Risks and Side Effects of Bioidentical Hormone Replacement Therapy

Cardiovascular and Thrombotic Risks

Bioidentical HRT increases the risk of stroke, with a relative risk of 1.12 (95% CI, 1.01 to 1.23) according to meta-analyses of observational studies 3, 4
Venous thromboembolism risk is significantly increased with HRT use (RR, 2.14 [95% CI, 1.64 to 2.81]), with highest risk occurring within the first year of use (RR, 3.49 [95% CI, 2.33 to 5.59]) 1, 5
HRT may increase the risk of coronary heart disease rather than decrease it, as was previously thought 4, 6
Transdermal administration of estrogen is associated with lower thrombotic risk compared to oral routes (odds ratio for venous thromboembolism of 0.9 compared to 4.2 for oral preparations) 7

Unopposed estrogen therapy significantly increases the risk of endometrial cancer (RR, 2.3 [95% CI, 2.1 to 2.5]), with risk increasing with duration of use (RR, 9.5 for 10 years of use) 1, 5
Combined estrogen-progestin therapy has shown increased breast cancer incidence (RH, 1.26 [95% CI, 1.00 to 1.59]) in the Women's Health Initiative study 4, 8
Data on ovarian cancer risk are inconsistent, but some cohort studies report increased risks (RR, 1.8 to 2.2) for women who have taken HRT for 10 years or more 5, 6
Women with BRCA gene mutations should be particularly cautious about HRT use due to potential breast cancer risk 9

Increased risk of cholecystitis has been reported among current HRT users (RR, 1.8 [95% CI, 1.6 to 2.0]) and long-term users (>5 years) (RR, 2.5 [95% CI, 2.0 to 2.9]) 1, 5

17-β estradiol is preferred to ethinylestradiol or conjugated equine estrogens for estrogen replacement 9
Transdermal estradiol is the preferred method of delivery for women with hypertension 9, 7

Women with an intact uterus must use progestogen in combination with estrogen to protect the endometrium from hyperplasia and cancer 1, 5
Risk of venous thromboembolism is highest within the first year of HRT use 1, 5

Annual clinical reviews are recommended for women using bioidentical HRT, with particular attention to compliance 9