Menopause & Hormone Therapy Decisions

Menopause & Hormone Therapy Decisions

Lisa Keller, M.D.

Limited goals for the next 45 minutes: Define the syndrome, physiology, epidemiology.

Symptoms, potential pathophysiology. At-risk groups by age, time from menopause, as well as known risk profiles.

What we know about hormone therapy, what has shifted over the past decade, and where there is consensus.

What we don’t know, what appears likely, and how to synthesize all the above into therapeutic recommendations.

Why menopause?

So there can be grandmothers. Childbearing is a huge physiological burden.

Ovarian follicles: millions as fetus, thousands in youth, none by menopause.

Also CNS aging within the hypothalamic-pituitary axis, still being defined.

Postmenopausal Women in US

*Projected estimate.US Census Bureau. Statistical Abstract of the United States. 2000:15.US Census Bureau. National population projections. Available at: http://www.census.gov/population/www/projections/natsum-T3.html. Accessed January 3, 2002.

Po

pu

lati

on

Years

65 years

60-64 years

55-59 years

50-54 years

45-49 years

0

10,000

20,000

30,000

40,000

50,000

60,000

70,000

80,000

90,000

100,000

2000 2010* 2020* 2030* 2040* 2050*

Age

Perimenopausal Transition Years

100

75

50

25

0 30

Age (years)

Postmenopause

Reproductive Years

Wo

men

(%

)

35 40 45 50 55 60

Perimenopause

Reduction in viable ovarian follicles and follicular resistance to gonadotropins

Erratic hormonal milieu, erratic symptomatology

Although cycle length begins to shorten, potential for ovulation and pregnancy is preserved for a number of years

Menstrual Cycle Changes

Usually shorter cycle length (eg, by 2 to 7 days)

Longer or irregular later in transition

Changes in quality Lighter volume. If heavier, more likely due to

myomata or hyperplasia

Spotting prior to menses is common

Menopause-Related Changes Vasomotor symptoms Sleep quality Mood changes Urogenital symptoms Sexual well-being Skin changes Bone loss Coronary heart disease (CHD) risk increases Eye dryness Joint inflammation

Hormone Deficiency Effects

Last period

Age (year)

Bone loss/osteopenia

40 90+45 5550 60 65 70 75 80 85

Vasomotor symptoms

Sexual complaints

Urogenital atrophy and symptoms

Vascular and heart disease

Osteoporosis

0

5

10

15

20

25

30

35

40

45

50

Years

Nu

mb

er o

f S

ub

ject

sHot Flushes May Continue

Years After Menopause

Number of years women report having hot flushes as estimated by a survey of 501 untreated women who experienced hot flushes

0 2 4 6 8 10 12 14 16 18 20 22 24 28 30 36 41

Ages 29 to 82 Years

Mean age of natural menopause was 49.5 years; mean age of surgical menopause was 43.7 years.Kronenberg F. Ann N Y Acad Sci. 1990;592:52-86. Used with permission.

Non-hormonal Therapies Herbal therapy — black cohosh, St. John’s wort

Biologically based substances — phytoestrogens: isoflavones from soy protein or red clover (unknown breast effects)

Lifestyle modifications — relaxation, paced respiration, moderate physical activity, modulation of responsibilities, sleep time

Prescription systemic hormone therapy, either as combined estrogen-progestogen therapy (EPT) or estrogen (ET), remains the gold standard for treatment in women without contraindications

Oral contraceptives are an option for perimenopausal women, especially those needing contraception

Treatment of moderate to severe vasomotor symptoms

Genitourinary Symptoms Associated With Menopause

Genital

Irritation, burning, pruritus

Leukorrhea

Dyspareunia

Decreased vaginal secretions

Shortening/lessening of vaginal distensibility

Urinary

Frequency, urgency

Dysuria

Nocturia

Incontinence*

*Controversial.

