Hormone Replacment Therapy

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Hormone Replacment Therapy and other options

• Marc Childress, MD

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Risks vs. Benefitsin a post-WHI world

• Cancer Risk
• Osteoporosis
• Dementia
• Vasomotor Symptoms
• Urogenital Symptoms
• Cardiovascular Disease

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Breast Cancer

• Mixed Results
• Long-time association of increased estrogen
  levels and breast CA
• WHI arm of est/pro showed relative risk of 1.24
  (over 5 years) 1 case/1000pt-years
• Est alone RR of .77 (? significance)
• Excess risk approx ½ of anticipated
• Question of prognosis, timeframe of concern

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Gratuitous Perspective Slide

• Increased risk of breast CA with 10 weight gain
  (2 addl cases per 1000 pt-years)
• Increased risk of breast CA with combined tx (0.8
  addl cases per 1000 pt-years)

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Endometrial Cancer

• Known increase in risk with unopposed estrogen
• WHI showed no signif risk of CA with combined tx
• Increased risk of bx for irregular bleeding

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Ovarian Cancer

• No overt correlation b/w combined HRT and ovarian
  CA risk
• 42 vs 27 cases per 100,000 pt/years (RR 1.6, but
  small numbers)
• There IS a signif risk reduction associated with
  OCPs
• Risk reduction after 3 mos, lasts 15 years

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Colorectal Cancer

• Signif Risk Reduction of Colon CA with combined
  Est/Pro
• 43 vs 72 cases
• While less cases, trend toward worse prognosis
  (nodal spread)
• No risk reduction observed with estrogen alone

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Osteoporosis

• Well established
• Risk reduced at hip, vertebrae, and wrist over
  placebo
• Similar numbers for estrogen alone vs combined tx.

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Dementia

• Presumed correlation with long-term estrogen and
  cognitive fxn
• WHIMS (memory study)
• NO benefit
• Insignificant increase in incidence
• No evid for short or long term use in prevention
  of Alzheimers

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Vasomotor Symptoms

• Signif Reduction in hot flashes
• Mod improvement in sleep
• Well-known and unchanged (WHI predominantly
  asymptomatic, older women, not target of study)

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Urogenital Symptoms

• Can preclude occurrence of atrophic vaginitis
• Thought to prevent urinary incontinence,
  contradicted by WHI and HERS

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Cardiovascular Disease

• Counter to previous belief, very small increase
  in risk of CV events with combined tx (6-7 cases
  per 10,000 person/years, increase in non-fatal
  MI)
• Corroboration of HERS-I, HERS-II, WAVE
• Estrogen alone did not show increase in risk of
  CV events, ? protective effect for
  younger women

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CV Disease, contd

• Stroke
• Confusing results based on where you look for
  data
• Meta-analysis of randomized trials to include
  WHI, HERS, WEST suggest increase in ischemic, but
  not hemorrhagic stroke
• Stroke more likely fatal in patients taking oral
  estrogen

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CV Disease, contd

• Venous Thromboembolism
• Small numbers, but roughly 2-fold increase in
  incidence with oral combined therapy (3.5 vs 1.7
  events per 1000 patient/years)
• Less significant risk increase with estrogen
  alone (still present, HR 1.3)

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What they want you to know

• 2003, q. 106
• A 60 year-old female has been on conjugated
  equine estrogens/medroxyprogesterone (prempro)
  since she went through menopause at age 52. She
  still has her uterus and ovaries. She is having
  no side effects that she is aware of and is
  experiencing no vaginal bleeding. She is worried
  about the health effects of her hormone
  replacement therapy and asks your advice about
  risks versus benefits.
• Which one of the following would be accurate
  advice regarding these risks and benefits?
• The incidence of stroke is decreased
• The incidence of myocardial infarction is
  decreased
• The incidence of pulmonary embolism is decreased
• The risk of breast cancer is increased
• The incidence of colorectal cancer is increased

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Overview

• Current indications (brief? Tx)
• Vasomotor sxs
• Sleep disturbance
• Urogenital changes
• Additional benefits
• Osteoporosis prevention
• Risks include
• Increase in ischemic stroke
• Increase in DVT, PE
• Mild increase in breast CA risk for combined tx
• Increase in inconclusive mammograms
• Increase in GB dz with combined tx

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Additional Options
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Osteoporosis

• Everything you already knew, remember that!

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Vasomotor Symptoms

• Pharmacologic Therapies
• SNRIsVenlafaxine (Effexor) shows good results
• SSRIsParoxetine with good data, fluoxetine less
  but helpful
• Megestrol Acetate (synthetic progestin)hot flash
  reduction of 85 vs 21 for placebo (wt gain side
  effect)

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Vasomotor Symptoms

• Pharmacologic Therapies
• Clonidine--alpha-2 adrenergic agonist
• Consider in women with hypertension
• Gabapentinunknown mechanism, generally
  demonstrates reduction in hot flashes

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Herbal Options

• These wonderful adaptogenic and balancing plants
  are truly the wealth of the rainforest. Women
  rely on in their time of need.
• the ingredients may be subject to change

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Vasomotor Symptoms

• Herbal/Complementary Compounds
• Black CohoshEuropean studies support use, mixed
  (mostly positive results in small trials)
• Soy Compoundsflaxseed, red cloverlong term
  studies and meta-analyses show no benefit

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Vasomotor Symptoms

• Not Helpful
• ginseng, dong quai, evening primrose oil,
  acupuncture, wild yam, progesterone creams,
  vitamin E

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What they want you to know

• 2003, q. 131
• In the postmenopausal woman with hot flashes who
  cannot take estrogen, which one of the following
  may help?
• Diazepam (Valium)
• B-Blockers
• Clonidine (Catapres)
• Meclizine (Antivert)
• Vitamin C

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What they want you to know

• 2003, q. 14
• Black Cohosh (Cimicifuga racemosa) is an herbal
  remedy used by patients for
• dementia
• menopausal symptoms
• nausea and vomiting
• benign prostatic hypertrophy
• osteoarthritis

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Urogenital Symptoms

• Can use local estrogen
• Cream
• Rings
• Estring
• low dose, local effect
• No effect on vasomotor symptoms
• FemRing
• higher dose, systemic effect
• May be used for vasomotor symptoms
• Rememeber your progestin in patients with uterus

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Urogenital Symptoms

• Local estrogen can improve atrophic vaginitis,
  irritative symptoms, coital discomfort
• No clear evidence to support use for presumed
  secondary incontinence
• Pursue alternative diagnoses

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Questions ?