WHI and menopause

Question 1

Interpretation of WHI data

Answer 1

• Can’t be extrapolated to the typical population using HRT Avg. age was 63 at screening.
• Majority of women initiate HRT to alleviate menopausal symptoms
• Women with severe menopausal symptoms were excluded from trial
• 75% of HRT users initiate therapy within 5 years of menopause; mean age of menopause, 51 years
• Menopausal age of patients in WHI has not yet been reported

Question 2

Comparison of WHI data with observational studies

Answer 2

• AGREE:
• increase in VTE with oral HRT
• increase in Breast cancer diagnosis with HRT
• Increase CVA when started in older women (1.2x greater risk)
• decrease hip fracture
• decrease in colon cancer
• DISAGREE
• increase in CHD
• increase in dementia only >age70 in first year of HRT (found to be decreased with ERT in cohort study)
• E alone protective in breast cancer

Question 3

Problems with WHI study

Answer 3

• HTN not controlled
• high rates of unblinding in the HRT vs placebo arm of study
• global index created for the study not validated and significance of assigning equal weights to various conditions unexamined
• statistical analyses: confusion in reporting type of Confidence interval used

Question 4

Endocrine changes of menopause

Answer 4

• Menopause is permanent cessation of menstruation (usually around 51) due to low endogenous ovarian estrogen production causing lack of endometrial growth
• Etiology is depletion of functioning ovarian follicles which would normally produce E2 in response to LH/FSH
• Causes hypergonatotropic hypogonadism (GnRH/LH/FSH levels rise dramatically, inhibin levels fall in response to low E)
• Results in dramatically lower systemic E levels

Question 5

Effects of menopause

Answer 5

• Quality of life: lack of estrogen causes hot flashes/sweats (changes in hypothalamic thermoregulation), fatigue, depression, decreased libido, vaginal atrophy, incontinence
• CV system: favors atherosclerosis progression (changes lipid profile, promotes vasoconstriction and platelet aggregation)
• CNS: irritability, mood swings, lack of concentration/memory
• Skeleton: decreased bone density due to increased bone resorption (E inhibits resorption)

Question 6

Compare benefits and risks of administering ERT/HRT to menopausal women 1

Answer 6

• QOL: benefits: improves hot flashes, sexual functions, sleep problems, muscle/joint pain, decreases mortality ages 50-59
• QOL risks: causes breast tenderness, vaginal moisture, uterine bleeding
• CVD benefits: improves lipid profile (increases HDL, decreases LDL), improves carb metabolism (decreases DM risk), improves cardiac contractility and coronary artery blood flow
• CVD risks: ERT must be initiated early, if started after age 70 there is detrimental effect on CV health, in all HRT there is increased risk of thromboembolic events
• CNS benefits: protective effect against alzheimers if initiated early (before 60), no increased risk of CVA/dementia if started on low dose before age 60

Question 7

Compare benefits and risks of administering ERT/HRT to menopausal women 2

Answer 7

• CNS risks: after age 60 increased risk of CVA/dementia due to deleterious effect on narrowed cerebral arteries, does not improve AD Sxs or progression
• Osteoporosis benefits: decreases risk of hip Fx and vertebral Fx by inhibiting bone resorption
• Gallbladder disease risk is increased w/ ERT or HRT
• CRC: HRT decreases risk of CRC
• HRT does not increase risk for ovarian CA
• Risks of CA: endometrial CA risk is substantial when there is unopposed E (add P to stabilize endometrium and reduce CA risk), breast CA risk is mildly increased on HRT since P stimulates mitosis in breast tissue (E alone seems to have protective effect against breast CA)