Vaginal Cytology

Premenopause Postmenopause

Risks and Benefits of HT

It is known with good certainty that Changes in the urogenital tract are among the most

consistent hypoestrogenic features of the climacteric

HT administered vaginally or systemically provides effective relief from atrophic vaginitis, including reduction in vaginal dryness, irritation, pruritus, and dyspareunia

ACOG Task Force on HT. Obstet Gynecol. 2004;104 (suppl 4):56s-61s.

Blue area represents placebo-treated population of oophorectomized women.Lindsay R, et al. Lancet. 1976;1:1038-41.

Met

acar

pal B

one

Min

eral

Con

tent

(m

g/m

m)

Years

At Oophorectomy

3 Years After Oophorectomy

6 Years After Oophorectomy

44

42

40

38

36

34

0 2 4 6 8 10 12 14 16

Effect of Delayed Initiation of HT on Bone Loss

WHI: Reduction in Fracture Risk With E+P and E Alone

0.5 1.0 2.0

Hip

Vertebral

Lower Arm/Wrist

All Fractures

Hazard Ratio

CEE/MPA (95% nCI)

CEE alone (95% nCI)

WHI Fracture Results:Clinical Implications

Women treated with E alone or E+P for menopausal symptoms do not need another antiresorptive agent

HT is the only therapy that has been demonstrated to prevent fractures in a population of postmenopausal women at relatively low risk of fracture

ACOG Task Force on HT. Obstet Gynecol. 2004;104(suppl 4):66s-76s.AACE Osteoporosis Task Force. Endocrine Pract. 2003;9:544-64.

Menopause, HT, & Depression

Several observational studies report increased risk for onset of major depression during perimenopause

Perimenopause seems associated with increased risk of clinically significant depressive illness for subgroup of women

Some prospective studies, although not all, have demonstrated improvements of ~ 80% in newly depressed perimenopausal women started on HT (placebo 20%)

Insufficient evidence to support HT use for depression treatment , but consider in new onset

Contraindications To HT Estrogen-dependent neoplasms (endometrial

carcinoma, hyperplasia, breast cancer), venous or arterial thrombosis, high risk of cardiovascular disease, and/or liver disorders.

Oral conjugated equine estrogen (CEE) significantly increases triglyceride levels. So, oral estrogen therapy is not optimal for women with elevated triglycerides. But these patients may benefit from transdermal estriadol therapy.

Oral estrogen is not recommended for heavy smokers.

Consistent Terminology Urged

ET — Estrogen therapy

EPT — Combined estrogen-progestogen therapy

HT — Hormone therapy (encompassing both ET and EPT)

CC-EPT — Continuous-combined estrogen-progestogen therapy (daily administration of both estrogen and progestogen)

CS-EPT — Continuous-sequential estrogen-progestogen therapy (estrogen daily, with progestogen added on set sequence)

Progestogen — Both progesterone and progestin

Observational Trial Results

1976: Lowers risk of osteoporosis

1981: CHD benefit, inconclusive for stroke

1988: Reduction in mortality

1994: Reduction in Alzheimer’s risk

Accelerated use of hormone therapy

>27,000 postmenopausal women randomized and enrolled from 1993 to 1998

Mean age at baseline, ~63 years

Women with vasomotor symptoms discouraged from participating

Primary outcomes: CHD, breast cancer

E+P trial stopped in July 2002

– Breast cancer crossed monitoring boundary

E alone trial stopped February 2004

– Trend toward increased stroke

Women’s Health Initiative (WHI) Clinical Trials of HT

WHI Limitations Only one estrogen was used (CEE, alone and with

MPA) and only one progestogen (MPA)

Only one route of administration was used (oral) and only one dosage (0.625 mg/2.5 mg)

Subjects were: Older (mean age, 63 years)

Most more than 10 years beyond menopause

Had more risk factors than younger women who typically use HT for menopausal symptoms

