Hormone Replacment Therapy… and other options

1. Hormone Replacment Therapy… and other options Marc Childress, MD

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

3. 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

4. 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)

5. 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

6. 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

7. 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

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

9. 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 Alzheimer’s

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

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

12. 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

13. CV Disease, cont’d • 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

14. CV Disease, cont’d • 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)

15. 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

16. 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 Overview

17. Additional Options

18. Osteoporosis • Everything you already knew, remember that!

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

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

21. 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”

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

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

24. 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

25. 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

26. 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

27. 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

28. Questions ?