Hormones and Heart Disease

Jewish Hospital Cholesterol Center, Charles J. Glueck MD, Director, James E. Lang MD, Associate Director, LeAnn Coberly MD Assistant Medical Director. Jewish Hospital Cholesterol Center, 3200 Burnet Ave, Cincinnati, Ohio 45229. 

Phone: 513-585-7800 Fax: 513-585-7950
E-mail: glueckch@healthall.com or cglueck@fuse.net  
web: http://www.jewishhospitalcincinnati.com/cholesterol

Estrogen Replacement Therapy should not be used if a woman has:

• blood clots
• severe chronic migraine headaches        
• breast or uterine cancer
• triglycerides above 300 mg/dl   
• hepatitis
• factor V Leiden gene mutation           
• unexplained vaginal bleeding
• prothrombin gene mutation           
• pregnant or chance of pregnancy                                

Estrogen Replacement Therapy probably should not be used if a woman has:

• gallbladder disease
• heart or kidney failure
• uterine fibroids
• impaired liver function 
• high blood pressure
• fibrocystic breast changes
• asthma
• family history of breast or uterine cancer
• seizures
• not quit smoking
• high calcium in the blood

Estrogen Replacement Therapy is indicated if a woman has none of the above but has:

• moderate to severe hot flashes             
• vaginal or urethral atrophy
• osteoporosis prevention
• hormonal imbalance associated with endometrial hypoplasia or atrophy
• surgical removal of ovaries before age 50

Estrogen/Progesterol (E/P), Triglycerides, Blood Clots:

1. Never give E/P unless fasting plasma triglycerides have first been measured. 
   • triglyceride >300 and <500 mg/dl, then E/P relatively contraindicated
   • if >500, absolutely contraindicated
2. Some women (6% of Caucasians) have a genetic defect (mutant factor V Leiden) which puts them at greater risk for blood clots.  If you have a family history of clotting problems or strokes, it may be a good idea to talk to your doctor about genetic testing for this gene before going on estrogen or estrogen-containing oral contraceptives.

Women's Health Initiative (WHI) trial

(Rossouw J, et al, JAMA 2002:288:321-333)

Subjects:
16,608 women (ages 50-79) with intact uterus

Design:
Randomly assigned to receive estrogen/progestin (8,506 women) or placebo (8,102 women) 

Outcomes:
Primary Outcome Measure: coronary heart disease (CHD)
Primary Adverse Outcome: breast cancer
Additional Outcomes Assessed:

• stroke
• pulmonary embolism (PE)
• endometrial cancer
• colorectal cancer
• hip fracture
• death due to other causes

Results:
Estimated Hazard Ratios (HR)

• CHD was 1.29, 95% CI 1.02-1.63
• HR for breast cancer 1.26
• HR for stroke 1.41
• HR for PE 2.13

Composite Results:

• Total cardiovascular disease HR: 1.22, 95% CI 1.09-1.36
• Total cancer HR =1.06

Absolute excess risks per 10,000 person-years:

• 7 more CHD events
• 8 more strokes
• 8 more PEs
• 8 more invasive breast cancers

Risk reductions included:

• 6 fewer colorectal cancers
• 5 fewer hip fractures

Absolute excess risk of events was 19/10,000 person years:

The increases in the numbers of invasive breast cancers, CHD, stroke, and PE made approximately equal contributions to harm in the estrogen-progestin group compared with placebo.

Conclusion:

Women should not start or continue combined HRT for the prevention of CHD.
To prevent heart attack and stroke in women treat CHD risk factors

• high LDL cholesterol with diet and statins
• high triglycerides with diet and fibric acid derivatives
• high blood pressure
• homocysteine
• etc.

Speculation:

Much of the CHD and PE could be attributable to the atherothrombotic interaction between exogenous estrogen and the thrombophlic Factor V Leiden and Prothrombin gene mutations which occur in ~6% and 6% of the Caucasian female population (Glueck CJ et al, Metabolism 2002; 51:724-732.

E-mail: glueckch@healthall.com
or cglueck@fuse.net
Fax: 513-585-7950