Largely asymptomatic

0

10

20

30

40

50

60

ColorectalCancer

EndometrialCancer

WHI E+P: Absolute Risks & BenefitsN

um

ber

per

Yea

r p

er 1

0,00

0 W

om

en

CHD* Stroke BreastCancer

VTE HipFractures

Total Deaths

More Cases in E+P Group

No Significant Difference in #

of Cases

Fewer Cases in E+P Group

CEE/MPAPlacebo

PE

0

10

20

30

40

50

60

70

80

90

WHI E Alone: Absolute Risks & BenefitsN

um

ber

per

Yea

r p

er 1

0,00

0 W

om

en

CEEPlacebo

ColorectalCancer

CHDStrokes BreastCancer

VTE HipFractures

Total Deaths

PE

More Cases in EGroup

No Significant Difference in # of Cases

Fewer Cases in EGroup

More Recent WHI Analyses of Younger Women (50-59 years)

7% decrease in CHD with ET or EPT (2 fewer cases per 10,000 per year of use)

24% increase in breast cancer with EPT (9 more cases per 10,000 per year of use)

20% decrease in breast cancer with ET (7 fewer cases per 10,000 per year of use)

30% decrease in total mortality with ET or EPT (10 fewer deaths per 10,000 per year of use)

ET = CE; EPT = CE + MPA

WHI: Effect of CEE Alone on Risk of CHD by Age Group

1.11

0.94

0.63

1.00.0 0.5 1.5 2.0

Dotted vertical line represents the HR for CHD in the overall cohort (0.95; 95% CI = 0.79-1.16)P = .07 for interaction with ageHsia J, et al. Arch Intern Med. 2006;166:357-65.

Age

50–59 y

60–69 y

70–79 y

0.0 1.01.0 2.0 3.00.5 1.51.5 2.52.5Years SinceMenopause

<10

10–19

>20

0.89

1.22

1.71

Hazard Ratio for CHD

Effect of E+P on CHD in Postmenopausal Women

Hazard Ratio for CHD

Manson JE, et al. N Engl J Med. 2003;349:523-34.

1.44

0.0 1.01.0 2.0 3.00.5 1.51.5 2.52.5Age (years)

50–59

60–69

70–79

1.05

1.27

WHI Cardiovascular SummaryEffects per 10,000 women/year of ET use (50-59 yrs)

10 fewer deaths

10 fewer CHD events

2 fewer strokes

4 additional VTE

Effects per 10,000 women/year of EPT use (<10 years postmenopause)

6 fewer deaths

4 fewer CHD events

5 more strokes

11 additional VTE


It is known with good certainty that HT does not increase CHD risk in women who

initiate therapy close to the onset of menopause (within ~ 9 years of last menses)

HT does not prevent and may increase the risk of CHD in women who initiate therapy years after menopause

0.5 1.0 5.02.0

WHI HT Trials: Increased Risk of Venous Thromboembolism

1Cushman M, et al. JAMA. 2004;292:1573-80.2Women's Health Initiative Steering Committee. JAMA. 2004;291:1701-12.

Hazard Ratio

E+P1

E alone2

HR (95% CI)

2.06 (1.57, 2.70)

1.33 (0.99, 1.79)


Meta-analyses find a small increased risk of stroke in postmenopausal women taking HT

Whether this increased risk is modified by hormone preparation, dose, or route of administration has not been established by randomized controlled trials

The risk of stroke for women taking HT increases with age, but the risk for younger women does not appear to be insignificant (still “rare” by WHO criterion)

ACOG Task Force on HT. Obstet Gynecol. 2004;104(suppl 4): 97s-105s.

Additional research of HT on risk of stroke is needed to clarify the effect

HT and Venous Thromboembolism

Significant increase in VTE risk in postmenopausal women using systemic HT

Risk increased with both EPT and ET

VTE risk appears during first 1-2 years after therapy initiation and decreases over time

Transdermal 17ß-estradiol and oral therapies may have different risk

Lower doses of oral estrogens may be safer than higher doses

WHI and Breast Cancer RiskWith EPT use

Relative risk = 1.24 (24% increased risk)

Absolute risk = 9 more cancers per 10,000 women per year of EPT use

With ET use

Relative risk = 0.80 (20% decreased risk)

Absolute risk = 7 fewer cancers per 10,000 women per year of ET use

33% statistically significant decreased risk when adherent to treatment (i.e., used ET 80% of the time)

Million Women Study: Breast Cancer Relative Risks

1.3

2

1.45

1.32

1.24

1.65

1.66

1.22

1 1.5 2

Mortality

Current use

Implanted estrogen

Transdermal estrogen

Oral estrogen

Tibolone

E + P

Estrogen only

Lancet. 2003;362:419-427.

