared to not taking HT

§ UK study- 58% increase associated with oral preparations with wide variation among oral users

§ First study to provide a more detailed picture,of the VTE risks for different preparations

Global Consensus Statement 2013 NAMS HT§ WHI results apply to asymptomatic

postmenopausal women: caution in symptomatic perimenopausal women

§ HT: most effective Rx for vasomotor symptoms§ Estrogen favorable in surgical and premature

menopause§ Hormone therapy may decrease mortality by

30% when started in women younger than 60 years of age

§ Non oral routes haven advantages, no long term trials to document

§ Transdermal HT: caution re. transfer to children and animals

§ Use vaginal ET for atrophic vaginitis (GSM) § Discontinuation of HT: risk of vasomotor

symptom recurrence is 50%, independent of age or duration of use

§ HT use with EPT <3yrs. Has limited effect on breast cancer risk

§ HT better benefit risk profile in younger postmenopausal women

§ Extended use of lowest effective dose acceptable in:

§ informed patient who feels that benefits outweigh risks

§ patient at risk of fracture when alternative Rx is not appropriate

§ HT not indicated to prevent weight gain§ HT should not be use as antidepressant§ HT should not be use to prevent cognitive

decline or dementia§ HT is not recommended as sole treatment for

sexual dysfunction§ HT should not be used for prevention of

chronic disease

§ HT is not recommended for breast cancer survivors

§ HT in breast cancer survivors: conflicting results:

§ Few observational studies: no harm

§ One RCT: RR 2.4 of new breast cancer events

climacteric:2013:16 203-204

menopause 2012.19(3)257-271

NAMS 2015 Statement on continuing Systemic HT after age 65

§ Extending lowest effective dose is acceptable under certain circumstances

§ Advise patient of the increase risks associated continuing HT>65

§ Use should be individualized not stopped base on age

§ Decision to continue or discontinue should be made jointly by provider and patient

FDA position on HT§ Approves use of HT for:

1. Mod. To severe hot flashes and night sweats2. Mod. To sever vaginal dryness3. Prevention and treatment of osteoporosis

§ Should not be used for heart disease prevention

§ Should not be used if risks of VTE, Stroke, breast cancer

Oral Estrogen§ Conjugated estrogens: 0.3mg; 0,45mg;

0.625mg; 0.9mg;1.25mg

§ Estradiol: 0.5mg; 1mg; 2mg

§ Esterified estrogens: 0.3mg; 0.625mg; 1.25mg; 2.5mg

§ Estropipate: 0.75mg; 1.5mg; 3mg

Progestins

§ Traditional regimens: Medroxyprogesterone acetate (MPA),Micronized progesterone1. Continuous: MPA 2.5mg/day or micronized

progesterone 200mg/day

2. Cyclical: 10-14 days/ month

§ Alternative regimens:1. Low dose continuous: MPA 1.5mg/day,

micronized progesterone 100mg/day

2. Long interval cyclic: MPA 10mg/day x 14 days q 6months

Transdermal hormonal products§ Estradiol patch§ Estradiol + Norethindrone patch§ Estradiol cream§ Estradiol gel§ Estradiol spray

Transdermal Estradiol

§ Estradiol 0.05mg/day§ Minimal lipid effects

Less affective than oral estrogen on:ú Liver functionú Clottingú Sex hormone binding globulin

Ultra low-dose transdermal

§ Transdermal estradiol 14mcg/day§ FDA approved for osteoporosis prevention§ Progestin 1-2 times a year, 14 days at a time

Start up

§ Use lowest dose to start:§ Oral esterified estrogens 0.3mg/day

ú Transdermal estradiol 25mcg/dayú Conjugate estrogens/MPA 0.3/1.5mg/day Increase

dose if symptoms not controlled within 4 weeksú Can hold progestin in first 2 months to asses

estrogen effect and adjust doseú Cyclic progestin (vs. continuous) better in

perimenopausal and early menopausal

Unexpected bleeding on HT

§ Keep diary of any bleeding§ Expect irregular spotting/bleeding within 6-9

months of continuous progestin regimens§ Evaluate endometrium (US,EMB) if:§ Bleeding after 6-9 months on continuous

progestin§ Bleeding out of phase on cyclic progestin§ Heave or prolonged bleeding at any time

