Hormone Replacment Therapy and other options

Risks vs. Benefits in 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/1000ptyears Est alone RR of .77 (? significance)

Excess risk approx of anticipated Question of prognosis, timeframe of concern

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)

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 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 Alzheimers

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 nonfatal 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, 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

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)

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 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

Osteoporosis

Everything you already knew, remember that!

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)

Vasomotor Symptoms

Pharmacologic Therapies
Clonidine--alpha-2 adrenergic agonist

Consider in women with hypertension

Gabapentinunknown mechanism, generally demonstrates reduction in hot flashes

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

Vasomotor Symptoms

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

Vasomotor Symptoms

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

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

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

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

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

Questions ?