European Trials — HT after BCA

One (HABITS) with continuous E+P showed ^ BCA recurrence risk

Other (Scandinavian trial) with ET and only intermittent P, showed 18% < BCA recurrence risk


It is known with good certainty that

E+P use >5 years is associated with an increased risk of breast cancer1,2

– Absolute risk is small; about 2 additional cases per 1000 women using E+P for 5 years1

Use of unopposed E does not increase breast cancer risk in women with previous hysterectomy3

1ACOG Task Force on HT. Obstet Gynecol. 2004;104(suppl 4):11s-6s.


Like CHD, findings from observational studies and the WHI do not agree. Stratification by age and the “healthy cell bias” may explain discrepancy

HT initiation in older postmenopausal women appears to increase risk of dementia

Research is ongoing to determine the effects of HT on cognitive function and dementia

HT in the Woman With Premature Ovarian Failure (POF)

POF is associated with premature osteoporosis and increased CV morbidity and mortality

Effective management involves early identification of POF, use of HT to relieve symptoms and prevent osteoporosis, and regular monitoring for associated conditions

Nelson LM, et al. Fertil Steril. 2005;83:1327-32.

Conclusions

Extrapolate with caution WHI date when considering risks of HT during or soon after the menopausal transition

Future research is critical to clarify optimal timing and duration of HT

WHI data do not address benefits and risks in women with premature menopause

ACOG Task Force on HT. Obstet Gynecol. 2004;104(suppl 4):1s-4s.North American Menopause Society (NAMS). Menopause. 2003;10:497-506.

SteroidsNatural

Found in NatureSynthetic

Laboratory Synthesized

Pregnane Derivatives• MPA

• Megestrol acetate• Cyproterone

acetate• Chlormadinone

acetate• Medrogestone

• Dydrogesterone

Structurally Related to Progesterone

Structurally Related to Testosterone

19-Norpregnane Derivatives

• Nomegestrol acetate

• Demegestone• Trimegestone• Promegestone

• Nesterone

Non-ethinylated• Dienogest

• Drospirenone

Ethinylated• Norethindrone• Norethynodrel• Lynestrenol

• Norethindrone acetate (NETA)• Tibolone

• Ethynodiol acetate• Levonorgestrel

• Desogestrel• Norgestimate• Gestodene

Stanczyk FZ. Rev Endocr Metab Disord. 2002;3:211-24.

Native Synthetic• Progesterone

Progestins

RR [95% CI]Estrogen alone RR = 1.1 [0.8-1.6]

TRANSDERMAL ESTROGENS

With micronized progesterone

RR = 0.9 [0.7-1.2] cases = 55

With oral synthetic progestins

RR = 1.4 [1.2-1.7] cases =187RR = 1.4 [1.2-1.7] cases =187

ORAL ESTROGENSWith oral synthetic progestins

RR = 1.5 [1.1-1.9] casesRR = 1.5 [1.1-1.9] cases = 80

Fournier et al, Int J Cancer, 2004.

EPIC

Medroxyprogesterone Acetate

Most common progestin used in USA

Most intensely studied progestin

Only progestin with substantial data proving ability to prevent endometrial cancer long term

Challenges regarding cardiac, thrombotic and breast effects

Gradyan D, Obstet Gynecol. 1995 Feb;85(2):304-13.

