Hormone Replacement HRTin Postmenopausal Women

1
Hormone Replacement (HRT)in Postmenopausal Women

• Sorting Through the Issues

2
Underlying Concerns

• Increasing life expectancy after menopause
  average is 30 years
• Uncomfortable symptoms associated with hormonal
  decline
• Bone loss and increased LDL levels associated
  with hormonal decline
• Potential risks with hormonal replacement

3
Interesting Facts

• HRT is one of most commonly prescribed drug
  regimens for postmenopausal women in the US
• Women can lose up to 10 of their bone mass in
  the first 5 years after menopause
• Up to 70 of women 80 have osteoporosis

4
Likelihood of Chronic Disease

• In postmenopausal woman
• Heart disease 47
• Stroke 20
• Hip fracture 15
• Breast cancer 10
• Uterine cancer 2.6

5
Additional Concerns

• Postmenopausal women have a 1.4 to 3.0-fold
  higher risk of Alzheimers disease than do men
• Lifetime risk for colorectal cancer for a US
  woman is 6, with 90 of cases occurring after
  50 years of age
• Many of these causes of chronic disease appear
  influenced by estrogen/ progestins

6
What Does the Research Show?

• Wide range of trials on HRT
• Varying estrogen/ progestin combinations,
  although most studies have used conjugated equine
  estrogren (CEE) and/or medroxyprogesterone (MPA)
• US Preventive Services Task Force has compiled
  the best evidence from a number of trials

7
Osteoporosis

• HERS (Heart and Estrogen/Progestin Replacement
  Study) no decrease in hip, wrist, spine or total
  fractures with hormone therapy
• WHI (Womens Health Initiative) significant
  decrease in total fracture decrease in spine and
  hip fracture

8
Osteoporosis (cont)

• Meta-analysis of 22 trials of estrogen reported
  an overall 27 decrease in non-spine fractures
• There was variation in study quality
• overall there appears to be potential benefit
  with increased bone density and decreased
  fracture risk

9
Colorectal Cancer

• HERS reduced incidence of colon cancer
• Meta-analysis of 18 trials of postmenopausal
  women showed a 20 decrease in colon cancer 19
  decrease in rectal cancer
• Similar results in WHI with women taking CEE/MPA
• probable reduced colorectal cancer risk

10
Mental Status

• Variation in assessment outcomes of studies with
  some indication of decreased risk for dementia in
  postmenopausal women on HRT
• WHI estrogenprogestin therapy increased the
  risk for probable dementia in postmenopausal
  women 65 it did not prevent mild cognitive
  impairment

11
Mental Status (cont)

• Insufficient evidence to be certain about
  effects of HRT on dementia and cognitive function

12
Breast Cancer

• WHI increased breast cancer incidence no effect
  on breast cancer mortality
• HERS comparable increase in breast cancer in
  women on estrogen/ MPA over 6.8 years
• Conflicting evidence in several cohort studies
• WHI no increase risk on estrogen alone after 5
  years of follow-up so far

13
Breast Cancer

• good evidence for increased risk for breast
  cancer, but equivocal data regarding mortality
  from breast cancer

14
Heart Disease (CHD)

• WHI increased risk for fatal and nonfatal MI for
  those on daily CEE/MPA
• Mortality was not significantly increased
• Meta-analysis of observational studies showed
  significant reduction in CHD among current HRT
  users
• Selection bias (tendency for healthier women to
  use HRT) may account for protective effect in
  observational studies

15
Heart Disease (cont)

• HRT does not decrease and may in fact increase
  the incidence of CHD no definitive effect on
  mortality, however

16
Stroke

• WHI increased incidence of stroke in women
  taking daily CEE/MPA
• fair evidence for increased risk of stroke with
  HRT

17
Blood Clots (DVT/ PE)

• WHI 2-fold increased rate of venous
  thromboembolic disease for those on CEE/MPA
• Risk highest in first year in 5 of 6 studies
  reporting use over time
• good evidence for increase risk of venous
  thromboembolism

18
Uterine/ Ovarian Cancer

• Uterine cancer increased with unopposed estrogen
  decreased with combined therapy
• Inconsistent correlation between HRT and ovarian
  cancer 2 good cohort studies report increased
  risk
• Insufficient evidence to determine effect of
  HRT on ovarian cancer

19
Gallbladder Disease

• Nurses Health Study reported increased risk of
  cholecystitis for those on HRT
• HERS increase in biliary surgery for those on
  HRT
• Fair evidence for increase risk of cholecystitis

20
Summary
21
US Preventive Task Force

• Recommendations
• Against routine use of estrogen/ progestin for
  the prevention of chronic conditions in
  postmenopausal women
• Did not evaluate use of HRT to treat
  postmenopausal symptoms
• Insufficient evidence regarding estrogen alone to
  prevent chronic conditions

22
Clinical Considerations

• Absolute risk increase from HRT is modest for
  women aged 50-79, 10,000 taking estrogen/
  progestin for 1 yr might have
• 7 additional CHD events
• 8 more strokes 8 more blood clots
• 8 more invasive breast cancers
• 6 fewer cases of colorectal cancer
• 5 fewer hip fractures

23
Clinical Considerations (cont)

• We lack information on variations in dose,
  duration and type of estrogen/ progestin for HRT
• We need to use a shared-decision making model,
  reviewing individual risk factors and preferences
• Might natural estrogens/ progestins be more
  protective?

24
Conjugated Equine Estrogen

• Premarin (CEE)
• Derived from horse urine, which contains a dozen
  different estrogen compounds, only one of which
  is an exact replica of a human estrogen compound
  (estradiol)
• Most pills, patches, creams also only contain
  this one human estrogen compound

25
Natural Estrogens

• Exact chemical replica of what our body produces
• Estradiol aggressive estrogen about 10 of body
  make-up
• Estrone also more aggressive estrogen about 10
  of body make-up
• Estriol more benign estrogen about 80 of body
  make-up thought to be protective

26
Progestins

• Also a differentiation between chemical hormonal
  substitutes such as medroxyprogesterone (Provera)
  (MPA) and natural, hormone replicas such as
  progesterone
• Chemical substitutes cannot exactly match our
  bodys hormone communication pathways
• Little research on natural hormones

27
Are There Other Options?

• Bone?
• Hot flashes?
• Natural estrogens/ progestins?
• Soy?

28
Resources

• www.preventiveservices.ahrq.gov
• www.womenshealth.com
• National Womens Health Hotline [phone]