Hormone Replacment Therapy… and other options

Marc Childress, MD

Risks vs. Benefitsin a post-WHI world

• Cancer Risk• Osteoporosis• Dementia• Vasomotor

Symptoms• Urogenital

Symptoms• Cardiovascular

Disease*

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

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

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

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

Osteoporosis

• Well established• Risk reduced at

hip, vertebrae, and wrist over placebo

• Similar numbers for estrogen alone vs combined tx.

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

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

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

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

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)

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

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

Additional OptionsAdditional Options

OsteoporosisOsteoporosis

Everything you already knew, Everything you already knew, remember that!remember that!

Vasomotor SymptomsVasomotor Symptoms

Pharmacologic TherapiesPharmacologic Therapies– SNRIs—Venlafaxine (Effexor) shows SNRIs—Venlafaxine (Effexor) shows

good resultsgood results– SSRIs—Paroxetine with good data, SSRIs—Paroxetine with good data,

fluoxetine less but helpfulfluoxetine less but helpful– Megestrol Acetate (synthetic Megestrol Acetate (synthetic

progestin)—hot flash reduction of progestin)—hot flash reduction of 85% vs 21% for placebo (wt gain 85% vs 21% for placebo (wt gain side effect)side effect)

Vasomotor SymptomsVasomotor Symptoms

Pharmacologic TherapiesPharmacologic Therapies– Clonidine--alpha-2 adrenergic Clonidine--alpha-2 adrenergic

agonistagonist Consider in women with hypertensionConsider in women with hypertension

– Gabapentin—unknown mechanism, Gabapentin—unknown mechanism, generally demonstrates reduction in generally demonstrates reduction in hot flasheshot flashes

Herbal OptionsHerbal Options

““These wonderful These wonderful adaptogenic and adaptogenic and balancing plants are balancing plants are truly the wealth of truly the wealth of the rainforest. the rainforest. Women rely on in Women rely on in their time of need.”their time of need.”

““*the ingredients *the ingredients may be subject to may be subject to change”change”

Vasomotor SymptomsVasomotor Symptoms

Herbal/Complementary Herbal/Complementary CompoundsCompounds– Black Cohosh—European studies Black Cohosh—European studies

support use, mixed (mostly positive support use, mixed (mostly positive results in small trials)results in small trials)

– Soy Compounds—flaxseed, red Soy Compounds—flaxseed, red clover—long term studies and meta-clover—long term studies and meta-analyses show no benefitanalyses show no benefit

Vasomotor SymptomsVasomotor Symptoms

Not HelpfulNot Helpful– ginseng, dong quai, evening ginseng, dong quai, evening

primrose oil, acupuncture, wild yam, primrose oil, acupuncture, wild yam, progesterone creams, vitamin Eprogesterone creams, vitamin E

What they want you to What they want you to know…know…

2003, q. 1312003, q. 131

In the postmenopausal woman with hot In the postmenopausal woman with hot flashes who cannot take estrogen, which one flashes who cannot take estrogen, which one of the following may help?of the following may help?

Diazepam (Valium)Diazepam (Valium) B-BlockersB-Blockers Clonidine (Catapres)Clonidine (Catapres) Meclizine (Antivert)Meclizine (Antivert) Vitamin CVitamin C

What they want you to What they want you to know…know… 2003, q. 142003, q. 14

Black Cohosh (Cimicifuga racemosa) is an Black Cohosh (Cimicifuga racemosa) is an herbal remedy used by patients forherbal remedy used by patients for

dementiadementia menopausal symptomsmenopausal symptoms nausea and vomitingnausea and vomiting benign prostatic hypertrophybenign prostatic hypertrophy osteoarthritisosteoarthritis

Urogenital SymptomsUrogenital Symptoms

Can use local estrogenCan use local estrogen– CreamCream– RingsRings

EstringEstring– low dose, local effectlow dose, local effect– No effect on vasomotor symptomsNo effect on vasomotor symptoms

FemRingFemRing– higher dose, systemic effecthigher dose, systemic effect– May be used for vasomotor symptoms May be used for vasomotor symptoms – Rememeber your progestin in patients with Rememeber your progestin in patients with

uterusuterus

Urogenital SymptomsUrogenital Symptoms

Local estrogen can improve Local estrogen can improve atrophic vaginitis, irritative atrophic vaginitis, irritative symptoms, coital discomfortsymptoms, coital discomfort

No clear evidence to support use No clear evidence to support use for presumed secondary for presumed secondary incontinenceincontinence– Pursue alternative diagnosesPursue alternative diagnoses

Questions ?Questions ?