Norethindrone Acetate

CHC

O

O

OCCH2

Synthetic, patented in 1950 Pro-drug, rapidly converted to norethindrone NETA long half life

Most common progestin in EU NETA converts to ethinyl estradiol In high dose, 0.7 - 1% 6 micrograms EE/1 milligram NETA

Natural Progesterone

CH3

C

O

O

Bioidentical

Several formulations

Short half life

No long term safety outcomes

Primary Prevention of Coronary Atherosclerosis with CEE and MPA vs

Estradiol and Progesterone

0

0.1

0.2

0.3

No TX CEE CEE + MPA MPA

Adams et al. Arterioscler Thromb Vasc Biol. 1997;17:217Adams et al. Arteriosclerosis. 1990;10:1051.

Co

ron

ary

Pla

qu

e S

ize

(mm

2 )0

0.1

0.2

0.3

No TX E2 E2 + P

Coronary Artery Vasospasm in Monkeys Treated With E2 and Progesterone or MPA

.15 .15 ± .04± .04.37 .37 ± .02± .02Minimum Minimum

coronary artery coronary artery diameterdiameter

6/66/60/60/6Number of Number of

vasospasmsvasospasms

EE22 + MPA + MPAEE22 + Progesterone + ProgesteroneParameterParameter

Miyagawa et al. Nature Med. 1997;3:324.

Alternative ProgestinsBrand Name

Progestational agent

Available dosesDose for Sequential

Dose for Continuous

Ovrette® Norgestrel 0.075 mg 0.075 - 0.150 mg 0.035 mg

Micronor®

Nor-QD® Norethindrone 0.35 mg 0.70 mg0.35 mg (0.25 mg

– 1 mg)

Climara Pro

Levonorgestrel0.045 e/ 0.015 mg day, transdermal

NA0.045 e/ 0.015 mg day, transdermal

Crinone or Prochieve™

Progesterone vaginal cream

0.4 and 0.8% daily x 10 days1 applicator

(45 mg or 90 mg q 3-5 days)

Pro-metrium

Micronized natural progesterone

100 mg, 200 mg 200mg/d x 10 d 100 mg

Mirena IUC Levonorgesterol 20 mcg/day (5 yrs) N/A N/A

Breast vs Endometrial Risk

Million Women, Lancet 2005; 365: 1543–51

Commentary

If endometrial and breast cancer are regarded as equally bad events, limiting short-term (3-5 years) hormone therapy for menopausal management to use of estrogen alone even in women with an intact uterus makes considerable sense.

If breast cancer is regarded as clinically more serious than endometrial cancer, this conclusion only becomes stronger.

Diana Petitti, MD MPH

Kaiser Permanente Southern California, Pasadena, CA, USA

This conclusion will generate This conclusion will generate great controversy and discussiongreat controversy and discussion

This conclusion will generate This conclusion will generate great controversy and discussiongreat controversy and discussion

Million Women, Lancet 2005; 365:

Off-Label EPT Uses

Insufficient endometrial safety evidence to recommend off-label use of:

Long-cycle progestogen (ie, progestogen every 3-6 mo for 12-14 days)

Vaginal administration of progesterone

The contraceptive levonorgestrel-releasing intrauterine system

Low-dose estrogen without progestogen

Micronized oral progesterone (transdermal noted to not absorb well, not advised)

Close endometrial surveillance recommended with these approaches

Conclusions

While implications of recent studies suggest that estrogen alone may be safer than E+P, standard of care remains combined therapy

It is also unclear if CCHT or SCHT offers a higher degree of safety

Role of progestins in breast cancer is unsettled, but in endometrial cancer its role is crystal clear

Is there such a thing as a good cancer?

Conclusions (cont.)

MPA is the only progestin in the USA with data on long term endometrial safety

Micronized progesterone may offer some superior QOL attributes and cardiovascular protection

Micronized progesterone long term EM safety is not substantiated

Newer progestins may offer metabolic profile of micronized progesterone with the potency of MPA

International Prescribing Patterns

IMS Database.

