menopause & hormone therapy decisions
DESCRIPTION
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. - PowerPoint PPT PresentationTRANSCRIPT
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Menopause & Hormone Therapy Decisions
Lisa Keller, M.D.
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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.
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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.
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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
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Perimenopausal Transition Years
100
75
50
25
0 30
Age (years)
Postmenopause
Reproductive Years
Wo
men
(%
)
35 40 45 50 55 60
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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
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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
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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
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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
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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.
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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
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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
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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.
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Vaginal Cytology
Premenopause Postmenopause
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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.
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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
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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)
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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.
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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
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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.
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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
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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
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>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
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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
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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
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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
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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
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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
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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
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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
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Risks and Benefits of HT
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
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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)
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Risks and Benefits of HT
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
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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
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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)
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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.
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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
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Risks and Benefits of HT
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.
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Risks and Benefits of HT
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
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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.
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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.
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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
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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
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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.
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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
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Natural Progesterone
CH3
C
O
O
Bioidentical
Several formulations
Short half life
No long term safety outcomes
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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
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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.
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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
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Breast vs Endometrial Risk
Million Women, Lancet 2005; 365: 1543–51
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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:
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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
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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?
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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
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International Prescribing Patterns
IMS Database.
76
100
20
40
60
80
Products Containing 17-Estradiol
Products Containing CEE
% of% of Total RxTotal Rx
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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
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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
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Transdermal Delivery Systems
Avoid liver first pass
Assumptions about TD route being safer than oral delivery
• Patches
• Gels
• Creams
• Sprays
EvamistEvamist
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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
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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.
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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
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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
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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
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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:
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Testosterone therapy should be administered at the lowest dose for the shortest time that meets treatment goals
Management Recommendations:During Testosterone Treatment
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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
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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
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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
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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.
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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
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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
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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
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Estradiol Therapeutic Range
0 25 50 75 100 125 150 175
Optimal 40-80 pg/ml
Acceptable 35-125 pg/ml
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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
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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
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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.
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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
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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
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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
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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
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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
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Questions
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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)