Tapering and stopping HT

§ Unclear that tapering is better§ Tapering options:

1. Decrease daily dose by half2. Take usual dose q.o.d. for 2 weeks, then 3rd

day for 2 weeks3. Go back to previous dose if symptoms recur

and taper more slowly4. Continue progestins at least every 3 months in

process of decreasing estrogen dose

Delivery systems§ Vaginal hormone products

1. CEE2. Estradiol creams3. Eels4. Vaginal tablets 5. Rings

§ Oral Estrogens1. CEE 2. Estradiol 3. Esterified estrogens 4. Estropipate

§ Transdermal1. Patches 2. Creams 3. Gels 4. Estradiol spray

§ Progestins1. Medroxyprogesterone acetate (MPA)2. Micronized progesterone

Conclusions§ HRT is still the gold standard§ Therapy should be started within first 2-3 yrs. of

menopause§ Transdermals are highly effective with much less

risks§ No increase risk of CAD in women

postmenopausal less than 10 yrs.§ HT at lowest effective dose can be used for

treating menopausal symptoms for shortest possible duration

§ HT is safe if individualized and monitored

§ ACOG, NAMS, The Endocrine Society do not recommend bioidenticals

§ HRT appropriate for treatment not prevention of vasomotor symptoms

§ Women <60 or within 10 yrs of menopause are candidates to start HRT

§ Avoid in women with high risk of breast cancer, VTE, CVD, and liver disease, history of stroke

§ Start at the lowest dose for 6-8 weeks before increasing dose

§ Transdermal therapy may be a lower risk for VTE/CVD than oral

§ Transdermals may be discontinued less frequently than other options

§ SSRIs and gabapentin are effective short term not as effective as HRT

§ HT provide valuable therapy but may pose serious risks. Communicate with patients to see if benefits outweigh the risks of individual patients

§ HT users are likely to have higher levels of education, engage in physical exercise, and have a high level of fiber intake. Caution is required when interpreting observational studies of HT effects, selection bias may be in operation

§ All major societies and guidelines recommend against use of compounded bioidentical hormones due to inability to assure dosing and safety.

§ NAMS, NICE(UK National institute for Health and Care Excellence), International Menopause Society, FDA,USPTF(US Preventive Services Task Force)

§ MenoPro App (NAMS)

Question 1: Which of the following are FDA approved indications for hormone therapy in menopausal women?

A. Treatment of menopausal symptoms

B. Prevention of menopausal osteoporosis

C. Prevention of colorectal cancer and dementia

D. A and BE. All of the above

Answer 1

Answer 2

Answer 3

Answer 4

Answer 5

20% 20% 20%20%20%

30

Question 2: Which of the following is TRUE about bioidenticals according to NAMS?

A. Most have not undergone any rigorous clinical testing for safety or efficacy

B. Because of biovavailability and activity, underdosages and overdosages are possible

C. Compounded bioidenticals are recommended in preference to conventional hormone therapy

D. A and BE. All of the above Answ

er 1

Answer 2

Answer 3

Answer 4

Answer 5

20% 20% 20%20%20%

30

Question 3: What has the NAMS, and other organizations indicated for management of vasomotor symptoms in women undergoing menopause?

A. Systematic hormone therapy, oral routes, alone or combined with a progestin

B. Systematic HT, including transdermal routes, alone or combined with a progestin

C. Systematic HT, including oral and transdermal routes, alone or combined with a progestin

D. Compounded bioidentical FDA approved products

Answer 1

Answer 2

Answer 3

Answer 4

Answer 5

20% 20% 20%20%20%

30

Question 4: What is the NAMS, and ACOG statement on discontinuing systemic HT?

A. Therapy should be used only for 5 yrs.

B. Therapy should be stopped at age 65

C. Standardized protocols should be use for tapering or discontinuing HT

D. Therapy should be discontinued after 10 yrs even in symptomatic patients

E. None of the above

Answer 1

Answer 2

Answer 3

Answer 4

Answer 5

20% 20% 20%20%20%

30

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