76

100

20

40

60

80

Products Containing 17-Estradiol

Products Containing CEE

% of% of Total RxTotal Rx

Rationale for 17-Estradiol

Biologic effects in reproductive-age women predominantly due to 17-estradiol

Plant sterol derived synthetic mimic of naturally occurring hormone

Extensive international experience Therapeutic efficacy comparable to

other estrogens

Dose and Risk of VTE

Birth control pills 80 mcg > 50 mcg > 35 mcg Insufficient data on 20 mcg or less Is the curve linear at the lower end

HT Higher doses appear to carry higher risk Lowest threshold for risk unknown

Interaction with thrombophilias

Transdermal Delivery Systems

Avoid liver first pass

Assumptions about TD route being safer than oral delivery

• Patches

• Gels

• Creams

• Sprays

EvamistEvamist

Transdermal Estrogen Benefit

Circumventing first-pass metabolism

Non-elevation of triglycerides or high-density lipoproteins

Stable levels of circulating estrogen

Comparable efficacy at lower concentrations

Reduced frequency of dosing

Suitable alternative for women who chose not to use oral medication

Evidence of less thrombogenic potential

HT Therapy and Lipid Levels

Oral E Oral E+P Transdermal E

Transdermal E+P

Total cholesterol

LDL-cholesterol

HDL-cholesterol () ()

Triglycerides ()

E+P is estrogen + progestin combination. Parentheses indicate blunted effect relative to unopposed estrogen.

Lipid Profile and ET

-10

-5

0

5

10

15

20

% C

ha

ng

e

Oral estradiol 1 mg/d (n=94)

Transdermal estradiol 0.05 mg/d (n=267)

CEE 0.625 mg/d (n=1513)

*P<0.05 vs. baseline.†Analysis of 248 studies of postmenopausal women.

*

*

*

*

Total cholesterol

LDL- cholesterol

HDL- cholesterol Triglycerides

*

*

*

*

*** *

Godsland IF. Fertil Steril. 2001;75:898-915.LDL = low-density lipoprotein; HDL = high-density lipoprotein

Route of Administration

Non-oral routes of ET/EPT administration may offer advantages and disadvantages vs. oral routes, but the long-term risk-benefit ratio has not been demonstrated

Possible lower risk of deep venous thrombosis (DVT) with non-oral route

Similar breast cancer risks with oral and transdermal estrogens per large observational study

Indicated for diminished libido and sexual response in postmenopausal women on ET

Politically charged. No FDA approval yet.

EstraTest in 2 dosages, is oral Estrone and Methyltestosterone, FDA approved for hot flashes not responsive to ET alone

Particularly helpful in oovariectomized women

Testosterone Treatment

Before initiating testosterone treatment:

Establish baseline profiles for serum lipids and liver function tests, blood pressure

Consider retesting at 3 months

If stable, annual testing is advised

Management Recommendations:

Testosterone therapy should be administered at the lowest dose for the shortest time that meets treatment goals

Management Recommendations:During Testosterone Treatment

Use with caution. Understand transdermal dosage adjustments (2% = 20 mg/gm = 10x recommended female dosage). Know your pharmacist.

Dosing may be more inconsistentvs. government-approved products

Compounded Testosterone Products

Due to insufficient data, conclusions cannot be made regarding the efficacy and safety of testosterone therapy exceeding 6 months

Therapeutic monitoring should include subjective assessments of:

sexual response, desire, and satisfaction and

evaluation for potential adverse effects

Long-Term Use of Testosterone

Similar to those associated with estrogen therapy

Do not initiate testosterone therapy in postmenopausal women with:

Breast or uterine cancer

Cardiovascular disease

Liver disease

Testosterone Contraindications

Custom-Compounded HT?

Lack of controlled clinical trials of safety and efficacy

– No evidence that they are safer

– Clinical trials unlikely to be performed because of high cost and lack of patent protection

Compounding is allowable for individual patients unable to tolerate FDA-approved products

Mass production and marketing beyond state lines does not meet federal guidelines

Prescribers are responsible for risk/benefit education

Boothby LA, et al. Menopause. 2004;11:356-67.

