Hormone Replacment Therapy… and other options

Risks vs. Benefits in a post-WHI world
• • • • Cancer Risk Osteoporosis Dementia Vasomotor Symptoms • Urogenital Symptoms • Cardiovascular Disease*

timeframe of concern .Breast Cancer • Mixed Results • Long-time association of increased estrogen levels and breast CA • WHI arm of est/pro showed relative risk of 1.77 (? significance) • Excess risk approx ½ of anticipated • Question of prognosis.24 (over 5 years) ~1 case/1000ptyears • Est alone RR of .

Gratuitous Perspective Slide • Increased risk of breast CA with 10% weight gain (2 add’l cases per 1000 pt-years) • Increased risk of breast CA with combined tx (0.8 add’l cases per 1000 pt-years) .

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 .

000 pt/years (RR 1. lasts 15 years . but small numbers) • There IS a signif risk reduction associated with OCPs • Risk reduction after 3 mos.6.Ovarian Cancer • No overt correlation b/w combined HRT and ovarian CA risk • 42 vs 27 cases per 100.

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 .

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

Dementia • Presumed correlation with longterm estrogen and cognitive fxn • WHIMS (memory study) • NO benefit • Insignificant increase in incidence • No evid for short or long term use in prevention of Alzheimer’s .

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

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

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

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

HR 1.5 vs 1.3) .7 events per 1000 patient/years) • Less significant risk increase with estrogen alone (still present. cont’d • Venous Thromboembolism • Small numbers.CV Disease. but roughly 2-fold increase in incidence with oral combined therapy (3.

What they want you to know… • • 2003. She still has her uterus and ovaries. q. 106 A 60 year-old female has been on conjugated equine estrogens/medroxyprogesterone (prempro) since she went through menopause at age 52. 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 The The The The incidence of stroke is decreased incidence of myocardial infarction is decreased incidence of pulmonary embolism is decreased risk of breast cancer is increased incidence of colorectal cancer is increased • • • • • • .

Overview • Current indications (brief? Tx) • Vasomotor sxs • Sleep disturbance • Urogenital changes • • Additional benefits Risks include • Osteoporosis prevention • 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 .

Additional Options .

remember that! .Osteoporosis  Everything you already knew.

fluoxetine less but helpful – Megestrol Acetate (synthetic progestin)— hot flash reduction of 85% vs 21% for placebo (wt gain side effect) .Vasomotor Symptoms  Pharmacologic Therapies – SNRIs—Venlafaxine (Effexor) shows good results – SSRIs—Paroxetine with good data.

Vasomotor Symptoms  Pharmacologic Therapies – Clonidine--alpha-2 adrenergic agonist  Consider in women with hypertension – Gabapentin—unknown mechanism. generally demonstrates reduction in hot flashes .

Herbal Options  ―These wonderful adaptogenic and balancing plants are truly the wealth of the rainforest.‖ ―*the ingredients may be subject to change‖  . Women rely on in their time of need.

mixed (mostly positive results in small trials) – Soy Compounds—flaxseed.Vasomotor Symptoms  Herbal/Complementary Compounds – Black Cohosh—European studies support use. red clover— long term studies and meta-analyses show no benefit .

Vasomotor Symptoms  Not Helpful – ginseng. evening primrose oil. progesterone creams. vitamin E . wild yam. acupuncture. dong quai.

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      . q.What they want you to know…   2003.

What they want you to know…  2003. 14 Black Cohosh (Cimicifuga racemosa) is an herbal remedy used by patients for dementia menopausal symptoms nausea and vomiting benign prostatic hypertrophy osteoarthritis       . q.

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

Urogenital Symptoms   Local estrogen can improve atrophic vaginitis. coital discomfort No clear evidence to support use for presumed secondary incontinence – Pursue alternative diagnoses . irritative symptoms.

Questions ? .

.

.37.

19590. 36515..65:.

.

.37.

331465:.5 59. 65:195645.79.75.9.6556.:: .55256540./.5:4  .75.:910. 3.5:65  ./..

 /:/0.1.50573.5 ..:.46 51   .7.5915.65: ':65193 ..3.650.3"7.9.60.93.569:.:4.5. 9.9/.9 .51 /. 64593 655.3.6.

3:  &6647651:3.9647651:  3.0266:967.:646.1::7769.3647345..:1 910369 &6647651:3. 3.33.9.94:.69&47.9:3.1:.5:.:5 :4.376:.:1 910369 365..0266: : 41 46:.64: 9/.514.

365.1:.514.94:.

5. ..3:: :656/5.

4 796:.9 31..69&47.4: .373  5:5 1658.0750..:646. 5579496:63  .45 .965 09.64: !6.

6 256Ã  8  5.3.5.556. 633654.965 0656.4567.5....4 ..364.7...2:.:: 60.:.76:.37 .34 .6.6.

.79: 035 5..36029: 36515 ..45 . .9.

.: .6 256Ã  8  3..:.967 6:...3 941:1/7..59/.5 /55796:.9. 4567.:69 145.5.6.. :.6.:.079.9..64: 5.5.3:47.0266: 40..5164.9.046:..

:646.64:  %44/969796:.3&47.4  %5: :.64: .95  3616: 360.9: .557..3:..64: 4%5  916: ::.400.965.5.  .  !60./:169.5:360.30.:646.69:47.965  9.69:47..65.:.

550  #9:.6:7769. !603.3:.5.1.3 1:06469.3.54796.9670 ..95.965..:69 79:41:0651.95065...: 99.64: 06.:47..9650.3&47.56:: ..9150.64: 60.

65: .$:.