What are the estimated risks of Hormone Replacement Therapy (HRT) per 100 women treated?

HRT Risks Per 100 Women Treated

For every 100 women taking combined estrogen-progestin HRT for one year, expect approximately 1 additional stroke, 1 additional venous thromboembolism (DVT or PE), and 1 additional breast cancer case compared to non-users. 1

Absolute Risk Estimates from the Women's Health Initiative

Combined Estrogen-Progestin Therapy (per 10,000 women-years)

Cardiovascular Events:

• 9 additional strokes (HR 1.34,95% CI 1.05-1.71) 1
• 12 additional deep venous thromboses (HR 1.88,95% CI 1.38-2.55) 1
• 9 additional pulmonary emboli (HR 1.98,95% CI 1.36-2.87) 1

Cancer:

• 8 additional invasive breast cancers (HR 1.25,95% CI 1.07-1.46) 1
• 5 additional lung cancer deaths (HR 1.71,95% CI 1.16-2.52) 1

Gastrointestinal:

• 20 additional cases of gallbladder disease (HR 1.61,95% CI 1.30-2.00) 1

Cognitive:

• 22 additional cases of probable dementia (HR 2.05,95% CI 1.21-3.48) in women aged 65+ 1

Urinary:

• 872 additional cases of urinary incontinence (HR 1.39,95% CI 1.27-1.52) 1

Estrogen-Only Therapy (per 10,000 women-years)

Cardiovascular Events:

• 11 additional strokes (HR 1.36,95% CI 1.08-1.71) 1
• 7 additional deep venous thromboses (HR 1.47,95% CI 1.06-2.05) 1

Cancer:

• 8 fewer invasive breast cancers (HR 0.77,95% CI 0.62-0.95) 1
• 2 fewer breast cancer deaths (HR 0.37,95% CI 0.13-0.91) 1

Gastrointestinal:

• 33 additional cases of gallbladder disease (HR 1.79,95% CI 1.44-2.22) 1

Urinary:

• 1,271 additional cases of urinary incontinence (HR 1.53,95% CI 1.37-1.71) 1

Benefits (per 10,000 women-years)

Combined Estrogen-Progestin:

• 6 fewer hip fractures (HR 0.67,95% CI 0.47-0.95) 1
• 6 fewer vertebral fractures (HR 0.68,95% CI 0.48-0.96) 1
• 46 fewer total fractures (HR 0.76,95% CI 0.69-0.83) 1
• 15 fewer diabetes cases (HR 0.79,95% CI 0.67-0.93) 1

Estrogen-Only:

• 7 fewer hip fractures (HR 0.61,95% CI 0.41-0.91) 1
• 6 fewer vertebral fractures (HR 0.62,95% CI 0.42-0.93) 1
• 56 fewer total fractures (HR 0.70,95% CI 0.63-0.79) 1

Converting to Per 100 Women-Years

To express these risks per 100 women treated for one year, divide all the above numbers by 100:

Combined Estrogen-Progestin (per 100 women-years):

• 0.9 additional strokes
• 1.2 additional DVTs
• 0.9 additional PEs
• 0.8 additional breast cancers
• 2.0 additional gallbladder disease cases
• 0.6 fewer hip fractures
• 4.6 fewer total fractures

Estrogen-Only (per 100 women-years):

• 1.1 additional strokes
• 0.7 additional DVTs
• 0.8 fewer breast cancers
• 3.3 additional gallbladder disease cases
• 0.7 fewer hip fractures
• 5.6 fewer total fractures

Critical Risk Modifiers

Timing of Initiation:

• Venous thromboembolism risk is highest within the first year of use (RR 3.49,95% CI 2.33-5.59) 1

Duration of Use:

• Breast cancer risk increases by a factor of 1.023 per year of use among current users 2
• After 5+ years of combined therapy, relative risk reaches 1.35 (95% CI 1.21-1.49) 2
• Endometrial cancer risk with unopposed estrogen reaches RR 9.5 after 10 years 1, 3

Route of Administration:

• Transdermal estrogen significantly reduces VTE risk compared to oral (OR 0.9 vs 4.2) 4, 5

Essential Clinical Pitfalls to Avoid

Never prescribe unopposed estrogen to women with an intact uterus - endometrial cancer risk is unacceptably high (RR 2.3, escalating to 9.5 with prolonged use) 1, 3

Do not use HRT for chronic disease prevention - the cardiovascular and cancer risks outweigh benefits for this indication 3

Recognize that risks are cumulative - absolute risk in a single year appears small, but multiplies with duration of therapy 6