Saliva and Hair Tests for Hormones

No reference standards available

Lack of correlation with serum levels Data from saliva does not tell you what is going on in the

target tissue

No way to determine appropriate dosing through these tests

Inter- and intrapatient variability

In reality, dosage adjustments based on symptomatology

No evidence to suggest that “individualized estrogen or progesterone regimens” based on these tests increase efficacy or improve safety

Duration of HT Use

FDA 20031

Recommends shortest duration and lowest dose consistent with treatment goals

ACOG 20042

The lowest effective estrogen dose should be used for the shortest possible time to alleviate symptoms

NAMS 20043

Recommends duration and dose consistent with treatment goals

Optimal Dose of Estradiol

Optimal dose for vasomotor symptoms at serum level of 60 pg/ml 50%, 120 pg/ml 100%

Optimal dose for bone is the highest dose 0.5 mg arrest losses in 60%, while 1-2 mg superior efficacy

Optimal dose for endometrium, breast, triglyceride and coagulation

lowest

Estradiol Therapeutic Range

0 25 50 75 100 125 150 175

Optimal 40-80 pg/ml

Acceptable 35-125 pg/ml

If you must use PremPro:

Standard dose = 0.625/2.5

Newer options = 0.45/1.5 and

0.30/1.5

Less is probably better

Lowest effective dose has yet to be determined for most products

CEE 0.3 mg ♦

0.15 mg appears ineffective

Oral estradiol 0.5 mg ♦

0.25 mg appears ineffective

TD estradiol 25 mcg♦ 20 mcg in trials

Indications for Extended Use of HT

♦ After informed discussion and with ongoing supervision

– For the woman for whom, in her opinion, benefits of symptom relief outweigh risks, notably after failing an attempt to withdraw from HT

– For women with moderate-to-severe menopausal symptoms and at high risk for osteoporotic fracture

– For prevention of osteoporosis in a high-risk woman when alternate therapies are not appropriate

North American Menopause Society. Menopause. 2003;10:497-506.

Discontinuing HT Use

♦ Symptoms have ~50% chance of recurring when HT is discontinued, independent of age and duration of HT use

♦ The decision to continue HT should be individualized, based on severity of symptoms, current risk-benefit ratio considerations, and when the woman in consultation with her healthcare provider believes that continuation is warranted

HT-Related Breakthrough Bleeding All available continuous-combined E+P regimens

are associated with breakthrough bleeding

Less breakthrough bleeding with lower doses

Most postmenopausal women will experience amenorrhea within 1 year of initiating therapy

All bleeding other than withdrawal bleeding should be investigated

– Workup can include vaginal sonogram and endometrial biopsy or both

– Endometrial sonogram showing 5 mm or more endometrial thickness should be followed by a biopsy

Pretreatment Evaluation

Complete health evaluation including history, lipids

Mammography as per national guidelines and age, preferably within 12 months of therapy

Other specific examinations, (eg, bone densitometry) on a case-by-case basis

Shared Decision-Making on HT

No universal recommendation for all women regarding the use of HT

The decision to use (or not use) HT is a personal one that should be made in consultation with a woman’s health care provider

The decision should be based on a woman’s individual health needs, concerns, and risk factors, taking into account menopause-associated symptoms and their effect on quality of life

Summary The benefits of using E+P therapy in healthy early

postmenopausal women with symptoms outweigh the risks

Women using E-only have fewer risks than those shown in the E+P arm of the WHI

Alternate estrogens and progestins appear to carry less risk than oral CEE/MPA. Studies ongoing re: formulations, delivery route.

Postmenopausal HT should be prescribed at the lowest dose for the shortest amount of time, consistent with treatment goals

Questions

More Info on the Web

www.HormoneCME.org

www.Hormone.org

www.familydoctor.org

www.menopause.org

(North American Menopause Society NAMS)

www.afwh.org (Alexander Foundation for Women’s Health)

Documents

Menopause & Hormone Therapy Decisions